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Summary: We determined the prognostic value of nutritional status for outcome after hip fracture. Nutritional status was a strong independent prognostic factor for clinical outcome and 5-year mortality. Physical function showed incomplete recovery. Elderly care should focus on prevention already before hip fracture. Purpose: To determine the prognostic value of nutritional status in hip fracture patients for multiple clinical and functional outcomes over 6 months, and for new fractures and survival over 5 years post-fracture. Methods: We included 152 well-characterized subjects (age 55+ years) with a hip fracture from a previously published randomized controlled trial. Nutritional status was appraised using the Mini Nutritional Assessment (MNA). Multivariable linear, logistic and Cox regression models were fitted, adjusted for age, sex, ASA score, group and additional prognostic covariates identified in backward regression models. Results: At baseline, impaired nutritional status was significantly associated with physical disability, depression, impaired cognition and lower quality of life. Prospective analyses showed that impaired baseline nutritional status was an independent prognostic factor for postoperative complications (OR 2.00, 95%CI 1.01–3.98, p = 0.047), discharge location from hospital (home vs. rehabilitation clinic, OR 0.41, 95%CI 0.18–0.98, p = 0.044), hospital readmission (OR 4.59, 95%CI 1.70–12.4, p = 0.003) and total length of hospital stay (HR of being discharged: 0.63, 96%CI 0.44–0.89, p = 0.008), as well as for 5-year mortality (HR 3.94, 95%CI 1.53–10.2, p = 0.005), but not for risk of new fractures (5y-HR 0.87, 95%CI 0.34–2.24, p = 0.769). Curves of physical disability over time showed that the three nutritional status categories followed almost parallel trajectories from baseline until 6 months after hip fracture, without complete recovery and even with further deterioration in malnourished subjects from 3 to 6 months post-fracture. Conclusion: As baselline nutritional status is a strong independent prognostic factor for clinical outcome after hip fracture, affecting even five-year survival, elderly health care should focus on prevention and identification of at-risk individuals already before hip fracture. [ABSTRACT FROM AUTHOR]

Since the late 20th century, a combination of sociodemographic changes and increasing costs of pensions, health and social care challenged the intergenerational welfare contract. Besides, governments have been substituting more parts of care services for informal care. Given this reality, little is known to what extent informal cares prefer a higher government responsibility. Nonetheless, they demonstrate solidarity towards other generations through their actions. In this article, we question whether the intensity of informal caregiving, expressed in hours a week, and age group affects preferences towards welfare distributions and policies supporting informal caregivers. To do so, we have used a unique dataset of stratified, representative data about intergenerational exchanges between individuals in Belgium. We only see a significant effect of high intensity caregiving on general welfare state support. For the policy that targets informal caregivers we see no differences between informal caregivers and non‐carers. We argue that informal care status or age cannot fully grasp people's preferences of welfare state support, but lies in the intersection of individual characteristics. A recent study about informal caregivers in Flanders highlighted significant differences in support needs across age groups. Notably, the persons at working age, would feel most helped by reconciliation measures such as paid informal care leave. Moreover, support needs correlated with the intensity of caregiving, as those providing 10 h or more expressed a greater need for financial support, work‐life balance policies and help from professional services (Bracke et al. Zorgenquête 2021: Inhoudelijk rapport, 2022). Recognizing the importance of different support needs of informal caregivers, underscores the necessity for comprehensive approaches in family and informal care policies to address both caregiver and recipient needs effectively. [ABSTRACT FROM AUTHOR]

This paper takes a new look at how the aerodynamic interactions of multiple bodies in high-speed flow affect their motion behaviors. The influence of the body shape and orientation on aerodynamic and stability behavior in the case of shock–shock and wake–shock interactions is the focus of this publication. Experiments were performed in the hypersonic wind tunnel H2K at the German Aerospace Center (DLR) in Cologne. Free-flight tests with tandem arrangements of spheres and cubes were performed with a synchronized dropping of both objects at various initial conditions of relative streamwise and vertical distance as well as pitch angle. A high-speed stereo-tracking captured the model motions during free-flight, and high-speed schlieren videography provided documentation of the flow topology. Based on the measured 6-degrees-of-freedom (6DoF) motion data, aerodynamic coefficients were determined. As a result, the final lateral velocity of trailing cubes is found to be many times greater than that of spheres regarding shock-wave surfing. For rotating cubes, the results showed that stable shock-wave surfing can become possible over an increasingly wide range of initial positions. This study has identified that the trailing drag coefficient of two axially aligned objects varies strongly with their relative streamwise distance. Furthermore, it was shown that the wake is a region of stability for downstream objects. [ABSTRACT FROM AUTHOR]

Summary: Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture. Purpose Introduction: Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means. Methods: In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ − 2SD to < − 1 (impaired) and < − 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses. Results: A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59–74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (P < 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (B) (95%CI) = − 0.25 [− 0.34, − 0.16]; hip: B = − 0.32 [− 0.47, − 0.17], VF: B = − 0.22 [− 0.34, − 0.11]), TUG; (major: B = − 0.54 [− 0.75, − 0.33]; hip: B = − 1.72 [− 2.08, -1.35], VF: B = − 0.61 [− 0.88, − 0.57]), 6MWT (major: B = − 0.34 [− 0.47, − 0.21]; hip: B = − 0.99 [− 1,22, − 0.77], VF: B = − 0.36 [− 0.53, − 0.19]). Conclusions: Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia. [ABSTRACT FROM AUTHOR]

• Prevalence of thyroid and adrenal incidentalomas on chest CT imaging in a less selected cohort of COVID-19 suspected patients was 4.8% and 6.7%, respectively. • In this study, diagnostic work-up of the incidentalomas did not impact the clinical management in an overwhelming majority (97.7%) of the analyzed patients. • The low incidence of malignancies and other clinically relevant findings among thyroid and adrenal incidentalomas raises the question regarding the necessity of intensive diagnostic work-up of thyroid and adrenal incidentalomas for all patients. Due to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. A retrospective, observational cohort study. We included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. A total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71–80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. Prevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients. [ABSTRACT FROM AUTHOR]

Background: In response to the COVID-19 pandemic, the World Health Organization established a number of key recommendations such as educational activities especially within primary care practices (PCPs) which are a key component of this strategy. This paper aims to examine the educational activities of PCPs during COVID-19 pandemic and to identify the factors associated with these practices across 38 countries. Methods: A "Patient Education (PE)" score was created based on responses to six items from the self-reported questionnaire among PCPs (n = 3638) compiled by the PRICOV-19 study. Statistical analyses were performed on 3638 cases, with PCPs with missing PE score values were excluded. Results: The PE score features a mean of 2.55 (SD = 0.68) and a median of 2.50 (2.16 – 3.00), with a maximum of 4.00, and varies quite widely between countries. Among all PCPs characteristics, these factors significantly increase the PE score: the payment system type (with a capitation payment system or another system compared to the fee for service), the perception of average PCP with patients with chronic conditions and the perception of adequate governmental support. Conclusion: The model presented in this article is still incomplete and requires further investigation to identify other configuration elements favorable to educational activities. However, the results already highlight certain levers that will enable the development of this educational approach appropriate to primary care. [ABSTRACT FROM AUTHOR]

