Clinical characteristics and outcome of patients with enterococcal liver abscess.

Epidemiology of bacteria isolated from pyogenic liver abscesses change, and an increase in enterococci has been reported in European hospitals. The aim of this study was to investigate the clinical characteristics and outcome of enterococcal PLA. We performed a retrospective analysis of patients with microbiologically confirmed PLA at three German university centers. Indicators of enterococcal PLA were determined using binary logistic regression, and survival analysis was performed using Kaplan-Meier statistics and Cox regression analysis. Enterococci were isolated in 51/133 (38%) patients with PLA. Patients with enterococcal PLA had smaller abscess diameter (4.8 vs. 6.7 cm, p = 0.03) than patients with non-enterococcal PLA, but had more frequent polymicrobial culture results. In univariate logistic regression analysis, alcohol abuse (OR 3.94, 95% CI 1.24-12.49, p = 0.02), hepatobiliary malignancies (OR 3.90, 95% CI 1.86-8.18, p < 0.001) and cirrhosis (OR 6.36, 95% CI 1.27-31.96, p = 0.02) were associated with enterococcal PLA. Patients with enterococcal PLA had a higher mortality than patients with non-enterococcal PLA (hazard ratio 2.92; 95% confidence interval 1.09-7.80; p = 0.03), which remained elevated even after excluding patients with hepatobiliary malignancies, cirrhosis, and transplant recipients in a sensitivity analysis. The increased mortality was associated with non-fecal enterococci but not in patients with Enterococcus faecalis. In this retrospective, multicenter study, enterococcal PLA was common and indicated an increased risk of mortality, underscoring the need for close clinical monitoring and appropriate treatment protocols in these patients.

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

AIMS: Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. METHODS: Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. RESULTS: Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). CONCLUSIONS: White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.

Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey.

Aging decreases the density of spines and the proportion of thin spines in the non-human primate (NHP) dorsolateral prefrontal cortex (dlPFC). In this study, we used confocal imaging of dye-loaded neurons to expand upon previous results regarding the effects of aging on spine density and morphology in the NHP dlPFC and compared these results to the effects of aging on pyramidal neurons in the primary visual cortex (V1). We confirmed that spine density, and particularly the density of thin spines, decreased with age in the dlPFC of rhesus monkeys. Furthermore, the average head diameter of non-stubby spines in the dlPFC was a better predictor than chronological age of the number of trials required to reach criterion on both the delayed response test of visuospatial working memory and the delayed nonmatching-to-sample test of recognition memory. By contrast, total spine density was lower on neurons in V1 than in dlPFC, and neither total spine density, thin spine density, nor spine size in V1 was affected by aging. Our results highlight the importance and selective vulnerability of dlPFC thin spines for optimal prefrontal-mediated cognitive function. Understanding the nature of the selective vulnerability of dlPFC thin spines as compared to the resilience of thin spines in V1 may be a promising area of research in the quest to prevent or ameliorate age-related cognitive decline.

Continuously delivered ovarian steroids do not alter dendritic spine density or morphology in macaque dorsolateral prefrontal cortical neurons.

Aged ovariectomized (OVX) female monkeys, a model for menopause in humans, show a decline in spine density in the dorsolateral prefrontal cortex (dlPFC) and diminished performance in cognitive tasks requiring this brain region. Previous studies in our laboratory have shown that long-term cyclic treatment with 17ß-estradiol (E) produces an increase in spine density and in the proportion of thinner spines in layer III pyramidal neurons in the dlPFC of both young and aged OVX rhesus monkeys. Here we used 3D reconstruction of Lucifer yellow-loaded neurons to investigate whether clinically relevant schedules of hormone therapy would produce similar changes in prefrontal cortical neuronal morphology as long-term cyclic E treatment in young female monkeys. We found that continuously delivered E, with or without a cyclic progesterone treatment, did not alter spine density or morphology in the dlPFC of young adult OVX rhesus monkeys. We also found that the increased density of thinner spines evident in the dlPFC 24h after E administration in the context of long-term cyclic E therapy is no longer detectable 20days after E treatment. When compared with the results of our previously published investigations, our results suggest that cyclic fluctuations in serum E levels may cause corresponding fluctuations in the density of thin spines in the dlPFC. By contrast, continuous administration of E does not support sustained increases in thin spine density. Physiological fluctuations in E concentration may be necessary to maintain the morphological sensitivity of the dlPFC to E.

Morphological transformations in a dually thermoresponsive coil-rod-coil bioconjugate.

