HYDROGEN ROCKS!

Bij de presentatie van de Europese Waterstofstrategie in juli 2020, vroeg een journalist of deze technologie niet ‘besmet’ was, wijzend op wat er gebeurde toen de mens de vorige keer probeerde dit gas te benutten. Het is duidelijk dat de technologie ver is gekomen sinds de ramp met de Hindenburg. Waterstof heeft nu een groeiende schare aan fans – en terecht. Een groot deel van de energietransitie is gericht op directe elektrificatie. Maar voor sommige sectoren, zoals staal, cement, zwaar transport of scheepvaart, is elektrificatie geen oplossing. Hernieuwbare waterstof als brandstof en grondstof kan helpen deze puzzel op te lossen. Bovendien kan waterstof als energieopslag het potentieel van wind- en zonne-energie maximaliseren door een back-up te bieden voor seizoensgebonden schommelingen in duurzame energieproductie en door productielocaties met verder gelegen vraagcentra te verbinden. Waterstof is dus hard op weg de rockster van de energiewereld te worden. De nieuw ontdekte kansen van waterstof en de cruciale rol ervan in ons toekomstige energiesysteem hebben waterstof een steeds aantrekkelijker investering gemaakt. Bijna dagelijks worden nieuwe waterstofprojecten aangekondigd. Schaalvergroting van zowel het gebruik als de productie van hernieuwbare waterstof is essentieel om onze economieën verder koolstofvrij te maken. De technologieën om schone waterstof te produceren bestaan al. De komende jaren moeten onze inspanningen er dus op gericht zijn de markt te vergroten en waterstof de kans geven commercieel concurrerend te worden. Schone waterstof is de sleutel voor een sterke, concurrerende en koolstofvrije Europese economie. Onze Waterstofstrategie heeft ambitieuze doelen gesteld en via de European Clean Hydrogen Alliance werken we samen met de industrie en andere belanghebbenden om de meest veelbelovende projecten snel van de grond te krijgen, zodat we tegen 2030 de geplande capaciteit van 40 GW aan hernieuwbare waterstof elektrolysers kunnen realiseren. Europa loopt momenteel voorop, en met de huidige stand van technologie, de economische basis en de beleidsinstrumenten, kunnen we voorop blijven lopen. Waterstof zal nieuwe groene banen opleveren en zo de Europese industrie de 21ste eeuw in stuwen. De beste manier om dit alles samen te vatten? Hydrogen rocks

Do Traumatic Events Have More Impact on the Development of Dental Anxiety Than Negative, Non-traumatic Events?

The importance of exposure to traumatic events for the development of dental anxiety has not been investigated. The aim of the present study was to test the hypotheses that individuals who reported having been exposed to a traumatic event [that is, fulfilling Criterion A of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), for post-traumatic stress disorder (PTSD)] as the cause of their dental anxiety would report significantly higher levels of dental anxiety, typical trauma-related (PTSD) symptoms, and greater disturbance of memories involving these events than those who reported being exposed to non-traumatic events. Patients of a specialized dental fear clinic (n = 90) were divided into those who reported a traumatic event that initiated their dental trait anxiety and those who did not. The two groups did not differ in their severity of dental anxiety and number of PTSD symptoms, but the memories of those who had been exposed to traumatic events were significantly more vivid than the memories of those in the reference group. Length of time since the event took place did not play a role. Hence, traumatic events are remembered more vividly, but do not seem to initiate more severe forms of dental anxiety than other events

Effects of propranolol on fear of dental extraction: Study protocol for a randomized controlled trial

