Association of Cognitive Performance with Frailty in Older Individuals with Cognitive Complaints.

OBJECTIVES: Frailty is a risk factor for poor cognitive performance in older adults. However, few studies have evaluated the association of cognitive performance with frailty in a low- to middle-income country (LMIC). This study aimed to investigate an association between cognitive performance and frailty in older adults with memory complaints in Brazil. Secondarily, we aim to assess an association of cognitive performance with gait speed and grip strength. DESIGN: Cross-sectional study. SETTING: Outpatient service from a LMIC. PARTICIPANTS: Older adults with memory complaints reported by the participants, their proxies, or their physicians. MEASUREMENTS: Frailty was evaluated using the Cardiovascular Health Study criteria. A neuropsychological battery evaluated memory, attention, language, visuospatial function, executive function. Linear regression analysis with adjustment for age, sex, and education was used. We also evaluated the interaction of education with frailty, grip strength, and gait speed. RESULTS: Prefrailty was associated with poor performance in the memory domain, as well as slower gait speed was associated with worse performance in memory, attention, language, and executive function. Frailty and grip strength were not associated with cognitive performance. Interactions of education with gait speed were significant for global performance, as well as for attention and visuospatial ability. CONCLUSION: In elderly patients with memory complaints, prefrailty was associated with poor memory performance. Slowness was associated with poorer performance in some cognitive domains, mainly in participants with low education.

Mechanical Properties of Long Leaves: Experiment and Theory.

The static properties of leaves with parallel venation from terrestrial orchids of the genus Epipactis were modelled as coupled elastic rods using the geometrically exact Cosserat theory and the resulting boundary-value problem was solved numerically using a method from Shampine, Muir and Xu. The response of the leaf structure to the applied force was obtained from preliminary measurements. These measurements allowed the Young's modulus of the Epipactis leaves to be determined. The appearance of wrinkles and undulation characteristics for some leaves has been attributed to the small torsional stiffness of the leaf edges.

[Heart and lung in X-ray images : Lost art (?)]. / Herz und Lunge im Röntgenbild : Lost Art (?).

BACKGROUND: Echocardiography is the standard for the diagnosis of heart diseases. Nevertheless, thoracic X­ray is a frequently used examination method, also for questions regarding the cardiac situation of patients. QUESTION: How relevant is the conventional radiological assessment of heart disease? MATERIALS AND METHODS: Long-known knowledge about pathophysiology of heart disease and its radiological correlation are discussed. RESULTS: Knowledge of the normal anatomy of the heart is a basic prerequisite for the assessment of pathologies. For the question of heart disease, it is essential to also assess the pulmonary vascularization. The size of the entire heart and the individual cardiac cavities is assessed by direct and indirect signs, such as heart-lung ratio, cava triangle, vascular pedicle or the size of the aorta and of the main pulmonary artery. The most common cause of heart enlargement is valve disease, which shows various conventional radiological images. CONCLUSION: Conventional thoracic radiography still plays a central role in the diagnosis of cardiopulmonary diseases and is an important diagnostic tool for quickly obtaining an overview of the patient's cardiopulmonary situation. The interplay between physiology and X­ray symptoms is complex, so close attention should be paid not only to the heart anatomy and configuration, but also primarily to the pulmonary blood flow.

Changes in Dynamic Pelvic Floor Magnet Resonance Imaging and Patient Satisfaction after Resection Rectopexy for Obstructed Defecation Syndrome.