We report the conformational and assembly behavior of a thermoresponsive triblock biohybrid conjugate under aqueous conditions. The triblock comprises of poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) conjugated to the ends of a triple-helix forming collagen-like peptide. The circular dichroism (CD) experiment confirms the ability of the collagen-like peptide middle block to assemble as a triple helix in the hybrid conjugate. Above the LCST (~35 °C), the collapse of the thermoresponsive PDEGMEMA polymer at the ends of the peptide domain resulted in a concomitant increase in the conformational stability of the peptide domain towards thermal denaturation. Upon cooling back, the kinetic conformational refolding behavior was still observed for the peptide domain in the hybrid conjugate. Static light scattering (SLS) experiments suggested the formation of supramolecular structures upon increasing solution temperatures to above the LCST. The scattering intensity increased with increasing temperature, until at 75 °C then it was found to decrease. Cryogenic scanning electron microscopy and regular transmission electron microscopy suggested the formation of spherical aggregates that increased in size with increasing temperature up to 65 °C and a morphological transformation into fibrils was also observed at 75 °C. The synergistic effect of dual thermoresponsive behavior from the peptide and the polymer block in the triblock hybrid is suggested for the observed conformational and assembly behaviors.

Integrin-mediated adhesion and proliferation of human MSCs elicited by a hydroxyproline-lacking, collagen-like peptide.

In this study, we evaluated the competence of a rationally designed collagen-like peptide (CLP-Cys) sequence - containing the minimal essential Glycine-Glutamic acid-Arginine (GER) triplet but lacking the hydroxyproline residue - for supporting human mesenchymal stem cell (hMSC) adhesion, spreading and proliferation. Cellular responses to the CLP-Cys sequence were analyzed by conjugating the peptide to two different substrates - a hard, planar glass surface and a soft hyaluronic acid (HA) particle-based hydrogel. Integrin-mediated cell spreading and adhesion were observed for hMSCs cultivated on the CLP-Cys functionalized surfaces, whereas on control surfaces lacking the peptide motif, cells either did not adhere or maintained a round morphology. On the glass surface, CLP-Cys-mediated spreading led to the formation of extended and well developed stress fibers composed of F-actin bundles and focal adhesion complexes while on the soft gel surface, less cytoskeletal reorganization organization was observed. The hMSCs proliferated significantly on the surfaces presenting CLP-Cys, compared to the control surfaces lacking CLP-Cys. Competitive binding assay employing soluble CLP-Cys revealed a dose-dependent inhibition of hMSC adhesion to the CLP-Cys-presenting surfaces. Blocking the α(2)ß(1) receptor on hMSC also resulted in a reduction of cell adhesion on both types of CLP-Cys surfaces, confirming the affinity of CLP-Cys to α(2)ß(1) receptors. These results established the competence of the hydroxyproline-free CLP-Cys for eliciting integrin-mediated cellular responses including adhesion, spreading and proliferation. Thus, CLP-Cys-modified HA hydrogels are attractive candidates as bioactive scaffolds for tissue engineering applications.

Protein- and peptide-modified synthetic polymeric biomaterials.

This review presents an overview on bio-hybrid approaches of integrating the structural and functional features of proteins and peptides with synthetic polymers and the resulting unique properties in such hybrids, with a focus on bioresponsive/bioactive systems with biomaterials applications. The review is divided in two broad sections. First, we describe several examples of bio-hybrids produced by combining versatile synthetic polymers with proteins/enzymes and drugs that have resulted in (1) hybrid materials based on responsive polymers, (2) responsive hydrogels based on enzyme-catalyzed reactions, protein-protein interactions and protein-drug sensing, and (3) dynamic hydrogels based on conformational changes of a protein. Next, we present hybrids produced by combining synthetic polymers with peptides, classified based on the properties of the peptide domain: (1) peptides with different conformations, such as alpha-helical, coiled-coil, and beta-sheet; (2) peptides derived from structural protein domains such as silk, elastin, titin, and collagen; and (3) peptides with other biofunctional properties such as cell-binding domains and enzyme-recognized degradation domains.

Supramolecular assembly of electrostatically stabilized, hydroxyproline-lacking collagen-mimetic peptides.

