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Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood–brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury. [ABSTRACT FROM AUTHOR]

Background: The post‐operative course after Liver Transplantation (LT) can be complicated by early allograft dysfunction (EAD), primary nonfunction (PNF) and death. A lactate concentration at the end of transplant of ≥5 mmol/L was recently proposed as a predictive marker of PNF, EAD, and mortality; this study aimed to validate these previous reports in a large single center cohort. Methods: This retrospective cohort study included adult liver transplant recipients who received grafts from deceased donors at our center between June 2012 and May 2021. Receiver operating characteristic (ROC) curves for the lactate concentration at the end of transplantation were computed to determine the AUC for PNF, EAD and mortality at 90 days. Results: In our cohort of 1137 cases, the AUCs for lactate to predict EAD, PNF and mortality were respectively.56 (95% confidence interval [CI]:.53–.60),.69 (95% CI:.52–.85), and.74 (95% CI:.63–.84). Conclusion: The clinical value of lactate concentration at the end of transplantation to predict PNF, EAD and mortality at 90 days was, at best, modest, as shown by the relatively low AUCs. Our findings cannot validate previous reports that the lactate level alone is a good predictor of poor outcomes after liver transplantation. [ABSTRACT FROM AUTHOR]

Background and Aims: Metabolic dysfunction (MD)‐associated fatty liver disease has been proposed to identify individuals at risk of liver events irrespectively of the contemporary presence of other liver diseases. The aim of this study was to examine the impact of MD in patients cured of chronic hepatis C (CHC). Patients and Methods: We analysed data from a real‐life cohort of 2611 Italian patients cured of CHC with direct antiviral agents and advanced liver fibrosis, without HBV/HIV, transplantation and negative for hepatocellular carcinoma (HCC) history (age 61.4 ± 11.8 years, 63.9% males, median follow‐up 34, 24–40 months). Information about ultrasonographic steatosis (US) after sustained virological response was available in 1978. Results: MD affected 58% of patients, diagnosed due to the presence of diabetes (MD‐diabetes, 19%), overweight without diabetes (MD‐overweight, 37%) or multiple metabolic abnormalities without overweight and diabetes (MD‐metabolic, 2%). MD was more frequent than and not coincident with US (32% MD‐only, 23% MD‐US and 13% US‐only). MD was associated with higher liver stiffness (p < 0.05), particularly in patients with MD‐diabetes and MD‐only subgroups, comprising older individuals with more advanced metabolic and liver disease (p < 0.05). At Cox proportional hazard multivariable analysis, MD was associated with increased risk of HCC (HR 1.97, 95% CI 1.27–3.04; p = 0.0023). Further classification according to diagnostic criteria improved risk stratification (p < 0.0001), with the highest risk observed in patients with MD‐diabetes. Patients with MD‐only appeared at highest risk since the sustained virological response achievement (p = 0.008), with a later catch‐up of those with combined MD‐US, whereas US‐only was not associated with HCC. Conclusions: MD is more prevalent than US in patients cured of CHC with advanced fibrosis and identifies more accurately individuals at risk of developing HCC. [ABSTRACT FROM AUTHOR]

In the course of military operations in modern war theaters, blast exposures are associated with the development of a variety of mental health disorders associated with a post-traumatic stress disorder-related features, including anxiety, impulsivity, insomnia, suicidality, depression, and cognitive decline. Several lines of evidence indicate that acute and chronic cerebral vascular alterations are involved in the development of these blast-induced neuropsychiatric changes. In the present study, we investigated late occurring neuropathological events associated with cerebrovascular alterations in a rat model of repetitive low-level blast-exposures (3 × 74.5 kPa). The observed events included hippocampal hypoperfusion associated with late-onset inflammation, vascular extracellular matrix degeneration, synaptic structural changes and neuronal loss. We also demonstrate that arteriovenous malformations in exposed animals are a direct consequence of blast-induced tissue tears. Overall, our results further identify the cerebral vasculature as a main target for blast-induced damage and support the urgent need to develop early therapeutic approaches for the prevention of blast-induced late-onset neurovascular degenerative processes. [ABSTRACT FROM AUTHOR]

