Annelies Geeraerts

Syndecan-syntenin-ALIX regulates the biogenesis of exosomes

The biogenesis of exosomes, small secreted vesicles involved in signalling processes, remains incompletely understood. Here, we report evidence that the syndecan heparan sulphate proteoglycans and their cytoplasmic adaptor syntenin control the formation of exosomes. Syntenin interacts directly with ALIX through LYPX(n)L motifs, similarly to retroviral proteins, and supports the intraluminal budding of endosomal membranes. Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs, and impact on the trafficking and confinement of FGF signals. This study identifies a key role for syndecan–syntenin–ALIX in membrane transport and signalling processes.

19 The Flemish version of the Triage Risk Screening Tool (TRST): a multidimensional short screening tool for the assessment of elderly patients

The mean total cost per patient for the medication prescribed during radiotherapy (concomitant and supportive care medications), was €612 for the elderly and €992 for the younger patients. The cost for supportive care for the elderly and younger patients was €358 and €647 respectively. When costs were analyzed on the basis of the type of treatment (palliative or radical), the same pattern was noted. More specifically, the mean total medication cost per person for the younger group of patients undergoing radical radiotherapy was €1005, as compared to €976 for the elderly. The mean total medication cost per person for the younger and elderly patients undergoing palliative radiotherapy, was €742 and €423 respectively. Conclusions: Our study showed that elderly patients had a higher co morbidity rate than the younger patients, being prescribed a greater amount of medications for the management of co morbidities. During radiotherapy the need of medication for supportive care was higher for the younger group of patients, resulting in a higher mean total medication cost per patient. The mean total prescription cost per patient was markedly higher for the younger patients undergoing palliative radiotherapy (as compared to the elderly patients undergoing the same type of therapy). Finally, the cost of supportive care medications seems to be more expensive than the concomitant prescribed regiments for both groups.

Use of a Fall Prevention Practice Guideline for Community-Dwelling Older Persons at Risk for Falling: A Feasibility Study

Background: Falls among older persons occur frequently and are a common cause of physical and psychological morbidity and healthcare utilization. The problem can be attributed to a complex interaction between health-related, behavioral and environmental factors. To ensure a uniform and evidence-based approach, a practice guideline was developed for fall prevention in community-dwelling older persons at risk for falls. Objective: To test the feasibility of integrating a fall prevention practice guideline into the daily practice of 4 primary healthcare disciplines, i.e. general practitioners, nurses, occupational therapists and physiotherapists. Methods: This was a descriptive study which was carried out by 10 local health networks located throughout Flanders. The subjects involved in the study were 99 primary care workers and 1,142 community-dwelling older patients (65 years or older) who could rise from a chair and transfer independently. For 6 months, primary care workers implemented our fall prevention guideline, which consisted of 3 parts (case finding, multifactorial in-depth assessment and interventions). After the 6-month trial phase, participating primary care workers were asked to complete a semistructured questionnaire to evaluate the feasibility of using the guideline in daily practice. Results: The average time spent on carrying out the guideline was 32.0 ± 14.0 min. Healthcare workers from all 4 disciplines considered case finding to be their responsibility. The picture was different for the evaluation of risk factors and interventions. Although 87.5% considered fall prevention to be an important issue, healthcare workers from different disciplines failed to agree about how to integrate the prevention guideline into daily practice. Perceived barriers to implementing the guideline were lack of time (57.3%), poor motivation of the target population (53.3%) and insufficient cooperation between healthcare workers (37.3%). Conclusion: A guideline can be used to initiate the integration of prevention strategies into daily practice. Case finding is feasible for all disciplines. Multifactorial assessment and interventions require specific task allocation, multidisciplinary cooperation and clear communication.