Cylinder-pressure-based control is a key enabler for advanced pre-mixed combustion concepts. In addition to guaranteeing robust and safe operation, it allows for cylinder pressure and heat release shaping. This requires fast control-oriented combustion models. Over the years, mean-value models have been proposed that can predict combustion metrics (e.g., gross indicated mean effective pressure ( IMEP g ), or the crank angle where 50% of the total heat is released (CA50)) or models that predict the full in-cylinder pressure. However, these models are not able to capture cycle-to-cycle variations. The inclusion of the cycle-to-cycle variations is important in the control design for combustion concepts, like reactivity-controlled compression ignition, that can suffer from large cycle-to-cycle variations. In this study, the in-cylinder pressure and cycle-to-cycle variations are modelled using a data-based approach. The in-cylinder conditions and fuel settings are the inputs to the model. The model combines principal component decomposition and Gaussian process regression. A detailed study is performed on the effects of the different hyperparameters and kernel choices. The approach is applicable to any combustion concept, but is most valuable for advance combustion concepts with large cycle-to-cycle variation. The potential of the proposed approach is successfully demonstrated for a reactivity-controlled compression ignition engine running on diesel and E85. The average prediction error of the mean in-cylinder pressure over a complete combustion cycle is 0.051 bar and of the corresponding mean cycle-to-cycle variation is 0.24 bar2. This principal-component-decomposition-based approach is an important step towards in-cylinder pressure shaping. The use of Gaussian process regression provides important information on cycle-to-cycle variation and provides next-cycle control information on safety and performance criteria. [ABSTRACT FROM AUTHOR]

The proportion of patients who undergo lumbar microdiscectomy due to lumbar radiculopathy who are also overweight or obese is high. However, whether high body mass index (BMI) affects clinical outcomes is not well-studied. To investigate the difference in the clinical course between normal weight, overweight, and obese patients with radiculopathy who underwent lumbar microdiscectomy followed by physical therapy and to evaluate whether high BMI is associated with poor recovery. A prospective cohort study with a 12-month follow-up was conducted in a multidisciplinary clinic. We included 583 patients (median [IQR] age: 45 [35–52] years; 41% female) with clinical signs and symptoms of lumbar radiculopathy, consistent with magnetic resonance imaging findings, who underwent microdiscectomy followed by postoperative physical therapy. Outcomes were leg pain and back pain intensity measured with a visual analogue scale, disability measured with the Roland Morris Disability Questionnaire at 3 and 12-month follow-ups, and complications. Patients were classified as being normal weight (46.9%), overweight (38.4%), or obese (14.7%). A linear mixed-effects model was used to assess the difference in the clinical course of pain and disability between the three BMI categories. The association between BMI and outcomes was evaluated using univariable and multivariable logistic regression analyses. All three patient groups experienced a significant improvement in leg pain, back pain, and disability over 3 and 12-month follow-up. Patients who were overweight, obese, or normal weight experienced comparable leg pain (p=.14) and disability (p=.06) over the clinical course (p=.14); however, obese patients experienced higher back pain (MD=−6.81 [95%CI: −13.50 to −0.14]; p=.03). The difference in back pain scores was not clinically relevant. In the first year following lumbar microdiscectomy, patients demonstrated clinical improvements and complications that were unrelated to their preoperative BMI. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer and has a poor prognosis. Patients with PDAC are at high risk of developing thromboembolic events, which is a leading cause of morbidity and mortality following cancer progression. Plasma-derived coagulation is the most studied process in cancer-associated thrombosis. Other blood components, such as platelets, red blood cells, and white blood cells, have been gaining less attention. This narrative review addresses the literature on the role of cellular components in the development of venous thromboembolism (VTE) in patients with PDAC. Blood cells seem to play an important role in the development of VTE. Altered blood cell counts, i.e., leukocytosis, thrombocytosis, and anemia, have been found to associate with VTE risk. Tumor-related activation of leukocytes leads to the release of tissue factor-expressing microvesicles and the formation of neutrophil extracellular traps, initiating coagulation and forming a scaffold for thrombi. Tissue factor-expressing microvesicles are also thought to be released by PDAC cells. PDAC cells have been shown to stimulate platelet activation and aggregation, proposedly via the secretion of podoplanin and mucins. Hypofibrinolysis, partially explained by increased plasminogen activator inhibitor-1 activity, is observed in PDAC. In short, PDAC-associated hypercoagulability is a complex and multifactorial process. A better understanding of cellular contributions to hypercoagulability might lead to the improvement of diagnostic tests to identify PDAC patients at highest risk of VTE. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular diseases (CVD) are the leading cause of death globally. Inflammation is an important driver of CVD where tissue damage may lead to the formation of deadly thrombi. Therefore, antithrombotic drugs, such as platelet inhibitors, are crucial for secondary risk prevention in coronary artery disease (CAD) and peripheral artery disease (PAD). For severe forms of the disease, dual-pathway inhibition (DPI) where low-dose aspirin is combined with rivaroxaban has shown improved efficacy in reducing cardiovascular mortality. Methods: Given this greater improvement in mortality, and the importance of inflammation in driving atherosclerosis, the potential for off-target inflammation-lowering effects of these drugs was evaluated by looking at the change in immune cell distribution and responsiveness to ex vivo lipopolysaccharide (LPS) stimulation after 3 months of DPI in patients with CAD. Results: We observed no changes in whole blood or peripheral blood mononuclear cell (PBMC) immune cell responsiveness to LPS after 3 months of DPI. Additionally, we did not observe any changes in the distribution of total white blood cells, monocytes, neutrophils, lymphocytes, or platelets during the study course. Signs of systemic inflammation were studied using Olink proteomics in 33 patients with PAD after 3 months of DPI. No changes were observed in any of the inflammatory proteins measured after the treatment period, suggesting that the state of chronic inflammation was not altered in these subjects. Conclusion: Three months of DPI does not result in any meaningful change in immune cell responsiveness and distribution in patients with CAD or PAD. Trial Registration: ClinicalTrials.gov ID: NCT05210725 [ABSTRACT FROM AUTHOR]

The finite element method (FEM) is commonly used in computational cardiac simulations. For this method, a mesh is constructed to represent the geometry and, subsequently, to approximate the solution. To accurately capture curved geometrical features many elements may be required, possibly leading to unnecessarily large computation costs. Without loss of accuracy, a reduction in computation cost can be achieved by integrating geometry representation and solution approximation into a single framework using the isogeometric analysis (IGA) paradigm. In this study, we propose an IGA framework suitable for echocardiogram data of cardiac mechanics, where we show the advantageous properties of smooth splines through the development of a multi-patch anatomical model. A nonlinear cardiac model is discretized following the IGA paradigm, meaning that the spline geometry parametrization is directly used for the discretization of the physical fields. The IGA model is benchmarked with a state-of-the-art biomechanics model based on traditional FEM. For this benchmark, the hemodynamic response predicted by the high-fidelity FEM model is accurately captured by an IGA model with only 320 elements and 4700 degrees of freedom. The study is concluded by a brief anatomy-variation analysis, which illustrates the geometric flexibility of the framework. The IGA framework can be used as a first step toward an efficient workflow for an improved understanding of, and clinical decision support for, the treatment of cardiac diseases like heart rhythm disorders. [ABSTRACT FROM AUTHOR]

In this paper, we discuss the applicability of the consensus document, prepared by the Special Interest Research Group on quality of life (QoL) of the International Association for the Scientific Study of Intellectual Disabilities in August 2000, for persons with Profound Intellectual and Multiple disabilities (PIMD). We compare our findings from previous empirical research with some elements of the themes and principles of the consensus document. We will reflect (1) on the domains of QoL mentioned in the consensus document, and (2) on the assessment by proxies. We recommend reflection on the following aspects when composing a new consensus document, which includes QoL of persons with PIMD: first, reconsider whether all eight domains are useful in care practice for—and research about—persons with PIMD. We assert that the domains of health, well‐being, capability to influence the environment, and also (family) relationships, are particularly relevant for the QoL of persons with PIMD and, second, accept interpretation of signals and signs by proxies in the assessment of QoL in persons with PIMD and do not value this as second best. [ABSTRACT FROM AUTHOR]

