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In Alzheimer's disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology. The Liver X receptor (LXR) family, consisting of LXRα and LXRβ, was reported to inhibit angiogenesis and particularly LXRα was shown to secure BBB stability, suggesting a major role in vascular function. In this study, we unravel the regulatory mechanism exerted by LXRα to preserve BBB integrity in human brain endothelial cells (BECs) and investigate its role during pathological conditions. We report that LXRα ensures BECs identity via constitutive inhibition of the transcription factor SNAI2. Accordingly, deletion of brain endothelial LXRα is associated with impaired DLL4-NOTCH signalling, a critical signalling pathway involved in vessel sprouting. A similar response was observed when BECs were exposed to hypoxia, with concomitant LXRα decrease and SNAI2 increase. In support of our cell-based observations, we report a general increase in vascular SNAI2 in the occipital cortex of AD patients with and without capCAA. Importantly, SNAI2 strongly associated with vascular amyloid-beta deposition and angiopoietin-like 4, a marker for hypoxia. In hypoxic capCAA vessels, the expression of LXRα may decrease leading to an increased expression of SNAI2, and consequently BECs de-differentiation and sprouting. Our findings indicate that LXRα is essential for BECs identity, thereby securing BBB stability and preventing aberrant angiogenesis. These results uncover a novel molecular pathway essential for BBB identity and vascular homeostasis providing new insights on the vascular pathology affecting AD patients., (© 2023. The Author(s).)

Background: The General Practice (GP) postgraduate program exists for 80% out of workplace learning. The quality of the clinical learning environment (CLE) has a direct effect on the quality of training and the professional development of GP trainees., Methodology: Participatory research was used to involve all stakeholders in the development process of a 360° evaluation tool that should improve the average quality of GP training practices, guide GP trainees towards the best training practices and detect and remediate GP trainers of lower quality., Results: TOEKAN (Tool for Communication and Evaluation of Quality Standards) was developed, which consists of a 72-item questionnaire for GP trainees and GP trainers and an 18-item questionnaire for those who coach and remediate GP trainers. The outcomes of the TOEKAN questionnaires are visualized in an online dashboard., Discussion: TOEKAN is the first 360° evaluation tool for CLE in GP education. All stakeholders will complete the survey on a regular basis and have access to the results. By creating intrinsic and extrinsic motivation as well as mediation measures, the quality of CLE will improve. Continuous monitoring of the use and outcomes of TOEKAN will allow to critically review and improve this new evaluation tool as well as support the broader implementation.

Background: Recent studies suggest that extended interval dosing of ocrelizumab, an anti-B cell therapy, does not affect its clinical effectiveness in most patients with multiple sclerosis (MS). However, it remains to be established whether certain B cell subsets are differentially repopulated after different dosing intervals and whether these subsets relate to clinical efficacy., Methods: We performed high-dimensional single-cell characterization of the peripheral immune landscape of patients with MS after standard (SID; n = 43) or extended interval dosing (EID; n = 37) of ocrelizumab and in non-ocrelizumab-treated (control group, CG; n = 28) patients with MS, using mass cytometry by time of flight (CyTOF)., Results: The first B cells that repopulate after both ocrelizumab dosing schemes were immature, transitional and regulatory CD1d + CD5 + B cells. In addition, we observed a higher percentage of transitional, naïve and regulatory B cells after EID in comparison with SID, but not of memory B cells or plasmablasts. The majority of repopulated B cell subsets showed an increased migratory phenotype, characterized by higher expression of CD49d, CD11a, CD54 and CD162. Interestingly, after EID, repopulated B cells expressed increased CD20 levels compared to B cells in CG and after SID, which was associated with a delayed repopulation of B cells after a subsequent ocrelizumab infusion. Finally, the number of/changes in B cell subsets after both dosing schemes did not correlate with any relapses nor progression of the disease., Conclusions: Taken together, our data highlight that extending the dosing interval of ocrelizumab does not lead to increased repopulation of effector B cells. We show that the increase of CD20 expression on B cell subsets in EID might lead to longer depletion or less repopulation of B cells after the next infusion of ocrelizumab. Lastly, even though extending the ocrelizumab interval dosing alters B cell repopulation, it does not affect the clinical efficacy of ocrelizumab in our cohort of patients with MS., (© 2023. BioMed Central Ltd., part of Springer Nature.)

