Effect of Long-Duration Spaceflight on Postural Control During Self-Generated Perturbations

This report is the first systematic evaluation of the effects of prolonged weightlessness on the bipedal postural control processes during self-generated perturbations produced by voluntary upper limb movements. Spaceflight impacts humans in a variety of ways, one of which is compromised postflight postural control. We examined the neuromuscular activation characteristics and center of pressure motion (COP) associated with arm movement of eight subjects who experienced long duration spaceflight (3-6 months) aboard the Mir space station. Surface electromyography (EMG), arm acceleration, and COP motion were collected while astronauts performed rapid unilateral shoulder flexions prior to and after spaceflight. Subjects displayed compromised postural control after flight as evidenced by modified peak-to-peak COP anterior-posterior and medio-lateral motion and COP pathlength relative to preflight values. These changes were associated with disrupted neuromuscular activation characteristics, particularly after the completion of arm acceleration (i.e. when subjects were attempting to maintain their upright posture). These findings suggest that although the subjects were able to assemble coordination modes that enabled them to generate rapid arm movements, the subtle control necessary to maintain bipedal equilibrium evident in their preflight performance is compromised after long duration spaceflight

Communication Gaps Associated With Donor‐Derived Infections

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109830/1/ajt12978.pd

Investigation of the Role of TNF-α Converting Enzyme (TACE) in the Inhibition of Cell Surface and Soluble TNF-α Production by Acute Ethanol Exposure

Toll-like receptors (TLRs) play a fundamental role in the immune system by detecting pathogen associated molecular patterns (PAMPs) to sense host infection. Ethanol at doses relevant for humans inhibits the pathogen induced cytokine response mediated through TLRs. The current study was designed to investigate the mechanisms of this effect by determining whether ethanol inhibits TLR3 and TLR4 mediated TNF-α secretion through inhibition of transcription factor activation or post-transcriptional effects. In NF-κB reporter mice, activation of NF-κB in vivo by LPS was inhibited by ethanol (LPS alone yielded 170,000±35,300 arbitrary units of light emission; LPS plus ethanol yielded 56,120±16880, p = 0.04). Inhibition of protein synthesis by cycloheximide revealed that poly I:C- or LPS-induced secreted TNF-α is synthesized de novo, not released from cellular stores. Using real time RT-PCR, we found inhibition of LPS and poly I:C induced TNF-α gene transcription by ethanol. Using an inhibitor of tumor necrosis factor alpha converting enzyme (TACE), we found that shedding caused by TACE is a prerequisite for TNF-α release after pathogen challenge. Flow cytometry was used to investigate if ethanol decreases TNF-α secretion by inhibition of TACE. In cells treated with LPS, ethanol decreased both TNF-α cell surface expression and secretion. For example, 4.69±0.60% of untreated cells were positive for cell surface TNF-α, LPS increased this to 25.18±0.85%, which was inhibited by ethanol (86.8 mM) to 14.29±0.39% and increased by a TACE inhibitor to 57.88±0.62%. In contrast, cells treated with poly I:C had decreased secretion of TNF-α but not cell surface expression. There was some evidence for inhibition of TACE by ethanol in the case of LPS, but decreased TNF-α gene expression seems to be the major mechanism of ethanol action in this system

Impact of Virologic Breakthrough and HBIG Regimen on Hepatitis B Recurrence After Liver Transplantation

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1–81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log 10 copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79358/1/j.1600-6143.2010.03046.x.pd

Somatotopic map and inter- and intra-digit distance in Brodmann area 2 by pressure stimulation

The somatotopic representation of the tactile stimulation on the finger in the brain is an essential part of understanding the human somatosensory system as well as rehabilitation and other clinical therapies. Many studies have used vibrotactile stimulations and reported finger somatotopic representations in the Brodmann area 3 (BA 3). On the contrary, few studies investigated finger somatotopic representation using pressure stimulations. Therefore, the present study aimed to find a comprehensive somatotopic representation (somatotopic map and inter- and intra-digit distance) within BA 2 of humans that could describe tactile stimulations on different joints across the fingers by applying pressure stimulation to three joints-the first (p1), second (p2), and third (p3) joints-of four fingers (index, middle, ring, and little finger). Significant differences were observed in the inter-digit distance between the first joints (p1) of the index and little fingers, and between the third joints (p3) of the index and little fingers. In addition, a significant difference was observed in the intra-digit distance between p1 and p3 of the little finger. This study suggests that a somatotopic map and inter- and intra-digit distance could be found in BA 2 in response to pressure stimulation on finger joints.ope

Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes

Numerical Solution of Differential Equations by the Parker-Sochacki Method

A tutorial is presented which demonstrates the theory and usage of the Parker-Sochacki method of numerically solving systems of differential equations. Solutions are demonstrated for the case of projectile motion in air, and for the classical Newtonian N-body problem with mutual gravitational attraction.Comment: Added in July 2010: This tutorial has been posted since 1998 on a university web site, but has now been cited and praised in one or more refereed journals. I am therefore submitting it to the Cornell arXiv so that it may be read in response to its citations. See "Spiking neural network simulation: numerical integration with the Parker-Sochacki method:" J. Comput Neurosci, Robert D. Stewart & Wyeth Bair and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717378

The reproductive capacity of Monk Parakeets Myiopsitta monachus is higher in their invasive range

Breeding parameters for Monk Parakeets Myiopsitta monachus nesting in Barcelona, Spain, were collected for 651 nests over five breeding seasons. This invasive population has a high reproductive capacity compared with the species in the native range: fledging success was double, the percentage of pairs attempting second broods three times higher and 55% of first-year birds bred compared with almost zero in South America

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases