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Transcatheter aortic valve implantation (TAVI) has been adopted as an alternative to surgery in severe aortic stenosis treatment, even in low-intermediate risk. The aim of this study is to retrospectively report our single-centre 13-year TAVI experience with emphasis on learning curve, referral indication and trends in outcomes over time.We included 361 consecutive patients who underwent TAVI from January 2008 to December 2020, grouped according to similar per-year volume of procedures: G1 (2008-2014), G2 (2015-2017) and G3 (2018-2020).The number of procedures increased (group size: 59Favourable trends were observed across the groups, with an improvement in periprocedural outcomes and cardiovascular mortality at 1-year. These improvements could depend on increased expertise because mortality reduction was noted only after reaching a significant procedure volume. A trend towards lower risk patients selection was present in our cohort, as previously described worldwide.

Background Continuous positive airway pressure (CPAP) is the mainstay of treatment for obstructive sleep apnea (OSA). However, data about its effect on the upper airway, especially the epiglottis, are scarce. The aim of this study was to investigate the changes in upper airway dimensions and inspiratory flow in response to incremental pressure levels. Methods This is a secondary analysis of a prospective clinical trial in which patients with moderate to severe OSA underwent drug-induced sleep endoscopy with simultaneous recordings of flow and mask pressure. CPAP was titrated in small increments. For each pressure level a representative 3-breath segment was selected to determine specific flow features. The corresponding endoscopic footage was reviewed to assess the degree of upper airway collapse in a semi-quantitative manner. Results A total of 214 breath segments were obtained from 13 participants (median [Q1–Q3]; apnea-hypopnea index, 24.9 [20.1–43.9] events/h; body mass index 28.1 [25.1–31.7] kg/m²). CPAP significantly increased cross-sectional dimensions of the soft palate, lateral walls and tongue base, but not of the epiglottis, and induced epiglottis collapse in one subject. Increased pressure improved peak inspiratory flow and median ventilation in all patients, even in the presence of persistent epiglottis collapse. Conclusion CPAP does not effectively address epiglottis collapse in patients with OSA. However, it normalizes inspiratory flow regardless of its effect on the epiglottis. This clinical trial was registered on January 18th, 2020 on ClinicalTrials.gov with identifier NCT04232410.

Encouraged by randomized controlled trials demonstrating non-inferiority of transfemoral transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) across all surgical risk categories, there has been a dramatic increase in the use of TAVI in a younger patient cohort with severe aortic stenosis, endorsed by both European and American Cardiac Societies. However, the standard use of TAVI in younger, less co-morbid patients with a longer life expectancy can only be supported if there is sound data demonstrating long-term durability of transcatheter aortic valves (TAVs). In this article, we have reviewed available randomized and observational registry clinical data pertaining to TAV long-term durability, placing emphasis on trials and registries using the new standardized definitions of bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF). Despite inherent difficulties in interpreting the available data, the determination reached is that the risk of structural valve deterioration (SVD) is potentially lower after TAVI than SAVR at 5 to 10 years, and that the two treatment modalities have a similar risk of BVF. This supports the adoption of TAVI in younger patients evident in current practice. However, the routine use of TAVI in younger patients with bicuspid aortic valve stenosis should be cautioned due to insufficient long-term TAV durability data in this particular patient population. Finally, we highlight the importance of future research into the unique potential mechanisms that can potentially contribute to TAV degeneration.

Study objectives The aim of this pilot study was to evaluate the clinical effectiveness of subjective titration versus objectively guided titration during polysomnography (PSG) and drug-induced sleep endoscopy (DISE) in mandibular advancement device (MAD) therapy for patients with obstructive sleep apnea (OSA). Methods In this pilot cross-over study, patients underwent three titration procedures in randomized order: (1) subjective titration, (2) PSG-guided titration using a remotely controlled mandibular positioner (RCMP) and (3) DISE-assisted titration using RCMP. After each titration procedure, patients used the MAD for 1 month at the targeted protrusion obtained according to the preceding titration procedure. For each procedure, a follow-up PSG was performed after 1 month of MAD use in order to evaluate the efficacy of the MAD. Results Ten patients were included in the study. Overall, no significant differences in targeted optimal protrusion compared to maximal comfortable protrusion among the three titration methods were observed. There was no significant difference in reduction in AHI. In this study, PSG titration correctly classified 50% of patients as ‘responder’. A higher predictive accuracy was found for DISE titration with a sensitivity of 83.3% and a specificity of 100%. Conclusions This pilot randomized cross-over trial showed no differences in optimal mandibular positioning and corresponding efficacy of MAD between subjective titration, DISE titration or PSG titration.

With the increasing worldwide rate of chronic diseases, such as cancer, the development of novel techniques to improve the efficacy of therapeutic agents is highly demanded. Nanoparticles are especially well suited to encapsulate drugs and other therapeutic agents, bringing additional advantages, such as less frequent dosage requirements, reduced side effects due to specific targeting, and therefore increased patient compliance. However, with the increasing use of nanoparticles and their recent launch on the pharmaceutical market, it is important to achieve high-quality control of these advanced systems. In this review, we discuss the properties of different nanoparticles, the pharmacokinetics, the biosafety issues of concern, and conclude with novel nanotherapeutics and nanotheragnostics for cancer drug delivery.