The characterization of the nuclear dynamics of syntenin-2, a PIP2 binding PDZ protein

Cellular signaling is largely dependent on the presence, that is, assembly/disassembly, of supramolecular complexes. Postsynaptic density protein, Discs‐large, Zona occludens (PDZ) domains play important roles in the assembly of various signaling complexes. Syntenin‐2 (S2) is a PDZ protein that interacts with nuclear phosphatidylinositol 4,5‐bisphosphate (PIP2). Although nuclear lipids emerge as key players in nuclear processes, the global significance of nuclear phosphoinositide‐protein interactions is still poorly understood. Those phosphoinositide‐protein interactions that have been studied in detail appear to have profound physiological effects. To our knowledge none of these were investigated by dynamic studies such as Fluorescence Correlation Spectroscopy (FCS), Fluorescence Cross‐Correlation Spectroscopy (FCCS), or Fluorescence Recovery After Photobleaching (FRAP). Although the exact function of S2 is unknown, siRNA experiments suggest that this PDZ protein plays a role in the organization of nuclear PIP2, cell division, and cell survival. As a consequence of its PIP2 interaction, its reported self‐association in a yeast two‐hybrid study and its speculated interaction with many, yet unidentified, proteins one can hypothesize that S2 plays an important role in cell signaling. Therefore, we studied the dynamics of S2 using FCS, FCCS, and FRAP, utilizing an active truncated form deleted for the first 94 amino acids (S2‐ΔN). We showed that S2‐ΔN self‐associates and is distributed in three groups. One immobile group, one slow diffusing group, which interacts with the nuclear environment and one fast diffusing group, which is not incorporated in high molecular weight complexes. In addition, our FCS and FRAP measurements on S2‐ΔN mutants affected in their PIP2 binding showed that PIP2 plays an important role in the distribution of S2‐ΔN among these groups, and favors the enrichment of S2‐ΔN in the slow diffusing and immobile group. This work indicates that S2 relies on nuclear PIP2 to interact with practically immobile structures, possibly chromatin.

Preventie van valincidenten bij thuiswonende ouderen: een kostenbesparende interventie?

SamenvattingNationale en internationale cijfers tonen aan dat 1 op 3 thuiswonende 65-plussers en nagenoeg de helft van de 80-plussers minstens eenmaal per jaar valt. Bij ongeveer 40% van hen resulteert dit in een letsel.1-4 Ongeveer 10% van de valpartijen bij ouderen leidt tot ernstige letsels, waaronder heupfracturen (1-2%), andere fracturen (3-5%) en letsels van de weke delen en hoofdtrauma (5%).1,3-5Nationale en internationale cijfers tonen aan dat 1 op 3 thuiswonende 65-plussers en nagenoeg de helft van de 80-plussers minstens eenmaal per jaar valt. Bij ongeveer 40% van hen resulteert dit in een letsel.1-4 Ongeveer 10% van de valpartijen bij ouderen leidt tot ernstige letsels, waaronder heupfracturen (1-2%), andere fracturen (3-5%) en letsels van de weke delen en hoofdtrauma (5%).1,3-5

O6 Prospective descriptive cohort study on the detection of depression and cognitive decline with short screening tools in elderly cancer patients

Background: A growing and diverse aging population, recent advances in research on aging and cancer, and the fact that a disproportional burden of cancer still occurs in people aged 65 years and older have generated great interest in delivering better cancer care for older adults. Cancer and its treatment precipitate classic geriatric syndromes such as falls, malnutrition, delirium, and urinary incontinence. Comprehensive Geriatric Assessment (CGA) offers a model of integrating medical care with social support services and is characterized by a multidimensional assessment of the general health where functional, cognitive and psychosocial parameters are evaluated by validated tools. However, the drawbacks of CGA include a time-consuming realization for busy clinicians, the lack of trained staff even in large academic hospitals and no financial rewards by most health insurance systems. For these reasons, CGA is rarely applied in clinical practice. There is increasing interest in the use of shorter screening tools and their validation is eagerly awaited. The aim of this study is to examine the sensitivity and specificity of the 2-item Geriatric Depression Scale (GDS) and the Watson clock test compared to the more routinely used 15-item GDS and the Mini Mental State Examination (MMSE) in the detection of depression and cognitive decline in elderly cancer patients. Methods: The study was conducted between 11-2003 and 3-2005 in the University Hospitals of Leuven, Belgium. It was designed as a prospective descriptive cohort study. One hundred five patients with various cancers (breast tumour 38.1%, gastrointestinal tumour 28.6%, various 33.3%) were included with a mean age of 76.4 years (SD= 5.18). All the patients were about to start a new treatment with chemotherapy or elective cancer surgery. The patient underwent a brief interview by 3 dedicated nurses using the 2-item GDS, the 15-item GDS, the Watson clock test and the MMSE. The Watson clock test and MMSE data were missing in 3 patients. Results: Table 1: The 2-item GDS compared to the 15-item GDS as gold standard in n = 105 patients