Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

Jovian Auroral Ion Precipitation: X‐Ray Production From Oxygen and Sulfur Precipitation

Many attempts have been made to model X‐ray emission from both bremsstrahlung and ion precipitation into Jupiter's polar caps. Electron bremsstrahlung modeling has fallen short of producing the total overall power output observed by Earth‐orbit‐based X‐ray observatories. Heavy ion precipitation was able to reproduce strong X‐ray fluxes, but the proposed incident ion energies were very high ( urn:x-wiley:jgra:media:jgra55396:jgra55396-math-00011 MeV per nucleon). Now with the Juno spacecraft at Jupiter, there have been many measurements of heavy ion populations above the polar cap with energies up to 300–400 keV per nucleon (keV/u), well below the ion energies required by earlier models. Recent work has provided a new outlook on how ion‐neutral collisions in the Jovian atmosphere are occurring, providing us with an entirely new set of impact cross sections. The model presented here simulates oxygen and sulfur precipitation, taking into account the new cross sections, every collision process, the measured ion fluxes above Jupiter's polar aurora, and synthetic X‐ray spectra. We predict X‐ray fluxes, efficiencies, and spectra for various initial ion energies considering opacity effects from two different atmospheres. We demonstrate that an in situ measured heavy ion flux above Jupiter's polar cap is capable of producing over 1 GW of X‐ray emission when some assumptions are made. Comparison of our approximated synthetic X‐ray spectrum produced from in situ particle data with a simultaneous X‐ray spectrum observed by XMM‐Newton shows good agreement for the oxygen part of the spectrum but not for the sulfur part

Depression diagnoses following the identification of bipolar disorder: costly incongruent diagnoses

<p>Abstract</p> <p>Background</p> <p>Previous research has documented that the symptoms of bipolar disorder are often mistaken for unipolar depression prior to a patient's first bipolar diagnosis. The assumption has been that once a patient receives a bipolar diagnosis they will no longer be given a misdiagnosis of depression. The objectives of this study were 1) to assess the rate of subsequent unipolar depression diagnosis in individuals with a history of bipolar disorder and 2) to assess the increased cost associated with this potential misdiagnosis.</p> <p>Methods</p> <p>This study utilized a retrospective cohort design using administrative claims data from 2002 and 2003. Patient inclusion criteria for the study were 1) at least 2 bipolar diagnoses in 2002, 2) continuous enrollment during 2002 and 2003, 3) a pharmacy benefit, and 4) age 18 to 64. Patients with at least 2 unipolar depression diagnoses in 2003 were categorized as having an incongruent diagnosis of unipolar depression. We used propensity scoring to control for selection bias. Utilization was evaluated using negative binomial models. We evaluated cost differences between patient cohorts using generalized linear models.</p> <p>Results</p> <p>Of the 7981 patients who met all inclusion criteria for the analysis, 17.5% (1400) had an incongruent depression diagnosis (IDD). After controlling for background differences, individuals who received an IDD had higher rates of inpatient and outpatient psychiatric utilization and cost, on average, an additional $1641 per year compared to individuals without an IDD.</p> <p>Conclusions</p> <p>A strikingly high proportion of bipolar patients are given the differential diagnosis of unipolar depression <it>after </it>being identified as having bipolar disorder. Individuals with an IDD had increased acute psychiatric care services, suggesting higher levels of relapses, and were at risk for inappropriate treatment, as antidepressant therapy without a concomitant mood-stabilizing medication is contraindicated in bipolar disorder. Further prospective research is needed to validate the findings from this retrospective administrative claims-based analysis.</p

Flexion Relaxation and Its Relation to Pain and Function over the Duration of a Back Pain Episode

BACKGROUND: Relaxation of the erector spinae often occurs in healthy individuals as full trunk flexion is achieved when bending forward from standing. This phenomenon, referred to as flexion relaxation is often absent or disrupted (EMG activity persists) in individuals reporting low back pain (LBP). METHODS AND RESULTS: Self-reported pain and disability scores were compared to EMG measures related to the flexion relaxation (FR) phenomenon by 33 participants with LBP at up to eight sessions over a study period of up to eight weeks. Fourteen participants served as a control group. In the protocol, starting from standing participants bent forward to a fully flexed posture, and then extended the trunk to return to standing position. A thoracic inclinometer was used to measure trunk posture. Surface electrodes located at the L2 and L5 levels recorded EMG amplitudes of the erector spinae. Ratios of EMG amplitudes recorded during forward bending to amplitudes at full flexion, and ratios of extension to full flexion were calculated. EMG amplitudes and their ratios were compared between control and LBP groups at the initial visit. No significant differences between groups were found except at the L5 location at full flexion. Correlations of the ratios to pain and function scores recorded in repeated sessions over the LBP episode also were compared between LBP group participants classified as having transient, recurrent or chronic symptoms. In another analysis participants were grouped by whether their symptoms resolved over the study period. CONCLUSIONS: The transient LBP group had significantly stronger correlations between pain and function to both ratios, than did those with more chronic LBP symptoms. Participants who experienced symptom resolution generally had stronger correlations of ratios to both pain and function than those with partial or no resolution. Improved understanding of these relationships may provide insight in clinical management of LBP

Tissue Harvester with Functional Valve (THFV): Shidham's device for reproducibly higher specimen yield by fine needle aspiration biopsy with easy to perform steps