Background: Undergoing an extraction has been shown to pose a significantly increased risk for the development of chronic apprehension for dental surgical procedures, disproportionate forms of dental anxiety (that is, dental phobia), and symptoms of post-traumatic stress. Evidence suggests that intrusive emotional memories of these events both induce and maintain these forms of anxiety. Addressing these problems effectively requires an intervention that durably reduces both the intrusiveness of key fear-related memories and state anxiety during surgery. Moreover, evidence suggests that propranolol is capable of inhibiting "memory reconsolidation" (that is, it blocks the process of storing a recently retrieved fear memory). Hence, the purpose of this trial is to determine the anxiolytic and fear memory reconsolidation inhibiting effects of the ß-adrenoreceptor antagonist propranolol on patients with high levels of fear in anticipation of a dental extraction. Methods/Design: This trial is designed as a multicenter, randomized, placebo-controlled, two-group, parallel, double-blind trial of 34 participants. Consecutive patients who have been referred by their dentist to the departments of oral and maxillofacial surgery of a University hospital or a secondary referral hospital in the Netherlands for at least two tooth and/or molar removals and with self-reported high to extreme fear in anticipation of a dental extraction will be recruited. The intervention is the administration of two 40 mg propranolol capsules 1 hour prior to a dental extraction, followed by one 40 mg capsule directly postoperatively. Placebo capsules will be used as a comparator. The primary outcome will be dental trait anxiety score reduction from baseline to 4-weeks follow-up. The secondary outcomes will be self-reported anxiety during surgery, physiological parameters (heart rate and blood pressure) during recall of the crucial fear-related memory, self-reported vividness, and emotional charge of the crucial fear-related memory. Discussion: This randomized trial is the first to test the efficacy of 120 mg of perioperative propranolol versus placebo in reducing short-term ("state") anxiety during dental extraction, fear memory reconsolidation, and lasting dental ("trait") anxiety in a clinical population. If the results show a reduction in anxiety, this would offer support for routinely prescribing propranolol in patients who are fearful of undergoing dental extractions. Trial registration: ClinicalTrials.gov identifier: NCT02268357 , registered on 7 October 2014. The Netherlands National Trial Register identifier: NTR5364 , registered on 16 August 2015

Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial

Background: Promising results from a trauma reactivation study on post-traumatic stress disorder suggest that propranolol is capable of attenuating symptoms of traumatically induced mental disorders by blocking memory reconsolidation. Methods: A randomized, parallel, placebo-controlled, quadruple-blind trial was designed to determine the effectiveness of perioperative propranolol during exposure to dental extractions in reducing dental anxiety in patients with dental anxiety or dental phobia. Between November 2014 and December 2018, 52 patients with high levels of fear in anticipation of dental extractions who were referred to a department of oral and maxillofacial surgery for at least two tooth and/or molar removals with 1 month in between were included. On the first visit participants received either 120 mg of perioperative oral propranolol (n = 19) or placebo (n = 17), and a core fear memory was reactivated 1 h preoperatively. The primary outcome was change in severity of dental anxiety from baseline to 1-month follow-up, as indexed by the short version of the dental anxiety inventory (S-DAI). Secondary outcome measures were change in intra-operative state anxiety and specific phobia diagnoses. Results: Linear mixed model (LMM) yielded no statistically significant difference in change of dental trait anxiety from baseline to 1-month follow-up between propranolol and placebo groups (Cohen's d = 0.23). S-DAI scores decreased in both study arms from baseline to follow-up (propranolol arm: from 32.1 [SD = 7.3] to 29.1 [SD = 8.8]; placebo arm: from 31.6 [SD = 7.5] to 27.1 [SD = 6.5]). Also, administering propranolol was not associated with a significant difference in change of intra-operative state anxiety or phobia diagnoses between groups over time. Conclusions: The results do not concur with earlier findings regarding post-traumatic stress disorder, and suggest that individuals with traumatically induced fears or phobias do not benefit from the application of perioperative propranolol

The "lipid accumulation product" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison

BACKGROUND: Body mass index (BMI, kg/m(2)) may not be the best marker for estimating the risk of obesity-related disease. Consistent with physiologic observations, an alternative index uses waist circumference (WC) and fasting triglycerides (TG) concentration to describe lipid overaccumulation. METHODS: The WC (estimated population minimum 65 cm for men and 58 cm for women) and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults) were used to compute a "lipid accumulation product" [LAP = (WC-65) × TG for men and (WC-58) × TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors. RESULTS: Nearly half of the represented population was discordant for their quartile assignments to LAP and BMI. When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex) the former had more adverse risk levels than the latter (p < 0.002) for seven lipid variables, uric acid concentration, heart rate, systolic and diastolic blood pressure. Further adjustment for age did not materially alter these comparisons except for blood pressures (p > 0.1). As continuous variables, LAP provided a consistently more adverse beta coefficient (slope) than BMI for nine cardiovascular risk variables (p < 0.01), but not for blood pressures (p > 0.2). CONCLUSION: LAP (describing lipid overaccumulation) performed better than BMI (describing weight overaccumulation) for identifying US adults at cardiovascular risk. Compared to BMI, LAP might better predict the incidence of cardiovascular disease, but this hypothesis needs prospective testing

Genetic Determinants of Variability in Glycated Hemoglobin (HbA1c) in Humans: Review of Recent Progress and Prospects for Use in Diabetes Care

Glycated hemoglobin A1c (HbA1c) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA1c represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA1c levels are genetically determined, with heritability of 47% to 59%. Over the past few years, inroads into understanding genetic predisposition by glycemic and nonglycemic factors have been achieved through genome-wide analyses. Here I review current research aimed at discovering genetic determinants of HbA1c levels, discussing insights into biologic factors influencing variability in the general and diabetic population, and across different ethnicities. Furthermore, I discuss briefly the relevance of findings for diabetes monitoring and diagnosis

Injection therapy and denervation procedures for chronic low-back pain: a systematic review

Injection therapy and denervation procedures are commonly used in the management of chronic low-back pain (LBP) despite uncertainty regarding their effectiveness and safety. To provide an evaluation of the current evidence associated with the use of these procedures, a systematic review was performed. Existing systematic reviews were screened, and the Cochrane Back Review Group trial register was searched for randomized controlled trials (RCTs) fulfilling the inclusion criteria. Studies were included if they recruited adults with chronic LBP, evaluated the use of injection therapy or denervation procedures and measured at least one clinically relevant outcome (such as pain or functional status). Two review authors independently assessed studies for eligibility and risk of bias (RoB). A meta-analysis was performed with clinically homogeneous studies, and the GRADE approach was used to determine the quality of evidence. In total, 27 RCTs were included, 14 on injection therapy and 13 on denervation procedures. 18 (66%) of the studies were determined to have a low RoB. Because of clinical heterogeneity, only two comparisons could be pooled. Overall, there is only low to very low quality evidence to support the use of injection therapy and denervation procedures over placebo or other treatments for patients with chronic LBP. However, it cannot be ruled out that in carefully selected patients, some injection therapy or denervation procedures may be of benefit

A Generic Platform for Cellular Screening Against Ubiquitin Ligases

Ubiquitin signalling regulates most aspects of cellular life, thus deregulation of ubiquitylation has been linked with a number of diseases. E3 ubiquitin ligases provide substrate selectivity in ubiquitylation cascades and are therefore considered to be attractive targets for developing therapeutic molecules. In contrast to established drug target classes, such as protein kinases, GPCRs, hormone receptors and ion channels, ubiquitin drug discovery is in its early stages. This is, in part, due to the complexity of the ubiquitylation pathways and the lack of robust quantitative technologies that allow high-throughput screening of inhibitors. Here we report the development of a Ubiquitin Ligase Profiling system, which is a novel and generic cellular technology designed to facilitate identification of selective inhibitors against RING type E3 ubiquitin ligases. Utilization of this system requires a single co-transfection of cells with assay vectors, thereby enabling readout of E3 ubiquitin ligase catalytic activity within the cellular environment. Therefore, our robust high-throughput screening platform offers novel opportunities for the development of inhibitors against this difficult-to-target E3 ligase enzyme class