Comparison of early and late depression after TBI; (the SHEFBIT study)

OBJECTIVE: Evaluate the prevalence and risk factors for depression at 1 year after traumatic brain injury (TBI) and contrast against those at 10 weeks. METHODS: Prospective TBI admissions over 2 years to an emergency department were recruited to form a representative TBI population. Depression was recorded at 10 weeks and 1 year by HADS (Hospital Anxiety and Depression Scale) with score>8. Demographic and injury features were analyzed for association with depression. RESULTS: A total of 774 individuals were recruited of whom 690 attended  1-year follow-up; 38 had died. Only 6% of the cohort was lost to follow-up. The prevalence of depression at 10 weeks was 56.3% [95% CI 52.8-59.8] and at 1 year 41.2% [95% CI 37.6-44.9] A multivariable analysis identified the independent predictors of 1 year depression as an abnormal CT scan, past psychiatric history, alcohol intoxication, and female gender. TBI severity, age, etiology, and medical comorbidity were not significant. By contrast at 10weeks, increasing severity and CT findings were highly significant. CONCLUSIONS: Depression at 1 year post-TBI remains high but injury features are less predictive than early after injury. It is likely that pre-injury personality and coping mechanisms are more important in determining long term outcome. The predictors identified may allow targeting of vulnerable sub-populations

Localization of Eosinophilic Esophagitis from H&E stained images using multispectral imaging

This study is an initial investigation on the capability of multispectral imaging to capture subtle spectral information that would enable the automatic delineation between the eosinophilic esophagitis and other eosin stained tissue components, especially the RBCs. In the method, a principal component analysis (PCA) was performed on the spectral transmittance samples of the different tissue components, excluding however the transmittance samples of the eosinophilic esophagitis. From the average spectral error configuration of the eosinophilic esophagitis transmittance samples, i.e. the difference between the actual transmittance and the estimated transmittance using m PC vectors, we indentified two spectral bands by which we can localize the eosinophils. Initial results show the possibility of automatically localizing the eosinophilic esophagitis by utilizing spectral information

The crossroads of evidence-based medicine and health policy: implications for urology

As healthcare spending in the United States continues to rise at an unsustainable rate, recent policy decisions introduced at the national level will rely on precepts of evidence-based medicine to promote the determination, dissemination, and delivery of “best practices” or quality care while simultaneously reducing cost. We discuss the influence of evidence-based medicine on policy and, in turn, the impact of policy on the developing clinical evidence base with an eye to the potential effects of these relationships on the practice and provision of urologic care

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n=5) and its germ-free (GF) equivalent (n=5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myo-inositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations

Testing foundations of quantum mechanics with photons

The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

Minimization of free radical damage by metal catalysis of multivitamin/multimineral supplements

Multivitamin/multimineral complexes are the most common dietary supplements. Unlike minerals in foods that are incorporated in bioorganic structures, minerals in dietary supplements are typically in an inorganic form. These minerals can catalyze the generation of free radicals, thereby oxidizing antioxidants during digestion. Here we examine the ability of a matrix consisting of an amino acid and non-digestible oligosaccharide (AAOS) to blunt metal-catalyzed oxidations. Monitoring of ascorbate radical generated by copper shows that ascorbate is oxidized more slowly with the AAOS matrix than with copper sulfate. Measurement of the rate of oxidation of ascorbic acid and Trolox® by catalytic metals confirmed the ability of AAOS to slow these oxidations. Similar results were observed with iron-catalyzed formation of hydroxyl radicals. When compared to traditional forms of minerals used in supplements, we conclude that the oxidative loss of antioxidants in solution at physiological pH is much slower when AAOS is present

Methylated BSA Mimics Amyloid-Related Proteins and Triggers Inflammation

The mechanistic study of inflammatory or autoimmune diseases requires the generation of mouse models that reproduce the alterations in immune responses observed in patients. Methylated bovine serum albumin (mBSA) has been widely used to induce antigen-specific inflammation in targeted organs or in combination with single stranded DNA (ssDNA) to generate anti-nucleic acids antibodies in vivo. However, the mechanism by which this modified protein triggers inflammation is poorly understood. By analyzing the biochemical properties of mBSA, we found that mBSA exhibits features of an intermediate of protein misfolding pathway. mBSA readily interact with a list of dyes that have binding specificity towards amyloid fibrils. Intriguingly, mBSA displayed cytotoxic activity and its binding to ssDNA further enhanced formation of beta-sheet rich amyloid fibrils. Moreover, mBSA is recognized by the serum amyloid P, a protein unanimously associated with amyloid plaques in vivo. In macrophages, we observed that mBSA disrupted the lysosomal compartment, signaled along the NLRP3 inflammasome pathway, and activated caspase 1, which led to the production of IL-1β. In vivo, mBSA triggered rapid and prominent immune cell infiltration that is dependent on IL-1β induction. Taken together, these data demonstrate that by mimicking amyloidogenic proteins mBSA exhibits strong innate immune functions and serves as a potent adjuvant. These findings advance our understanding on the underlying mechanism of how aberrant immune responses lead to autoimmune reactions

Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.</p> <p>Results</p> <p>We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.</p> <p>Conclusion</p> <p>Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.</p