Liver X receptor alpha ensures blood-brain barrier function by suppressing SNAI2.

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 LXRß, 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.

Markers of aging: Unsupervised integrated analyses of the human plasma proteome.

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.

Crossing borders in Alzheimer's disease: A T cell's perspective.

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.

Interpositional arthroplasty with Gore-Tex, Marlex or tendon for osteoarthritis of the trapeziometacarpal joint. A retrospective comparative study.

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.

Pseudotumor of the palm due to an anomalous flexor digitorum superficialis muscle belly.

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.

[Absence of blood circulation following toe-hand transplantation in a 7-year-old girl with monodactyle form of symbrachydactyly]. / Ausbleibende Blutzirkulation nach einer Zehen-Hand-Transplantation bei einem siebenjährigen Mädchen mit monodaktyler Form der Symbrachydaktylie.

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?

The "cocaine body packer" syndrome. Case report and review of the literature.

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.

Traumatic injuries to the porta hepatis: case report and review of the literature.

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.

Propofol for induction and maintenance of anaesthesia: comparison between younger and older patients.

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.

Three-point arthrography of the wrist.

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.

Gastric rupture from blunt abdominal trauma.

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.

Propofol emulsion for induction and maintenance of anaesthesia. A combined technique of general and regional anaesthesia.

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.

Intrinsic fasciotomy. When and why?

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.

A plate osteosynthesis for femoral shaft fractures in adults.

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.

Fibrinous tissue glue in artery anastomosis. Physiological, histological and scanning evaluation.

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.

Bovine graft and polytetrafluorethylene prosthesis as an access to circulation for haemodyalisis.

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.

The treatment of flexor tendon lesions of the fingers.

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.