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Human brain organoid technology has the potential to generate unprecedented insight into normal and aberrant brain development. It opens up a developmental time window in which the effects of gene or environmental perturbations can be experimentally tested. However, detection sensitivity and correct interpretation of phenotypes are hampered by notable batch-to-batch variability and low reproducibility of cell and regional identities. Here, we describe a detailed, simplified protocol for the robust and reproducible generation of brain organoids with cortical identity from feeder-independent induced pluripotent stem cells (iPSCs). This self-patterning approach minimizes media supplements and handling steps, resulting in cortical brain organoids that can be maintained over prolonged periods and that contain radial glial and intermediate progenitors, deep and upper layer neurons, and astrocytes.

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OBJECTIVE This cohort study aimed to prospectively determine the impact of multidisciplinary team meetings (MDTs) on treatment plans in vascular patients. METHODS The weekly MDT at the institution consists of a structured discussion of vascular cases in the presence of at least one representative of each specialty from vascular surgery, angiology, and interventional radiology. Participants were asked to examine the cases entered on the digital MDT platform and to fill in forms with a detailed open text treatment recommendation for each patient. Individual recommendations were compared with the final MDT decision, which was based on a shared decision upon discussion of clinical and radiological data. The primary endpoint was the agreement rate. The rate of decision implementation was determined to verify the adherence to MDT recommendations. RESULTS Four hundred consecutive case discussions in 367 patients between November 2019 and March 2021 were included, excluding patients needing urgent treatment, yielding MDT discussion in 88.5% of carotid artery cases, 83% of aorto-iliac cases, and 51.7% of peripheral arterial cases, which included 56.9% of the chronic limb threatening ischaemia cases. The overall average agreement rate was 71% ± 41%. Analysis according to the specialty of the attending physician showed agreement rates of 82% ± 30% for senior vascular surgeons, 62% ± 44% for junior vascular surgeons, 71% ± 43% for interventional radiologists, 58% ± 50% for angiologists (p < .001), and 75% ± 38% considering only senior practitioners. The inter-rater agreement, resulted in kappa coefficients of 0.60 - 0.68 for senior vascular surgeons, 0.29 - 0.31 for junior vascular surgeons, 0.39 - 0.52 for interventional radiologists, and 0.25 for angiologists. The MDT treatment decision was implemented in 353 (96.2%) cases. CONCLUSION The impact of MDT discussion on treatment recommendations and the adherence to MDT recommendations were significant and in line with results reported from other specialties.

OBJECTIVES A survey was performed to evaluate the methods used for reduction or elimination of the aortic impulse (REAI) to facilitate precise stent graft placement and balloon moulding during thoracic endovascular aortic repair (TEVAR). METHODS A total of 127 physicians (1 per hospital) were contacted and asked to fill out a short, comprehensive questionnaire on an internet-based platform. RESULTS Fifty physicians (39.4%) responded and completed the survey. Routine use of REAI for stent graft deployment is most frequently used in the ascending aorta and less frequently in the aortic arch and the descending aorta (86.4% vs 69.4% vs 56%). Some physicians based the decision of whether to use REAI on the type of stent graft in the respective location (13.6% vs 24.5% vs 24.0%). Stent-graft deployment without REAI, irrespective of the type of stent graft used, was never done in the ascending aorta (0.0%), in 3 centres in the aortic arch (6.1%) and in 10 centres in the descending aorta (20%). The REAI method most frequently used was dependent on the aortic segment (ascending aorta vs aortic arch vs descending aorta) rapid right ventricular pacing (90.9% vs 59.2% vs 28.0%), followed by pharmacological blood pressure reduction (13.6% vs 53.1% vs 64.0%) and venous inflow occlusion (13.6% vs 14.3% vs 4.0%), respectively. Tip capture and non-occlusive deployment systems were frequently quoted as reasons for not using REAI. CONCLUSIONS REAI is the fundament for TEVAR in all thoracic aortic segments, with a decline in usage from proximal (ascending) to distal (descending). Rapid right ventricular pacing is the preferred REAI method used in TEVAR. Most procedures are performed with the patient under general anaesthesia. The types of stent grafts and moulding balloons used have an impact on the use or non-use of REAI.

