Behavioral recovery from traumatic brain injury after membrane reconstruction using polyethylene glycol

Polyethylene glycol (PEG; 2000 MW, 30% by volume) has been shown to mechanically repair damaged cellular membranes and reduce secondary axotomy after traumatic brain and spinal cord injury (TBI and SCI respectively). This repair is achieved following spontaneous reassembly of cell membranes made possible by the action of targeted hydrophilic polymers which first seal the compromised portion of the plasmalemma, and secondarily, allow the lipidic core of the compromised membranes to resolve into each other. Here we compared PEG-treated to untreated rats using a computer-managed open-field behavioral test subsequent to a standardized brain injury. Animals were evaluated after a 2-, 4-, and 6-hour delay in treatment after TBI. Treated animals receive a single subcutaneous injection of PEG. When treated within 2 hours of the injury, injured PEG-treated rats showed statistically significant improvement in their exploratory behavior recorded in the activity box when compared to untreated but brain-injured controls. A delay of 4 hours reduced this level of achievement, but a statistically significant improvement due to PEG injection was still clearly evident in most outcome measures compared at the various evaluation times. A further delay of 2 more hours, however, eradicated the beneficial effects of PEG injection as revealed using this behavioral assessment. Thus, there appears to be a critical window of time in which PEG administration after TBI can provide neuroprotection resulting in an enhanced functional recovery. As is often seen in clinically applied acute treatments for trauma, the earlier the intervention can be applied, the better the outcome

Optical Fiber-Based Sensing of Strain and Temperature at High Temperature

In-line intensity-based and Fabry-Perot silica optical fiber sensors have been developed to measure strain and temperature at temperatures up to 1500°F. The intensity-based sensor is an air gap splice in which the gap spacing changes as the length of the sensor housing changes. Two silica multimode optical fibers are placed in a hollow silica tube so their ends are separated by an initial gap spacing. As the sensor is strained, the gap spacing varies, resulting in a predictable change in output intensity. The Fabry-Perot sensor uses both single-mode and multimode fibers which are axially aligned inside a similar hollow core fiber. The four percent reflections which occur at both the glass-air interface at the end of the input singlemode fiber and at the air-glass interface at the surface of the multimode fiber differ in phase by an amount proportional to the separation between the two fiber ends. As the sensor is strained, the separation distance between these fiber ends changes, and the output signal intensity varies due to the interference between the reflected signals

Remembering the forgotten non-communicable diseases

The forthcoming post-Millennium Development Goals era will bring about new challenges in global health. Low- and middle-income countries will have to contend with a dual burden of infectious and non-communicable diseases (NCDs). Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and diabetes, cause much health loss worldwide and are already widely recognised as doing so. However, 55% of the global NCD burden arises from other NCDs, which tend to be ignored in terms of premature mortality and quality of life reduction. Here, experts in some of these 'forgotten NCDs' review the clinical impact of these diseases along with the consequences of their ignoring their medical importance, and discuss ways in which they can be given higher global health priority in order to decrease the growing burden of disease and disability.MerckUniv Melbourne, Sch Populat & Global Hlth, Melbourne, Vic 3053, AustraliaUniv London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Med, London W2 1NY, EnglandKEMRI Wellcome Trust Res Programme, Kilifi, KenyaUniv British Columbia, St Pauls Hosp, Vancouver, BC V6Z 1Y8, CanadaVA Med Ctr, Med Serv, Birmingham, AL USAVA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USAUniv Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USAMayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USAUniv London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, EnglandCtr Addict & Mental Hlth, Toronto, ON, CanadaTech Univ Dresden, D-01062 Dresden, GermanyUniv Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, CanadaUniv Toronto, Dept Psychiat, Toronto, ON, CanadaUofT, Inst Med Sci, Toronto, ON, CanadaNIDA, NIH, Rockville, MD USANIAAA, NIH, Bethesda, MD 20892 USAHosp Alemao Oswaldo Cruz, Inst Educ & Hlth Sci, BR-01323903 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Psychobiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Psychobiol, BR-04023062 São Paulo, BrazilWeb of Scienc

Fetal Brain Biometric Measurements on 3D Super-Resolution Reconstructed T2-Weighted MRI: An Intra- and Inter-observer Agreement Study.

We present the comparison of two-dimensional (2D) fetal brain biometry on magnetic resonance (MR) images using orthogonal 2D T2-weighted sequences (T2WSs) vs. one 3D super-resolution (SR) reconstructed volume and evaluation of the level of confidence and concordance between an experienced pediatric radiologist (obs1) and a junior radiologist (obs2). Twenty-five normal fetal brain MRI scans (18-34 weeks of gestation) including orthogonal 3-mm-thick T2WSs were analyzed retrospectively. One 3D SR volume was reconstructed per subject based on multiple series of T2WSs. The two observers performed 11 2D biometric measurements (specifying their level of confidence) on T2WS and SR volumes. Measurements were compared using the paired Wilcoxon rank sum test between observers for each dataset (T2WS and SR) and between T2WS and SR for each observer. Bland-Altman plots were used to assess the agreement between each pair of measurements. Measurements were made with low confidence in three subjects by obs1 and in 11 subjects by obs2 (mostly concerning the length of the corpus callosum on T2WS). Inter-rater intra-dataset comparisons showed no significant difference (p > 0.05), except for brain axial biparietal diameter (BIP) on T2WS and for brain and skull coronal BIP and coronal transverse cerebellar diameter (DTC) on SR. None of them remained significant after correction for multiple comparisons. Inter-dataset intra-rater comparisons showed statistical differences in brain axial and coronal BIP for both observers, skull coronal BIP for obs1, and axial and coronal DTC for obs2. After correction for multiple comparisons, only axial brain BIP remained significantly different, but differences were small (2.95 ± 1.73 mm). SR allows similar fetal brain biometry as compared to using the conventional T2WS while improving the level of confidence in the measurements and using a single reconstructed volume

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure

Interfibrillar stiffening of echinoderm mutable collagenous tissue demonstrated at the nanoscale

The mutable collagenous tissue (MCT) of echinoderms (e.g., sea cucumbers and starfish) is a remarkable example of a biological material that has the unique attribute, among collagenous tissues, of being able to rapidly change its stiffness and extensibility under neural control. However, the mechanisms of MCT have not been characterized at the nanoscale. Using synchrotron small-angle X-ray diffraction to probe time-dependent changes in fibrillar structure during in situ tensile testing of sea cucumber dermis, we investigate the ultrastructural mechanics of MCT by measuring fibril strain at different chemically induced mechanical states. By measuring a variable interfibrillar stiffness (E(IF)), the mechanism of mutability at the nanoscale can be demonstrated directly. A model of stiffness modulation via enhanced fibrillar recruitment is developed to explain the biophysical mechanisms of MCT. Understanding the mechanisms of MCT quantitatively may have applications in development of new types of mechanically tunable biomaterials

The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice.

The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse