Fluorene benzothiadiazole co-oligomer based aqueous self-assembled nanoparticles.

Self-assembled π-conjugated nanoparticles with tunable optical characteristics are appealing for sensing and imaging applications due to their intrinsic fluorescence, supramolecular organization and dynamics. Here we report on the facile synthesis of fluorene benzothiadiazole co-oligomers in which structural backbone alterations induce bathochromically shifted optical characteristics. Moreover, the nature of the oligomer side-chains revealed the role of bulkiness and polarity on the optical and self-assembly behavior. Co-assemblies were prepared that showed energy transfer between the different oligomers which allows for tuning of the emission color. These compounds thus extend the π-conjugated-oligomer toolbox from which nanoparticles can be prepared with tailored physicochemical properties that may result in supramolecular materials for biosensing.

Patient-centered integrated healthcare improves quality of life in Parkinson's disease patients: a randomized controlled trial.

INTRODUCTION: Improving quality of life (QoL) is a key issue when dealing with Parkinson's disease (PD). Integrative care shows potential to achieve improvements in QoL. Here, we analyzed whether a community-based, open-label, integrated approach improves QoL in PD patients. METHODS: PD patients were screened for eligibility and evaluated by a university-based PD specialist, a PD nurse, and a general neurologist at a local practice. Patients were randomly assigned to a control group (CG), receiving standard German neurological treatment including a baseline assessment and follow-up visit at 6 months, or an interventional group (IG) who received an individually tailored therapy plan and additional home visits. Patients and investigators were not blinded for either intervention. Primary outcome analysis compared the differential change of PDQ-39 from baseline to 6-month follow-up between CG and IG. Between-group changes in mood, motor/non-motor functioning, and cognition were secondary outcomes. RESULTS: 300 patients were included and randomized equally to IG and CG. 132 IG and 125 CG patients had a valid PDQ-39 at follow-up and qualified for the modified ITT analysis. PDQ-39 improved more in IG compared to CG [2.2 points (95% CI - 4.4 to 0.1); p = 0.044]. Likewise, change scores between IG and CG favored IG for UPDRS III (p < 0.001, mean change 3.3, 95% CI - 4.9 to - 1.7) and PD-NMS (p < 0.001, mean change 11.3, 95% CI - 17.1 to - 5.5). CONCLUSIONS: Data show that an integrated approach, compared to regular PD care, improves QoL as well as motor and nonmotor PD symptoms over 6 months. Future studies need to address the cost-benefit ratio and whether positive effects can be maintained beyond intervention.

Cerebral vasospasm and delayed cerebral ischemia in intraventricular hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) with intraventricular extension (IVH) is a devastating disease with a particular high mortality. In some aspects, IVH may resemble subarachnoid hemorrhage. The incidence and role of cerebral vasospasm in ICH with IVH are poorly understood. Here, we aimed to analyze the incidence and relationship of cerebral vasospasm to clinical characteristics, in-hospital mortality, and functional outcome at 3 months in patients suffering ICH with IVH. METHODS: Patients with ICH and IVH treated on a neurological intensive care unit were prospectively enrolled in a single-center observational study. Vasospasm was defined using established ultrasound criteria. Delayed cerebral ischemia (DCI) was defined as a new hypodensity on follow-up cranial CT. Functional outcome at 3 months was assessed using the modified Rankin Scale. RESULTS: 129 patients with ICH and IVH were screened for the study. 62 patients entered the final analysis. The incidence of significant vasospasm was 37 %. A strong trend was found for the association between all cerebral vasospasm and DCI (P = 0.046). Early (up to 48 h) vasospasm was significantly associated with a DCI (P = 0.033). Overall mortality and outcome after 3 months did not differ between the groups. CONCLUSION: Cerebral vasospasm seems to be a frequent complication after ICH with IVH and might be associated with DCI. Larger studies are warranted to confirm this hypothesis.

Recurrent amaurosis fugax in a patient after stanford type a dissection depending on blood pressure and haemoglobin level.