Background: To share the results of a web-based expert panel discussion focusing on the management of acute and chronic aortic disease during the coronavirus (COVID-19) pandemic. Methods: A web-based expert panel discussion on April 18, 2020, where eight experts were invited to share their experience with COVID-19 disease touching several aspects of aortic medicine. After each talk, specific questions were asked by the online audience, and results were immediately evaluated and shared with faculty and participants. Results: As of April 18, 73.3% answered that more than 200 patients have been treated at their respective settings. Sixty-four percent were reported that their hospital was well prepared for the pandemic. In 57.7%, the percentage of infected healthcare professionals was below 5% whereas 19.2% reported the percentage to be between 10% and 20%. Sixty-seven percent reported the application of extracorporeal membrane oxygenationin less than 2% of COVID-19 patients whereas 11.8% reported application in 5%–10% of COVID-19 patients. Thirty percent of participants reported the occurrence of pulmonary embolism in COVID-19 patients. Three percent reported to have seen aortic ruptures in primarily elective patients having been postponed because of the anticipated need to provide sufficient ICU capacity because of the pandemic. Nearly70% reported a decrease in acute aortic syndrome referrals since the start of the pandemic. Conclusion: The current COVID-19 pandemic has—besides the stoppage of elective referrals—also led to a decrease of referrals of acute aortic syndromes in many settings. The reluctance of patients seeking medical help seems to be a major driver. The number of patients, who have been postponed due to the provisioning of ICU resources but having experienced aortic rupture in the waiting period, is still low. Further, studies are needed to learn more about the influence that the COVID-19 pandemic has on the treatment of patients with acute and chronic aortic disease.

We present OpenFish: an open source soft robotic fish which is optimized for speed and efficiency. The soft robotic fish uses a combination of an active and passive tail segment to accurately mimic the thunniform swimming mode. Through the implementation of a novel propulsion system that is capable of achieving higher oscillation frequencies with a more sinusoidal waveform, the open source soft robotic fish achieves a top speed of $0.85~\mathrm{m/s}$. Hereby, it outperforms the previously reported fastest soft robotic fish by $27\%$. Besides the propulsion system, the optimization of the fish morphology played a crucial role in achieving this speed. In this work, a detailed description of the design, construction and customization of the soft robotic fish is presented. Hereby, we hope this open source design will accelerate future research and developments in soft robotic fish.

Transcription pause-release is an important, highly regulated step in the control of gene expression. Modulated by various factors, it enables signal integration and fine-tuning of transcriptional responses. Mutations in regulators of pause-release have been identified in a range of neurodevelopmental disorders that have several common features affecting multiple organ systems. This review summarizes current knowledge on this novel subclass of disorders, including an overview of clinical features, mechanistic details, and insight into the relevant neurodevelopmental processes.

It is important for organizations to support employees with suitable workspaces during different activities. Increasingly the activity-based office is seen as the optimal solution, as it provides people with choice between different types of workspaces to perform specific activities. This study addresses the trade-offs knowledge workers make when choosing a workspace for performing three different categories of activities (individual concentration work, informal interactions, and formal interactions). A stated choice experiment was performed through a questionnaire among 251 Dutch knowledge workers in 14 organizations, measuring preferences for hypothetical workspaces described by their six most relevant aspects. Multinomial logit models were estimated to identify the workspace preferences during each activity. Additionally, Latent class models were estimated to find possible segments of workers with specific preferences that need to be supported differently by workplace managers. Findings showed that preferences for psychosocial design aspects (noise, workspace enclosure and control) were more important for workspace selection than indoor environmental quality aspects. They also show more differences between specific activities. Also, not everybody finds full enclosure important for individual concentrated work, and relatively older employees appear to be more critical about workspace suitability to support both formal and informal interaction.KEYWORDS: Occupant surveys, workplace effectiveness, workplace design, decision-making, stated choice

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Conspiracy theories are popular during the COVID-19 pandemic. Conspiratorial thinking is characterised by the strong conviction that a certain situation that one sees as unjust is the result of a deliberate conspiracy of a group of people with bad intentions. Conspiratorial thinking appears to have many similarities with paranoid delusions.To explore the nature, consequences, and social-psychological dimensions of conspiratorial thinking, and describe similarities and differences with paranoid delusions.Critically assessing relevant literature about conspiratorial thinking and paranoid delusions.Conspiratorial thinking meets epistemic, existential, and social needs. It provides clarity in uncertain times and connection with an in-group of like-minded people. Both conspiratorial thinking and paranoid delusions involve an unjust, persistent, and sometimes bizarre conviction. Unlike conspiracy theorists, people with a paranoid delusion are almost always the only target of the presumed conspiracy, and they usually stand alone in their conviction. Furthermore, conspiracy theories are not based as much on unusual experiences of their inner self, reality, or interpersonal contacts. CONCLUSIONS Conspirational thinking is common in uncertain circumstances. It gives grip, certainty, moral superiority and social support. Extreme conspirational thinking seems to fit current psychiatric definitions of paranoid delusions, but there are also important differences. To make a distinction with regard to conspiratorial thinking, deepening of conventional definitions of delusions is required. Instead of the strong focus on the erroneous content of delusions, more attention should be given to the underlying idiosyncratic, changed way of experiencing reality.

