Adipose-derived mesenchymal stem cells from patients with atherosclerotic renovascular disease have increased DNA damage and reduced angiogenesis that can be modified by hypoxia

Representative flow cytometric plots (FACS) showing that AMSCs expressed HLA-ABC, CD44, CD90, CD29, CD73, and CD105 markers, and did not express HLA-DR, CD45, CD14 or CD34 markers. (JPG 233 kb

Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension

BACKGROUND: Renovascular hypertension (RVH) impairs cardiac structure and left ventricular (LV) function, but whether mitochondrial injury is implicated in RVH-induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swine RVH is partly attributable to cardiac mitochondrial injury. METHODS AND RESULTS: After 12 weeks of hypercholesterolemic (HC)-RVH or control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial-targeted peptide (MTP), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner-membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector-computed tomography and oxygenation by blood-oxygen-level-dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic-reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert-butyl hydroperoxide (tBHP) untreated or treated with MTP. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin-sensitive sarcoplasmic reticulum Ca(2+)-ATPase activity that declined in HC-RVH normalized in MTP-treated pigs. Mitoprotection also improved LV relaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in MTP-treated pigs. In tBHP-treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics. CONCLUSIONS: Chronic mitoprotection blunted myocardial hypertrophy, improved LV relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained HC-RVH, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy

Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64330/1/21877_ftp.pd

NIH Workshop 2018: Towards Minimally-invasive or Non-invasive Approaches to Assess Tissue Oxygenation Pre- and Post-Transfusion

Because blood transfusion is one of the most common therapeutic interventions in hospitalized patients, much recent research has focused on improving the storage quality in vitro of donor red blood cells (RBCs) that are then used for transfusion. However, there is a significant need for enhancing our understanding of the efficacy of the transfused RBCs in vivo. To this end, the NIH sponsored a one-and-a-half-day workshop that brought together experts in multiple disciplines relevant to tissue oxygenation (e.g., transfusion medicine, critical care medicine, cardiology, neurology, neonatology and pediatrics, bioengineering, biochemistry, and imaging). These individuals presented their latest findings, discussed key challenges, and aimed to construct recommendations for facilitating development of new technologies and/or biomarker panels to assess tissue oxygenation in a minimally-invasive to non-invasive fashion, before and after RBC transfusion. The workshop was structured into four sessions: (1) Global Perspective; (2) Organ Systems; (3) Neonatology; and (4) Emerging Technologies. The first day provided an overview of current approaches in the clinical setting, both from a global perspective, including the use of metabolomics for studying RBCs and tissue perfusion, and from a more focused perspective, including tissue oxygenation assessments in neonates and in specific adult organ systems. The second day focused on emerging technologies, which could be applied pre- and post-RBC transfusion, to assess tissue oxygenation in minimally-invasive or non-invasive ways. Each day concluded with an open-microphone discussion among the speakers and workshop participants. The workshop presentations and ensuing interdisciplinary discussions highlighted the potential of technologies to combine global “omics” signatures with additional measures (e.g., thenar eminence measurements or various imaging methods) to predict which patients could potentially benefit from a RBC transfusion and whether the ensuing RBC transfusion was effective. The discussions highlighted the need for collaborations across the various disciplines represented at the meeting to leverage existing technologies and to develop novel approaches for assessing RBC transfusion efficacy in various clinical settings. Although the Workshop took place in April, 2018, the concepts described and the ensuing discussions were, perhaps, even more relevant in April, 2020, at the time of writing this manuscript, during the explosive growth of the COVID-19 pandemic in the United States. Thus, issues relating to maintaining and improving tissue oxygenation and perfusion are especially pertinent because of the extensive pulmonary damage resulting from SARS-CoV-2 infection [1], compromises in perfusion caused by thrombotic-embolic phenomena [2], and damage to circulating RBCs, potentially compromising their oxygen-carrying capacity [3]. The severe end organ effects of SARS-CoV-2 infection mandate even more urgency for improving our understanding of tissue perfusion and oxygenation, improve methods for measuring and monitoring them, and develop novel ways of enhancing them

NIH Workshop 2018: Towards Minimally Invasive or Noninvasive Approaches to Assess Tissue Oxygenation Pre- and Post-transfusion

Because blood transfusion is one of the most common therapeutic interventions in hospitalized patients, much recent research has focused on improving the storage quality in vitro of donor red blood cells (RBCs) that are then used for transfusion. However, there is a significant need for enhancing our understanding of the efficacy of the transfused RBCs in vivo. To this end, the NIH sponsored a one-and-a-half-day workshop that brought together experts in multiple disciplines relevant to tissue oxygenation (eg, transfusion medicine, critical care medicine, cardiology, neurology, neonatology and pediatrics, bioengineering, biochemistry, and imaging). These individuals presented their latest findings, discussed key challenges, and aimed to identify opportunities for facilitating development of new technologies and/or biomarker panels to assess tissue oxygenation in a minimally-invasive to non-invasive fashion, before and after RBC transfusion