Purpose. A transient painless monocular visual loss due to a decrease in retinal circulation-also known as "amaurosis fugax"-often precedes acute territorial cerebral ischaemia. The case we present underlines the importance of a comprehensive diagnostic workup in patients with amaurosis fugax. Case Report. A 44-year-old man who had suffered from a dissection of the ascending aorta (Stanford Type A) five months ago presented with recurrent monocular vision problems. Episodes with sectional vision loss mainly occurred in combination with low blood pressure levels. Furthermore, the haemoglobin level was chronically low (Hb 9.7 mg/dL), and the patient was by mistake on a simultaneous therapy with phenprocoumon and unfractionated heparin. Carotid artery duplex scanning revealed a high-grade stenosis of the proximal right common carotid artery. MR imaging corroborated hypoperfusion in brain area corresponding to the right MCA. Conclusion. Our patient is an example in whom transient retinal ischaemic attacks may originate from haemodynamic reasons.

State markers of depression in sleep EEG: dependency on drug and gender in patients treated with tianeptine or paroxetine.

Tianeptine enhances while paroxetine inhibits serotonin reuptake into neurons; however, both show an antidepressive action. A subgroup of 38 depressed patients from a drug trial comparing the efficacy of tianeptine with that of paroxetine was studied with regard to their effects on sleep regulation, especially in relation to treatment response. We recorded sleep EEGs at day 7 and day 42 after the start of treatment with either compound, which allows measurement of changes due to the antidepressive medication in relation to the duration of treatment. Spectral analysis of the non-REM sleep EEG revealed a strong decline in the higher sigma frequency range (14-16 Hz) in male treatment responders independent of medication, whereas nonresponders did not show marked changes in this frequency range independent of gender. The patients receiving paroxetine showed less REM sleep and more intermittent wakefulness compared to the patients receiving tianeptine. REM density after 1 week of treatment was a predictor of treatment response in the whole sample. Psychopathological features with regard to the score in single items of the HAMD revealed predictive markers for response, some of which were opposite in the gender groups, especially those related to somatic anxiety. Changes in REM density were inversely correlated to the changes in HAMD in the paroxetine, but not the tianeptine, group. Our data suggest the importance of taking gender into account in the study of the biological effects of drugs. The study further points to the importance of the higher sigma frequency range in the sleep EEG of non-REM sleep and REM density as a marker of treatment response.

Reconciliation in captive Guyanese squirrel monkeys (Saimiri sciureus).

The tendency for agonistic interaction to increase the probability of friendly interaction between social partners has been demonstrated across a range of Old World primates. While research on such post-conflict behavior proceeds into an hypothesis-testing phase, new comparative information must accumulate to provide full phylogenetic perspective on primate social behavior. Data from New World and prosimian primates are yet extremely limited. We studied captive squirrel monkeys (Saimiri sciureus) via post-conflict (PC) and matched control (MC) observations and analyzed results using both the PC-MC and time-rule methods. Former opponents maintaining affiliative relationships soon engaged in friendly interaction following large proportions of agonistic interactions, whereas non-affiliated individuals, including virtually all male-female pairs, reconciled conflicts rarely. Close-proximity approaching and huddling contact constituted the principal modes of post-conflict amicability. Agonistic interactions of relatively high intensity were most likely to be reconciled and most likely to be reconciled via physical contact. High vulnerability of Saimiri to predation may have favored this species' strong inclination to reconcile soon after agonistic interaction. Research on free-living populations of this and other primate species is needed to illuminate similarities and differences across taxa.

Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study.