OBJECTIVES The aim of this study was to evaluate the effects of the coronavirus 2019 pandemic on elective and acute thoracic aortic surgery in the Netherlands. METHODS The Netherlands Heart Registration database was used to compare the volume of elective and acute surgery on the thoracic aorta in 2019 and 2020, starting from week 11 in both years. A sub-analysis was done to assess the impact of the pandemic on high-volume and low-volume aortic centres. RESULTS During the pandemic, the number of elective thoracic aortic operations declined by 18% [incidence rate ratio (IRR) 0.82 [0.73–0.91]; P < 0.01]. The decline in volume of elective surgery was significant in both high-volume (IRR 0.82 [0.71–0.94]; P < 0.01) and low-volume aortic centres (IRR 0.81 [0.68–0.98]; P = 0.03). The overall number of acute aortic operations during the pandemic remained similar to that in 2019 (505 vs 499; P = 0.85), but an increased share of these operations occurred at high-volume centres. The number of acute operations performed in high-volume centres increased by 20% (IRR 1.20 [1.01–1.42]; P = 0.04), while the number of acute operations performed in low-volume centres decreased by 17% (IRR 0.83 [0.69–1.00]; P = 0.04). CONCLUSIONS The coronavirus 2019 pandemic led to a significant decrease in elective thoracic aortic surgery but did not cause a change in the volume of acute thoracic aortic surgery in the Netherlands. Moreover, the pandemic led to a centralization of care for acute thoracic aortic surgery., The coronavirus disease 19 (COVID-19) pandemic has impacted the delivery of health care around the world.

Background: Severe acute respiratory syndrome from coronavirus-2 (SARS-CoV-2) has been associated with an increased risk of venous thromboembolism (VTE). Different anticoagulation protocols have been applied in several studies in the absence of clear evidence. A reliable deep venous thrombosis (DVT) indicator in critical patients with SARS-CoV-2 could guide the anticoagulation treatment; however, it has not yet been identified, and clinical applicability of the most common markers is debatable. The aim of our study was to determine the actual incidence of DVT in critically ill SARS-CoV-2 patients and to find a reliable tool to identify patients who might benefit from therapeutic-intensity anticoagulation.Methods: From March 1, 2020 to May 31, 2020, all patients admitted to the intensive care unit (ICU) for SARS-CoV-2 at Ospedale Regionale di Locarno, Locarno, Switzerland, were prospectively enrolled and screened daily with ultrasound for DVT. Following international consensus, a higher-intensity thromboprophylaxis was administered to all patients who were not at increased risk for bleeding. Sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores were calculated and time-to-DVT event in a COX proportional-hazard regression model was performed. A receiver operating characteristic (ROC) curve was used to determine sensitivity and specificity and the Youden's Index to establish the best threshold.Results: A total of 96 patients were enrolled. Deep venous thrombosis was detected in 37% of patients. Sepsis-induced coagulopathy and SOFA scores were both correlated to DVT. A SIC score of 1 vs. ≥2 showed a close association with DVT, with sensitivity, specificity, and positive and negative predictive values of 90.0, 48.1, and 49.1, and 89.7%, respectively. Most significantly though, a SOFA score of 1 or 2 points was shown to be the most accurate value in predicting the absence of DVT, indicating no need for therapeutic-intensity anticoagulation. Its sensitivity, specificity, and positive and negative predictive values were 87.9, 100, and 100, and 93.7%, respectively. The D-dimer test showed lower sensitivity and specificity whereas platelet count and aPTT were not found to be correlated to DVT.Conclusions: Patients with SOFA scores of 1 or 2 are at low risk of developing DVT and do not require therapeutic-intensity anticoagulation. Conversely, patients with scores ≥3 are at high risk of developing DVT.