PURPOSE: Resection rectopexy (RR) provides good functional results and low recurrence rates for the treatment of obstructed defecation syndrome based on rectal prolapse and cul-de-sac syndrome, whereas little is known about changes in pelvic floor dynamics and patient satisfaction after surgery. MATERIALS AND METHODS: Within three years 26 consecutive female patients were prospectively included. Indications for RR (22 laparoscopic, 3 primary open and 1 converted-to-open) were rectal prolapse III° in 11 patients and cul-de-sac syndrome in 15 patients. Patients' quality of life (QOL), fecal behavior and defecation-associated pain were investigated before and after surgical treatment using anamnesis and clinical examination, Rand 36-idem health survey (SF-36), Cleveland-Clinic Incontinence Score (CCIS) and the visual analog scale for defecation-associated pain (VAS). Dynamic pelvic floor magnet resonance imaging (dPF-MRI) was used for the investigation of changes in pelvic floor anatomy and function before and after surgery. RESULTS: RR improved the rate of fecal incontinence (p < 0.01) and CCIS (p = 0.01). The use of laxatives (p = 0.01), the need for self-digitation (p = 0.02) and VAS (p < 0.01) were decreased, leading to improvements in QOL (overall p < 0.01). RR led to shortening of the H-line but not of the M-line under rest (p < 0.01) and during defecation (p = 0.04). A rectocele was co-incident in all patients in dPF-MRI before surgery. RR led to a reduction (p < 0.01) and declined protrusion (p = 0.03) of the rectocele. This results in a decreased rate of cul-de-sac (p < 0.01) and increased rate of complete defecation (p < 0.01) after surgery. At the 36-month follow-up no recurrence was observed. CONCLUSION: RR promises high rates of patient satisfaction and improvement in pelvic floor anatomy in select patients. KEY POINTS: • RR improves the pelvic floor anatomy of patients suffering from ODS. • RR improves the QOL of patients suffering from ODS. • An improvement in pelvic floor anatomy led to an improved QOL. • RR is an adequate treatment for select patients suffering from ODS.

First Report of 'Candidatus Phytoplasma asteris' Associated with "Witches'-Brooms" on Jointleaf Rush (Juncus articulatus) in Poland.

Juncus articulatus L. (Juncaceae) is a species of rush occurring in Eurasia, Canada, and the United States. In 2013, symptoms of "witches'-brooms," similar to those associated with phytoplasma infection in other plants, were observed on jointleaf rush plants in Lower Silesia (southwest Poland), with some pests feeding on them. Livia junci (Liviinae, Hemiptera) is a small plant-feeding sap-sucking insect that affects monocotyledonous plants. To confirm the presence of phytoplasma in 15 examined plants, total DNA was extracted from 100 mg of inflorescence and leaf samples collected in July 2013 in Bogatynia, Poland, from six symptomatic and six asymptomatic plants using a DNeasy Plant Mini Kit (Qiagen, Syngen Biotech, Wroclaw, Poland) according to the manufacturer's protocol. Additionally, three leaf samples from asymptomatic rush plants, collected from a location where the disease was not observed (Wroclaw, Poland), as well as water blank samples were included as negative controls. Moreover, thirty-two insects were collected from symptomatic plants and preserved in ethanol (75%). DNA from L. junci specimens (the imago and the last larva stage) was extracted using DNeasy Blood and Tissue Kit (Qiagen, Syngen Biotech). Extracted nucleic acids were used as templates for PCR employing a) phytoplasma universal rRNA primer pairs P1/P7 followed by R16F2n/R16R2 (1), b) primers rp1-rp2 followed by rp3-rp4, allowing amplification of fragments of ribosomal protein rpl22 and rps3 genes (3), and c) primers AYsecYF1/AYsecYR1 (2) for amplification of the secY gene. The phytoplasma was detected in all tested insects as well as in all six symptomatic and four out of six asymptomatic plant samples (10 out of 12 plant samples from Bogatynia were positive). No amplification products were detected in negative control samples from Wroclaw or in water blanks. The fact that we detected the pathogen in some asymptomatic plants indicated that a low concentration may have been present prior to the development of disease symptoms. Amplicons representing three genetic loci were sequenced in an AbiPrism 3100 Genetic Analyzer apparatus (Applied Biosystems, USA), at the Maria Sklodowska Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. To avoid sequencing errors, all DNA samples were sequenced twice in both directions. The obtained sequences were nearly identical, and representative sequences of 16S rDNA fragments (Accession Nos. KF774297, KF774298, and KF774299), secY gene (KJ394481, KJ394482, and KJ394483) and ribosomal protein gene (KJ394484, KJ394485, and KJ394486), isolated from two plants and one insect, were deposited in GenBank. BLAST analysis of the sequenced 16S rDNA fragments revealed that tested strains shared more than 99% sequence identity with the sequences of phytoplasmas from the aster yellows group (e.g., KJ556903, KJ494330, and KJ491100). The same analysis performed for ribosomal proteins and secY genes confirmed the highest identity (99%) of analyzed sequences with those of 'Candidatus Phytoplasma asteris' (HM626105 and KC354611, respectively). The impact of the detected phytoplasma in the regional ecosystem and the role of L. junci as a possible vector of this pathogen are being assessed. References: (1) I. M. Lee et al. Int. J. Syst. Evol. Microbiol. 48:1153, 1998. (2) I.-M. Lee et al. Mol. Cell. Probes 20:87, 2006. (3) H. Nakamura et al. Plant Dis. 80:302, 1996.