MRCP compared to diagnostic ERCP for diagnosis when biliary obstruction is suspected: a systematic review

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an alternative to diagnostic endoscopic retrograde cholangiopancreatography (ERCP) for investigating biliary obstruction. The use of MRCP, a non-invasive procedure, may prevent the use of unnecessary invasive procedures. The aim of the study was to compare the findings of MRCP with those of ERCP by the computation of accuracy statistics. METHODS: Thirteen electronic bibliographic databases, covering biomedical, science, health economics and grey literature were searched. A systematic review of studies comparing MRCP to diagnostic ERCP in patients with suspected biliary obstruction was conducted. Sensitivity, specificity, likelihood ratios, acceptability and adverse events were reported. RESULTS: 25 studies were identified reporting several conditions including choledocholithiasis (18 studies), malignancy (four studies), obstruction (three studies), stricture (two studies) and dilatation (five studies). Three of the 18 studies reporting choledocholithiasis were excluded from the analysis due to lack of data, or differences in study design. The sensitivity for the 15 studies of choledocholithiasis ranged from 0.50 to 1.00 while specificity ranged from 0.83 to 1.00. The positive likelihood ratio ranged: from 5.44–47.72 and the negative likelihood ratio for the 15 studies ranged from 0.00–0.51. Significant heterogeneity was found across the 15 studies so the sensitivities and specificities were summarised by a Receiver Operating Characteristic (ROC) curve. For malignancy, sensitivity ranged from 0.81 to 0.94 and specificity from 0.92 to 1.00. Positive likelihood ratios ranged from 10.12 to 43 and negative likelihood ratios ranged from 0.15 to 0.21, although these estimates were less reliable. CONCLUSION: MRCP is a comparable diagnostic investigation in comparison to ERCP for diagnosing biliary obstruction

PhagoSight: an open-source MATLAB® package for the analysis of fluorescent neutrophil and macrophage migration in a zebrafish model

Neutrophil migration in zebrafish larvae is increasingly used as a model to study the response of these leukocytes to different determinants of the cellular inflammatory response. However, it remains challenging to extract comprehensive information describing the behaviour of neutrophils from the multi-dimensional data sets acquired with widefield or confocal microscopes. Here, we describe PhagoSight, an open-source software package for the segmentation, tracking and visualisation of migrating phagocytes in three dimensions. The algorithms in PhagoSight extract a large number of measurements that summarise the behaviour of neutrophils, but that could potentially be applied to any moving fluorescent cells. To derive a useful panel of variables quantifying aspects of neutrophil migratory behaviour, and to demonstrate the utility of PhagoSight, we evaluated changes in the volume of migrating neutrophils. Cell volume increased as neutrophils migrated towards the wound region of injured zebrafish. PhagoSight is openly available as MATLAB® m-files under the GNU General Public License. Synthetic data sets and a comprehensive user manual are available from http://www.phagosight.org

Road traffic noise and children's inattention

BACKGROUND: An increasing number of children are exposed to road traffic noise levels that may lead to adverse effects on health and daily functioning. Childhood is a period of intense growth and brain maturation, and children may therefore be especially vulnerable to road traffic noise. The objective of the present study was to examine whether road traffic noise was associated with reported inattention symptoms in children, and whether this association was mediated by sleep duration. METHODS: This study was based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Parental reports of children's inattention at age 8 were linked to modelled levels of residential road traffic noise. We investigated the association between inattention and noise exposure during pregnancy (n = 1934), noise exposure averaged over 5 years (age 3 to 8 years; n = 1384) and noise exposure at age 8 years (n = 1384), using fractional logit response models. The participants were children from Oslo, Norway. RESULTS: An association with inattention at age 8 years was found for road traffic noise exposure at age 8 years (coef = .0083, CI = [.0012, .0154]; 1.2% point increase in inattention score per 10 dB increase in noise level), road traffic noise exposure average for the last 5 years (coef = .0090, CI = [.0016, .0164]; 1.3% point increase/10 dB), and for pregnancy road traffic noise exposure for boys (coef = .0091, CI = [.0010, .0171]), but not girls (coef = -.0021, CI = [-.0094, .0053]). Criteria for doing mediation analyses were not fulfilled. CONCLUSION: Results indicate that road traffic noise has a negative impact on children's inattention. We found no mediation by sleep duration