OBJECTIVE To perform a scoping review of how patients with COVID-19 are affected by acute limb ischaemia (ALI) and evaluate the recommendations of the 2020 ESVS ALI Guidelines for these patients. METHODS Research questions were defined, and a systematic literature search was performed following the PRISMA guidelines. Abstracts and unpublished literature were not included. The definition of ALI in this review is in accordance with the ESVS guidelines. RESULTS Most identified papers were case reports or case series, although population based data and data from randomised controlled trials were also identified. In total, 114 unique and relevant papers were retrieved. Data were conflicting concerning whether the incidence of ALI increased, or remained unchanged, during the pandemic. Case reports and series reported ALI in patients who were younger and healthier than usual, with a greater proportion affecting the upper limb. Whether or not this is coincidental remains uncertain. The proportion of men/women affected seems unchanged. Most reported cases were in hospitalised patients with severe COVID-19. Patients with ALI as their first manifestation of COVID-19 were reported. Patients with ALI have a worse outcome if they have a simultaneous COVID-19 infection. High levels of D-dimer may predict the occurrence of arterial thromboembolic events in patients with COVID-19. Heparin resistance was observed. Anticoagulation should be given to hospitalised COVID-19 patients in prophylactic dosage. Most of the treatment recommendations from the ESVS Guidelines remained relevant, but the following were modified regarding patients with COVID-19 and ALI: 1) CTA imaging before revascularisation should include the entire aorta and iliac arteries; 2) there should be a high index of suspicion, early testing for COVID-19 infection and protective measures are advised; and 3) there should be preferential use of local or locoregional anaesthesia during revascularisation. CONCLUSION Although the epidemiology of ALI has changed during the pandemic, the recommendations of the ESVS ALI Guidelines remain valid. The above mentioned minor modifications should be considered in patients with COVID-19 and ALI.

Purpose Ambulatory peripheral vascular interventions have been steadily increasing. In ambulatory procedures, 4F devices might be particularly useful having the potential to reduce access-site complications; however, further evidence on their safety and efficacy is needed. Materials and Methods BIO4AMB is a prospective, non-randomized mulitcentre, non-inferiority trial conducted in 35 centres in Europe and Australia comparing the use of 4F- and 6F-compatible devices. The main exclusion criteria included an American Society of Anaesthesiologists class ≥ 4, coagulation disorders, or social isolation. The primary endpoint was access-site complications within 30 days. Results The 4F group enrolled 390 patients and the 6F group 404 patients. Baseline characteristics were similar between the groups. Vascular closure devices were used in 7.7% (4F group) and 87.6% (6F group) of patients. Patients with vascular closure device use in the 4F group were subsequently excluded from the primary analysis, resulting in 361 patients in the 4F group. Time to haemostasis was longer for the 4F group, but the total procedure time was shorter (13.2 ± 18.8 vs. 6.4 ± 8.9 min, p p Conclusions Ambulatory peripheral vascular interventions are feasible and safe. The use of 4F devices resulted in similar outcomes compared to that of 6F devices.

Governments are increasingly implementing smart and digital approaches to promoting citizen participation. However, whether online participation platforms are tools that improve inclusivity in citizen participation remains underexplored. To address this gap, this article focuses on the role of recruitment messages and their effect on participation in an online participation platform by gender and age. A field experiment with a neighborhood census sample (N = 6,066) shows that online participation dips for younger and older citizens and is equal among women and men. For the age groups between 60 and 75, differences in the control and intervention recruitment messages significantly impacted participation. These findings can help public managers tailor recruitment strategies to facilitate inclusive participation and represent a first step toward learning what types of messages are effective for whom.

Background. No clear guidelines exist for the management of phlegmasia cerulea dolens. This case report shows how a hybrid approach might be successful. It also shows how rare pathologies can combine to create a life- and limb-threatening condition. Case Presentation. A 75-year-old man, known for nephrotic syndrome currently under investigation, presented to the emergency department with a 24-hour history of left leg swelling followed by intense pain. The left lower limb showed a phlegmasia cerulean dolens. Renal function, coagulation profile, and inflammatory parameters were normal; D-Dimers 5,6 mg/L. The CT scan showed juxtarenal thrombosis of the hypoplastic IVC, involving both renal veins, reaching the left iliac-femoral-popliteal axis, with collateralization to the pelvic and mesenteric veins, associated with bilateral segmental pulmonary embolisms. A suspected left breast nodule was also found. Intravenous heparin was immediately administered, and urgent hybrid procedure with surgical thrombectomy and venous angiography and thromboaspiration, liberating the iliolumbar collaterals, was performed. A lateral leg fasciotomy was mandatory due to the phlegmasia cerulea. Postoperative Doppler US showed a good venous compressibility of the left leg. Thrombophilia screening was negative. The breast nodule was biopsied showing an invasive ductal carcinoma. The patient was discharged with oral rivaroxaban and indication for left mastectomy and oncological therapy with aromatase inhibitors. Conclusion. This case highlights the dramatic consequence of different risk factors for venous thromboembolism as cancer and nephrotic syndrome in a patient with hypoplasia of the inferior cava vein. Venous thromboaspiration has been used in order to timely recanalize important collaterals. Phlegmasia cerulea dolens was resolved after the procedure and lateral calf fasciotomy. Further evidence is needed to clearly define the role of venous thromboaspiration in the treatment of complex proximal deep venous thrombosis of the lower extremity.

Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia

In this work, an approach to integrate the downstream processing of bioactive compounds present in the microalgae cells by combining the use of tensioactive compounds and aqueous biphasic systems (ABS) is proposed. For this purpose, several aqueous solutions using solvents with and without tensioactive nature were investigated on their capacity to disrupt the microalgae cells as well as to extract the different classes of biomolecules, namely pigments (chlorophylls a and b, and lutein), proteins and carbohydrates. Cationic tensioactive compounds were selected due to their high ability to simultaneously extract the different classes of compounds present in the Neochloris oleoabundans biomass. To fractionate pigments, proteins and carbohydrates extracted from the microalgae, ABS formed by polyethylene glycol (PEG 8000) and sodium polyacrylate (NaPA 8000) were used, with the solvent selected to disrupt the cells acting as electrolyte. This allowed to tune the biomolecule’s partition reaching a selective fractionation. This approach provided the simultaneous extraction of different biomolecules (pigments, protein and carbohydrates) from the cells and, the subsequent origin of two fractions, one rich in proteins (extraction efficiencies of 100%) and carbohydrates (extraction efficiency of 80%) and the second concentrated in pigments (e.g. lutein, extraction efficiency of 98%). The further isolation of the biomolecules from the ABS forming solvents is proposed aiming at the development of an integrated downstream process, including the cell disruption/compounds extraction, the fractionation, and the isolation of the biomolecules.

Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Summary Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How NIPBL mutations affect brain development is not understood. Here we identify Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from cortical neural progenitors in vivo is detrimental to neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control cortical neuron migration. We find that Zfp609 and Nipbl interact with the Integrator complex, which functions in RNA polymerase 2 pause release. Indeed, Zfp609 and Nipbl co-localize at gene promoters containing paused RNA polymerase 2, and Integrator similarly regulates neuronal migration. Our data provide a rationale and mechanistic insights for the role of Nipbl in the neurological defects associated with CdLS., Highlights • Nipbl interacts with the transcription factor Zfp609 and the Integrator complex • Nipbl, Zfp609, and Integrator are required for cortical neuron migration • Nipbl, Zfp609, and Integrator co-occupy genomic binding sites independently of cohesin • Nipbl, Zfp609, and Integrator directly regulate neuronal migration genes, NIPBL mutations cause Cornelia de Lange syndrome, but Nipbl function in brain development is not well understood. Van den Berg et al. show that Nipbl interacts with Zfp609 and the Integrator complex to transcriptionally regulate cortical neuron migration.

The authors regret there were mistakes in Table 12 concerning adjusted risk estimation for surgical site infections of the lower limbs. The authors would like to thank Dr Tresson and colleagues for their careful reading and to apologise for any inconvenience. Table 12 should be read as below

Cell disintegration is, in general, the first step in the biorefinery of algae, since it allows the release of biomolecules of interest from the cells into the bulk medium. For high-value commercial applications, the disintegration process must be selective, energy efficient and mild. Developing a process with such features would demand extensive experimental effort. In the present study, we attempt to provide a tool for developing an efficient disintegration process via bead milling, by proposing a modelling strategy that allows the prediction of the kinetics of cell disintegration while having as input not only process parameters but also strain-specific parameters like cell size and cell-wall strength. The model was validated for two different algal strains (Tetraselmis suecica and Chlorella vulgaris), at various values of bead size (0.3–1 mm) and bead fillings (2.5–75%) and at two different scales of 80 and 500 mL. Since the kinetics of disintegration is proportional to the kinetics of release of biomolecules, the model can be further used for scale-up studies and to establish a window of operation to selectively target cells or metabolites of interest. Furthermore, the energy consumption in the mill was evaluated and it was found that operating at high bead fillings (>65%) is crucial to ensure an energy efficient process. Paid Open Access