GWAS have identified numerous genes associated with human cognition but their cell type expression profiles in the human brain are unknown. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether these gene sets are expressed in adult human cortical neurons, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 pyramidal neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger total dendritic length (TDL) and faster action potential (AP) kinetics, properties previously linked to intelligence. We identify a subset of genes associated with TDL or AP kinetics with predominantly synaptic functions and high abundance of HARs., (© 2023. The Author(s).)

Aging associates with an increased susceptibility for disease and decreased quality of life. To date, processes underlying aging are still not well understood, leading to limited interventions with unknown mechanisms to promote healthy aging. Previous research suggests that changes in the blood proteome are reflective of age-associated phenotypes such as frailty. Moreover, experimentally induced changes in the blood proteome composition can accelerate or decelerate underlying aging processes. The aim of this study is to identify a set of proteins in the human plasma associated with aging by integration of the data of four independent, large-scaled datasets using the aptamer-based SomaScan platform on the human aging plasma proteome. Using this approach, we identified a set of 273 plasma proteins significantly associated with aging (aging proteins, APs) across these cohorts consisting of healthy individuals and individuals with comorbidities and highlight their biological functions. We validated the age-associated effects in an independent study using a centenarian population, showing highly concordant effects. Our results suggest that APs are more associated to diseases than other plasma proteins. Plasma levels of APs can predict chronological age, and a reduced selection of 15 APs can still predict individuals' age accurately, highlighting their potential as biomarkers of aging processes. Furthermore, we show that individuals presenting accelerated or decelerated aging based on their plasma proteome, respectively have a more aged or younger systemic environment. These results provide novel insights in the understanding of the aging process and its underlying mechanisms and highlight potential modulators contributing to healthy aging., Competing Interests: Author BL was employed by the Alkahest Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Coenen, Lehallier, de Vries and Middeldorp.)

Alzheimer's disease (AD) is the most common form of dementia affecting millions of people worldwide. While different immunotherapies are imminent, currently only disease-modifying medications are available and a cure is lacking. Over the past decade, immunological interfaces of the central nervous system (CNS) and their role in neurodegenerative diseases received increasing attention. Specifically, emerging evidence shows that subsets of circulating CD8 + T cells cross the brain barriers and associate with AD pathology. To gain more insight into how the adaptive immune system is involved in disease pathogenesis, we here provide a comprehensive overview of the contribution of T cells to AD pathology, incorporating changes at the brain barriers. In addition, we review studies that provide translation of these findings by targeting T cells to combat AD pathology and cognitive decline. Importantly, these data show that immunological changes in AD are not confined to the CNS and that AD-associated systemic immune changes appear to affect brain homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: COVID-19 has changed General Practice (GP) education as well as GP clinical activities. These changes have had an impact on the well-being of medical trainees and the role of GP plays in the society. We have therefore aimed to investigate the impact that COVID-19 has had on GP trainees and trainers in four domains: education, workload, practice organization and the role of GP in society., Design: a cross-sectional study design was used., Methods: The Interuniversity Centre for the Education of General Practitioners sent an online survey with close-ended and open-ended questions to all GP trainees and trainers in Flanders, active in the period March - September 2020. Descriptive statistics were performed to analyze the quantitative data and thematic analysis for the qualitative data., Results: 216 (response 25%) GP trainees and 311 (response 26%) trainers participated. GP trainees (63%, N = 136) and trainers (76%, N = 236) reported new learning opportunities since the COVID-19 pandemic. The introduction of telehealth consulting and changing guidelines required new communication and organizational skills. Most of the GP trainees (75%, n = 162) and trainers (71%, n = 221) experienced more stress at work and an overload of administrative work. The unfamiliarity with a new infectious disease and the fact that COVID-19 care compromised general GP clinical activities, created insecurity among GP trainers and trainees. Moreover, GP trainees felt that general GP activities were insufficiently covered during the COVID-19 pandemic for their training in GP. GP trainers and trainees experienced mutual support, and secondary support came from other direct colleagues. Measures such as reducing the writing of medical certificates and financial support for administrative and (para) medical support can help to reprioritize the core of GP care. COVID-19 has enhanced the use of digital learning over peer-to-peer learning and lectures. However, GP trainees and trainers preferred blended learning educational activities., Conclusions: COVID-19 has created learning opportunities such as telehealth consulting and a flexible organization structure. To ensure quality GP education during the pandemic and beyond, regular GP care should remain the core activity of GP trainees and trainers and a balance between all different learning methods should be found., (© 2022. The Author(s).)