Background: Specialist palliative care teams are consulted during hospital admission for advice on complex palliative care. These consultations need to be timely to prevent symptom burden and maintain quality of life. Insight into specialist palliative care teams may help improve the outcomes of palliative care. Methods: In this retrospective observational study, we analyzed qualitative and quantitative data of palliative care consultations in a six-month period (2017 or 2018) in four general hospitals in the northwestern part of the Netherlands. Data were obtained from electronic medical records. Results: We extracted data from 336 consultations. The most common diagnoses were cancer (54.8%) and organ failure (26.8%). The estimated life expectancy was less than three months for 52.3% of all patients. Within two weeks after consultation, 53.2% of the patients died, and the median time until death was 11 days (range 191) after consultation. Most patients died in hospital (49.4%) but only 7.5% preferred to die in hospital. Consultations were mostly requested for advance care planning (31.6%). End-of-life preferences focused on last wishes and maintaining quality of life. Conclusion: This study provides detailed insight into consultations of palliative care teams and shows that even though most palliative care consultations were requested for advance care planning, consultations focus on end-of-life care and are more crisis-oriented than prevention-oriented. Death often occurs too quickly after consultation for end-of-life preferences to be met and these preferences tend to focus on dying. Educating healthcare professionals on when to initiate advance care planning would promote a more prevention-oriented approach. Defining factors that indicate the need for timely palliative care team consultation and advance care planning could help timely identification and consultation. [ABSTRACT FROM AUTHOR]

Background Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs. Methods Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients. Results Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11 , HGC1 , and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non- albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval,.46–3.26]). Conclusions MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6 -dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed. [ABSTRACT FROM AUTHOR]

When running on a curve, the lower limbs interact with the ground to redirect the trajectory of the centre of mass of the body (CoM). The goal of this paper is to understand how the trajectory of the CoM and the work done to maintain its movements relative to the surroundings (Wcom) are modified as a function of running speed and radius of curvature. Eleven participants ran at different speeds on a straight line and on circular curves with a 6 m and 18 m curvature. The trajectory of the CoM and Wcom were calculated using force-platforms measuring the ground reaction forces and infrared cameras recording the movements of the pelvis. To follow a circular path, runners overcompensate the rotation of their trajectory during contact phases. The deviation from the circular path increases when the radius of curvature decreases and speed increases. Interestingly, an asymmetry between the inner and outer lower limbs emerges as speed increases. The method to evaluate Wcom on a straight-line was adapted using a referential that rotates at heel strike and remains fixed during the whole step cycle. In an 18 m radius curve and at low speeds on a 6 m radius, Wcom changes little compared to a straight-line run. Whereas at 6 m s-1 on a 6 m radius, Wcom increases by ~25%, due to an augmentation in the work to move the CoM laterally. Understanding these adaptations provides valuable insight for sports sciences, aiding in optimizing training and performance in sports with multidirectional movements. [ABSTRACT FROM AUTHOR]

Self-control is a personality dimension that is associated with better physical health and a longer lifespan. Here, we examined (1) whether self-control is associated with buccal and saliva DNA-methylation (DNAm) measures of biological aging quantified in children, adolescents, and adults, and (2) whether biological aging measured in buccal DNAm is associated with self-reported health. Following preregistered analyses, we computed two DNAm measures of advanced biological age (principal-component PhenoAge and GrimAge Acceleration) and a DNAm measure of pace of aging (DunedinPACE) in buccal samples from the German Socioeconomic Panel Study (SOEP-G[ene], n = 1058, age range 0–72, Mage = 42.65) and saliva samples from the Texas Twin Project (TTP, n = 1327, age range 8–20, Mage = 13.50). We found that lower self-control was associated with advanced biological age in older adults (PhenoAge Acceleration β = −.34, [−.51, −.17], p <.001; GrimAge Acceleration β = −.34, [−.49, −.19], p <.001), but not young adults, adolescents or children. These associations remained statistically robust even after correcting for possible confounders such as socioeconomic contexts, BMI, or genetic correlates of low self-control. Moreover, a faster pace of aging and advanced biological age measured in buccal DNAm were associated with self-reported disease (PhenoAge Acceleration: β =.13 [.06,.19], p <.001; GrimAge Acceleration: β =.19 [.12,.26], p <.001; DunedinPACE: β =.09 [.02,.17], p =.01). However, effect sizes were weaker than observations in blood, suggesting that customization of DNAm aging measures to buccal and saliva tissues may be necessary. Our findings are consistent with the hypothesis that self-control is associated with health via pathways that accelerate biological aging in older adults. [ABSTRACT FROM AUTHOR]

Purpose: Running at a given speed can be achieved by taking large steps at a low frequency or on the contrary by taking small steps at a high frequency. The consequences of a change in step frequency, at a fixed speed, affects the stiffness of the lower limb differently. In this study, we compared the running mechanics and kinematics at different imposed step frequencies (from 2 step s−1 to 3.6 step s−1) to understand the relationship between kinematic and kinetic parameters. Methods: Eight recreational male runners ran on a treadmill at 5 different speeds and 5 different step frequencies. The lower-limb segment motion and the ground reaction forces were recorded. Mechanical powers, general gait parameters, lower-limb movements and coordination were investigated. Results: At low step frequencies, in order to limit the magnitude of the ground reaction force, the vertical stiffness is reduced and thus runners deviate from an elastic rebound. At high step frequencies, the stiffness is increased and the elastic rebound is optimised in its ability to absorb and restore energy during the contact phase. Conclusion: We studied the consequences of a change in step frequency on the bouncing mechanics of running. We showed that the lower limb stiffness and the intersegmental coordination of the lower-limb segments are affected by running step frequency rather than speed. The runner rather adapts their lower limb stiffness to match a step frequency for a given speed than the opposite. [ABSTRACT FROM AUTHOR]

Exercise is a recommended part of phase IV cardiovascular rehabilitation (CR). The 1 km treadmill walk test (1-KTWT) is a submaximal continuous exercise test to predict cardiorespiratory fitness in patients with cardiovascular disease. We examined physiological, metabolic and subjective responses in patients with cardiovascular disease with self-selected, unchanging walking speed for two 1-KTWTs. Fifteen men (age: 65 ± 9 yr, height: 174 ± 5 cm, body mass: 86 ± 17 kg, BMI: 28.5 ± 5.5 kg·m−2, body fat%: 27.7 ± 7.5%, 10 on beta-blockers) were recruited from phase IV CR groups in the United Kingdom. Participants established a self-selected walking speed for the 1-KTWT and performed the 1-KTWT on separate days with recording of physiological responses to predict V ˙ O2peak with equations. For the two 1-KTWTs, no differences existed for walking speed, mean and maximal heart rates, oxygen uptake, predicted V ˙ O2peak (1st 1-KTWT (range: 41–78% V ˙ O2peak, 95%CI, 53–65; 2nd 1-KTWT range: 43–78% V ˙ O2peak, 95%CI, 52–65) and rating of perceived exertion. In phase IV cardiac patients, the 1-KTWT with self-selected, unchanging walking speed can be used for V ˙ O2peak prediction without the need for a full familiarisation. The self-selected constant walking speed for the first 1-KTWT can be used to support nonsupervised physical activity for phase IV CR patients. [ABSTRACT FROM AUTHOR]