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors., eLife digest Stem cells in embryos give rise to all the tissues in the body. Adults also have stem cells, but they are fewer in number and they are usually dedicated to repairing and regenerating specific tissues. A region of the brain called the hippocampus, which is involved in learning, memory and mood, has a pool of neural stem cells. These cells can produce new brain cells long into adulthood, but maintaining their regenerative potential is a balancing act. Enough new brain cells need to be made to keep up with the brain’s demands, but if every stem cell matured into a brain cell, the brain’s capacity for repair would be lost. So, some neural stem cells hit a metaphorical snooze button to enter a resting state known as quiescence. Stem cells in the hippocampus make a protein called Ascl1 that interacts with DNA to switch on quiescent cells so they will divide and mature. Left unchecked, Ascl1 could deplete the stem cell supply, so resting stem cells must have a way to turn Ascl1 off, but it was previously unknown how. Clues point to the E proteins, which interact with Ascl1 to allow it to bind to DNA. If the E proteins are not present, Ascl1 cannot work as a genetic switch. E proteins can also interact with inhibitor of DNA binding/differentiation proteins, known as Id proteins for short. To find out whether Id proteins affect Ascl1 activity, Blomfield et al. looked at stem cells in the hippocampus of adult mice, and at quiescent stem cells grown in the laboratory. Blomfield et al. showed that all stem cells in the hippocampus make Ascl1, but its levels are much lower when stem cells are resting. This difference was down to an Id protein called Id4. In resting stem cells, Id4 interacted with E proteins, preventing them from binding to Ascl1, and stopping Ascl1 from ‘waking up’ the cells. This not only left Ascl1 unable to activate its target genes, it also made it vulnerable to destruction by the cell's protein recycling system. Mice with no Id4 in their hippocampus stem cells had higher levels of Ascl1, and their stem cells were more active. The number of stem cells in a resting state increases as we age, and in illnesses like depression, limiting brain cell replacement. Uncovering the signals that switch Id4 on or off could reveal why stem cells rest more with age and illness. This could help us find ways to kick-start the production of new brain cells in adulthood.

OBJECTIVE: Procedural characteristics, including stent design, may influence the outcome of carotid artery stenting (CAS). A thorough comparison of the effect of stent design on outcome of CAS is thus warranted to allow for optimal evidence-based clinical decision making. This study sought to evaluate the effect of stent design on clinical and radiologic outcomes of CAS. METHODS: A systematic search was conducted in MEDLINE, Embase, and Cochrane databases in May 2018. Included were articles reporting on the occurrence of clinical short- and intermediate-term major adverse events (MAEs; any stroke or death) or radiologic adverse events (new ischemic lesions on postprocedural magnetic resonance diffusion-weighted imaging [MR-DWI], restenosis, or stent fracture) in different stent designs used to treat carotid artery stenosis. Random effects models were used to calculate combined overall effect sizes. Metaregression was performed to identify the effect of specific stents on MAE rates. RESULTS: From 2654 unique identified articles, two randomized, controlled trials and 66 cohort studies were eligible for analysis (including 46,728 procedures). Short-term clinical MAE rates were similar for patients treated with open cell vs closed cell or hybrid stents. Use of an Acculink stent was associated with a higher risk of short-term MAE compared with a Wallstent (risk ratio [RR], 1.51; P = .03), as was true for use of Precise stent vs Xact stent (RR, 1.55; P < .001). Intermediate-term clinical MAE rates were similar for open vs closed cell stents. Use of open cell stents predisposed to a 25% higher chance (RR, 1.25; P = .03) of developing postprocedural new ischemic lesions on MR-DWI. No differences were observed in the incidence of restenosis, stent fracture, or intraprocedural hemodynamic depression with respect to different stent design. CONCLUSIONS: Stent design is not associated with short- or intermediate-term clinical MAE rates in patients undergoing CAS. Furthermore, the division in open and closed cell stent design might conceal true differences in single stent efficacy. Nevertheless, open cell stenting resulted in a significantly higher number of subclinical postprocedural new ischemic lesions detected on MR-DWI compared with closed cell stenting. An individualized patient data meta-analysis, including future studies with prospective homogenous study design, is required to adequately correct for known risk factors and to provide definite conclusions with respect to carotid stent design for specific subgroups.

The Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here, we purify Mediator from neural stem cells (NSCs) and identify 75 protein-protein interaction partners. We identify super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalize with Mediator at enhancers and super enhancers. Transcription factor families with high affinity for Mediator dominate enhancers and super enhancers and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator of NSCs. Tcf4 interacts with Mediator, colocalizes with Mediator at super enhancers and regulates neurogenic transcription factor genes with super enhancers and broad H3K4me3 domains. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity., The Mediator complex regulates transcription by connecting enhancers to promoters. Here, the authors purify Mediator from neural stem cells (NSCs), identify 75 novel protein-protein interaction partners and characterize the Mediator-interacting network that regulates transcription and establishes NSC identity.

A mild fractionation process to extract functional biomolecules from green microalgae was implemented. The process includes bead milling, centrifugation, and filtration with several membrane cut-offs. For each fraction, the corresponding composition was measured, and the surface activity and gelation behavior were determined. A maximum protein yield of 12% was obtained in the supernatant after bead milling and between 3.2 and 11.7% after filtration. Compared to whey protein isolate, most of the algae fractions exhibited comparable or enhanced functionality. Surface activity for air-water and oil-water interfaces and gelation activities were notably superior for the retentate fractions compared to the permeates. It is proposed that such functionality in the retentates is due to the presence of hydrophobic compounds and molecular complexes exhibiting a similar behavior as Pickering particles. We demonstrated that excellent functionality can be obtained with crude fractions, requiring minimum processing and, thus, constituting an interesting option for commercial applications.

The use of a single controlled bead milling step of the microalga Tetraselmis suecica resulted in a soluble fraction, rich in functional proteins. This was achieved by fine-tuning the processing time, thereby exploiting the difference in rates of protein and carbohydrate release during milling. Soluble proteins were extracted under mild conditions -room temperature, no addition of chemicals, pH 6.5-, with a yield of 22.5% and a specific energy consumption of 0.6 kWh kgDW−1, which is within the recommended minimum energy for an extraction step in a biorefinery process. The resulting protein extract contained 50.4% (DW) of proteins and 26.4% carbohydrates, showed light green color and displayed superior surface activity and gelation behavior compared to whey protein isolate. The proposed process is simple (only one bead milling step), scalable, and allows the mild extraction of functional proteins, making it interesting for industrial applications in the food industry.

SUMMARYQuiescence is essential for the long-term maintenance of adult stem cells and tissue homeostasis. However, how stem cells maintain quiescence is still poorly understood. Here we show that stem cells in the dentate gyrus of the adult hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activation state. We found that the inhibitor of DNA binding protein Id4 suppresses Ascl1 activity in neural stem cell cultures. Id4 sequesters Ascl1 heterodimerisation partner E47, promoting Ascl1 protein degradation and neural stem cell quiescence. Accordingly, elimination of Id4 from stem cells in the adult hippocampus results in abnormal accumulation of Ascl1 protein and premature stem cell activation. We also found that multiple signalling pathways converge on the regulation of Id4 to reduce the activity of hippocampal stem cells. Id4 therefore maintains quiescence of adult neural stem cells, in sharp contrast with its role of promoting the proliferation of embryonic neural progenitors.

“Context” plays an important role in any discourse about trauma. Not only does it serve as a precondition for the manifestation of trauma in the first place, but also determines the way in which trauma is received, interpreted and represented. The sensitivity of the reception context towards the represented traumatic events also determines whether only knowledge about the events are mediated or whether the uncanny nature of trauma is transmitted. If the latter occurs, a secondary trauma manifests itself as result. In the Dutch novel Tralievader (translated as Nightfather) by Carl Friedman the transmission of the Holocaust trauma within a particular family is represented. This transmission can be seen as the result of the impact of one context on another—that of the parent on that of the child. With the complex issue of the transmission of trauma kept in mind, specific dangers in the interpretation and transmission of trauma in a collective sense are identified. Suggestions are also made on how to deal with trauma in a productive way.Keywords: contextuality, Holocaust, mediation of trauma, narrative.

Three-dimensional (3D) guidance for endovascular procedures has developed over the last decade from 3D rotational angiography to the use of dynamic 3D roadmap techniques. The latest development is image merging. This technique combines real-time feedback of fluoroscopy with optimal soft-tissue contrast of previously performed computed tomography (CT) or magnetic resonance angiography. Merging of CT angiography and cone-beam CT/fluoroscopic images is feasible, and preliminary results look promising. Merging will allow us to further reduce radiation exposure, contrast dose, and procedural time, and its main use and benefit will be in complex endovascular interventions.