Background: Teenage pregnancies occur frequently in developing countries and are associated with social issues, including poverty, lower levels of health and educational attainment. Although frequent in European countries in the 20th century today, teenage pregnancies account for only 4% of first children. These pregnancies are usually unplanned and they are considered a vulnerability factor during the pregnancy and the postnatal period, both for the mother and the child. The purpose of our study was to evaluate the evolution of mothers and children of teenage pregnancies, several years after childbirth and to identify factors which may protect or increase the patient's vulnerability., Subjects and Methods: We conducted a retrospective search in our patient database in order to identify all teenage pregnancies between 2010-2014 at CHU Brugmann Hospital. Outcome date data were obtained from the medical files. Mothers were contacted by phone and asked to complete our questionnaire which focused on maternal and paediatric care; and infant and child development after hospitalization., Results: Out of the 342 patients identified, 84 patients were contactable and only 72 patients completed the full questionnaire. With only 4 patients originating from Belgium, our population was largely immigrant. Despite this, obstetrical, maternal and paediatric outcomes were remarkably favorable when compared to other published studies., Conclusion: Our study suggests that some migrant teenage mothers may have a dual advantage in terms of the wealth of a developed country in which have settled and the low social stigma related to their country of origin. More research needs to be done to further investigate this hypothesis.

Introduction: A cortical lined impaction on the radiodorsal side of the ulnar head may be at the origin of a "second ulnar groove" (SUG). The goal of this article is to illustrate this MRI sign, prompting for further investigation of the distal radioulnar joint (DRUJ). Hence associated soft tissue pathology may be detected, which may lead to instability., Material and Methods: Following an anterior luxation of the ulna at the DRUJ a second cortical lined groove in a previously normal distal ulna was discovered. A data base review from January 2008 to August 2016 of the axial FS PD-TSE WI 1.5T MRI views of 1.716 patients was accomplished in search of similar bone defects., Results: Eight patients with previous severe wrist trauma presented with a similar posttraumatic ulnar bone defect. The preceding anterior luxation at the DRUJ was only clearly demonstrated in five patients. However, two more patients had a residual anterior subluxation. Different imaging techniques are discussed and the differential diagnosis is well illustrated., Conclusions: The type of trauma, the specific location and the morphology of a second ulnar groove, all compatible with a sequel of an anterior luxation of the ulna at the DRUJ, should lead to a further specific clinical and MRI revaluation of the DRUJ., (Copyright © 2017 Elsevier B.V. All rights reserved.)

There is a lack of knowledge in environmental pollution of the anthropogenic contaminants in wastewater and surface water. Several organic compounds merit special attention, because of their potential risk to the aquatic environment. Therefore, gas chromatography-mass spectrometry-based screening analyses were performed in order to identify anthropogenic organic contaminants and to reveal information on the structural diversity of individual compounds and to characterize their environmental behavior. Wastewater samples from wastewater treatment plants in Germany, representing various capacities, and surface water samples from corresponding receiving waters were analyzed. Numerous substances were identified in the samples. Several compounds were treated inadequately during wastewater treatment, and their identification in surface waters highlights their potential impact on the aquatic environment. Contaminants were selected according to available information about their environmental relevance (e.g. persistence, bioaccumulation potential), their possible application or usage and their occurrence within the environment. Based on the results of this study, it is recommended that non-target screening analyses be undertaken to identify the structural diversity of anthropogenic organic contaminants and that further investigations of specific anthropogenic compounds be undertaken as a high priority.