Antegrade wiring using only antegrade guiding catheter without contralateral injection (defined as "blind antegrade wiring") may represent a valid initial treatment strategy for selected chronic coronary total occlusions (CTOs) due to the potentially lower risk of vascular complications. A careful selection of lesions eligible for this strategy as well as an accurate balance between the likelihood of success and failure is paramount. The aim of the study is to determine the rate of successful revascularization, the potential predictors of failure and the incidence of major complications, when using a "blind antegrade wiring" technique.In this multicentric study, consecutive patients with CTO undergoing percutaneous coronary intervention (PCI) were retrospectively screened. All cases approached using "blind antegrade wiring" technique were included.Out of 155 consecutive CTO-PCIs, 94 involved initial "blind antegrade wiring" strategy. Successful revascularization by means of "blind antegrade wiring" technique was achieved in 73 (78%) patients. Final successful revascularization was obtained in 19 of the remaining 21 procedures with "blind antegrade wiring" failure using other techniques (by adding a second contralateral guiding catheter; 98% total successful revascularization). Logistic regression analysis identified higher J-CTO score as the only predictor of "blind antegrade wiring" failure. One complication occurred (wire-based coronary perforation)."Blind antegrade wiring" may be considered as initial strategy for selected CTO-PCI, mainly for CTOs with low J-CTO score. This strategy would allow in a substantial number of cases to avoid "a priori" dual injection, keeping it as secondary strategy in case of "blind antegrade wiring" failure.

Item does not contain fulltext Moving towards person-centered care, with equal partnership between healthcare professionals and patients, requires a solid role for the patient in the education of students and professionals. Patients can be involved as teachers, assessors, curriculum developers, and policy-makers. Yet, many of the initiatives with patients are isolated, small events for targeted groups and there is a lack of patient involvement at the institutional level. To support educators in involving patients, both at the institutional level and at single educational encounters, we offer twelve practical tips. This paper came about through an innovative collaboration between healthcare professionals, educators, teachers, and patients. These tips can be used as a tool to start or reinforce patient involvement in health professions education and provide guidance on how to make it a sustainable part of the curriculum. The article involves organizational conditions for success, tips for sustainable partnerships, ideas for curriculum design and proposes concrete teaching strategies. Finally, besides practical tips, we stress that involving patients in education is not business as usual, and paradoxically this needs to be acknowledged before it can become business as usual. 01 januari 2023

Having a brother or sister with a disability can impact the well-being and mental health of their siblings. For example, in a recent meta-analysis it has been found that siblings of children with chronic health conditions ‘may be at increased risk of depression’ (Martinez et al., 2022). In order to gain understanding of the experiences of these siblings, several studies including interviews with siblings of children with chronic health conditions have been done (Mandleco & Webb, 2015; Moyson & Roeyers, 2012; Vella Gera et al., 2021). Based on these interviews, implications were made about the support needs of siblings. It has for example been concluded that siblings need support with dealing with the behaviour of their brother or sister, or will benefit from learning that they are not alone in their experiences (Mandleco & Webb, 2015; Moyson & Roeyers, 2012). In other studies, siblings were asked about their support needs directly. For example, one study investigated the support needs of siblings (age 12-14 years) of children with cancer through focus groups and one-on-one interviews with siblings and caregivers, resulting in 10 domains of need (Patterson et al., 2011). Another study used retrospective one-on-one interviews with adult siblings of persons with disabilities or chronic illness, focusing both on their childhood experiences and the support they missed (Hanvey et al., 2022). A third study used questionnaires and one-on-one interviews about online support needs with siblings (age 11-21 years) of children with chronic conditions (Joosten et al., 2019). However, no studies have been found in which school age (6-12 years) siblings of children with intellectual disability (ID) or visual impairment (VI) were interviewed directly about their support needs. Focusing on the other end, the support that is being offered to siblings, several systematic reviews about studied sibling interventions have been computed. For example in a recent systematic mixed-methods review it has been found that the researched sibling support programs can improve sibling well-being, although research methods are not always sound and accessibility could be improved (Wolff et al., 2022). Looking more into which resources are accessible, the available support sources for siblings of youth with chronic health conditions have recently been identified and analysed, finding that there are gaps in the available support (Nguyen et al., 2021). In order to offer support resources that match the support needs of siblings, more knowledge is needed about which interventions should be offered to which siblings and how (Wolff et al., 2022), Therefore, in the current study the support needs of siblings of children with intellectual disability (ID) and/or visual impairment (VI) will be investigated through one-on-one interviews with siblings between the age of six and twelve years old. Thematic analysis will be used to find themes of support needs, received support, and desired types of support. In addition, a systematic inventory of the available Dutch support resources for siblings in the Netherlands and Belgium will be made. Next, the available support will be linked to the self-reported support needs of siblings, by coding the support resources with a checkbox created based on the interview results. This study will provide the clinical field with an overview of support needs and available resources, and will point out which support needs still need to be met. The definition of support that will be used in this study is: ‘‘Supports are resources and strategies that aim to promote the development, education, interests, and personal well-being of a person and that enhance individual functioning’ (Luckasson et al., 2002, p. 151). Support needs are defined based on ‘felt needs’: “what the person wants or perceives as needed” (Thompson et al., 2009).

RATIONALE: Cassava production faces challenges in a changing climate. Pulse labelling cassava with 13 C-CO2 has the potential to elucidate carbon allocation mechanisms of cassava under drought stress and with potassium application. Understanding these mechanisms could guide efforts to mitigate effects of drought in cassava cropping systems. METHODS: Forty-eight cassava plants received a nutrient solution high or low in potassium. Water deficit was imposed on half of the plants at bulk root initiation stage, after which they were labelled for 8 h with 13 C-CO2 in a 15 m3 growth chamber. Plants were harvested 8 h, 9 days and 24 days after labelling, and separated into leaves, stems and roots. δ13 C values of the different parts were measured using an isotope ratio mass spectrometer, from which 13 C excess was calculated. RESULTS: Water deficit decreased transpiration (P

Cassava production faces challenges in a changing climate. Pulse labelling cassava withForty-eight cassava plants received a nutrient solution high or low in potassium. Water deficit was imposed on half of the plants at bulk root initiation stage, after which they were labelled for 8 h withWater deficit decreased transpiration (P 0.001) and increased carbon respiration (P 0.05). Potassium application increased assimilate distribution to the roots (P 0.05) at 9 days after labelling, more strongly for plants under water deficit. The opposite was found at 24 days (P 0.05) with the legacy of water deficit additionally increasing assimilate distribution to roots (P 0.05). Youngest, fully expanded leaves contained up to 47% of initialPulse labelling proved to be successful in shedding light on carbon allocation in relation to water and potassium availability. This technique, once adapted to field conditions, could further be used to improve fertilizer recommendations or change agronomic practices to cope with plant stress.