This article reviews the arterial access sites used in the treatment of peripheral arterial disease, including common femoral, superficial femoral, and popliteal arterial puncture. The optimal approach and techniques for arterial puncture will be described and technical tips and tricks will be discussed. An overview of the currently available vascular closure devices will also be presented. Indications, contraindications, and complications will be discussed. Results of the use of vascular closure devices compared with manual compression will be presented.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mild and efficient separation processes have to be developed to convert microalgal biomass into high valuable products. Aqueous two-phase system (ATPS) was adopted as a new approach in microalgae to separate hydrophilic from hydrophobic components. In this work, three biocompatible ATPSs polyethylene glycol (PEG) 400-Potassium citrate, Iolilyte 221PG-potassium citrate and PEG 400-Cholinium dihydrogen phosphate ATPS were selected based on their interaction with Ribulose-1,5-biphosphate carboxylase/oxygenase (Rubisco), a protein predominantly present in microalgae and used as ingredient in human and animal food. Binodal curves were constructed for each system and the parameters influencing phase formation were investigated. Iolilyte 221PG-potassium citrate has a stronger ability to form ATPS compared with the PEG-based systems. This stronger ability was attributed to hydrophobic and electrostatic interactions between the phase-forming components. After characterization, we investigated the performance of the ATPSs in the partitioning of Rubisco. In this study, the effect of the tie-line length (TLL), pH and type of phase-forming components on Rubisco extraction efficiency (%) was analyzed. In a single step, the appropriate parameters lead to extraction efficiencies between 80 and 100%. Additionally, stability studies were performed to see if ATPS retain the native protein structure. Iolilyte 221PG-Citrate was found to be the most efficient ATPS in Rubisco separation. However, stability studies indicated that PEG-based ATPSs have a better performance in retaining the Rubisco integrity.

We report the first documented case of distal thromboembolism originating from an abdominal aortic aneurysm (AAA) after a blunt trauma. A 72-year-old man with a known 6.2 cm AAA was brought to our emergency department with signs of bilateral acute limb ischemia developing immediately after an accidental fall. The occlusion was confirmed at computed tomographic angiography, and the aneurysm showed a fragmentated/ulcerated mural thrombus, morphologically different as compared to the previous computed tomography (CT). A thromboembolectomy was performed and, after treatment of the ischemic complications, the aneurysm was repaired by open surgery. Embolization from aneurysms in the setting of a trauma is a challenge for the vascular surgeon, also because of its rare occurrence. We describe the management and discuss the operative strategy we opted for in this patient.

The new species Roscidotoga lamingtonia is described, a leafminer on Sloanea woollsii (Elaeocarpaceae) from the subtropical rainforests of Lamington National Park, southern Queensland, and Border Ranges National Park, New South Wales. R. callicomae Hoare, 2000 is recorded for the first time from Queensland, and from Lamington National Park. These records fall within the genus’ limited range in the rainforests in eastern Australia. R. lamingtonia is the second species of the genus feeding on Elaeocarpaceae. On the basis of a few possible apomorphies we hypothesize one host-shift from Cunoniaceae to Elaeocarpaceae. DNA barcodes for R. lamingtonia and R. callicomae are given.

The common femoral artery is the most widely used route of access to the arterial system for coronary and peripheral percutaneous vascular interventions. This article addresses anatomical aspects relating to common femoral artery puncture, the choice of optimal puncture site and methods to increase the efficacy and safety of the common femoral artery puncture. Complications of vascular access relating to either manual compression or closure devices will be described. Tips and tricks to reduce the occurrence of vascular complications related to vascular access are discussed.

Microorganisms are generally sensitive to high concentrations of products that they excrete. Such product inhibition and toxicity effects can significantly be reduced by the integration of fermentations with separation technologies to remove the products continuously. Cost-calculations are required to select the preferred integration method. This paper presents a shortcut calculation method that provides easy interpretable results to assist the reader in making rational design choices. The method distinguishes four main cost categories, being capital and operational expenditure for both fermentation and product recovery. We have applied these cost correlations to the production of three typical bio-based bulk chemicals. The results show the origin of the most significant costs in the investigated integrated bio-processes. The presented method can be used to direct future research efforts and might assist in evaluating the impact of integrated product recovery techniques on total production costs of bio-chemicals. © 2010 Elsevier Ltd.