Sphingosine‐1‐phosphate receptor (S1PR) modulators are clinically used to treat relapse‐remitting multiple sclerosis (MS) and the early phase of progressive MS when inflammation still prevails. In the periphery, S1PR modulators prevent lymphocyte egress from lymph nodes, hence hampering neuroinflammation. Recent findings suggest a role for S1PR modulation in remyelination. As the Giα‐coupled S1P1 subtype is the most prominently expressed S1PR in oligodendrocyte precursor cells (OPCs), selective modulation (functional antagonism) of S1P1 may have direct effects on OPC functionality. We hypothesized that functional antagonism of S1P1 by ponesimod induces remyelination by boosting OPC differentiation. In the cuprizone mouse model of demyelination, we found ponesimod to decrease the latency time of visual evoked potentials compared to vehicle conditions, which is indicative of functional remyelination. In addition, the Y maze spontaneous alternations test revealed that ponesimod reversed cuprizone‐induced working memory deficits. Myelin basic protein (MBP) immunohistochemistry and transmission electron microscopy of the corpus callosum revealed an increase in myelination upon ponesimod treatment. Moreover, treatment with ponesimod alone or in combination with A971432, an S1P5 monoselective modulator, significantly increased primary mouse OPC differentiation based on O4 immunocytochemistry. In conclusion, S1P1 functional antagonism by ponesimod increases remyelination in the cuprizone model of demyelination and significantly increases OPC differentiation in vitro. [ABSTRACT FROM AUTHOR]

The field of dysmorphology has been changed by the use Artificial Intelligence (AI) and the development of Next Generation Phenotyping (NGP). The aim of this study was to propose a new NGP model for predicting KS (Kabuki Syndrome) on 2D facial photographs and distinguish KS1 (KS type 1, KMT2D-related) from KS2 (KS type 2, KDM6A-related). We included retrospectively and prospectively, from 1998 to 2023, all frontal and lateral pictures of patients with a molecular confirmation of KS. After automatic preprocessing, we extracted geometric and textural features. After incorporation of age, gender, and ethnicity, we used XGboost (eXtreme Gradient Boosting), a supervised machine learning classifier. The model was tested on an independent validation set. Finally, we compared the performances of our model with DeepGestalt (Face2Gene). The study included 1448 frontal and lateral facial photographs from 6 centers, corresponding to 634 patients (527 controls, 107 KS); 82 (78%) of KS patients had a variation in the KMT2D gene (KS1) and 23 (22%) in the KDM6A gene (KS2). We were able to distinguish KS from controls in the independent validation group with an accuracy of 95.8% (78.9–99.9%, p < 0.001) and distinguish KS1 from KS2 with an empirical Area Under the Curve (AUC) of 0.805 (0.729–0.880, p < 0.001). We report an automatic detection model for KS with high performances (AUC 0.993 and accuracy 95.8%). We were able to distinguish patients with KS1 from KS2, with an AUC of 0.805. These results outperform the current commercial AI-based solutions and expert clinicians. [ABSTRACT FROM AUTHOR]

Prospective audit with feedback during infectious diseases ward rounds (IDWR) is a common antimicrobial stewardship (AMS) practice on the Paediatric Intensive Care Unit (PICU). These interdisciplinary meetings rely on the quality of handover, with high risk of omission of information. We developed an electronic platform integrating infection-related patient data (COSARAPed). In the mixed PICU of a Belgian tertiary hospital we conducted an observational prospective cohort study comparing patient handovers during IDWRs using the COSARAPed-platform to those with access only to conventional resources. The quality of handover was investigated directly by assessment if the narrative was in accordance with Situation-Background-Assessment-Recommendation principles and if adequate demonstration of diagnostic information occurred, and also indirectly by registration if this was only achieved after intervention by the non-presenting AMS team members. We also recorded all AMS-recommendations. During a 6-month study period, 24 IDWRs and 82 patient presentations were assessed. We could only find a statistically significant advantage in favor of COSARAPed by indirect evaluation. We registered 92 AMS-recommendations, mainly resulting in reduced antibiotic pressure. We concluded that the IDWR is an appropriate platform for AMS on the PICU and that the utilisation of COSARAPed may enhance the quality of patient handover. [ABSTRACT FROM AUTHOR]

Introduction: Pulsed field ablation (PFA) represents a novel, nonthermal energy modality that can be applied for single‐shot pulmonary vein isolation (PVI) in atrial fibrillation (AF). Comparative data with regard to deep sedation to established single‐shot modalities such as cryoballoon (CB) ablation are scarce. The aim of this study was to compare a deep sedation protocol in patients receiving PVI with either PFA or CB. Methods: Prospective, consecutive AF patients undergoing PVI with a pentaspline PFA catheter were compared to a retrospective CB‐PVI cohort of the same timeframe. Study endpoints were the requirements of analgesics, cardiorespiratory stability, and sedation‐associated complications. Results: A total of 100 PVI patients were included (PFA n = 50, CB n = 50, mean age 66 ± 10.6, 61% male patients, 65% paroxysmal AF). Requirement of propofol, midazolam, and sufentanyl was significantly higher in the PFA group compared to CB [propofol 0.14 ± 0.04 mg/kg/min in PFA vs. 0.11 ± 0.04 mg/kg/min in CB (p =.001); midazolam 0.00086 ± 0.0004 mg/kg/min in PFA vs. 0.0006295 ± 0.0003 mg/kg/min in CB (p =.002) and sufentanyl 0.0013 ± 0.0007 µg/kg/min in PFA vs. 0.0008 ± 0.0004 µg/kg/min in CB (p <.0001)]. Sedation‐associated complications did not differ between both groups (PFA n = 1/50 mild aspiration pneumonia, CB n = 0/50, p >.99). Nonsedation‐associated complications (PFA: n = 2/50, 4%, CB: n = 1/50, 2%, p >.99) and procedure times (PFA 75 ± 31, CB 84 ± 32 min, p =.18) did not differ between groups. Conclusions: PFA is associated with higher sedation and especially analgesia requirements. However, the safety of deep sedation does not differ to CB ablation. This study sought to compare the requirements and safety of deep sedation in patients undergoing pulmonary vein isolation (PVI) with either a pentaspline pulsed field ablation (PFA) catheter, a novel energy modality, or cryoballoon (CB) ablation, an established energy source. In 100 patients undergoing PVI (PFA: n = 50, CB: n = 50), the requirement of analgosedation was significantly higher in the PFA group compared to CB, especially with regard to analgesics. There was no difference in sedation‐associated and nonsedation‐associated complications between groups. [ABSTRACT FROM AUTHOR]

Background: An increasing number of commercially available wearables provide real‐time feedback on running biomechanics with the aim to reduce injury risk or improve performance. Objective: Investigate whether real‐time feedback by wearable insoles (ARION) alters running biomechanics and improves running economy more as compared to unsupervised running training. We also explored the correlation between changes in running biomechanics and running economy. Methods: Forty recreational runners were randomized to an intervention and control group and performed ~6 months of in‐field training with or without wearable‐based real‐time feedback on running technique and speed. Running economy and running biomechanics were measured in lab conditions without feedback pre and post intervention at four speeds. Results: Twenty‐two individuals (13 control, 9 intervention) completed both tests. Both groups significantly reduced their energetic cost by an average of −6.1% and −7.7% for the control and intervention groups, respectively. The reduction in energy cost did not significantly differ between groups overall (−0.07 ± 0.14 J∙kg∙m−1, −1.5%, p = 0.63). There were significant changes in spatiotemporal metrics, but their magnitude was minor and did not differ between the groups. There were no significant changes in running kinematics within or between groups. However, alterations in running biomechanics beyond typical session‐to‐session variation were observed during some in‐field sessions for individuals that received real‐time feedback. Conclusion: Alterations in running biomechanics as observed during some in‐field sessions for individuals receiving wearable‐based real‐time feedback did not result in significant differences in running economy or running biomechanics when measured in controlled lab conditions without feedback. [ABSTRACT FROM AUTHOR]

During a series of irregular visits to Inhaca Island, Mozambique in the years 1982-1987, J.H.C. Walenkamp, often aided by students and staff of the Faculty of Biology in Maputo, made extensive collections of littoral and infralittoral invertebrates. Among the extensive collections of Brachyura, several caridean shrimps were encountered, upon which we herein report. Cuapetes cf. ensifrons is recorded from Mozambique for the first time. [ABSTRACT FROM AUTHOR]