We investigated whether infants can transfer their goal attribution between situations that contain different types of information about the goal. We found that 12-month-olds who had attributed a goal based on the causal efficacy of a means-end action generated expectations about the actor's action in another scenario in which the actor could choose between alternative outcomes. This finding suggests that, by 12 months, infants possess a unitary concept of goal., (2011 Blackwell Publishing Ltd.)

In this retrospective study of 26 patients with arthritis of the thumb carpometacarpal joint, we report the use of expanded polytetrafluoroethylene (ePTFE) (Gore-Tex) and polypropylene (Marlex) as interpositional materials for resection arthroplasty of the trapeziometacarpal joint. We have compared the results with those of "conventional" tendon interposition and those in the literature. In three patients the use of ePTFE (Gore-Tex) was complicated by marked clinical synovitis, resembling findings in silicone synovitis. Therefore, the use of ePTFE has been discontinued. Polypropylene seems to be a valuable alternative to tendon interposition arthroplasty.

A pseudotumor of the palm was due to an anomalous flexor digitorum superficialis muscle belly. Magnetic resonance imaging is an excellent diagnostic tool to define the three dimensional extension of such an anomaly. Surgical resection of the anomalous muscle belly resulted in a complete relief of all symptoms.

In a toe transplantation in a child with symbrachydactyly the authors were faced with a no-reflow phenomenon. The medication they used in prophylaxis was not an absolute guarantee to prevent this problem. Success also depends on some general measures, as a stable blood pressure, a constant blood volume, normal body temperature, short operation time, and an early revision in case of a no-reflow phenomenon. Some questions about the appearance of spasm still remain: are they provoked by pain, stress, medication as anaesthetics, or is a congenital structural vessel problem responsible?

Twelve arterial anastomoses are performed using fibrinous tissue glue. Long term patency is controlled. Histological and scanning electron microscopical evaluation of the clot formation is performed.

In this article results are compared of the bovine graft and the Goretex graft as a shunt from an artery to a vein in view of the access to the circulation for haemodialysis. Drawing conclusions would seem premature as yet, but there seems to be some indication that the Goretex graft stays open more easily. In our opinion the Goretex graft is easier to handle during the operation. We want to point out once again that, in all probability, our ample experience with the Goretex graft plays a role in the evaluation of the outcome.

To provide general anaesthesia with endotracheal intubation during regional blockades, three dose regimens of propofol emulsion were studied: induction 2 mg kg-1, infusion rate 9 mg kg-1 h-1 (Group 1); induction 2.5 mg kg-1, infusion rate 12 mg kg-1 h-1 (Group 2); induction 2.5 mg kg-1, infusion rate 9 mg kg-1 (Group 3). Each group comprised 10 healthy (ASA class 1 or 2) unpremedicated patients. The induction times measured from the start of injection until counting ceased (+/- 50 s) and until eye-lash reflex disappeared (+/- 80 s) showed no statistical differences between groups. In five patients in Group 1 and one patient in each of Groups 2 and 3 the induction dose was too low for intubation. Pain on injection was seen in 13 cases (mild 6, moderate 6 and severe 1). Cough accompanied by hypersalivation was the most important side-effect. Recovery times varied widely and showed no statistical differences. Answering simple questions was possible after 14 min in Group 1, 23 min in Group 2 and 19 min in Group 3. Apart from a short period of euphoria, recovery was uneventful. There was no tendency to fall asleep again. None of the combinations of induction doses and infusion rates provided good anaesthesia conditions for an acceptable number of patients.

In this study we checked the functional results of flexor tendon sutures in a group of 50 non-selected patients, observed during 4 to 5 years. The functional results of our 84 flexor tendon sutures speak well for primary suturing with favourable wound conditions. This applies to all zones, even to Zone Ii where a primary repair does not exclude the possibility of a successful secondary tendon graft using Hunter's method. In case of a cut of the profundus and superficialis tendons in Zones II and III, the question of whether both tendons or just the profundus should be repaired, will be answered by the levels of the cuts. In Zone II the superficialis tendon is better left untouched, as a resection produces less favourable results owing to the traumatization of the tissues. For the pollicis longus a critical localization of the tendon sheath, distal to the metacarpophalangeal joint, may be an indication for a tendon transfer or transplantation. The minimally traumatizing technique and adequate postoperative rehabilitation and follow-up do explain the good results, even in Zone II where they reached a 66% rate.