Introduction: Due to Brazilian population aging, prevalence of aortic stenosis, and limited number of scores in literature, it is essential to develop risk scores adapted to our reality and created in the specific context of this disease. Methods: This is an observational historical cohort study with analysis of 802 aortic stenosis patients who underwent valve replacement at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, from 1996 to 2018. With the aid of logistic regression, a weighted risk score was constructed based on the magnitude of the coefficients β of the logistic equation. Two performance statistics were obtained: area under the receiver operating characteristic curve and the chi-square (χ2) of Hosmer-Lemeshow goodness-of-fit with Pearson's correlation coefficient between the observed events and predicted as a model calibration estimate. Results: The risk predictors that composed the score were valve replacement surgery combined with coronary artery bypass grafting, prior renal failure, New York Heart Association class III/IV heart failure, age > 70 years, and ejection fraction < 50%. The receiver operating characteristic curve area was 0.77 (95% confidence interval: 0.72-0.82); regarding the model calibration estimated between observed/predicted mortality, Hosmer-Lemeshow test χ2 = 3,70 (P=0.594) and Pearson's coefficient r = 0.98 (P<0.001). Conclusion: We propose the creation of a simple score, adapted to the Brazilian reality, with good performance and which can be validated in other institutions. [ABSTRACT FROM AUTHOR]

Simple Summary: Monitoring cetacean health is important considering the high strain from both natural and human-related threats. Most of these, such as Cetacean morbillivirus and man-made pollution in form of toxins and noise, affect nervous tissues and brain function. Neuropathological research in cetaceans has been qualitative or semiquantitative. Here, we use stereology to quantify protein expression in neurons, axons, and glial cells in the auditory nuclei of a bottlenose dolphin and correlate the values to their pre-processed volumes from MRI scans. This multimodal approach is aims to avoid artifacts that may arise using either methodology. Similarities in protein expression between a healthy dolphin and a human with brain trauma implies that dolphins might have a baseline neurochemical buffer against low oxygen (hypoxia). This study will help expand our quantitative understanding of health and disease in cetacean brains. The importance of assessing neurochemical processes in the cetacean brain as a tool for monitoring their cognitive health and to indirectly model human neurodegenerative conditions is increasingly evident, although available data are largely semiquantitative. High-resolution MRI for post-mortem brains and stereology allow for quantitative assessments of the cetacean brain. In this study, we scanned two brains of bottlenose dolphins in a 7-Tesla (7T) MR scanner and assessed the connectivity of the inferior colliculi and ventral cochlear nuclei using diffusion tensor imaging (DTI). Serial thick sections were investigated stereologically in one of the dolphins to generate rigorous quantitative estimates of identifiable cell types according to their morphology and expression of molecular markers, yielding reliable cell counts with most coefficients of error <10%. Fibronectin immunoreactivity in the dolphin resembled the pattern in a human chronic traumatic encephalopathy brain, suggesting that neurochemical compensation for insults such as hypoxia may constitute a noxious response in humans, while being physiological in dolphins. These data contribute to a growing body of knowledge on the morphological and neurochemical properties of the dolphin brain and highlight a stereological and neuroimaging workflow that may enable quantitative and translational assessment of pathological processes in the dolphin brain in the future. [ABSTRACT FROM AUTHOR]