Despite the proliferation of studies on interest group influence, there has been limited research on the conditions that facilitate their ability to impact policy agendas. This study investigates the role of supportive alignments in enhancing interest groups’ agenda-setting influence, with a specific focus on the European Union. We argue that organisations aligning closely with institutional and societal actors are better positioned to push their ‘dream’ issues on the policy agenda while keeping ‘nightmare’ issues off. To assess this argument, we rely on a novel dataset comprising 301 mobilised interest groups on 56 specific issues. Our findings underscore the pivotal role of institutional alignments in gaining agenda-setting influence. Moreover, aligning with the public and other interest groups increases the chances of preference attainment. However, it does not lead to a higher likelihood of being perceived as an influential agenda-setter. Overall, our study contributes to a more comprehensive understanding of interest group influence, extending insights beyond legislative politics. [ABSTRACT FROM AUTHOR]

Background: The electronic community health information system has been increasingly developed and deployed to quantify and support quality health service delivery by community health workers in Ethiopia. However, the success and failure of the electronic community health information system depend on the acceptability and use by its users. This study assessed the acceptability and use of the electronic community health information system and its determinants among health extension workers in Ethiopia. Methods: A retrospective cross-sectional observational study was conducted among 587 randomly selected health extension workers from six regions of Ethiopia. The Revised Technology Acceptance Model was used as a theoretical framework for the study. Descriptive statistics, structural equation modeling, and principal component analysis techniques were used to analyze the data. For all significance tests, multiple comparison adjustments were made using the Bonferroni Correction Method. Results: There was near universal acceptance of the electronic community health information system, ranging from 94.4 to 97.4% among health extension workers. However, actual use of the system was considerably lower, at 50%. Perceived usefulness of the electronic community health information system had a direct and positive effect on acceptability (β3 = 0.415, p < 0.001). Perceived ease of use had both direct and indirect positive effects on electronic community health information system acceptability (β2 = 0.340, p < 0.001 and β1*β3 = 0.289, p < 0.001, respectively), while acceptability had a direct and positive effect on the use of the electronic community health information system (β3 = 0.297, p < 0.001). Conclusions: Despite the very high acceptability of the electronic community health information system among health extension workers, actual use of the system is considerably lower. Hence, an integrated and coordinated approach is required to close the acceptance-use gap. [ABSTRACT FROM AUTHOR]

OVX836, a recombinant vaccine containing the nucleoprotein of the influenza A virus A/WSN/1933 (H1N1) and the oligomerisation domain OVX313, has displayed a good safety profile and elicited dose-dependent humoral and cellular immune responses at 90 μg or 180 μg (intramuscularly) in previous clinical trials. The aim of this study was to explore higher doses, since no maximum tolerated dose had been reached. In this phase 2a, randomised, double-blind, placebo-controlled study, we recruited 137 healthy adults aged 18–55 years in a single centre in Belgium. Participants were randomly assigned (interactive web response system; block size=4) using SAS (version 9.4) to receive one single intramuscular administration of OVX836 influenza vaccine at three doses (180 μg [n=33], 300 μg [n=35], and 480 μg [n=36]) or placebo (n=33). The two primary endpoints were the safety and the cell-mediated immune response to OVX836 at the three doses in terms of change of nucleoprotein-specific IFNγ spot forming cell (SFC) frequencies in the peripheral blood mononuclear cell (PBMC) population, measured by IFNγ ELISpot, at day 8 versus pre-injection baseline (day 1). The population used for the safety analysis is the modified intention-to-treat cohort. The population used for the immunogenicity analysis is the per-protocol cohort. This trial is registered with ClinicalTrials.gov , NCT05060887 , and EudraCT, 2021-002535-39. Participants were recruited between Nov 15, 2021, and Feb 1, 2022. OVX836 had a favourable safety profile up to 480 μg without reaching the maximum tolerated dose, and showed a good safety profile at all doses with mild local and systemic reactogenicity. 7 days after vaccination, although no significant differences were observed between the doses, OVX836 increased the frequency of nucleoprotein-specific IFNγ SFCs per million PBMCs from days 1 to 8 (primary endpoint): by 124 SFCs per 106 PMBCs (95% CI 67 to 180; p=0·002) at 180 μg; by 202 SFCs per 106 PMBCs (95% CI 138 to 267; p<0·0001) at 300 μg; by 223 SFCs per 106 PMBCs (95% CI 147 to 299; p<0·0001) at 480 μg; and decreased by 1 SFCs per 106 PMBCs (95% CI –24 to 22] in the placebo group (Kruskal-Wallis test p<0·0001 followed by Mann-Whitney's tests; per-protocol cohort). Dose-dependent and polyfunctional nucleoprotein-specific CD4 T-cell responses were observed, and CD8 T-cell responses were elicited at 300 μg and 480 μg (secondary endpoints). OVX836 appears to be a safe and well tolerated candidate vaccine that elicits humoral and cellular nucleoprotein-specific immune responses (including CD8 T cells at the highest dose levels) and showed a preliminary signal of protection against influenza. Therefore, OVX836 is a promising vaccine candidate for universal influenza A prevention, that warrants further trials. OSIVAX, Bpifrance, Wallonia Region, and the EUs Horizon 2020 Research and Innovation Program. [ABSTRACT FROM AUTHOR]

Background: Current treatment options for Alzheimer's disease (AD) are limited, inefficient, and often have serious side effects. Oxytocin is a neuropeptide implicated in a variety of central processes, such as social and reproductive behaviors. Among others, it has garnered attention in various domains of psychiatric research, while its role in the development and course of neurodegenerative disorders like AD is rather unknown. Objective: This study aimed to investigate the role of exogenous oxytocin administration on memory, specifically in view of AD, as a potential novel treatment option. Methods: We describe a novel treatment approach by using a relatively low dose of long-term intranasal oxytocin treatment, to restore memory deficits in female APPswePS1dE9 mice. Results: Female APPswePS1dE9 mice treated with oxytocin showed increased spatial memory performance in the object location task and improved working memory in the Y-Maze, while indicating decreased sociability. Conclusions: These results indicate that oxytocin is able to reverse acquired cognitive deficits in female APPswePS1dE9 mice. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic exposed the health equity gap between and within countries. Western countries were the first to receive vaccines and mortality was higher among socially deprived, minority and indigenous populations. Surprisingly, many sub-Saharan countries reported low excess mortalities. These countries share experiences with community organization and participation in health. The aim of this article was to analyse if and how this central role of people can promote a successful pandemic response. Methods: This analysis was partly based on local and national experiences shared during an international and Latin American conference on person-and people-centred care in 2021. Additionally, excess mortality data and pandemic control-relevant data, as well as literature on the pandemic response of countries with an unexpected low excess mortality were consulted. Results: Togo, Mongolia, Thailand and Kenya had a seven times lower mean excess mortality for 2020 and 2021 than the United States of America. More successful pandemic responses were observed in settings with experience in managing epidemics like Ebola and HIV, well-established community networks, a national philosophy of mutual aid, financial government assistance, more human resources for primary care and paid community health workers. Discussion: Since trust in authorities and health needs vary greatly, local strategies are needed to complement national and international pandemic responses. Three key levers were identified to promote locally-tailored pandemic management: well-organized communities, community-oriented primary care, and health information systems. An organized community structure stems from a shared ethical understanding of humanity as being interconnected with each other and the environment. This structure facilitates mutual aid and participation in decision making. Community-oriented primary care includes attention for collective community health and ways to improve health from its roots. A health information system supports collective health and health equity analysis by presenting health needs stratified for social deprivation, ethnicity, and community circumstances. Conclusions: The difference in excess mortality between countries during the COVID-19 pandemic and various country experiences demonstrate the potential of the levers in promoting a more just and effective health emergency response. These same levers and strategies can promote more inclusive and socially just health systems. [ABSTRACT FROM AUTHOR]

