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

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

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 Dutch chronic lower limb-threatening ischemia registry (THRILLER): A study protocol for popliteal and infrapopliteal endovascular interventions

INTRODUCTION: Chronic limb-threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD) and is associated with high amputation rates, mortality and disease-related health care costs. In infrapopliteal arterial disease (IPAD), endovascular revascularization should be considered for the majority of anatomical and clinical subgroups of CLTI. However, a gap of high-quality evidence exists in this field. The aim of the Dutch Chronic Lower Limb-Threatening Ischemia Registry (THRILLER) is to collect real world data on popliteal and infrapopliteal endovascular interventions. METHODS: THRILLER is a clinician-driven, prospective, multicenter, observational registry including all consecutive patients that undergo a popliteal or infrapopliteal endovascular intervention in seven Dutch hospitals. We estimate that THRILLER will include 400-500 interventions annually. Standardized follow-up visits with wound monitoring, toe pressure measurement and duplex ultrasonography will be scheduled at 6-8 weeks and 12 months after the intervention. The independent primary endpoints are primary patency, limb salvage and amputation free survival. Patients must give informed consent before participation and will be included according to predefined reporting standards. A data log of patients who meet the inclusion criteria but are not included in the registry will be maintained. We intend to conduct the first interim analysis two years after the start of inclusion. The results will be published in a scientific journal. DISCUSSION: Despite innovations in medical therapy and revascularization techniques, patients with CLTI undergoing endovascular revascularization still have a moderate prognosis. Previous prospective cohort studies were hampered by small sample sizes or heterogeneous reporting. Randomized controlled trials (RCTs) have high costs, potential conflicts of interest and give a limited reflection of daily practice. THRILLER aims to provide the largest prospective well phenotyped up-to-date dataset on treatment outcomes in CLTI patients to answer multiple underexplored research questions regarding diagnostics, medication, patient selection, treatment strategies and post intervention follow-up

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

The effect of hydraulic retention time on the removal of pollutants from sewage treatment plant effluent in a surface-flow wetland system

We evaluated the effect of four hydraulic retention times (HRT, 0.3, 0.8, 2.3, and 9.3 days) on pollutant removal in a surface-flow wetland system for polishing tertiary effluent from a sewage treatment plant (STP). The removal efficiency of pollutants at these HRTs was based on mass budgets of the water inputs and outputs in parallel ditches, which together with a presettling basin, made up the wetland system. Fecal coliform and N-removal efficiencies in the ditches were enhanced by increasing the HRT, with only little removal of fecal coliforms during spring-summer at a HRT of 0.3 days. A HRT of 4 days turned out to be required to meet the desired bathing water standard for fecal coliforms (103 cfu 100 ml-1) and the future standard of ammonium (1 mg N 1-1) all year. An annual N-removal efficiency of approximately 45% can be accomplished in the ditches at this HRT, corresponding to an annual N mass loading rate of 150 g N m-2 yr-1. Annual P removal was not improved by increasing the HRT even up to 9.3 days, largely because of the still high P mass loading rate (14 g P m-2 yr-1) in combination with relatively low P input concentrations. Substantial P removal can probably only be achieved at HRTs longer than 15 days, which will not be feasible for the situation investigated because of the large land area that would be required to reach such long HRTs. The future P standard (1 mg P 1 -1) can therefore only be met by additional chemical P removal. In a densely populated country such as the Netherlands, adequate polishing of tertiary STP effluent in surfaceflow wetlands with similar goals as for this wetland is restricted to small and medium-sized STPs. The simultaneous use of these treatment wetlands for other functions, such as nature conservation, recreation, and flood control, however, would permit the use of relatively larger land areas

Which Instruments can Detect Submaximal Physical and Functional Capacity in Patients With Chronic Nonspecific Back Pain?: A Systematic Review

Objective. To evaluate the validity of instruments that claim to detect submaximal capacity when maximal capacity is requested in patients with chronic nonspecific musculoskeletal pain.\ud \ud Summary of Background Data. Several instruments have been developed to measure capacity in patients with chronic pain. The detection of submaximal capacity can have major implications for patients. The validity of these instruments has never been systematically reviewed.\ud \ud Methods. A systematic literature search was performed including the following databases: Web of Knowledge (including PubMed and Cinahl), Scopus, and Cochrane. Two reviewers independently selected the articles based on the title and abstract according to the study selection criteria. Studies were included when they contained original data and when they objectified submaximal physical or functional capacity when maximal physical or functional capacity was requested. Two authors independently extracted data and rated the quality of the articles. The included studies were scored according to the subscales “Criterion Validity” and “Hypothesis Testing” of the COSMIN checklist. A Best Evidence Synthesis was performed.\ud \ud Results. Seven studies were included, 5 of which used a reference standard for submaximal capacity. Three studies were of good methodological quality and validly detected submaximal capacity with specificity rates between 75% and 100%.\ud \ud Conclusion. There is strong evidence that submaximal capacity can be detected in patients with chronic low back pain with a lumbar motion monitor or visual observations accompanying a functional capacity evaluation lifting test