PCR-based detection of Toxoplasma gondii DNA in blood and ocular samples for diagnosis of ocular toxoplasmosis.

PCR detection of Toxoplasma gondii in blood has been suggested as a possibly efficient method for the diagnosis of ocular toxoplasmosis (OT) and furthermore for genotyping the strain involved in the disease. To assess this hypothesis, we performed PCR with 121 peripheral blood samples from 104 patients showing clinical and/or biological evidence of ocular toxoplasmosis and from 284 (258 patients) controls. We tested 2 different extraction protocols, using either 200 µl (small volume) or 2 ml (large volume) of whole blood. Sensitivity was poor, i.e., 4.1% and 25% for the small- and large-volume extractions, respectively. In comparison, PCR with ocular samples yielded 35.9% sensitivity, while immunoblotting and calculation of the Goldmann-Witmer coefficient yielded 47.6% and 72.3% sensitivities, respectively. Performing these three methods together provided 89.4% sensitivity. Whatever the origin of the sample (ocular or blood), PCR provided higher sensitivity for immunocompromised patients than for their immunocompetent counterparts. Consequently, PCR detection of Toxoplasma gondii in blood samples cannot currently be considered a sufficient tool for the diagnosis of OT, and ocular sampling remains necessary for the biological diagnosis of OT.

Prognostic relevance of circulating tumor cells in metastatic uveal melanoma.

OBJECTIVE: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance. METHODS: Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics. RESULTS: CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis. CONCLUSION: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.

Role of TGF-ß in melanoma.

Human malignant melanoma is highly resistant to chemotherapy and current immunotherapeutic approaches induce long term remission only in the minority of patients. The transforming growth factor-ß (TGF-ß) has attracted much attention as a therapeutic target because it plays an important and pleiotropic role in melanoma progression. TGF-ß is a multifunctional cytokine involved in the regulation of many cellular processes including cell proliferation, differentiation and survival. Resistance to the growth inhibitory effects of TGF-ß without alterations of TGF-ß signaling molecules is characteristic of cutaneous melanoma. Melanoma produces increasing amounts of TGF-ß with disease progression, inhibiting immune responses and providing an optimal microenvironment for undisturbed tumor growth. In addition, TGF-ß exerts its tumor promoting functions via direct effects on tumor cell motility and invasiveness and indirectly by modulating tumor stroma and extracellular matrix, supporting angiogenesis and inhibiting immune surveillance. TGF-ß acts through multiple intracellular signaling pathways and the outcome of TGF-ß signaling is context-dependent. Defining the impact of the different TGF-ß signaling pathways on melanoma progression will help to identify suitable therapeutic targets. Here we review the current knowledge of TGF-ß in melanoma and discuss recent therapeutic approaches targeting the TGF-ß pathway.

Supervised daily consumption, contingent take-home incentive and non-contingent take-home in methadone maintenance.

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.

Novel homozygous mutation (c.175delG) in platelet glycoprotein ITGA2B gene as cause of Glanzmann's thrombasthenia type I.

BACKGROUND: Glanzmann's thrombasthenia (GT), is a rare autosomal recessive bleeding disorder. Platelets from patients with GT show quantitative or qualitative defects of the platelet membrane glycoprotein (GP) IIb/IIIa complex. A variety of genetic defects in ITGA2B and ITGB3 (genes for GPIIb and GPIIIa) has been described causing the clinical entity of GT. PATIENTS: A newborn with bleeding symptoms (petechiae) platelet analyses revealed an inherited primary hemostasis disorder. METHODS/RESULTS: Analyses of patient's platelets using flow cytometry and immunoblotting showed absence of GPIIb protein and reduced amount of GPIIIa. Using restriction fragment length polymorphism heterozygosity for the deletion could be identified in the parents and in two siblings. Expression studies in mammalian cells revealed that the mutant GPIIb is missing and additionally affects the expression of wildtype GPIIIa. This deletion leads to a truncation at the very N-terminal region of the GPIIb protein. CONCLUSION: The present study describes a patient with GT associated with a novel homozygous deletion (c.175delG) in exon 1 of ITGA2B. This deletion led to a reading frameshift and caused a severely truncated form of GPIIb.