The synthesis parameters, such as alkali activator type and content and water/binder (w/b) ratio, directly affect the dissolution and geopolymerization kinetics in geopolymers, playing a major role in its flow performance over time. However, the isolated effect of each parameter on the rheology of fresh metakaolin-based geopolymer is still not completely understood. This work assessed the effect of the alkali type (Na or K), concentration (15% or 20% by weight of the activating solution), and w/b ratio (from 0.70 to 0.80) on the fresh properties of metakaolin-based geopolymers. Minislump and Marsh cone tests with the use of image analysis and dynamic strain sweep rheometry were conducted at different testing times. The results showed that a high w/b ratio increased the initial flowability of paste (reduced the yield stress and Marsh cone time, and increased the minislump) as expected, whereas the flowability was reduced over time. Increasing the alkali concentration also increased the flowability of pastes regardless of the alkali type used. The most important finding is the corroboration that the type of alkali (Na+ or K+) was the parameter that had the greatest impact on the rheological behavior of pastes: mixes produced with potassium-based activator had higher flowability compared with those produced with sodium-based activator for the same concentration, w/b ratio, and testing time. The increased yield stress reduced workability, which might negatively affect its applicability and consequently the hardened performance of the material. Therefore, if high flowability is required, the use of potassium must be considered, either through its partial or complete presence in the alkali activator. [ABSTRACT FROM AUTHOR]

Copyright of Bio-grafía. Escritos Sobre la Biología y su Enseñanza is the property of Universidad Pedaggica Nacional and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome.Methods: Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress.Results: The multivariate Cox's proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000-1.034; P = 0.049). An angiopoietin-2 concentrations ≥ of 33,418 pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%.Conclusions: Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting. [ABSTRACT FROM AUTHOR]

Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury. [ABSTRACT FROM AUTHOR]

Military veterans who experience blast-related traumatic brain injuries often suffer from chronic cognitive and neurobehavioral syndromes. Reports of abnormal tau processing following blast injury have raised concerns that some cases may have a neurodegenerative basis. Rats exposed to repetitive low-level blast exhibit chronic neurobehavioral traits and accumulate tau phosphorylated at threonine 181 (Thr181). Using data previously reported in separate studies we tested the hypothesis that region-specific patterns of Thr181 phosphorylation correlate with behavioral measures also previously determined and reported in the same animals. Elevated p-tau Thr181 in anterior neocortical regions and right hippocampus correlated with anxiety as well as fear learning and novel object localization. There were no correlations with levels in amygdala or posterior neocortical regions. Particularly striking were asymmetrical effects on the right and left hippocampus. No systematic variation in head orientation toward the blast wave seems to explain the laterality. Levels did not correlate with behavioral measures of hyperarousal. Results were specific to Thr181 in that no correlations were observed for three other phospho-acceptor sites (threonine 231, serine 396, and serine 404). No consistent correlations were linked with total tau. These correlations are significant in suggesting that p-tau accumulation in anterior neocortical regions and the hippocampus may lead to disinhibited amygdala function without p-tau elevation in the amygdala itself. They also suggest an association linking blast injury with tauopathy, which has implications for understanding the relationship of chronic blast-related neurobehavioral syndromes in humans to neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Vascular structures in the developing brain are thought to form via angiogenesis from preformed blood vessels in the cephalic mesenchyme. Immunohistochemical studies of developing mouse brain from E10.5 to E13.5 revealed the presence of avascular blood islands of primitive erythroid cells expressing hemangioblast markers (Flk1, Tal1/Scl1, platelet endothelial cell adhesion molecule 1, vascular endothelial‐cadherin, and CD34) and an endothelial marker recognized by Griffonia simplicifolia isolectin B4 (IB4) in the cephalic mesenchyme. These cells formed a perineural vascular plexus from which angiogenic sprouts originated and penetrated the neuroepithelium. In addition, avascular isolated cells expressing primitive erythroid, hemangioblast and endothelial makers were visible in the neuroepithelium where they generated vasculogenic and hemogenic foci. From E10.5 to E13.5, these vasculogenic foci were a source of new blood vessel formation in the developing brain. In vitro, cultured E13.5 brain endothelial cells contained hemogenic endothelial cells capable of generating erythroid cells. Similar cells were present in primary cultures of dissociated cells from E10.5 embryonic head. Our results provide new evidence that the brain vasculature, like that of the yolk sac and the eye choriocapillaris and hyaloid vascular systems, develops at least in part via hemovasculogenesis, a process in which vasculogenesis and hematopoiesis occur simultaneously. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available β‐d‐Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut‐off values for IFI exclusion. Methods: BDG results by Wako β‐glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. Results: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1‐3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut‐offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). Conclusions: The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non‐ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population. [ABSTRACT FROM AUTHOR]

Copyright of Arte & Ensaio is the property of Arte & Ensaio and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Jehovah's Witnesses represent a tremendous clinical challenge when indicated to liver transplantation because they refuse blood transfusion on religious grounds and the procedure is historically associated with potential massive peri-operative blood loss. We herein describe a peri-operative management pathway with strategies toward a transfusion-free environment with the aim not only of offering liver transplant to selected Jehovah's Witnesses patients but also, ultimately, of translating this practice to all general surgical procedures. Methods: This is a retrospective review of prospective medical records of JW patients who underwent LT at our Institution. The peri-operative multimodal strategy to liver transplantation in Jehovah's Witnesses includes a pre-operative red cell mass optimization package and the intra-operative use of normovolemic haemodilution, veno-venous bypass and low central venous pressure. Results: In a 9-year period, 13 Jehovah's Witness patients received liver transplantation at our centre representing the largest liver transplant program from deceased donors in Jehovah's Witnesses patients reported so far. No patient received blood bank products but 3 had fibrinogen concentrate and one tranexamic acid to correct ongoing hyper-fibrinolysis. There were 4 cases of acute kidney injury (one required extracorporeal renal replacement treatment) and one patient needed vasoactive medications to support blood pressure for the first 2 postoperative days. Two patients underwent re-laparotomy. Finally, of the 13 recipients, 12 were alive at the 1 year follow-up interview and 1 died due to septic complications. Conclusions: Our experience confirms that liver transplantation in selected Jehovah's Witnesses patients can be feasible and safe provided that it is carried out at a very experienced centre and according to a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Background: Management of biliary adverse events (BAEs) after biliodigestive anastomosis is challenging. We propose a new endoscopic approach to improve BAEs in this clinical setting.Methods: Patients who had BAEs after a hepaticojejunostomy with Roux-en-Y loop or a Whipple procedure underwent creation of an entero-enteral endoscopic bypass (EEEB) between the duodenal/gastric wall and the biliary jejunal loop under endoscopic ultrasound (EUS) and fluoroscopic guidance using specifically designed fully covered self-expandable metal stents.Results: 32 consecutive patients underwent EEEB, which was successful in all but one patient. One procedural and five long-term mild adverse events occurred. Endoscopic retrograde cholangiography (ERC) through the EEEB successfully treated all types of BAEs in these patients. Disease recurred in two patients who were successfully re-treated through the EEEB.Conclusions: Our retrospective study showed that in patients with BAEs after biliodigestive anastomosis, EEEB is safe, feasible, and allows a successful long-term treatment of different BAEs in a tertiary referral center with high-level experience in both endoscopic retrograde cholangiopancreatography and EUS. [ABSTRACT FROM AUTHOR]

Abstract: Signaling via the androgen receptor (AR) stimulates myogenic progenitor differentiation. In addition, myogenic differentiation factor D (MyoD) and Numb, a Notch inhibitor, play key roles in regulating myogenic differentiation. Nandrolone, an anabolic steroid, upregulates both MyoD and Numb expression in myogenic cells. However, the molecular mechanisms by which MyoD is upregulated by nandrolone are unclear. Moreover, the potential crosstalk between nandrolone, MyoD, and Numb is not well understood. With these considerations in mind, we examined the effects of nandrolone on the expression of MyoD mRNA and protein, and determined the interactions of MyoD and Numb in the presence or absence of nandrolone in differentiating C2C12 myoblasts. Nandrolone increased MyoD mRNA and protein expression and significantly enhanced nuclear translocation of MyoD protein. The later effect of nandrolone was blunted by siRNA against Numb. Immunoprecipitation (IP) studies confirmed that Numb forms complexes with MyoD. Chromatin IP revealed that in the presence of nandrolone, Numb is recruited to a region of the MyH7 promotor containing the E‐box to which MyoD binds. These data indicate that nandrolone‐regulated MyoD activation occurs mainly through a posttranslational mechanism which promotes MyoD nuclear accumulation, and suggest that this effect of nandrolone is, at least in part, mediated by Numb. [ABSTRACT FROM AUTHOR]