BACKGROUND: Fine needle aspiration biopsy (FNAB) cytology has been a highly effective methodology for tissue diagnosis and for various ancillary studies including molecular tests. In addition to other benefits, FNAB predominantly retrieves the diagnostic loosely cohesive cells in the lesion as compared to the adjacent supporting stroma with relatively higher cohesiveness. However, FNAB procedure performed with currently available resources is highly skill dependent with inter-performer variability, which compromises its full potential as a diagnostic tool. In this study we report a device overcoming these limitations. METHODS: 'Tissue Harvester with Functional Valve' (THFV) was evaluated as part of a phase 1 National Institute of Health (NIH) research grant under Small Business Technology Transfer (STTR) Program. Working prototypes of the device were prepared. Each of the four cytopathologists with previous cytopathology fellowship training and experience in performing FNAB evaluated 5 THFV and 5 hypodermic needles resulting in 40 specimens (20 with THFV, 20 with hypodermic needles). A piece of fresh cattle liver stuffed in latex glove was used as the specimen. Based on these results a finished design was finalized. RESULTS: The smears and cell blocks prepared from the specimens obtained by THFV were superior in terms of cellularity to specimens obtained with hypodermic needles. The tissuecrit of specimens obtained with THFV ranged from 70 to 100 μl (mean 87, SD 10), compared to 17 to 30 μl (mean 24, SD 4) with conventional hypodermic needles (p < .0001, Student t-test). The technical ease [on a scale of 1 (easy) to 5 (difficult)] with THFV ranged from 1 to 2 as compared to 2 to 3 with hypodermic needles. CONCLUSION: The specimen yield with the new THFV was significantly higher when compared to hypodermic needles. Also, the FNAB procedure with THFV was relatively easier in comparison with hypodermic needles. The final version of Shidham's THFV device would improve the FNAB specimen yield by eliminating the skill factor. The increased specimen yield by this device would also facilitate wider application of FNAB specimens for various ancillary tests, including molecular tests

Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis

<p>Abstract</p> <p>Background</p> <p>Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE) on lipopolysaccharide (LPS)-induced NF-κB signaling in bone marrow derived-macrophages (BMM) and determined the therapeutic efficacy of this extract on colon inflammation.</p> <p>Methods</p> <p>The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The <it>in vivo </it>efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS)-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores.</p> <p>Results</p> <p>LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) in DSS-exposed mice was blocked by BTE.</p> <p>Conclusions</p> <p>These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.</p

Adult Body Weight Is Programmed by a Redox-Regulated and Energy-Dependent Process during the Pronuclear Stage in Mouse

In mammals fertilization triggers a series of Ca2+ oscillations that not only are essential for events of egg activation but also stimulate oxidative phosphorylation. Little is known, however, about the relationship between quantitative changes in egg metabolism and specific long-term effects in offspring. This study assessed whether post-natal growth is modulated by early transient changes in NAD(P)H and FAD2+ in zygotes. We report that experimentally manipulating the redox potential of fertilized eggs during the pronuclear (PN) stage affects post-natal body weight. Exogenous pyruvate induces NAD(P)H oxidation and stimulates mitochondrial activity with resulting offspring that are persistently and significantly smaller than controls. Exogenous lactate stimulates NAD+ reduction and impairs mitochondrial activity, and produces offspring that are smaller than controls at weaning but catch up after weaning. Cytosolic alkalization increases NAD(P)+ reduction and offspring of normal birth-weight become significantly and persistently larger than controls. These results constitute the first report that post-natal growth rate is ultimately linked to modulation of NAD(P)H and FAD2+ concentration as early as the PN stage

Intestinal Inflammation Responds to Microbial Tissue Load Independent of Pathogen/Non-Pathogen Discrimination

The intestinal immune system mounts inflammatory responses to pathogens but tolerates harmless commensal microbiota. Various mechanisms for pathogen/non-pathogen discrimination have been proposed but their general relevance for inflammation control is unclear. Here, we compared intestinal responses to pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered intestinal Peyer’s patches and, surprisingly, induced qualitatively and quantitatively similar initial inflammatory responses revealing a striking discrimination failure. Diverging inflammatory responses only occurred when Salmonella subsequently proliferated and induced escalating neutrophil infiltration, while harmless E. coli was rapidly cleared from the tissue and inflammation resolved. Transient intestinal inflammation induced by harmless E. coli tolerized against subsequent exposure thereby preventing chronic inflammation during repeated exposure. These data revealed a striking failure of the intestinal immune system to discriminate pathogens from harmless microbes based on distinct molecular signatures. Instead, appropriate intestinal responses to gut microbiota might be ensured by immediate inflammatory responses to any rise in microbial tissue loads, and desensitization after bacterial clearance

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

<p>Abstract</p> <p>Background</p> <p>During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).</p> <p>Methods</p> <p>Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.</p> <p>Results</p> <p>We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.</p> <p>Conclusions</p> <p>Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.</p

Historical Reconstruction Reveals Recovery in Hawaiian Coral Reefs

Coral reef ecosystems are declining worldwide, yet regional differences in the trajectories, timing and extent of degradation highlight the need for in-depth regional case studies to understand the factors that contribute to either ecosystem sustainability or decline. We reconstructed social-ecological interactions in Hawaiian coral reef environments over 700 years using detailed datasets on ecological conditions, proximate anthropogenic stressor regimes and social change. Here we report previously undetected recovery periods in Hawaiian coral reefs, including a historical recovery in the MHI (∼AD 1400–1820) and an ongoing recovery in the NWHI (∼AD 1950–2009+). These recovery periods appear to be attributed to a complex set of changes in underlying social systems, which served to release reefs from direct anthropogenic stressor regimes. Recovery at the ecosystem level is associated with reductions in stressors over long time periods (decades+) and large spatial scales (>103 km2). Our results challenge conventional assumptions and reported findings that human impacts to ecosystems are cumulative and lead only to long-term trajectories of environmental decline. In contrast, recovery periods reveal that human societies have interacted sustainably with coral reef environments over long time periods, and that degraded ecosystems may still retain the adaptive capacity and resilience to recover from human impacts