BACKGROUND: Functional imaging studies suggest a specific role of the anterior brain regions in the pathogenesis of major depression. The aim of this study was to evaluate possible neurochemical alterations in the frontomesial cortex in patients with major depressive episode using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Single voxel (1)H-MRS was performed in 19 patients with major depressive episodes and 18 age-matched healthy controls within the anterior cingulate cortex and the parietal white matter. Absolute concentrations were estimated for N-acetyl-aspartate, choline-containing compounds, total creatine, myo-inositol, unresolved glutamate and glutamine (Glx) and glutamate alone (Glu). Voxel composition was analyzed by image segmentation into cerebrospinal fluid (CSF), grey and white matter. RESULTS: MANOVA test for Glx and Glu using age, percent CSF and percent grey matter contribution as covariates yielded a significant group effect within the anterior cingulate due to decrease of Glx in patients (-10.4%, p =.013). Considering only severely depressed patients, both Glx and Glu (-14.3%, p =.03) showed a significant decrease. There was no significant group effect for the neuronal marker NAA, creatine, choline or myo-inositol in either localization. CONCLUSIONS: This study suggests a possible role of altered glutamatergic neurotransmission within the anterior cingulate in the pathogenesis of mood disorders. The otherwise unremarkable findings of major brain metabolites confirms lack of neurodegenerative or membrane metabolic changes in major depression.

Mapping loci for pentylenetetrazol-induced seizure susceptibility in mice.

DBA/2J (D2) and C57BL/6J (B6) mice exhibit differential sensitivity to seizures induced by various chemical and physical methods, with D2 mice being relatively sensitive and B6 mice relatively resistant. We conducted studies in mature D2, B6, F1, and F2 intercross mice to investigate behavioral seizure responses to pentylenetetrazol (PTZ) and to map the location of genes that influence this trait. Mice were injected with PTZ and observed for 45 min. Seizure parameters included latencies to focal clonus, generalized clonus, and maximal seizure. Latencies were used to calculate a seizure score that was used for quantitative mapping. F2 mice (n = 511) exhibited a wide range of latencies with two-thirds of the group expressing maximal seizure. Complementary statistical analyses identified loci on proximal (near D1Mit11) and distal chromosome 1 (near D1Mit17) as having the strongest and most significant effects in this model. Another locus of significant effect was detected on chromosome 5 (near D5Mit398). Suggestive evidence for additional PTZ seizure-related loci was detected on chromosomes 3, 4, and 6. Of the seizure-related loci identified in this study, those on chromosomes 1 (distal), 4, and 5 map close to loci previously identified in a similar F2 population tested with kainic acid. Results document that the complex genetic influences controlling seizure response in B6 and D2 mice are partially independent of the nature of the chemoconvulsant stimulus with a locus on distal chromosome 1 being of fundamental importance.

Genotyping microsatellite polymorphisms by agarose gel electrophoresis with ethidium bromide staining: application to quantitative trait loci analysis of seizure susceptibility in mice.

Agarose gel electrophoresis with ethidium bromide staining (AGE/EBS) is an efficient and reliable method for analyzing microsatellite polymorphisms. We report the use of AGE/EBS for analyzing DNA microsatellite polymorphisms in a preliminary quantitative trait loci (QTL) study of seizure susceptibility in which a candidate gene strategy was used to direct initial mapping efforts. F2 intercross progeny, derived from seizure-sensitive DBA/2J (D2) and seizure-resistant C57BL/6J (B6) inbred strains of mice, were tested for their sensitivity to the seizure-inducing effect of pentylenetetrazol (PTZ), a gamma-aminobutyric acid (GABA) receptor antagonist. A semi-automated method is described, in which DNA microsatellites were amplified by polymerase chain reaction (PCR) to yield products of 100-200 base pair (bp) in length. Alleles were separated on 3-6% MetaPhor agarose gels, stained with ethidium bromide, and visualized by ultraviolet (UV) illumination. Univariate analysis of genotype and phenotype data provides evidence for a seizure-related QTL on chromosome 5, near genes coding for the GABAA receptor subunits alpha 5 and gamma 3. Interestingly, this suggestive QTL derives from the more resistant B6 strain, but it nonetheless provides impetus for the characterization of possible strain differences in these two candidate genes. Overall, these results demonstrate that AGE/EBS can be useful for rapid screening of genomic regions of special interest in QTL mapping studies.