Since the start of the Precision Medicine Initiative by the United States of America in 2015, interest in personalized medicine has grown extensively. In short, personalized medicine is a term that describes medical treatment that is tuned to the individual. One possible way to realize personalized medicine is 3D printing. When using materials that can be tuned upon stimulation, 4D printing is established. In recent years, many studies have been exploring a new field that combines 3D and 4D printing with therapeutics. This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and, possibly, tailored to an individual. Moreover, the first 3D printed drug, Spritam®, has already found its way to the clinic. This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine., info:eu-repo/semantics/publishedVersion

Background Sleep disturbances are features of Parkinson's disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear. Methods We performed a retrospective case–control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density. Results Higher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis. Conclusions These findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.

Vascular access-related complications are one of the most frequent issues following percutaneous interventions of chronic total occlusions (CTO) because of the traditional use of large introducer sheaths for more back-up catheter support, and the need for multiple access sites, often including femoral access. In current practice, many operators still approach the revascularisation of CTO through femoral access despite the demonstrated advantage of radial procedures, mostly in terms of incidence of bleeding complications. Recently, an alternative strategy to deal with CTO, with the aim to minimise the number of access-related complications without affecting the successful revascularisation rate, has been proposed: the ‘minimalistic hybrid approach’ algorithm. This approach consists of the use of classic ‘hybrid algorithm’ techniques, but also aims to minimise the number of access sites, the size of the catheters used, and the adoption of the femoral access.

Pain often persists in patients with inflammatory diseases, even when the inflammation has subsided. The molecular mechanisms leading to this failure in resolution of inflammatory pain and the transition to chronic pain are poorly understood. Mitochondrial dysfunction in sensory neurons has been linked to chronic pain, but its role in resolution of inflammatory pain is unclear.Transient inflammation causes neuronal plasticity, called hyperalgesic priming, which impairs resolution of hyperalgesia induced by a subsequent inflammatory stimulus. We identified that hyperalgesic priming in mice caused disturbances in mitochondrial respiration, oxidative stress, and redox balance in dorsal root ganglia (DRG) neurons. Preventing these priming-induced disturbances restored resolution of inflammatory hyperalgesia. Concurrent with these mitochondrial and metabolic changes, the expression of ATPSc-KMT, a mitochondrial methyltransferase, was increased in DRG neurons in primed mice. ATPSc-KMT overexpression in DRG neurons of naive mice induced similar mitochondrial and metabolic changes as observed after priming, leading to failure in pain resolution. Inhibition of mitochondrial respiration, knockdown of ATPSCKMT expression, or NAD+ supplementation were sufficient to restore resolution of inflammatory pain and prevent chronic pain development. Thus, inflammation-induced mitochondrial-dependent disturbances in DRG neurons promote failure in inflammatory pain resolution and drive the transition to chronic pain.

Integrated landscape approaches (ILA) aim to reconcile multiple, often competing, interests across agriculture, nature conservation, and other land uses. Recognized ILA design principles provide guidance for implementation, yet application remains challenging, and a strong performance evidence-base is yet to be formed. Through a critical literature review and focus group discussions with practitioners, we identified considerable diversity of ILA in actors, temporal, and spatial scales, inter alia. This diversity hampers learning from and steering ILA because of the intractable nature of the concept. Therefore, we developed a tool—an ‘ILA mixing board’—to structure the complexity of ILA into selectable and scalable attributes in a replicable way to allow planning, diagnosing, and comparing ILA. The ILA mixing board tool presents seven qualifiers, each representing a key attribute of ILA design and performance (for example, project flexibility, inclusiveness of the dialogue, and the centrality of the power distribution). Each qualifier has five (non-normative) outcome indicators that can be registered as present or absent. This process in turn guides planners, evaluators and other participating stakeholders involved in landscape management to diagnose the ILA type, or its performance. We apply the ILA mixing board to three ILA cases in Nicaragua, Madagascar, and the Congo Basin to show some of the many possible configurations of qualifiers on the mixing board. Further application of the tool would allow comparative analysis of the complexity of ILA in a structured and manageable way thereby enhancing the understanding of ILA performance and informing the development of evidence-based land use policy., Environmental Science & Policy, 147, ISSN:1462-9011, ISSN:1873-6416