Compound heterozygous mutations in 2 siblings with Hermansky-Pudlak syndrome type 1 (HPS1).

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by the absence of dense (delta)-bodies. There are eight known human HPS GENES (HPS1-HPS8), each leading to a particular clinical HPS subtype. Restrictive lung disease, granulomatous colitis and cardiomyopathy have been described in HPS1 patients. PATIENTS: We identified HPS1 in Russian and in German siblings. All four patients show a typical HPS phenotype. The two older Russian patients demonstrate excessive bleeding after tooth extractions, recurrent epistaxis and hematomas. The two younger German patients suffer only from hematomas, so far. METHODS/RESULTS: Patients' platelets showed severe pathological agglutination/aggregation. Flow cytometry analysis demonstrated absence of platelet delta-granule secretion. Three different mutations in the HPS1 gene were found in the two families. Two mutations, p.H119delC and p.Q397delC identified in the Russian siblings had been previously described. The German siblings presented with a novel frameshift mutation (p.Q32_S33delCAGT) and the known p.Q397delC mutation. CONCLUSION: Patients with oculocutaneous albinism should be investigated for increased clinical bleeding symptoms. In case of increased bleeding symptoms, analyses of primary hemostasis should be initiated to confirm HPS. Molecular genetic investigations should be performed to distinguish the different subtypes of HPS which is important for therapy and prognosis.

Expression of the stem cell marker nestin in peripheral blood of patients with melanoma.

BACKGROUND: There is continued interest in markers indicative of circulating melanoma cells. Nestin is a neuroepithelial intermediate filament protein that was found to be expressed in melanoma and in various cancer stem cells. OBJECTIVES: We investigated expression of nestin in peripheral blood of patients with melanoma. METHODS: We analysed nestin expression by flow cytometry and by quantitative reverse transcription-polymerase chain reaction both in tissues (n = 23) and in blood samples (n = 102) from patients with American Joint Committee on Cancer stage III-IV melanoma. Forty-six negative controls were also added. RESULTS: Flow cytometry did not reveal nestin-expressing cells in peripheral blood of healthy volunteers. In patients with melanoma, however, nestin protein was expressed in a proportion of melanoma cells enriched from peripheral blood by immunomagnetic sorting. In melanoma tissue samples a significant correlation was found between mRNAs coding for nestin and tyrosinase (P = 0.001) and melan-A (P = 0.002), whereas in blood a significant correlation was observed only for tyrosinase (P = 0.015), but not for melan-A (P = 0.53). Nestin expression was higher in stage IV patients compared with stage III/IV with no evidence of disease, in patients with high tumour burden, and was positively correlated to expression of tyrosinase and melan-A. CONCLUSIONS: Nestin was found to be an additional marker of interest for circulating melanoma cells. Prospective studies should investigate its potential added informative value in comparison with markers already in use for melanoma cell detection.

NorthernLights in slide-based cytometry and microscopy.

In recent years, slide-based cytometry has become a key technology for polychromatic cytometric investigations, and many efforts have been made to increase the number of measurable fluorochromes for multiparametric analysis. Sequential photobleaching of fluorochromes next to very photostable dyes is one approach for this technology. As the ALEXA dyes are known to be photostable as compared to the conventional fluorochromes FITC, PE (Riggs et al., Am J Pathol 1958;34:1081-1097), and APC, a differentiation within a fluorochrome pair is possible. Here, we have analyzed the newly available NorthernLights secondary antibodies for use in slide-based cytometry and microscopy. Currently, these fluorochrome-conjugates are now available with three distinct excitation- and emission maxima (NL493, NL557, NL637). Their spectral properties are similar to the frequently used fluorochromes FITC, PE, and APC and can, therefore, be used with most common excitation sources of cytometers or microscopes. As the NorthernLights are bright, resistant to photobleaching, stable in alcohols and xylene and of affordable price, these dyes are promising candidates for use with most laser- and HBO/XBA-based fluorescence microscopy-like techniques.