Blast-related traumatic brain injury (TBI) has been a common cause of injury in the recent conflicts in Iraq and Afghanistan. Blast waves can damage blood vessels, neurons, and glial cells within the brain. Acutely, depending on the blast energy, blast wave duration, and number of exposures, blast waves disrupt the blood-brain barrier, triggering microglial activation and neuroinflammation. Recently, there has been much interest in the role that ongoing neuroinflammation may play in the chronic effects of TBI. Here, we investigated whether chronic neuroinflammation is present in a rat model of repetitive low-energy blast exposure. Six weeks after three 74.5-kPa blast exposures, and in the absence of hemorrhage, no significant alteration in the level of microglia activation was found. At 6 weeks after blast exposure, plasma levels of fractalkine, interleukin-1β, lipopolysaccharide-inducible CXC chemokine, macrophage inflammatory protein 1α, and vascular endothelial growth factor were decreased. However, no differences in cytokine levels were detected between blast-exposed and control rats at 40 weeks. In brain, isolated changes were seen in levels of selected cytokines at 6 weeks following blast exposure, but none of these changes was found in both hemispheres or at 40 weeks after blast exposure. Notably, one animal with a focal hemorrhagic tear showed chronic microglial activation around the lesion 16 weeks post-blast exposure. These findings suggest that focal hemorrhage can trigger chronic focal neuroinflammation following blast-induced TBI, but that in the absence of hemorrhage, chronic neuroinflammation is not a general feature of low-level blast injury. [ABSTRACT FROM AUTHOR]

Exosomes are vesicles released by many eukaryotic cells; their cargo includes proteins, mRNA and microRNA (miR) that can be transferred to recipient cells and regulate cellular processes in an autocrine or paracrine manner. While cells of the myoblast lineage secrete exosomes, it is not known whether skeletal muscle fibers (myofibers) release exosomes. In this study, we found that cultured myofibers release nanovesicles that have bilamellar membranes and an average size of 60–130 nm, contain typical exosomal proteins and miRNAs and are taken up by C2C12 cells. miR-133a was found to be the most abundant myomiR in these vesicles while miR-720 was most enriched in exosomes compared to parent myofibers. Treatment of NIH 3T3 cells with myofiber-derived exosomes downregulated the miR-133a targets proteins Smarcd1 and Runx2, confirming that these exosomes have biologically relevant effects on recipient cells. Denervation resulted in a marked increase in miR-206 and reduced expression of miRs 1, 133a, and 133b in myofiber-derived exosomes. These findings demonstrate that skeletal muscle fibers release exosomes which can exert biologically significant effects on recipient cells, and that pathological muscle conditions such as denervation induce alterations in exosomal miR profile which could influence responses to disease states through autocrine or paracrine mechanisms. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) results in muscle atrophy, reduced force generation and an oxidative-to-glycolytic fiber type shift. The mechanisms responsible for these alterations remain incompletely understood. To gain new insights regarding mechanisms involved in deterioration of muscle after SCI, global expression profiles of miRs in paralyzed gastrocnemius muscle were compared between sham-operated (Sham) and spinal cord-transected (SCI) rats. Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes. By qPCR, miRs 23a, 23b, 27b, 145, and 206, were downregulated in skeletal muscle 56 days after SCI. Using FISH, miR-145, a miR not previously implicated in the function of skeletal muscle, was found to be localized to skeletal muscle fibers. One predicted target of miR-145 was Cited2, a transcriptional regulator that modulates signaling through NF-κB, Smad3 and other transcription factors. The 3’ UTR of Cited2 mRNA contained a highly conserved miR-145 seed sequence. Luciferase reporter assays confirmed that miR-145 interacts with this seed sequence. However, Cited2 protein levels were similar between Sham and SCI groups, indicating a biochemical interaction that was not involved in the context of adaptations after SCI. Taken together, the findings indicate dysregulation of several highly expressed miRs in skeletal muscle after SCI and suggest that reduced expression of miR-23a, 145 and 206 may have roles in alteration in skeletal muscle mass and insulin responsiveness in muscle paralyzed by upper motor neuron injuries. [ABSTRACT FROM AUTHOR]