BackgroundChild maltreatment is a common negative experience and has potential long-lasting adverse consequences for mental and physical health, including increased risk for major depressive disorder (MDD) and metabolic syndrome. In addition, child maltreatment may increase the risk for comorbid physical health conditions to psychiatric conditions, with inflammation as an important mediator linking child maltreatment to poor adult health. However, it remains unresolved whether experiencing child maltreatment increases the risk for the development of comorbid metabolic syndrome to MDD. Therefore, we investigated whether child maltreatment increased the risk for comorbid metabolic syndrome to depressed mood. Subsequently, we examined whether C-reactive protein (CRP), as an inflammatory marker, mediated this association. In addition, we investigated whether effects differed between men and women.MethodsAssociations were examined within cross-sectional data from the multiethnic HELIUS study (N = 21,617). Adult residents of Amsterdam, Netherlands, self-reported on child maltreatment (distinct and total number of types experienced before the age of 16 years) as well as current depressed mood (PHQ-9 score ≥ 10), and underwent physical examination to assess metabolic syndrome. The CRP levels were assessed in N = 5,998 participants. Logistic and linear regressions were applied for binary and continuous outcomes, respectively. All analyses were adjusted for relevant demographic, socioeconomic, and lifestyle characteristics, including ethnicity.ResultsA higher number of maltreatment types as well as distinct types of emotional neglect, emotional abuse, and sexual abuse were significantly associated with a higher risk for current depressed mood. Child maltreatment was not significantly associated with the risk for metabolic syndrome in the whole cohort, nor within individuals with depressed mood. As child maltreatment was not significantly associated with the CRP levels, subsequent mediation analyses were not performed. No significant moderating effects by sex were observed.ConclusionIn this multiethnic urban cohort, child maltreatment was associated with a higher risk for depressed mood. Contrary to our expectations, child maltreatment was not significantly associated with an increased risk for metabolic syndrome, neither in the whole cohort nor as a comorbid condition in individuals with depressed mood. As the data were cross-sectional and came from a non-clinical adult population, longitudinal perspectives in relation to various stages of the investigated conditions were needed with more comprehensive assessments of inflammatory markers.

BACKGROUND: Professionals in child healthcare increasingly endorse the support of self-management in paediatric rehabilitation services for children with physical disability. Less understood though are their views regarding the role of the children's parents, as well as their own role in supporting parents. This study aimed to investigate the motivation of rehabilitation professionals to support self-management of parents regarding their child with physical disability, professionals' beliefs about parental self-management, and the perceptions underlying their motivation.METHODS: A mixed-methods strategy was followed using a survey among rehabilitation professionals (n = 175) and consecutive semi-structured interviews (n = 16). Associations between autonomous (intrinsic) versus controlled (extrinsic) motivation and beliefs on parental self-management were tested. For deeper understanding of their motivation, directed content analysis was used to address key themes in the qualitative data extracts.RESULTS: Professionals reported autonomous motivation for parental self-management support more often than controlled motivation (t(174) = 29.95, p < .001). Autonomous motivation was associated with the beliefs about the importance of parental self-management (r = .29, p < .001). Approximately 90% of the professionals believed that parents should have an active role, though less than ten percent considered it important that parents also are independent actors and initiative takers in the rehabilitation process. Interviews revealed that individual professionals struggled with striking a balance between keeping control and "giving away responsibility" to parents. A "professional-like" attitude was expected of parents with "involvement" and "commitment" as essential preconditions. Furthermore, professionals expressed the need for additional coaching skills to support parental self-management.CONCLUSION: Professionals were predominantly autonomously motivated to support self-management of parents. However, the dilemmas in giving or taking responsibilities within the partnership with parents, may limit their effectiveness in empowering parents. Reflection on the potential gaps between professionals' motivation, beliefs, and actual behaviour might be crucial to support parental self-management.

Rationale: Approximately a third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy. Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy. Methods: Baseline polysomnography data of the STAR trial were included. Raw baseline polysomnographic data from 91/126 patients were available for analysis. Traits—loop gain, arousal threshold, collapsibility, muscle compensation—were calculated from the baseline polysomnography data according to Sands et al. (AJRCCM 2018, SLEEP 2018). Logistic regression assessed AHI-adjusted associations between HGNS response (>50% reduction in AHI to

Rationale: Mandibular advancement device (MAD) treatment efficacy varies among patients with obstructive sleep apnea. Objectives: The current study aims to explain underlying individual differences in efficacy using obstructive sleep apnea endotypic traits calculated from baseline clinical polysomnography: collapsibility (airflow at normal ventilatory drive), loop gain (drive response to reduced airflow), arousal threshold (drive preceding arousal), compensation (increase in airflow as drive increases), and the ventilatory response to arousal (increase in drive explained by arousal). On the basis of previous research, we hypothesized that responders to MAD treatment have a lower loop gain and milder collapsibility. Methods: Thirty-six patients (median apnea–hypopnea index [AHI], 23.5 [interquartile range (IQR), 19.7–29.8] events/h) underwent baseline and 3-month follow-up full polysomnography, with MAD fixed at 75% of maximal protrusion. Traits were estimated using baseline polysomnography according to Sands and colleagues. Response was defined as an AHI reduction ≥ 50%. Results: MAD treatment significantly reduced AHI (49.7%(baseline) [23.9–63.6], median [IQR]). Responders exhibited lower loop gain (mean [95% confidence interval], 0.53 [0.48–0.58] vs. 0.65 [0.57–0.73]; P = 0.020) at baseline than nonresponders, a difference that persisted after adjustment for baseline AHI and body mass index. Elevated loop gain remained associated with nonresponse after adjustment for collapsibility (odds ratio, 3.03 [1.16–7.88] per 1–standard deviation (SD) increase in loop gain [SD, 0.15]; P = 0.023). Conclusions: MAD nonresponders exhibit greater ventilatory instability, expressed as higher loop gain. Assessment of the baseline degree of ventilatory instability using this approach may improve upfront MAD treatment patient selection. Clinical trial registered with www.clinicaltrials.gov (NCT 01532050)