Background: Although Klinefelter syndrome (KS) is the most frequent sex‐hormone disorder, there is ongoing uncertainty about the often associated sex‐hormone deficiency, its impact on common comorbidities, and therefore about prevention and treatment. In this study, we focus on bone loss, reported to occur in over 40% of KS patients, and the impact of testosterone replacement therapy (TRT) on this comorbidity. Objectives: This single‐center retrospective cohort study in a tertiary hospital compared the effect of treatment with TRT to no TRT on evolution of bone mineral density (BMD) in KS patients. Methods: After a medical chart review, a total of 52 KS subjects were included in this study. BMD was measured by dual‐energy X‐ray absorptiometry (DXA) and expressed as T‐scores. Results: The subjects were divided into three groups, according to TRT. In the subgroup that only started TRT after baseline measurements (mean age 31 years), we observed significant gain in BMD T‐score at the lumbar spine (0.58 ± 0.60, p = 0.003; mean gain of 0.62% areal BMD per year) and total femur T‐score (0.24 ± 0.39, p = 0.041; mean gain of 0.25% areal BMD per year) after a mean follow‐up period of 7.5 years. Compared to untreated subjects, a significant difference in evolution was demonstrated at the lumbar level (+0.58 ± 0.60 vs. −0.14 ± 0.42, p = 0.007). In untreated subjects with normal testosterone levels, a loss of BMD (−0.27 ± 0.37, p = 0.029; mean loss of 0.49% areal BMD per year) at the femoral neck was measured. This decline was equal to the predicted loss seen in the general male population. Conclusion: TRT results in BMD gain in patients with KS with testosterone deficiency, mainly at the lumbar spine. However, this effect is limited (0.62% per year). Patients who were not treated with TRT because of sufficient endogenous testosterone levels, showed only the predicted age‐related bone loss during follow‐up. The need for TRT in maintaining bone health in KS should be evaluated on an individual basis according to the degree of sex steroid deficiency. [ABSTRACT FROM AUTHOR]

Aims: To gain insights into the barriers towards the prevention and/or reduction of involuntary treatment in long‐term geriatric care. Design: Mixed methods. Background: Measures to which a person resists and/or does not provide consent for are defined as involuntary treatment. The use of involuntary treatment violates the autonomy of (older) persons and causes more harm than benefit. Moreover, it contradicts the values of person‐centred care. Nevertheless, its use among people living with dementia (PLWD) is still common practice. Methods: We conducted a cross‐sectional, mixed methods study, including an online survey for professional caregivers and a semistructured focus group interview with professional caregivers. Results: A total of 218 participants completed the questionnaire. The percentage of participants who perceived barriers in one of the 22 survey items ranged from 15% to 42%. Lack of time, the experienced need to use involuntary treatment, uncertainty about responsibilities of stakeholders and a lack of knowledge on methods to prevent and/or reduce the use of involuntary treatment were most seen as barriers. Nursing staff perceived a lack of time hindering them in the prevention or reduction of involuntary treatment more often than other professional caregivers. Working in home care and having no former experience with involuntary treatment usage increased perceived barriers. Participants of the focus group interview confirmed these findings and added that professional caregivers in general lack awareness on the concept of involuntary treatment. Conclusions: One out of four professional caregivers experiences barriers hindering prevention and/or reduction of involuntary treatment. More research is needed to gain a better understanding of how professional caregivers can be supported to remove barriers and, consequently, prevent and/or reduce the use of involuntary treatment. Relevance to Clinical Practice: Professional caregivers experience many barriers towards the prevention and reduction of involuntary treatment. Future initiatives should aim to remove the perceived barriers. [ABSTRACT FROM AUTHOR]

At the time of return-to-sport, anterior cruciate ligament reconstructed athletes still show altered neuromechanics in their injured leg during single leg hopping tasks. Part of these alterations can be magnified when these athletes are fatigued. So far, little is known whether fatigue-induced landing alterations persist after return-to-sport. Therefore, the aim of this study was to evaluate whether these alterations persist in the six months following return-to-sport. Sixteen anterior cruciate ligament reconstructed athletes performed five unilateral hop tasks before and after a fatigue protocol. The hop tasks were executed at three different time points (return-to-sport, 3 and 6 months post-return-to-sport). A 2-by-3 repeated measures ANOVA was performed to evaluate whether fatigue-induced landing alterations persisted 3 and 6 months following return-to-sport. At 6 months following return-to-sport, fatigue still induces a reduction in hamstring medialis activation and an increase in the knee abduction moment during a vertical hop with 90-degree inward rotation. Most fatigue-induced landing alterations present at the time of return-to-sport normalize after resumption of sports activities. However, a larger knee abduction moment in the injured leg after resumption of sports activities can still be observed. [ABSTRACT FROM AUTHOR]

Spatiotemporal metrics such as step frequency have been associated with running injuries in some studies. Wearables can measure these metrics and provide real‐time feedback in‐field, but are often not validated. This study assessed the validity of commercially available wireless instrumented insoles (ARION) for quantifying spatiotemporal metrics during level running at different speeds (2.78–5.0 m s−1,) and slopes (3° and 6° up/downhill) to an instrumented treadmill. Mean raw, percentage and absolute percentage error, and limits of agreement (LoA) were calculated. Agreement was statistically quantified using four thresholds: excellent, <5%; good, <10%; acceptable, <15%; and poor, >15% error. Excellent agreement (<5% error) was achieved for stride time across all conditions, and for step frequency across all but one condition with good agreement. Contact time and swing time generally showed at least good agreement. The mean difference across all conditions was −0.95% for contact time, 0.11% for stride time, 0.6% for swing time, −0.11% for step frequency, and −0.09% when averaged across all outcomes and conditions. The accuracy at an individual level was generally good to excellent, being <10% for all but two conditions, with these conditions being <15%. Additional experiments among four runners showed that step length could also be measured with an accuracy of 1.76% across different speeds with an updated version of the insoles. These findings suggests that the ARION wearable may not only be useful for large‐scale in‐field studies investigating group differences, but also to quantify spatiotemporal metrics with generally good to excellent accuracy for individual runners. [ABSTRACT FROM AUTHOR]

In March 2020, the Belgian government ordered a complete lockdown as an attempt to decrease the progression of the COVID‐19. The aim of the present study was to examine lockdown‐related changes in psycho‐affective states as well as their relations with experiential diversity and autobiographical memory. A total of 186 Belgian citizens completed an online survey assessing lockdown‐related changes in various dimensions: work, leisure activities, affective state, sleep quality, fatigue, and autobiographical memory. Results revealed that well‐being during the lockdown was related to changes in experiential diversity and to the richness of participants' memories. Moreover, the content and the phenomenology of memories were more negative when memories pertained to the lockdown situation. These findings provide new evidence that mental well‐being of Belgian citizens during the first lockdown was related to how pandemic‐related sanitary constraints affected the diversity of activities that they could undertake. [ABSTRACT FROM AUTHOR]

Background: Cognitive difficulties are a frequent complaint in long COVID and persist for more than a year post- infection. There is a lack of evidence-based data on effective intervention strategies. Non-pharmacological intervention programs that are used with other neurological populations have not yet been the subject of controlled trials. COVCOG is a multicentric, randomized trial comparing cognitive intervention and a cognitive-behavioural counselling. Methods/design: Patients with long covid are selected and recruited at least three months post-infection. Patients are randomised in a 1:1 ratio into the cognitive (neuropsychological psychoeducation) and affective (emotion management with cognitive-behavioural counselling) intervention arms. The inclusion of 130 patients is planned. The cognitive intervention includes psycho-educational modules on fatigue and sleep, attention and working memory, executive functions and long-term memory. The affective intervention includes modules on emotion recognition and communication, uncertainty management and behavioral activation. The main objective is to reduce cognitive complaints 2 months after the intervention. A Follow-up is also planned at 8 months. Discussion: Given the long-term effects of Covid on cognition and the negative effects of cognitive impairment on quality of life and social participation, it is important to determine whether low-dose, non-pharmacological interventions can be effective. The trial will determine which of the usual types of intervention is the most effective. Trial registration: Clinicaltrials.gov Number: NCT05167266 (21/12/ 2021). [ABSTRACT FROM AUTHOR]