Blast-related mild traumatic brain injury (mTBI) has been unfortunately common in veterans who served in the recent conflicts in Iraq and Afghanistan. The postconcussion syndrome associated with these mTBIs has frequently appeared in combination with post-traumatic stress disorder (PTSD). The presence of PTSD has complicated diagnosis, since clinically, PTSD and the postconcussion syndrome of mTBI have many overlapping symptoms. In particular, establishing how much of the symptom complex can be attributed to the psychological trauma associated with PTSD in contrast to the physical injury of traumatic brain injury has proven difficult. Indeed, some have suggested that much of what is now being called blast-related postconcussion syndrome is better explained by PTSD. The relationship between the postconcussion syndrome of mTBI and PTSD is complex. Association of the two disorders might be viewed as additive effects of independent psychological and physical traumas suffered in a war zone. However, we previously found that rats exposed to repetitive low-level blast exposure in the absence of a psychological stressor developed a variety of anxiety and PTSD-related behavioral traits that were present months following the last blast exposure. Here, we show that a single predator scent challenge delivered 8 months after the last blast exposure induces chronic anxiety related changes in blast-exposed rats that are still present 45 days later. These observations suggest that in addition to independently inducing PTSD-related traits, blast exposure sensitizes the brain to react abnormally to a subsequent psychological stressor. These studies have implications for conceptualizing the relationship between blast-related mTBI and PTSD and suggest that blast-related mTBI in humans may predispose to the later development of PTSD in reaction to subsequent psychological stressors. [ABSTRACT FROM AUTHOR]

Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressurewaves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. [ABSTRACT FROM AUTHOR]

The article inform the EC – Seal Products dispute arose out of complaints lodged by Canada and Norway against the legal regime for seal products established by the EU under Regulation (EC) No. 1007/2009 and Commission Regulation No. 737/2010 (collectively, "EU Seal Regime" or "measure")67. In order to address the EU consumers' public moral concerns regarding seal welfare.

Background: Presenilin-1 (PS1) is a transmembrane protein first discovered because of its association with familial Alzheimer’s disease. Mice with null mutations in PS1 die shortly after birth exhibiting multiple CNS and non-CNS abnormalities. One of the most prominent features in the brains of PS1−/− embryos is a vascular dysgenesis that leads to multiple intracerebral hemorrhages. The molecular and cellular basis for the vascular dysgenesis in PS1−/− mice remains incompletely understood. Because the extracellular matrix plays key roles in vascular development we hypothesized that an abnormal extracellular matrix might be present in endothelial cells lacking PS1 and examined whether the lack of PS1 affects expression of fibronectin a component of the extracellular matrix known to be essential for vascular development. Results: We report that primary as well as continuously passaged PS1−/− endothelial cells contain more fibronectin than wild type cells and that the excess fibronectin in PS1−/− endothelial cells is incorporated into a fibrillar network. Supporting the in vivo relevance of this observation fibronectin expression was increased in microvascular preparations isolated from E14.5 to E18.5 PS1−/− embryonic brain. Reintroduction of PS1 into PS1−/− endothelial cells led to a progressive decrease in fibronectin levels showing that the increased fibronectin in PS1−/− endothelial cells was due to loss of PS1. Increases in fibronectin protein in PS1−/− endothelial cells could not be explained by increased levels of fibronectin RNA nor based on metabolic labeling studies by increased protein synthesis. Rather we show based on the rate of turnover of exogenously added biotinylated fibronectin that increased fibronectin in PS1−/− endothelial cells results from a slower degradation of the fibronectin fibrillar matrix on the cell surface. Conclusions: These studies show that PS1 regulates the constitutive turnover of the fibronectin matrix in endothelial cells. These studies provide molecular clues that may help to explain the origin of the vascular dysgenesis that develops in PS1−/− embryonic mice. [ABSTRACT FROM AUTHOR]