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The concept of parental burnout has been proposed to be helpful for describing and understanding the impact of parenting children with complex care needs (CCN). The objective of this scoping review was to investigate, among parents of children with CCN (i) how burnout is conceptualized, (ii) differences in burnout scores, (iii) the prevalence of burnout, and (iv) the associated factors related to burnout. A stakeholder consultation including six parents of children with CCN, three healthcare professionals, and three researchers, was conducted to understand their perspectives on important insights and gaps from the literature. A total of 57 articles were eligible for inclusion. Conceptualization of parental burnout varied widely across studies, with few studies investigating the meaning of the concept for parents. Burnout scores were higher among parents of children with CCN and prevalence estimates varied between 20 and 77%, and exceeded burnout among parents of children without CCN. Few studies included associated factors in the context of parenting and caregiving. Stakeholders endorsed the importance of studies into the multifactorial determination of burnout in the context of parenting and caregiving children with CCN. The results highlight the extremes of stress and burden experienced by parents of children with CCN. An important gap regards the complex interplay between personal and contextual factors pertaining to risk and resilience.

We aimed to assess which bifurcation technique performs best in unprotected left-main (LM) percutaneous coronary intervention (PCI).Provisional stenting was considered the preferred technique for LM bifurcation PCI due to the supposed lower risks of thrombosis and restenosis. However, recent studies showed potential advantages of double kissing (DK)-crush technique over the other strategies.We performed a frequentist network meta-analysis comparing different stenting techniques in the setting of LM bifurcation. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched. Both randomized clinical trials and non-randomized clinical trials were considered eligible for inclusion. Incidence rate ratios (IRRs) were computed using a random-effects model for death, cardiac death, myocardial infarction, target-vessel revascularization, target-lesion revascularization, and stent thrombosis, including 95% confidence intervals (CIs).A total of 10 studies (2364 patients) were included. Compared with provisional stenting, DK-crush was associated with fewer cardiac deaths (IRR, 0.34; 95% CI, 0.17-0.70; P.01), myocardial infarctions (IRR, 0.19; 95% CI, 0.08-0.44; P.001), stent thromboses (IRR, 0.31; 95% CI, 0.14-0.69; P.01), target-vessel revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P.001), and target-lesion revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P.001). DK-crush was also associated with a lower risk of myocardial infarction (IRR, 0.19; 95% CI, 0.05-0.76; P=.02) when compared with standard crush and lower risk of target-lesion revascularization when compared with culotte (IRR, 0.32; 95% CI, 0.12-0.83; P=.02) and crush (IRR, 0.07; 95% CI, 0.02-0.28; P.001).DK-crush is the best technique for unprotected LM bifurcation PCI.

Macrophages are key effector cells in obesity-associated inflammation. G protein-coupled receptor kinase 2 (GRK2) is highly expressed in different immune cell types. Using LysM-GRK2+/− mice, we uncover that a reduction of GRK2 levels in myeloid cells prevents the development of glucose intolerance and hyperglycemia after a high fat diet (HFD) through modulation of the macrophage pro-inflammatory profile. Low levels of myeloid GRK2 confer protection against hepatic insulin resistance, steatosis and inflammation. In adipose tissue, pro-inflammatory cytokines are reduced and insulin signaling is preserved. Macrophages from LysM-GRK2+/− mice secrete less pro-inflammatory cytokines when stimulated with lipopolysaccharide (LPS) and their conditioned media has a reduced pathological influence in cultured adipocytes or naïve bone marrow-derived macrophages. Our data indicate that reducing GRK2 levels in myeloid cells, by attenuating pro-inflammatory features of macrophages, has a relevant impact in adipose-liver crosstalk, thus preventing high fat diet-induced metabolic alterations., We acknowledge support by Ministerio de Economía y Competitividad (MINECO/FEDER), Spain (grant SAF2017-84125-R to FM and CM and SAF2017-82436R to LB); CIBER de Enfermedades Cardiovasculares (CIBERCV). Instituto de Salud Carlos III, Spain (grant CB16/11/00278 to F.M., CB16/11/00222 to L.B., and, PI15/01114 to Francisco Tinaones (Universidad De Málaga, Spain), co-funded with European FEDER contribution); European Foundation for the Study of Diabetes (EFSD) Novo Nordisk Partnership for Diabetes Research in Europe Grant (to F.M.); and Programa de Actividades en Biomedicina de la Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE to FM and MF.. I.M.-I. was supported by the “MS type I” program (CP16/00163). The authors thank the Metagenomic Platform of the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (ISCIII), Spain. We appreciate the help of the CBMSO Facilities, in particular Flow Cytometry, Genomics and Animal Care. We acknowledge Paula Ramos for technical support. We also acknowledge the institutional support to the CBMSO from Fundación Ramón Areces.

Transcatheter aortic valve implantation (TAVR) is the first therapeutic option for elderly patients with severe symptomatic aortic stenosis, and indications are steadily expanding to younger patients and subjects with lower surgical risk and longer life expectancy. Commissural alignment between native and transcatheter valves facilitates coronary access after TAVR and is thus considered a procedural goal, allowing long-term management of coronary artery disease. Moreover, commissural alignment may potentially have a positive impact on transvalvular hemodynamic and valve durability. This review focus on technical hints to achieve commissural alignment and current evidence for different transcatheter aortic valves.

