521 research outputs found
Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome.
22q11.2 deletion syndrome (22q11DS) is a recurrent genetic mutation that is highly penetrant for psychosis. Behavioral research suggests that 22q11DS patients exhibit a characteristic neurocognitive phenotype that includes differential impairment in spatial working memory (WM). Notably, spatial WM has also been proposed as an endophenotype for idiopathic psychotic disorder, yet little is known about the neurobiological substrates of WM in 22q11DS. In order to investigate the neural systems engaged during spatial WM in 22q11DS patients, we collected functional magnetic resonance imaging (fMRI) data while 41 participants (16 22q11DS patients, 25 demographically matched controls) performed a spatial capacity WM task that included manipulations of delay length and load level. Relative to controls, 22q11DS patients showed reduced neural activation during task performance in the intraparietal sulcus (IPS) and superior frontal sulcus (SFS). In addition, the typical increases in neural activity within spatial WM-relevant regions with greater memory load were not observed in 22q11DS. We further investigated whether neural dysfunction during WM was associated with behavioral WM performance, assessed via the University of Maryland letter-number sequencing (LNS) task, and positive psychotic symptoms, assessed via the Structured Interview for Prodromal Syndromes (SIPS), in 22q11DS patients. WM load activity within IPS and SFS was positively correlated with LNS task performance; moreover, WM load activity within IPS was inversely correlated with the severity of unusual thought content and delusional ideas, indicating that decreased recruitment of working memory-associated neural circuitry is associated with more severe positive symptoms. These results suggest that 22q11DS patients show reduced neural recruitment of brain regions critical for spatial WM function, which may be related to characteristic behavioral manifestations of the disorder
Delivering mesenchymal stem cells in collagen microsphere carriers to rabbit degenerative disc - Reduced risk of osteophyte formation.
Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration.published_or_final_versio
High prevalence of Escherichia coli sequence type 131 among antimicrobial-resistant E. coli isolates from geriatric patients
Previous work on the subclones within Escherichia coli ST131 predominantly involved isolates from Western countries. This study assessed the prevalence and antimicrobial resistance attributed to this clonal group. A total of 340 consecutive, non-duplicated urinary E. coli isolates originating from four clinical laboratories in Hong Kong in 2013 were tested. ST131 prevalence among the total isolates was 18.5β% (63/340) and was higher among inpatient isolates (23.0β%) than outpatient isolates (11.8β%, P<0.001), and higher among isolates from patients aged β₯65 years than from patients aged 18β50 years and 51β64 years (25.4 vs 3.4 and 4.0β%, respectively, P<0.001). Of the 63 ST131 isolates, 43 (68.3β%) isolates belonged to the H30 subclone, whereas the remaining isolates belonged to H41 (nβ=β17), H54 (nβ=β2) and H22 (nβ=β1). All H30 isolates were ciprofloxacin-resistant, of which 18.6β% (8/43) belonged to the H30-Rx subclone. Twenty-six (41.3β%) ST131 isolates were ESBL-producers, of which 19 had bla CTX-M-14 (12 non-H30-Rx, two H30-Rx and five H41), six had bla CTX-M-15 (five non-H30-Rx and one H30-Rx) and one was bla CTX-M-negative (H30). In conclusion, ST131 accounts for a large share of the antimicrobial-resistant E. coli isolates from geriatric patients. Unlike previous reports, ESBL-producing ST131 strains mainly belonged to non-H30-Rx rather than the H30-Rx subclone, with bla CTX-M-14 as the dominant enzyme type.postprin
Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb
The reshaping and decorrelation of similar activity patterns by neuronal
networks can enhance their discriminability, storage, and retrieval. How can
such networks learn to decorrelate new complex patterns, as they arise in the
olfactory system? Using a computational network model for the dominant neural
populations of the olfactory bulb we show that fundamental aspects of the adult
neurogenesis observed in the olfactory bulb -- the persistent addition of new
inhibitory granule cells to the network, their activity-dependent survival, and
the reciprocal character of their synapses with the principal mitral cells --
are sufficient to restructure the network and to alter its encoding of odor
stimuli adaptively so as to reduce the correlations between the bulbar
representations of similar stimuli. The decorrelation is quite robust with
respect to various types of perturbations of the reciprocity. The model
parsimoniously captures the experimentally observed role of neurogenesis in
perceptual learning and the enhanced response of young granule cells to novel
stimuli. Moreover, it makes specific predictions for the type of odor
enrichment that should be effective in enhancing the ability of animals to
discriminate similar odor mixtures
Blood pressure and renal cancer risk: the HUNT Study in Norway
In a prospective study of 36β728 women and 35β688 men during 18 years of follow-up, compared to systolic pressure <130βmm Hg, levels of 130β149, 150β169 and β©Ύ170βmm Hg in women were associated with relative risks of renal cell cancer of 1.7, 2.0 and 2.0, respectively (P for linear trend, 0.11). In men, there was no association with blood pressure
Synthetic Toll Like Receptor-4 (TLR-4) Agonist Peptides as a Novel Class of Adjuvants
Background: Adjuvants serve as catalysts of the innate immune response by initiating a localized site of inflammation that is mitigated by the interactions between antigens and toll like receptor (TLR) proteins. Currently, the majority of vaccines are formulated with aluminum based adjuvants, which are associated with various side effects. In an effort to develop a new class of adjuvants, agonists of TLR proteins, such as bacterial products, would be natural candidates. Lipopolysaccharide (LPS), a major structural component of gram negative bacteria cell walls, induces the systemic inflammation observed in septic shock by interacting with TLR-4. The use of synthetic peptides of LPS or TLR-4 agonists, which mimic the interaction between TLR-4 and LPS, can potentially regulate cellular signal transduction pathways such that a localized inflammatory response is achieved similar to that generated by adjuvants. Methodology/Principal Findings: We report the identification and activity of several peptides isolated using phage display combinatorial peptide technology, which functionally mimicked LPS. The activity of the LPS-TLR-4 interaction was assessed by NF-kB nuclear translocation analyses in HEK-BLUE TM-4 cells, a cell culture model that expresses only TLR-4, and the murine macrophage cell line, RAW264.7. Furthermore, the LPS peptide mimics were capable of inducing inflammatory cytokine secretion from RAW264.7 cells. Lastly, ELISA analysis of serum from vaccinated BALB/c mice revealed that the LPS peptide mimics act as a functional adjuvant
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