The mechanical and biological functions of the native collagens remain an inspiration in materials design, but widespread application of de novo collagens has been limited in part by the need for hydroxylated proline in the formation of stable triple helical structures. To address this continued need and to expand the potential for recombinant expression of functional, hydroxyproline-lacking collagen-mimetic peptides, we have designed a hydrophilic, nonrepetitive, and thermally stable collagen-mimetic peptide via the incorporation of triple-helix-stabilizing charged triplets. The peptide sequence is also equipped with a type III-collagen-mimetic cystine knot at the C-terminus to facilitate covalent cross-linking of the triple helix via simple air oxidation. Circular dichroic spectroscopy (CD) studies of this collagen-mimetic peptide revealed a typical, thermally stable, collagen triple helix signature with a weak positive maximum at 225 nm and a triple helix melting temperature (T(m)) of 35 and 43 degrees C for the reduced and oxidized forms, respectively. The thermal behavior was confirmed via analysis by differential scanning calorimetry. Interestingly, this hydroxyproline-lacking, collagen-mimetic peptide also assembles into nanorods and microfibrillar structures as observed via transmission electron microscopy. The identification and demonstrated useful collagen-mimetic properties of this peptide suggests important opportunities in the recombinant design of new collagen-based biomaterials.

[Topic-centered psychotherapy groups in the rehabilitation of patients following myocardial infarct]. / Themenzentrierte Gesprächsgruppen in der Rehabilitation von Patienten nach Herzinfarkt.

Starting from the problem of psychological care for patients during rehabilitation following myocardial infarction the concept of a theme-centered group programme is presented. The essential goals of the programme are helping patients cope with the crisis of infarction, reducing risk factors, and changing coronary-prone Type A behaviour. The specific situation of a patient following myocardial infarction as well as typical defense mechanisms and coping styles are discussed. Topics covered in the programme are: Situation following myocardial infarction, Impact of psychosocial stress, Coping behaviours, and Returning home, return to work.

[Clinical perception and recovery in myocardial infarct patients at a rehabilitation clinic]. / Klinikwahrnehmung und Genesung von Herzinfarktpatienten in einer Rehabilitationsklinik.

The relationships between various indicators of (1) subjective perception of clinic environment, (2) subjective state of health and perceived health changes during rehabilitation, (3) clinical ratings (physician's ratings of health status and its changes), (4) medical-diagnostic laboratory data, and (5) patient history, were studied in a sample of 144 myocardial infarction patients who participated in a four- to six-week early rehabilitation programme. Canonical correlation analyses point to intricate, statistically significant interrelationships among subjective perceptions of treatment environment and subjective health status changes, physician's ratings and laboratory findings, as well as subjective perceptions of treatment environment and patient history. All other combinations of variables did not reveal statistically significant canonical correlations. The findings show that subjective perception of the treatment environment is an important psychosocial variable relevant to subjective well-being of myocardial infarction patients and their subjective recovery during rehabilitation.

Divergent selection for body weight and yolk precursor in Coturnix coturnix japonica. 2. Correlated responses in plasma lipoproteins and lipids.

Lipoproteins from generations five and six of Japanese quail (Coturnix coturnix japonica) divergently selected for increased (HW) or decreased (LW) body weight at 4 weeks of age or increased (HP) or decreased (LP) plasma yolk precursor at the initiation of egg production were separated into fractions of d less than 1.006 and d greater than 1.006. A randombred control (R1) was also sampled. Total lipids (TL), neutral lipids (NL), and phospholipids (PL) were determined. The NL's of the d less than 1.006 lipoprotein fractions were also analyzed for cholesterol esters (CE), triglycerides (TG), cholesterol (C), and a fraction of minor lipid components including digycerides (DG+). A correlation of .960 between total plasma phosphorus and TL of the d less than 1.006 lipoprotein fraction was observed. No strain effect was noted for TL, NL, or PL for either generation in the d greater than 1.006 fraction. In the d less than 1.006 fraction, TL, NL, and PL all varied concurrently, with the order being HP greater than HW, LW, R1 greater than LP. Percent NL and PL did not vary with strain in the S5 generation in the d less than 1.006 fraction. In the S6, the HP strain had a higher % NL and lower % PL in the d less than 1.006 fraction. No differences in % NL and PL were noted for the d greater than 1.006 fraction. In the d less than 1.006 fraction all lipid classes in the NL's tended to vary together. It was concluded that selecting for total plasma phosphorus in laying female Japanese quail is effective in quantitatively but not qualitatively altering the d less than 1.006 lipoprotein levels in the laying hen plasma, without affecting the d greater than 1.006 lipoproteins levels. It was also concluded that selecting for body weight for six generations did not affect laying female lipoprotein concentration.