Ballast tanks are expected to be coated according to the IMO Performance Standard for Protective Coating regulations (PSPC15), in addition to the paint application requirements of the paint producer. In general, a coating system should consist of minimum two spray coats of light-colored epoxy coating on flat surfaces with a Nominal total Dry Film Thickness (NDFT) of 320 μm and 90% of all thickness measurements greater than, or equal to the NDFT and none of the remaining measurements below 0.9 x NDFT (the “90/10 rule”). Allegedly, the value of 320 μm in this PSPC15 rule may be misconstrued as a benchmark for coating application on flat surfaces, eventually leading to a non-PSPC15 compliance due to the resulting variation in coating thickness violating this 90/10 rule. This study indicates that over the years, the arithmetic mean in-situ DFT appears to be 498±18 μm and that too high and low thicknesses, below 288 μm and above 800 μm, were noted in the field. Analysis of a survey of ballast tank coating performance of ships indicates that too low thicknesses appear to be negatively impacting the average theoretical ballast tank performance. However, when an application mean DFT benchmark of 525 μm is used, the coating will almost surely comply to the 90/10 rule and the risk of falling below the 288 μm threshold is small, less than 2% in most cases. Consequently, using 320 μm as a mean DFT benchmark could result in a non-PSPC15 compliance with the in-situ ascertained coating thickness variation as this does not exclude coating thicknesses below 288 μm, which may then result in a significantly less than average theoretical coating performance. If the coating application is performed very evenly, the benchmark may be reduced to 429 μm with a probability of falling below 288 μm reduced to 0.1%. It should therefore be emphasized that the PSPC15 requirement is a coating system framework description, and that the requirement should be broadened to include a mean DFT as a coating applicator benchmark together with a clearly specified minimum and maximum DFT, in order to avoid any misinterpretations.

Background Obstructive sleep apnea (OSA) is a modifiable risk factor of atrial fibrillation (AF) but is underdiagnosed in these patients. According to the 2020 European Society of Cardiology guidelines for the diagnosis and management of AF, it seems reasonable to test for OSA in symptomatic AF patients before initiation of rhythm control therapy. A good OSA screening pathway is lacking in the guidelines and in daily clinical practice in most centers today. Polysomnography (PSG) is the gold standard for diagnosing OSA but it is not an ideal screening method, due to its expensiveness, labour-intensiveness and limited availability. Purpose The aim of this study was to validate and examine the performance of different (cardiorespiratory) polygraphy (PG) devices, used with their automated algorithm to detect OSA in an AF cohort, compared with PSG as gold standard. Methods Prospective study with three PGs (ApneaLink Air (ALA), SOMNOtouch RESP (STR) and SpiderSAS (SpS) combined with ResMed Airview-, SomnoMedics DOMINO- and Microport SYNESCOPE software respectively) in consecutive AF patients who were referred for a PSG evaluation. Patients received the three devices with instructions for use after their PSG and were requested to use each one during three consecutive nights at home. Severity of OSA was classified according to the Apnea-Hypopnea Index (AHI) with 30= severe OSA. Results A total of 100 AF patients presenting for PSG were included (64.0±8.6 years, 73% male, 87% non-permanent AF, mean Body Mass Index 30.6±5.9 kg/m2, mean CHA2DS2-VASc score 2.4±1.7, mEHRA≥2 in 64%; mean AF history 5.4±5.6 years). PSG diagnosed ≥mild OSA in 90% of patients, ≥moderate in 69%, and severe OSA in 33%. Successful PG execution to determine the AHI, i.e. ≥4 hours of data on automated analysis, was obtained in 72.0%, 73.0% and 79.0% of patients with the ALA, STR and SpS respectively. In screening for clinically relevant OSA (i.e. at least moderate OSA), the PGs had an area under the curve of 0.802, 0.761 and 0.803 for the ALA, STR and SpS respectively (Figure 1). Conclusions This first analysis shows that PGs combined with an automated algorithm for AHI determination, can be used as OSA screening tools in AF patients before referral for PSG. Further optimisation is likely by choosing an appropriate AHI cut-off value for each PG. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study is supported by the Antwerp University Cardiology Research Fund, and is part of Limburg Clinical Research Center, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Figure 1

Background: The concept of parental burnout has been proposed to be helpful for describing and understanding the impact of parenting children with complex care needs (CCN). The objective of this scoping review was to investigate the aims, methods, and results of research on burnout among parents of children with CCN, and to inform the interpretation as well as implications for research and practice through a stakeholder consultation.Methods: The scoping review was guided by the JBI Reviewers’ Manual for scoping reviews. Primary studies on burnout among parents of children with CCN were identified through a comprehensive search of peer reviewed and grey literature. Metadata and findings were extracted and compiled for further synthesis and interpretation, guided by a stakeholder consultation, involving parents of children with CCN (n = 6), healthcare professionals (n = 3), and researchers (n = 3). The stakeholder consultation was structured according to a Delphi consultation method. Results: A total of 57 articles were eligible for inclusion. Prevalence of burnout among parents of children with CCN varied between 20 and 77%. Parents of children with CCN reported on average higher burnout scores than parents of children without CCN. While all studies focused on parents with children with CCN, very few studies specifically focused on burnout within the context of parenting a child with CCN. Stakeholders endorsed the importance of studies into the multifactorial determination of burnout in the context of having children with CCN. Conclusion:The concept of parental burnout highlights the extremes of stress and burden experienced by parents of children with CCN. By focusing more on contextualized definitions of parental burnout, research may unravel the complex interplay between personal and contextual factors pertaining to risk and resilience.

It is crucial to understand the underlying pathophysiology of obstructive sleep apnea (OSA). Upper airway collapsibility is an important pathophysiological factor that affects the upper airway in OSA. The aim of the current study was to review the existing body of knowledge on the pharyngeal collapsibility in OSA. After a thorough search through Medline, PubMed, Scopus, and Web of science, the relevant articles were found and used in this study. Critical closing pressure (Pcrit) is the gold standard measure for the degree of collapsibility of the pharyngeal airway. Various physiological factors and treatments affect upper airway collapsibility. Recently, it has been shown that the baseline value of Pcrit is helpful in the upfront selection of therapy options. The standard techniques to measure Pcrit are labor-intensive and time-consuming. Therefore, despite the importance of Pcrit, it is not routinely measured in clinical practice. New emerging surrogates, such as finite element (FE) modeling or the use of peak inspiratory flow measurements during a routine overnight polysomnography, may enable clinicians to have an estimate of the pharyngeal collapsibility. However, validation of these techniques is needed.