The propofol requirements for the induction and maintenance of anaesthesia were compared in groups of younger and older patients. Side effects, influence on the cardiovascular system and recovery times were compared between 20 unpremedicated ASA I-III, 25-40-yr-old patients and 20 65-80-yr-old patients all scheduled to undergo elective surgery. After induction with propofol, anaesthesia was maintained with a continuous infusion of the drug. Vecuronium and fentanyl were administered as required. In the young group propofol 2.2 mg kg-1 and in the elderly 1.7 mg kg-1 were needed for induction (P less than 0.05). The maintenance doses were 10.0 mg kg-1 h-1 and 8.6 mg kg-1 h-1, respectively (P less than 0.01). Side effects were more pronounced in the younger patients. Influences on the cardiovascular system were definite, but mild. The younger patients awoke sooner: 7.8 v. 14.3 min (P less than 0.01) after the discontinuation of the infusion of propofol.

The cocaine body packer syndrome is seen in drug traffickers swallowing hermetically packed cocaine. The condition can be diagnosed by serial abdominal roentgenograms. The double condom sign and the rosette form are two pathognomonic radiological signs. In the absence of complications, laxatives are administered and the patient is monitored for a prolonged period of time. In the event of a cocaine intoxication due to rupture of a package or in case of a gastrointestinal obstruction, an emergency surgical exploration should be carried out.

Diagnosis, surgical management and complications of gastric rupture from blunt abdominal trauma are reviewed. The diagnosis is mainly based on the clinical examination, to which peritoneal lavage is a valuable aid. Early surgery with a two layer suture technique and extensive peritoneal irrigation are emphasized.

Injuries to the porta hepatis present a rare but life-threatening condition. This report documents a patient surviving injuries to all three structures in the porta hepatis. A literature study sets out the guidelines for the optimal treatment of these lesions.

Three-point arthrography according to Levinsohn is a valuable technique in the evaluation of lesions of the ligaments of the wrist and in the prevention of severe sequelae.

Between 1978 and 1982 154 femoral shaft fractures were treated in 145 adults in our department of general surgery and traumatology. 52 fractures were nailed intramedullary. We reserved the intramedullary nailing for ideal cases like the transverse and the short oblique fractures in the middle 3/5 of the shaft. 102 fractures were treated by a dynamic compression plate applying the AO principles correctly. Condylar plates were not included in this study. 88 patients with 95 FSF were followed up. In our prospective study a significant relationship was found between the types of fractures, the consolidation, the rehabilitation (including walking), the hospitalisation time and the full weight-bearing results. The prognosis for simple fractures was better than for comminuted fractures. Polytrauma patients showed a significantly slower limb rehabilitation, a longer hospitalisation and a worse clinical result than patients with isolated fractures. A significant relationship was shown between the mobility of the knee and the localisation of the fracture. In the beginning of our study we thought a delayed osteosynthesis (1-2 weeks) should lead to a faster consolidation but afterwards we didn't notice any significant difference with the early operation. General complications were restricted to one fat embolism. Important bone shortening (greater than or equal to 2 cm) was only measured 4 times (4.2%). Distinct rotation or angulation deformities were not observed. Bone infection occurred twice (2.1%). All but two of the 9 comminuted fractures healed within a year in spite of an initial delayed union.

Major trauma to the upper extremity may lead to ischemic contracture of various muscle groups, sometimes including the intrinsic muscles of the hand. The clinical consequence of such necrotic fibrosis of the intrinsics is clawing of the digits with marked stiffness. After a short anatomical review of the fascias of the intrinsics, indications and operative techniques are discussed, in parallel with clinical cases. Intrinsic fasciotomy thus appears to be a major step in the prevention of digital clawing, when associated with early physiotherapy.