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.

Aims/hypothesis Understanding cellular and molecular events in diabetes mellitus will identify new approaches for therapy. Immune system cells are important modulators of chronic inflammation in diabetes mellitus, but the role of B cells is not adequately studied. The aim of this work was to define the function of B cells in diabetes mellitus patients through focus on B cell responses to pattern recognition receptors. Methods We measured expression and function of Toll-like receptors (TLRs) on peripheral blood B cells from diabetes mellitus patients by flow cytometry and multiplexed cytokine analysis. We similarly analysed B cells from non-diabetic donors and periodontal disease patients as comparative cohorts.

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Hospital readmission is a high-priority health care quality measure and target for cost reduction. Despite broad interest in readmission, relatively little research has focused on patients with diabetes. The burden of diabetes among hospitalized patients, however, is substantial, growing, and costly, and readmissions contribute a significant portion of this burden. Reducing readmission rates of diabetic patients has the potential to greatly reduce health care costs while simultaneously improving care. Risk factors for readmission in this population include lower socioeconomic status, racial/ethnic minority, comorbidity burden, public insurance, emergent or urgent admission, and a history of recent prior hospitalization. Hospitalized patients with diabetes may be at higher risk of readmission than those without diabetes. Potential ways to reduce readmission risk are inpatient education, specialty care, better discharge instructions, coordination of care, and post-discharge support. More studies are needed to test the effect of these interventions on the readmission rates of patients with diabetes.

In June 2016, Diabetes Technology Society convened a panel of US experts in inpatient diabetes management to discuss the current and potential role of continuous glucose monitoring (CGM) in the hospital. This discussion combined with a literature review was a follow-up to a meeting, which took place in May 2015. The panel reviewed evidence on use of CGM in 3 potential inpatient scenarios: (1) the intensive care unit (ICU), (2) non-ICU, and (3) transitioning outpatient CGM use into the hospital setting. Panel members agreed that data from limited studies and theoretical considerations suggested that use of CGM in the hospital had the potential to improve patient clinical outcomes, and in particular reduction of hypoglycemia. Panel members discussed barriers to widespread adoption of CGM, which patients would benefit most from use of this technology, and what type of outcome studies are needed to guide use of CGM in the inpatient setting.

In stark contrast to most aggressive predators, Dosidicus gigas (jumbo squids) do not use minerals in their powerful mouthparts known as beaks. Their beaks instead consist of a highly sclerotized chitinous composite with incremental hydration from the tip to the base. We previously reported L-3,4-dihydroxyphenylalanine (dopa)-histidine (dopa-His) as an important covalent cross-link providing mechanical strengthening to the beak material. Here, we present a more complete characterization of the sclerotization chemistry and describe additional cross-links from D. gigas beak. All cross-links presented in this report share common building blocks, a family of di-, tri-, and tetra-histidine-catecholic adducts, that were separated by affinity chromatography and high performance liquid chromatography (HPLC) and identified by tandem mass spectroscopy and proton nuclear magnetic resonance ( 1 H NMR). The data provide additional insights into the unusually high cross-link density found in mature beaks. Furthermore, we propose both a low molecular weight catechol, and peptidyl-dopa, to be sclerotization agents of squid beak. This appears to represent a new strategy for forming hard tissue in animals. The interplay between covalent cross-linking and dehydration on the graded properties of the beaks is discussed.Cephalopods such as squids, cuttlefish, and octopods are equipped with a hard beak that is as sharp as a knife and crucial for disabling prey and feeding. Beak chemistry has attracted much recent attention in materials science: in contrast to mammalian hard tissues, the beak is devoid of minerals, consisting instead of a composite of proteins and chitin fibers with varying degrees of hydration along the beak structure. In animals, this is a unique material design for hard tissues that function in biting. The Dosidicus beak biocomposite possesses a stiffness (elastic modulus, E) of 5 GPa at the distal tip that decreases incrementally to 50 MPa (wet conditions) in the proximal wing, which is tightly embedded within the muscular buccal mass (1). As the beak lacks any of the known strengthening entities previously associated with wear-resistant tissues such as biomineralization (2-5), metal ion cross-linking (6, 7), or protein halogenation (8, 9), it begs a question, namely, what sort of molecular processing can impart such impressive physical properties? A deeper understanding of the mechanisms by which beaks are sclerotized is also likely to reveal novel chemical paradigms for the fabrication of robust and biocompatible composites for a variety of restorative applications. Furthermore, synthesis of such polymer-based composite materials could inspire environmentally friendly routes as Dosidicus beak is formed under ambient seawater conditions and is wholly nontoxic.From a biochemical perspective the biomaterial most similar to Dosidicus beak is hard insect cuticle. Both are predominantly composed of chitin fibers, protein, and polyphenolic compounds (10, 11). In insect cuticle, the contribution of dehydration and cross-...

Chronic systemic inflammation links periodontal disease and diabetes to increased incidence of serious comorbidities. Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. Human B cells have been generally thought to lack these TLRs. However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. New data show that B cells from inflammatory disease patients secrete multiple cytokines in response to different classes of TLR ligands. Furthermore, the B cell response to combinations of TLR ligands is cytokine- and ligand-specific. Some cytokines (IL-1β and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-α) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. Parallel examination of B cells from periodontal disease and diabetes patients suggested that outcomes of TLR cross-talk are influenced by disease pathology. We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation.

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