A new method for automated sleep stage scoring of polysomnographies is proposed that uses a random forest approach to model feature interactions and temporal effects. The model mostly relies on features based on the rules from the American Academy of Sleep Medicine, which allows medical experts to gain insights into the model. A common way to evaluate automated approaches to constructing hypnograms is to compare the one produced by the algorithm to an expert's hypnogram. However, given the same data, two expert annotators will construct (slightly) different hypnograms due to differing interpretations of the data or individual mistakes. A thorough evaluation of our method is performed on a multi-labeled dataset in which both the inter-rater variability as well as the prediction uncertainties are taken into account, leading to a new standard for the evaluation of automated sleep stage scoring algorithms. On all epochs, our model achieves an accuracy of 82.7%, which is only slightly lower than the inter-rater disagreement. When only considering the 63.3% of the epochs where both the experts and algorithm are certain, the model achieves an accuracy of 97.8%. Transition periods between sleep stages are identified and studied for the first time. Scoring guidelines for medical experts are provided to complement the certain predictions by scoring only a few epochs manually. This makes the proposed method highly time-efficient while guaranteeing a highly accurate final hypnogram. ispartof: Frontiers in Digital Health vol:3 pages:1-13 ispartof: location:Switzerland status: published

Objectives To investigate the role of cytoreductive radical prostatectomy in addition to standard of care for patients with newly diagnosed metastatic prostate cancer. Materials and Methods This multicentre, prospective study included asymptomatic patients from 2014 to 2018 (NCT02138721). Cytoreductive radical prostatectomy was offered to all fit patients with resectable tumours, resulting in 40 patients. Standard of care was administered to 40 patients who were ineligible or unwilling to undergo surgery. The primary endpoint was castration resistant cancer-free survival at the time point of ≥50% events. The secondary endpoint was local event-free survival. Kaplan–Meier and Cox regression analyses with propensity-score analysis were applied. Results After a median (quartiles) follow-up of 35 (24–47) months, 42 patients became castration-resistant or died. The median castration resistant cancer-free survival was 53 (95% confidence interval [CI] 14–92) vs 21 (95% CI 15–27) months for cytoreductive radical prostatectomy compared to standard of care (P = 0.017). The 3-year estimates for local event-free survival were 83% (95% CI 71–95) vs 59% (95% CI 51–67) for cytoreductive radical prostatectomy compared to standard of care (P = 0.012). However, treatment group showed no significance in the multivariable models for castration resistant cancer-free survival (P = 0.5) or local event-free survival (P = 0.3), adjusted for propensity-score analysis. Complications were similar to the non-metastatic setting. Patients undergoing surgery were younger, with lower baseline prostate-specific antigen levels, alkaline phosphatase levels and metastatic burden. Conclusion The present LoMP study was unable to show a difference between the two inclusion groups regarding castration resistant cancer-free survival for asymptomatic patients with newly diagnosed metastatic prostate cancer. These results validate previous evidence that, in well-selected and informed patients, cytoreductive radical prostatectomy is feasible and safe, with corresponding continence rates compared to the non-metastatic, high-risk setting. Whether cytoreductive radical prostatectomy could be a valuable option to achieve good local palliation needs to be further researched. Overall, the role of cytoreductive radical prostatectomy needs to be further explored in randomized studies to correct for potential bias.

Cell-matrix interactions govern cell behavior and tissue function by facilitating transduction of biomechanical cues. Engineered tissues often incorporate these interactions by employing cell-adhesive materials. However, using constitutively active cell-adhesive materials impedes control over cell fate and elicits inflammatory responses upon implantation. Here, an alternative cell-material interaction strategy that provides mechanotransducive properties via discrete inducible on-cell crosslinking (DOCKING) of materials, including those that are inherently non-cell-adhesive, is introduced. Specifically, tyramine-functionalized materials are tethered to tyrosines that are naturally present in extracellular protein domains via enzyme-mediated oxidative crosslinking. Temporal control over the stiffness of on-cell tethered 3D microniches reveals that DOCKING uniquely enables lineage programming of stem cells by targeting adhesome-related mechanotransduction pathways acting independently of cell volume changes and spreading. In short, DOCKING represents a bioinspired and cytocompatible cell-tethering strategy that offers new routes to study and engineer cell-material interactions, thereby advancing applications ranging from drug delivery, to cell-based therapy, and cultured meat.

OBJECTIVES: For the diagnosis and treatment of disorders like congenital adrenal hyperplasia, the determination of steroids in saliva might form a more patient-friendly method. Therefore a selective and sensitive LC-MS/MS method was developed for androstenedione, cortisol, cortisone, 11-deoxycortisol, 21-deoxycortisol, 17α-hydroxyprogesterone, and testosterone in saliva. METHODS: Saliva was extracted and concentrated. Steroids were determined by LC-MS/MS, using multiple reaction monitoring upon electrospray ionization. RESULTS: A method was developed to determine seven steroids in saliva in one single LC-MS/MS run. Limits of quantification were 0.05 ng/mL for androstenedione, 0.25 ng/mL for cortisol, 0.50 ng/mL for cortisone, 0.125 ng/mL for 11-deoxycortisol, 0.125 ng/mL for 21-deoxycortisol, 0.125 ng/mL for 17α-hydroxyprogesterone, and 0.05 ng/mL for testosterone. The within-run repeatability was < 5% and the within-laboratory precision was < 5% for all analytes except androstenedione, where the saliva used in the validation study contained androstenedione levels below the LOQ. CONCLUSIONS: A sensitive and selective method was developed for the determination of a profile of seven steroids in saliva in one analytical run.