Long-acting opioid-agonists in the treatment of heroin addiction: why should we call them "substitution"?

Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.

Bendamustine, but not fludarabine, exhibits a low stem cell toxicity in vitro.

PURPOSE: We investigated the in vitro toxicity of bendamustine and fludarabine to hematopoietic progenitors and stem cells from healthy donors. METHODS: Clonogenic agar colony assays, non-clonogenic long-term liquid cultures (LTC) and apoptosis assays were used to assess the cytotoxicity of both the agents. RESULTS: Total colony-forming units (CFU) were more sensitive to fludarabine than to bendamustine in agar colony assays (IC(50) 0.7 microM/L and 8.5 microM/L, respectively). Using the Bliss independence model and combining the two agents yielded additive inhibition of progenitors. Non-clonogenic assays, including LTC and an apoptosis assay detecting activated caspases showed that stem cells are characterized by low sensitivity to bendamustine. In contrast, fludarabine strongly inhibited the viability and growth of stem cells in LTC. CONCLUSIONS: Our data show that bendamustine is characterized by lower in vitro toxicity to hematopoietic progenitors and stem cells than fludarabine and might thus be preferable in regimens prior to stem cells apheresis.

Universal intermittent properties of particle trajectories in highly turbulent flows.

We present a collection of eight data sets from state-of-the-art experiments and numerical simulations on turbulent velocity statistics along particle trajectories obtained in different flows with Reynolds numbers in the range R{lambda}in[120:740]. Lagrangian structure functions from all data sets are found to collapse onto each other on a wide range of time lags, pointing towards the existence of a universal behavior, within present statistical convergence, and calling for a unified theoretical description. Parisi-Frisch multifractal theory, suitably extended to the dissipative scales and to the Lagrangian domain, is found to capture the intermittency of velocity statistics over the whole three decades of temporal scales investigated here.

Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma.

OBJECTIVE: The aim of this study was to establish a preclinical mouse model to study metastases of paediatric rhabdomyosarcoma at the macroscopic and cellular levels, with different imaging methods. EXPERIMENTAL DESIGN: The alveolar rhabdomyosarcoma cell line Rh30 was stably transfected with the red fluorescent protein (DsRed2) then was xenotransplanted (intravenous injection [n = 8], and footpad injection [n = 8]) into nude mice (NMRI nu/nu). Macroscopic imaging of metastases was performed using DsRed2-fluorescence and flat-panel volumetric computed tomography scan. In a further series of animals (n = 8), in vivo cell trafficking of rhabdomyosarcoma cells using cellular imaging with an Olympus OV100 variable-magnification small-animal imaging system was used. RESULTS: Metastases in the pelvis, thoracic wall and skin were visualized by fluorescence imaging. Pelvic metastases were found after tail vein injection and at other metastatic sites after footpad injection. Flat-panel volumetric computed tomography scan data allowed highly specific analysis of contrast between tumour and surrounding tissue. Correlation between fluorescence and flat-panel volumetric computed tomography scan imaging data was observed. Single-cell imaging visualized tumour cells in the vessels and demonstrated the arrest of tumour cells at vessel junctions followed by extravasation of the tumour cells. CONCLUSION: We established a model for visualization of experimental metastatic invasion and describe relevant tools for imaging childhood rhabdomyosarcoma metastases at the macroscopic and cellular levels. Imaging of cell trafficking visualized the behaviour of tumour cells and development of metastases by accumulation and extravasation of rhabdomyosarcoma cells.

In vivo imaging in experimental preclinical tumor research--a review.