By applying dual proteome profiling to Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters with its epithelial host (here, S. Typhimurium infected human HeLa cells), a detailed interdependent and holistic proteomic perspective on host-pathogen interactions over the time course of infection was obtained. Data-independent acquisition (DIA)-based proteomics was found to outperform data-dependent acquisition (DDA) workflows, especially in identifying the downregulated bacterial proteome response during infection progression by permitting quantification of low abundant bacterial proteins at early times of infection when bacterial infection load is low. S. Typhimurium invasion and replication specific proteomic signatures in epithelial cells revealed interdependent host/pathogen specific responses besides pointing to putative novel infection markers and signalling responses, including regulated host proteins associated with Salmonella-modified membranes. Author summary: As causative agents of infectious diseases, intracellular bacterial pathogens have evolved diverse immune escape and survival strategies while thriving inside their hosts. Whereas the residence of the pathogen inside the host can impact the functioning of the latter drastically, the bacterial macromolecular content is typically vastly outstripped by that of the host. This sizeable difference in macromolecular content has thus far hindered proteome profiling of bacteria and its infected host in an integrated and unbiased manner. Here, the power of dual proteome profiling–a universal mass spectrometry-based proteomic strategy for unravelling the intricate interplay between pathogen and host—is presented for the exploration of host as well as pathogen proteomic responses over the time course of the infection, thereby advancing our understanding of infectious diseases. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is highly prevalent among Australian men and can have significant psychological impacts. Despite its prevalence, treatment options have traditionally been limited. In this study, we examined the current prescribing patterns of Australian dermatologists for male AGA. [ABSTRACT FROM AUTHOR]

Emotional words have consistently been shown to be processed differently than neutral words. However, few studies have examined individual variability in emotion word processing with longer, ecologically valid stimuli (beyond isolated words, sentences, or paragraphs). In the current study, we re-analysed eye-tracking data collected during story reading to reveal how individual differences in need for affect and narrative absorption impact the speed of emotion word reading. Word emotionality was indexed by affective-aesthetic potentials (AAP) calculated by a sentiment analysis tool. We found that individuals with higher levels of need for affect and narrative absorption read positive words more slowly. On the other hand, these individual differences did not influence the reading time of more negative words, suggesting that high need for affect and narrative absorption are characterised by a positivity bias only. In general, unlike most previous studies using more isolated emotion word stimuli, we observed a quadratic (U-shaped) effect of word emotionality on reading speed, such that both positive and negative words were processed more slowly than neutral words. Taken together, this study emphasises the importance of taking into account individual differences and task context when studying emotion word processing. [ABSTRACT FROM AUTHOR]

For prosthetic joint infections, antibiotic loaded poly methyl methacrylate (PMMA) spacer or beads can be used to release high concentrations of antibiotics locally at the infection site, while minimizing systemic toxicity. The aim of this study is to determine in vitro and in vivo pharmacokinetic release profile of antibiotics from PMMA spacers and PMMA beads. For the in vitro experiment, the PMMA spacers or beads were submerged in phosphate‐buffered saline and gentamicin concentrations were determined from collected specimen at several times points, measured with enzyme‐linked immunosorbent assays (ELISA). To assess the in vivo antibiotic release profile of different spacers, wound drainage fluid samples were collected after implantation of a spacer over a period of maximum 14 days. After 48 h, the burst gentamicin concentration elution was 9862 ± 1782 ng/ml (mean ± SD) from spacers versus 38,394 ± 7071 ng/ml (mean ± SD) for beads. Over 35 days, spacers had eluted a cumulative mean concentration of 13,812 ± 3548 versus 55,048 ± 12,006 ng/ml for beads (p < 0.001). Clinical samples of patients with a Vancogenx® spacer showed higher gentamicin release than Refobacin™ spacers (p < 0.001). This is the first study that measured the release data of local antibiotics with ELISA. Compare to spacers, the exact release values of gentamicin from PMMA beads are more than 10 times higher and reached a maximum much later than spacers. This makes the use of PMMA beads more preferable to use for treatment of the infection itself. [ABSTRACT FROM AUTHOR]

Background A proportion of patients with Lyme borreliosis (LB) report long-term persisting signs and symptoms, even after recommended antibiotic treatment, which is termed post-treatment Lyme disease syndrome (PTLDS). Consensus on guidance regarding diagnosis and treatment is currently lacking. Consequently, patients suffer and are left searching for answers, negatively impacting their quality of life and healthcare expenditure. Yet, health economic data on PTLDS remain scarce. The aim of this article is therefore to assess the cost-of-illness related to PTLDS, including the patient perspective. Methods PTLDS patients (N  = 187) with confirmed diagnosis of LB were recruited by a patient organization. Patients completed a self-reported questionnaire on LB-related healthcare utilization, absence from work and unemployment. Unit costs (reference year 2018) were obtained from national databases and published literature. Mean costs and uncertainty intervals were calculated via bootstrapping. Data were extrapolated to the Belgian population. Generalized linear models were used to determine associated covariates with total direct costs and out-of-pocket expenditures. Results Mean annual direct costs amounted to €4618 (95% CI €4070–5152), of which 49.5% were out-of-pocket expenditures. Mean annual indirect costs amounted to €36 081 (€31 312–40 923). Direct and indirect costs at the population level were estimated at €19.4 and 151.5 million, respectively. A sickness or disability benefit as source of income was associated with higher direct and out-of-pocket costs. Conclusions The economic burden associated with PTLDS on patients and society is substantial, with patients consuming large amounts of non-reimbursed healthcare resources. Guidance on adequate diagnosis and treatment of PTLDS is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Historically, patients with pancreatic ductal adenoma carcinoma were subjected to immediate surgical resection of the pancreatic tumor. Nowadays, more and more patients are treated with chemo(radio)therapy before surgical resection. It is known that patients with pancreatic cancer have a high risk of developing thrombosis. However, as patients underwent immediate surgery before, the incidence of thrombosis in patients with pancreatic cancer during neoadjuvant chemotherapy is understudied. Few studies have investigated the VTE incidence in this population and it is unclear whether these patients should use perioperative thromboprophylaxis to prevent thrombosis. This narrative review summarizes the evidence that is currently available. Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy. [ABSTRACT FROM AUTHOR]

New networks of public and private parties co-produce urban climate adaptation measures, for which different viewpoints and interests have to be bridged. While previous research has focused on individuals and organizations as intermediaries, little attention has been paid to boundary objects: conceptual or material objects that help to bridge competing values. This article aims to understand how local climate adaptation networks co-develop boundary objects and how they benefit the development of adaptation measures by conducting a qualitative case study comparison of two front-running Dutch networks: Amsterdam Rainproof and Water Sensitive Rotterdam. The conceptualization of a "water-sensitive city" attracted multiple stakeholders (professionals from different disciplines, communities, businesses), while material objects, such as interactive 3 D-models, addressed information needs. The objects contributed to adaptation measures by convening stakeholders, translating viewpoints and initiating collaborations. The limited diversity in the networks suggests that, rather than enabling participatory decision-making, the networks are instrumentally used by water authorities. [ABSTRACT FROM AUTHOR]

Maternal pertussis immunization using Tdap vaccine is recommended in many countries to protect newborns from severe post-natal infection. Immunological changes during pregnancy may influence the response to vaccines. The quality of IgG and memory B cell responses to Tdap immunization in pregnant women has not yet been described. The impact of pregnancy on the response to Tdap vaccination was assessed by comparing humoral immune responses in 42 pregnant and 39 non-pregnant women. The levels of serum pertussis antigens and tetanus toxoid-specific IgG, IgG subclasses, IgG Fc-mediated effector functions, as well as memory B cell frequencies were assessed before and at several time points after vaccination. Tdap immunization induced similar levels of pertussis and tetanus-specific IgG and IgG subclasses in pregnant and non-pregnant women. Pregnant women produced IgG promoting complement deposition, and neutrophils and macrophages phagocytosis at levels comparable to non-pregnant women. They were also able to expand pertussis and tetanus-specific memory B cells at similar frequencies as non-pregnant women, suggesting equivalent "boostability". Higher levels of vaccine-specific IgG, IgG subclasses, and IgG Fc-mediated effector functions were detected in cord blood as compared to maternal blood, indicating efficient transport across the placenta. This study demonstrates that pregnancy does not affect the quality of effector IgG and memory B cell responses to Tdap immunization and that polyfunctional IgG are efficiently transferred across the placenta. ClinicalTrials.Gov (NCT03519373). [ABSTRACT FROM AUTHOR]

Highly filled plastics may offer a suitable solution within the production process for bipolar plates. However, the compounding of conductive additives and the homogeneous mixing of the plastic melt, as well as the accurate prediction of the material behavior, pose a major challenge for polymer engineers. To support the engineering design process of compounding by twin-screw extruders, this present study offers a method to evaluate the achievable mixing quality based on numerical flow simulations. For this purpose, graphite compounds with a filling content of up to 87 wt.-% were successfully produced and characterized rheologically. Based on a particle tracking method, improved element configurations were found for twin-screw compounding. Furthermore, a method to characterize the wall slip ratios of the compounded material system with different filler content is presented, since highly filled material systems often tend to wall slip during processing, which could have a very large influence on accurate prediction. Numerical simulations of the high capillary rheometer were conducted to predict the pressure loss in the capillary. The simulation results show a good agreement and were experimentally validated. In contrast to the expectation, higher filler grades showed only a lower wall slip than compounds with a low graphite content. Despite occurring wall slip effects, the developed flow simulation for the design of slit dies can provide a good prediction for both low and high filling ratios of the graphite compounds. [ABSTRACT FROM AUTHOR]

Background: Antiseizure medication (ASM) as monotherapy or in combination is the treatment of choice for most patients with epilepsy. Therefore, knowledge about the typical adverse events (AEs) for ASMs and other coadministered drugs (CDs) is essential for practitioners and patients. Due to frequent polypharmacy, it is often difficult to clinically assess the AE profiles of ASMs and differentiate the influence of CDs. Objective: This retrospective analysis aimed to determine typical AE profiles for ASMs and assess the impact of CDs on AEs in clinical practice. Methods: The Liverpool AE Profile (LAEP) and its domains were used to identify the AE profiles of ASMs based on data from a large German multicenter study (Epi2020). Following established classifications, drugs were grouped according to their mode of action (ASMs) or clinical indication (CDs). Bivariate correlation, multivariate ordinal regression (MORA), and artificial neural network (ANNA) analyses were performed. Bivariate correlation with Fisher's z-transformation was used to compare the correlation strength of LAEP with the Hospital Anxiety and Depression Scale (HADS) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to avoid LAEP bias in the context of antidepressant therapy. Results: Data from 486 patients were analyzed. The AE profiles of ASM categories and single ASMs matched those reported in the literature. Synaptic vesicle glycoprotein 2A (SV2A) and voltage-gated sodium channel (VGSC) modulators had favorable AE profiles, while brivaracetam was superior to levetiracetam regarding psychobehavioral AEs. MORA revealed that, in addition to seizure frequency, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) modulators and antidepressants were the only independent predictors of high LAEP values. After Fisher's z-transformation, correlations were significantly lower between LAEP and antidepressants than between LAEP and HADS or NDDI-E. Therefore, a bias in the results toward over interpreting the impact of antidepressants on LAEP was presumed. In the ANNA, perampanel, zonisamide, topiramate, and valproic acid were important nodes in the network, while VGSC and SV2A modulators had low relevance for predicting relevant AEs. Similarly, cardiovascular agents, analgesics, and antipsychotics were important CDs in the ANNA model. Conclusion: ASMs have characteristic AE profiles that are highly reproducible and must be considered in therapeutic decision-making. Therapy using perampanel as an AMPA modulator should be considered cautiously due to its relatively high AE profile. Drugs acting via VGSCs and SV2A receptors are significantly better tolerated than other ASM categories or substances (e.g., topiramate, zonisamide, and valproate). Switching to brivaracetam is advisable in patients with psychobehavioral AEs who take levetiracetam. Because CDs frequently pharmacokinetically interact with ASMs, the cumulative AE profile must be considered. Trial registration: DRKS00022024, U1111-1252-5331. [ABSTRACT FROM AUTHOR]

Background: Children with medical complexity (CMC) require long-term care accompanied by different health- and social care professionals. Depending on the severity of the chronic condition, caregivers spend a lot of time coordinating appointments, communicating between providers, clarifying social legal issues, and more. Effective care coordination is seen as key to addressing the fragmented care that CMC and their families often face. Spinal muscular atrophy (SMA) is a rare genetic, neuromuscular disease which care involves drug therapy and supportive treatment. We examined the care coordination experiences through a qualitative interview analysis of n = 21 interviews with caregivers of children with SMA I or SMA II. Results: The code system consists of 7 codes and 12 sub-codes. “Disease and coordination management of the caregivers” describes the management of coordination-related illness demands. “General conditions of care” include enduring organizational aspects of the care network. “Expertise and skills” refers to both parent and professional expertise. “Coordination structure” describes the assessment of existing coordination mechanisms as well as the need for new ones. “Information exchange” defines the information exchange between professionals and parents as well as the exchange of parents among themselves and the perceived exchange between professionals. “Role distribution in care coordination” summarizes parents' “distribution” of coordinative roles among care network actors (including their own). “Quality of relationship” describes the perceived quality of the relationship between professionals and family. Conclusion: Care coordination is influenced peripherally (e.g., by general conditions of care) and directly (e.g., by coordination mechanisms, interaction in the care network). Access to care coordination appears to be dependent on family circumstances, geographic location, and institutional affiliation. Previous coordination mechanisms were often unstructured and informal. Care coordination is frequently in the hands of caregivers mainly as the care network’s interface. Coordination is necessary and must be addressed on an individual basis of existing resources and family barriers. Existing coordination mechanisms in the context of other chronic conditions could also work for SMA. Regular assessments, centralized shared care pathways, and staff training and empowerment of families for self-management should be central components of all coordination models. Trial registration: German Clinical Trials Register (DRKS): DRKS00018778; Trial registration date 05. December 2019—Retrospectively registered; . [ABSTRACT FROM AUTHOR]

The book "Bordeaux and Aquitaine in World War II" by Gerhard Bökel deals with the Nazi occupation and collaboration, the resistance of the Résistance, and post-war careers in Germany. It is based on archival research by the author in Germany and France, as well as conversations with eyewitnesses. The book contains nine chapters, including one about SS police chief Hans Luther and war judge Erich Schwinge. The article describes the role of Karl Luther, a German official during World War II, in the execution of hostages in Bordeaux. Luther was arrested and extradited to France, where he stood trial. He was acquitted but sentenced to imprisonment for ordering deportations. The article criticizes Luther's attempt to justify his involvement in war crimes and calls for a scholarly examination of the events. [Extracted from the article]

Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent risk of infection with multidrug-resistant bacteria. We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415. Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10–18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5–13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69–6·82) and cumulative incidence of infection (19%, 95% CI 15–25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate. The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention. The Netherlands Organization for Health Research and Development [ABSTRACT FROM AUTHOR]