PURPOSE: With the growing attention in pediatric rehabilitation services for supporting self-management, the need increases for more shared understanding of the concept. The aim of this study was to explore parent activation, associated factors of- and underlying perceptions on parental self-management of parents of children with chronic conditions.MATERIALS AND METHODS: Using a mixed-methods strategy, first variations in self-management behaviors, motivation and perceived autonomy support were assessed with a cross-sectional survey among parents of children with chronic conditions (N = 239). Statistical analysis involved descriptive statistics and univariate analysis of variance. The survey was followed by 18 in-depth interviews with parents. Thematic analysis was used to recognize relevant topics in the qualitative data.RESULTS: In the survey most parents reported being active self-managers. Nevertheless, only one third persisted in self-management when under stress. Autonomous motivation was strongly associated with parental self-management. In the interviews, parents mentioned attuning with professionals and finding balance as important aspects of self-management. To facilitate self-management, professionals were expected to have expert knowledge, be engaged and empathic.CONCLUSION: From the perspective of parents, self-management should be viewed as a collaborative effort in which they are supported by professionals, rather than having to manage it "by themselves". Implications for rehabilitation To facilitate self-management, parents expect professionals to have expert knowledge and additionally show interpersonal competences as openness, engagement and empathy. Motivating parents may facilitate their level of self-management regarding the care for their child with a chronic disorder. Good communication and collaboration with professionals appear to be key aspects of parental self-management. Parents expect pediatric rehabilitation teams to tune their services to the needs, desires and expectations of parents to support them in "self-managing" the care for their child.

Lysine methylation is an important post-translational modification that is also present on mitochondrial proteins, but the mitochondrial lysine-specific methyltransferases (KMTs) responsible for modification are in most cases unknown. Here, we set out to determine the function of human family with sequence similarity 173 member B (FAM173B), a mitochondrial methyltransferase (MTase) reported to promote chronic pain. Using bioinformatics analyses and biochemical assays, we found that FAM173B contains an atypical, noncleavable mitochondrial targeting sequence responsible for its localization to mitochondria. Interestingly, CRISPR/Cas9-mediated KO of FAM173B in mammalian cells abrogated trimethylation of Lys-43 in ATP synthase c-subunit (ATPSc), a modification previously reported as ubiquitous among metazoans. ATPSc methylation was restored by complementing the KO cells with enzymatically active human FAM173B or with a putative FAM173B orthologue from the nematode Caenorhabditis elegans. Interestingly, lack of Lys-43 methylation caused aberrant incorporation of ATPSc into the ATP synthase complex and resulted in decreased ATP-generating ability of the complex, as well as decreased mitochondrial respiration. In summary, we have identified FAM173B as the long-sought KMT responsible for methylation of ATPSc, a key protein in cellular ATP production, and have demonstrated functional significance of ATPSc methylation. We suggest renaming FAM173B to ATPSc-KMT (gene name ATPSCKMT).

This study's objective is to systematically review the literature on natural sleep endoscopy (NSE), including the set-up, different scoring systems, visualized collapse patterns during natural sleep, additional measurements, and comparison of upper airway collapse between NSE and drug-induced sleep endoscopy (DISE). A computerized search on Medline, Web of Science and the Cochrane library was conducted, obtaining 39 hits. Ten prospective studies were included in which NSE was performed in adults with obstructive sleep apnea (OSA). This study's findings suggest the soft palate to be the most frequent site of obstruction (58.8 %), followed by the tongue base (43.2 %), lateral walls (29.9 %), and epiglottis (22.4 %), which is in line with previous findings during DISE. Based on this literature review, the authors conclude that at this stage high quality, comparative research between DISE and NSE is missing. To adequately compare findings between OSA patients, endoscopic classification of upper airway collapse should be standardized. Non-invasive predictive tools to determine pharyngeal collapse are currently under investigation and may obviate the need for invasive endoscopy. This review highlights the contribution of NSE in validating such novel diagnostic methods and in studying upper airway mechanics in a research setting, yet larger and adequately powered studies are needed..

How long does the average person sleep? Here, Kocevska et al. conducted a meta-analysis including over 1.1 million people to produce age- and sex-specific population reference charts for sleep duration and efficiency.We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including >= 100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (>= 18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (>= 18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending >= 9 h in bed, whereas poor sleep quality was more frequent in those spending = 41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

// Heleen H. Van Acker 1 , Ottavio Beretta 2 , Sebastien Anguille 1, 3 , Lien De Caluwe 1, 4 , Angela Papagna 2 , Johan M. Van den Bergh 1 , Yannick Willemen 1 , Herman Goossens 1 , Zwi N. Berneman 1, 3 , Viggo F. Van Tendeloo 1 , Evelien L. Smits 1, 3, 5 , Maria Foti 2, * , Eva Lion 1, 3, * 1 Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium 2 School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy 3 Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium 4 Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 5 Center for Oncological Research (CORE), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium * Share senior authorship Correspondence to: Heleen H. Van Acker, email: heleen.vanacker@uantwerp.be Keywords: CCL4-CCR5 signaling, dendritic cell vaccination, γδ T cells, immune cell recruitment, NK cells Received: April 25, 2016 Accepted: January 03, 2017 Published: January 13, 2017 ABSTRACT Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8 + T cells, natural killer (NK) cells and gamma delta (γδ) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B + effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated γδ T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.