The multiparametric molecular cell and tissue analysis in vitro and in vivo is characterized by rapid progress in the field of image generation technologies, sensor biotechnology, and computational modeling. Fascinating new potentials in unraveling the detailed functions of single cells, organs, and whole organisms are presently emerging and permit the close monitoring i.e. tumor development or basic cell development processes with an unprecedented multiplicity of promising investigative possibilities. To answer basic questions of in vivo tumor development and progression fluorescence based imaging techniques provide new insights into molecular pathways and targets. Genetic reporter systems (eGFP, DsRED) are available and high sensitive detection systems are on hand. These techniques could be used for in vitro assays and quantified e.g. by microscopy and CCD based readouts. The introduction of novel fluorescent dyes emitting in the near infrared range (NIR) combined with the development of sensitive detector systems and monochromatic powerful NIR-lasers for the first time permits the quantification and imaging of fluorescence and/or bioluminescence in deeper tissues. Laser based techniques particularly in the NIR-range (like two-photon microscopy) offer superb signal to noise ratios, and thus the potential to detect molecular targets in vivo. In combination with flat panel volumetric computed tomography (fpVCT), questions dealing e.g. with tumor size, tumor growth, and angiogenesis/vascularization could be answered noninvasively using the same animal. The resolution of down to 150 microm/each direction can be achieved using fpVCT. It is demonstrated by many groups that submillimeter resolutions can be achieved in small animal imaging at high sensitivity and molecular specificity. Since the resolution in preclinical small animal imaging is down to approximately 10 microm by the use of microCT and to subcellular resolutions using ( approximately 1 microm) microscope based systems, the advances of different techniques can now be combined to "multimodal" preclinical imaging and the possibilities for in vivo intravital cytometry now become within one's reach.

Mild cognitive impairment: long-term course of four clinical subtypes.

OBJECTIVE: To empirically validate the expanded concept of mild cognitive impairment (MCI), which differentiates between four clinical subtypes-amnestic MCI-single domain, amnestic MCI-multiple domains, nonamnestic MCI-single domain, and nonamnestic MCI-multiple domains-and to examine the prevalence, course, and outcome of these four clinical MCI subtypes. METHODS: We studied a community sample of 980 dementia-free individuals aged 75 years or older who participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants were examined by neuropsychological testing based on 6 years of observation. The diagnoses of the four clinical MCI subtypes were made according to the original and to slightly modified criteria by Petersen et al. (2001) (both with a cutoff of 1.0 SD and with a cutoff of 1.5 SD). The complete range of outcome types (dementia, death, improvement, stable diagnosis, unstable diagnosis) was described for all subtypes. The relative predictive power of stable MCI for dementia onset was determined. RESULTS: MCI-single domain is more frequent than MCI-multiple domains, and the nonamnestic MCI type is as frequent as the amnestic MCI type. The "MCI modified, 1.0 SD" criteria have the highest relative predictive power for the development of dementia (sensitivity = 74%, specificity = 73%). Alzheimer disease (AD) was the most common type of dementia at follow-up in all but one MCI subtype. Participants with nonamnestic MCI-multiple domains were more likely to progress to a non-AD dementia. CONCLUSIONS: It has been assumed that each MCI subtype is associated with an increased risk for a particular type of dementia. We can only partially agree with this.

Human endothelial cell septins: SEPT11 is an interaction partner of SEPT5.

The septin SEPT11 is a novel member of the highly conserved septin family. Septins are cytoskeletal GTPases, which form heteropolymeric complexes. They are involved in cytokinesis and other cellular processes, such as vesicle trafficking and exocytosis. SEPT11 has strong homology to SEPT8. Previously, we identified the interaction of SEPT5 and SEPT8. Using the yeast two-hybrid system, we now demonstrate that SEPT11 partners with SEPT5. The molecular interaction of SEPT11 with SEPT5 was verified by coprecipitation of SEPT5 and SEPT11 from lysates of the human T-cell leukaemia cell line JURKAT and by fluorescence resonance energy transfer. The interaction between SEPT5 and SEPT11 requires the GTP-binding domain and the C-terminal extension. Western analysis in various mouse and human tissues revealed that expression of SEPT11 is restricted to the same tissues as those expressing SEPT5, suggesting that SEPT11 and SEPT5 are components of a cell-specific septin complex. SEPT5, which is expressed in human umbilical vein endothelial cells (HUVECs), has been reported to play an important role in exocytosis. We now report that HUVECs also express SEPT11. Given the interactivity between SEPT5 and SEPT11 as shown above and their coexpression in HUVECs, it may be that a complex formed by these two proteins is involved in the exocytosis mechanism in HUVECs.