Lectinhistochemistry of mixed gliomas demonstrating an intermediate cell type.

18 cases of low-graded mixed gliomas were studied using the two lectins Concanavalin A (Con A) and Peanut lectin (PNA). Con A stained cytoplasm and processes of tumoral astrocytes, whereas PNA stained cell membranes of tumoral oligodendrocytes. Con A and PNA are reliable markers for astrocyte and oligodendrocyte areas of mixed gliomas, respectively. A part of cells were overlappingly positive for both lectins. They expressed an oligosaccharide pattern of both glioma types and represented a third, intermediate cell type of mixed gliomas. The existence of intermediate cells close to astrocytic and oligodendroglial cell types in mixed gliomas could result from transformation processes of neoplastic glial cells or from the malignant transformation of a common glial precursor cell.

Coping, psychosocial well-being and anxiety in cancer patients at follow-up visits.

Coping, psychosocial well-being, situation-specific anxiety and cancer-related worry were assessed in 197 consecutive cancer patients attending follow-up visits. Participants completed questionnaire on three occasions: at the follow-up visit, some days later (n = 175) and three weeks later (n = 125). High levels of coping styles 'Anxious Preoccupation' and 'Helplessness/Hopelessness' were associated with low levels of psychosocial well-being, more situation-specific anxiety and more cancer-related worry. High levels of 'Fighting Spirit' and 'Fatalistic' were found to be associated with high psychosocial well-being and, for 'Fighting Spirit', also with less cancer-related worry. Patients with a 'dismal' prognosis were found to have higher levels of 'Helplessness/Hopelessness' than patients with a more 'favorable' prognosis. Clinical implications of these findings are discussed.

Anxiety and cancer-related worry of cancer patients at routine follow-up visits.

Anxiety and cancer-related worry were assessed in 197 consecutive cancer patients attending follow-up visits. Participants completed questionnaires on three occasions: at the visit, some days later, and three weeks later. Results show that while a majority of patients feel no or only mild anxiety in conjunction to the follow-up visit, about one-fifth report moderate or strong anxiety. Many patients (46%) worry about suffering a recurrence and about overlooking symptoms of new cancer (33%). Patients who were not in complete remission reported higher levels of cancer-related worry concerning the follow-up visit than did patients in remission. Among patients in remission, those who recently terminated treatment reported more overall distress than patients two or more years since treatment termination.

Instrumental noise effect in an optical heterodyne profiler.

An optical heterodyne profiler has been developed for measuring surface roughness at Brookhaven National Laboratory. The height measurement sensitivity and lateral resolution are 1.1 Å and 4 µm, respectively, when a 40× objective is used. A Zeeman-split He-Ne laser is the light source. A noncontact measurement system is designed as an optical common-path interferometer. Optical and electronic common-mode rejection techniques are employed to minimize the effects of environmental conditions. The effect of the system noise is analyzed in detail. The effect of varying the number of samples at each sampling point is shown. The comparisons of the system noises with different objectives, 5×, 10×, 20×, and 40×, are presented.

Modelling by homology of the HSV1-TK sequence embedded structural alignment.

Modelling by homology is an approach to the rational design of new drugs based on the construction of ligand protein interaction complexes. Because in most cases the 3D-structure of the target protein is not known from biophysical data, this approach yields a theoretical procedure which establishes at least parts of the protein by comparison with isofunctional proteins, assuming that much of the structural information is embedded in the amino acid sequence. This approach should be of considerable importance for proteins with divergent primary structures but with a high degree of isofunctionality, the latter demanding a similar active site folding pattern. This study is a pattern recognition approach based on additive secondary structure prediction and surface probabilities from residue variabilities. The comparison of the additive properties yields a sequence alignment of the viral thymidine kinases with the adenylate kinases having a closely related functionality. X-ray structures of adenylate kinases can then be used as templates to derive a 3D-structure prediction of the thymidine kinase active site.