Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease

Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging

The early bee catches the flower - circadian rhythmicity influences learning performance in honey bees, Apis mellifera

Circadian rhythmicity plays an important role for many aspects of honey bees’ lives. However, the question whether it also affects learning and memory remained unanswered. To address this question, we studied the effect of circadian timing on olfactory learning and memory in honey bees Apis mellifera using the olfactory conditioning of the proboscis extension reflex paradigm. Bees were differentially conditioned to odours and tested for their odour learning at four different “Zeitgeber” time points. We show that learning behaviour is influenced by circadian timing. Honey bees perform best in the morning compared to the other times of day. Additionally, we found influences of the light condition bees were trained at on the olfactory learning. This circadian-mediated learning is independent from feeding times bees were entrained to, indicating an inherited and not acquired mechanism. We hypothesise that a co-evolutionary mechanism between the honey bee as a pollinator and plants might be the driving force for the evolution of the time-dependent learning abilities of bees

The effect of osteoprotegerin administration on the intra-tibial growth of the osteoblastic LuCaP 23.1 prostate cancer xenograft

Osteoprotegerin (OPG) plays a central role in controlling bone resorption. Exogenous administration of OPG has been shown to be effective in preventing osteolysis and limiting the growth of osteolytic metastasis. The objective of this study was to investigate the effects of OPG on osteoblastic prostate cancer (CaP) metastases in an animal model. LuCaP 23.1 cells were injected intra-tibially and Fc-OPG (6.0 mg/kg) was administered subcutaneously three times a week starting either 24 hours prior to cell injection (prevention regimen) or at 4 weeks post-injection (treatment regimen). Changes in bone mineral density at the tumor site were determined by dual x-ray absorptiometry. Tumor growth was monitored by evaluating serum prostate specific antigen (PSA). Fc-OPG did not inhibit establishment of osteoblastic bone lesions of LuCaP 23.1, but it decreased growth of the tumor cells, as determined by decreases in serum PSA levels of 73.0 ± 44.3% ( P < 0.001) and 78.3 ± 25.3% ( P < 0.001) under the treatment and prevention regimens, respectively, compared to the untreated tumor-bearing animals. Administration of Fc-OPG decreased the proliferative index by 35.0% ( P = 0.1838) in the treatment group, and 75.2% ( P = 0.0358) in the prevention group. The results of this study suggest a potential role for OPG in the treatment of established osteoblastic CaP bone metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42587/1/10585_2004_Article_2869.pd

Non-Hodgkin's lymphoma and auricular hypoplasia: associated with juvenile colloid milium or ligneous conjunctivitis?

The exact nature of amyloid-like hyaline material deposits in the skin is not well understood in some disorders. Three of those - ligneous conjunctivitis, ligneous periodontitis and colloid milium - have been rarely reported in a same patient. We report a case of mucosal and skin deposits of an amyloid-like homogeneous material associated with non-Hodgkin's lymphoma and congenital auricular hypoplasia. We discussed and reviewed the literature on these unique associations to determine whether these are the same pathological process. We also noted whether this case represents a new syndrome or a coincidental association

Follow-up of Indigenous-specific health assessments - a socioecological analysis

OBJECTIVES: To describe patterns of uptake of Indigenous-specific health assessments and associated follow-up items, and examine the barriers and enablers to delivery and billing of follow-up over the first 3 years of implementation of the Indigenous Chronic Disease Package (ICDP). DESIGN, SETTING AND PARTICIPANTS: We used a socioecological approach to analyse data derived from the Sentinel Sites Evaluation of the ICDP - with data from 24 sites across Australia. Administrative data (1 May 2009 to 30 May 2012) and program data (1 March 2010 to 30 May 2012) were provided by the Department of Health. Data on barriers and enablers to follow-up of health assessments were obtained from community focus groups, in-depth interviews and discussions with key informants (1 November 2010 to 30 December 2012). MAIN OUTCOME MEASURES: Monthly number of Medicare Benefits Schedule items claimed for Indigenous-specific health services and follow-up; qualitative data on enablers and barriers categorised according to patient, patient-health service relationship, health service or organisation, community and policy environment levels or influence. RESULTS: There was an increase in the uptake of health assessments, but relatively limited delivery of follow-up care and billing for Indigenous-specific follow-up items. Follow-up was constrained by factors that operated at various levels: patient, interpersonal, health service, community and policy. Constraints included practitioners' lack of awareness of item numbers, staffing, poor state of clinical information systems, billing against non-Indigenous-specific items or more general follow-up items, emphasis on health assessments with less attention to requirements for follow-up, limited capacity to arrange and facilitate follow-up, and communication and transport challenges for patients. CONCLUSIONS: Work is required across various levels of the system to address barriers to follow-up care. Enhancing follow-up care is vital to achieving health benefits from the large financial and human resource investment in health assessments