miR-200b-3p accelerates diabetic wound healing through anti-inflammatory and pro-angiogenic effects.

The poor healing characteristics of diabetic foot ulcers are partially attributed to diabetes-induced pro-inflammatory wounds. Our previous study reported that both miR-146a-5p and miR-200b-3p decrease endothelial inflammation in human aortic endothelial cells and db/db diabetic mice. Although miR-146a-5p has been reported to improve diabetic wound healing, the role of miR-200b-3p is not clear. This study compared the roles of these miRNAs in diabetic wound healing. Two 8-mm full-thickness wounds were created in 12-week-old male db/db mice on the left and right back. After surgery, 100 ng miR-146a-5p, miR-200b-3p, or miR-negative control (NC) was injected in each wound. Full-thickness skin samples were harvested from mice at the 14th day for real-time polymerase chain reaction and immunohistochemistry analyses. At the 14th day, the miR-200b-3p group showed better wound healing and greater granulation tissue thickness than the miR-146a-5p group. The miR-200b-3p group showed a significant decrease of IL-6 and IL-1ß gene expression and a significant increase of Col3α1 gene expression compared to those in the miR-NC group. The miR-200b-3p group had the lowest gene expression of TGF-ß1, followed by the miR-146a-5p and miR-NC groups. Our findings suggest that the miR-200b-3p group had better healing characteristics than the other two groups. Immunohistochemical staining revealed that CD68 immunoreactivity was significantly decreased in both the miR-146a-5p and miR-200b-3p groups compared with that in the miR-NC group. In addition, CD31 immunoreactivity was significantly higher in the miR-200b-3p group than in the miR-146a-5p group. In conclusion, these results suggest that miR-200b-3p is more effective than miR-146a-5p in promoting diabetic wound healing through its anti-inflammatory and pro-angiogenic effects.

Toward solving the global green-green dilemma between wind energy production and bat conservation.

Wind energy production is growing rapidly worldwide in an effort to reduce greenhouse gas emissions. However, wind energy production is not environmentally neutral. Negative impacts on volant animals, such as bats, include fatalities at turbines and habitat loss due to land-use change and displacement. Siting turbines away from ecologically sensitive areas and implementing measures to reduce fatalities are critical to protecting bat populations. Restricting turbine operations during periods of high bat activity is the most effective form of mitigation currently available to reduce fatalities. Compensating for habitat loss and offsetting mortality are not often practiced, because meaningful offsets are lacking. Legal frameworks to prevent or mitigate the negative impacts of wind energy on bats are absent in most countries, especially in emerging markets. Therefore, governments and lending institutions are key in reconciling wind energy production with biodiversity goals by requiring sufficient environmental standards for wind energy projects.

Systemic Thrombolysis as Initial Treatment of COVID-19 Associated Acute Aortoiliac and Lower Extremity Arterial Thrombosis.

SARS-CoV-2 (COVID-19) patients with associated thromboembolic events have demonstrated poor outcomes despite the use of anticoagulation therapy and surgical intervention. We present a COVID-19 patient with acute limb ischemia, secondary to extensive thrombosis of an aortic aneurysm, iliac arteries, and infrainguinal arteries. Initial treatment with systemic thrombolysis, which restored patency of the aortoiliac occlusion, was followed by open thrombectomies of the infrainguinal occlusions.

Atrial Septostomy for Left Atrial Decompression During Extracorporeal Membrane Oxygenation by Inoue Balloon Catheter.

BACKGROUND: Refractory pulmonary edema is an infrequent but serious complication in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) for myocardial failure. Left atrial (LA) decompression in this setting is important. Although a few methods have been reported, the experience is mostly limited to children. We aimed to evaluate the feasibility of Inoue balloon catheter in percutaneous trans-septal LA decompression in adult cardiogenic patients.Methods and Results:We retrospectively analyzed 16 procedures of trans-septal LA decompression by Inoue balloon catheter in 15 VA-ECMO patients (aged 22-65 years, 6 men) with refractory pulmonary edema from May 2012 to December 2014. Mean left ventricular ejection fraction was 15%. The cause of cardiogenic shock included 7 cases of ischemic heart disease, 1 of dilated cardiomyopathy, 5 of myocarditis, and 2 of fatal ventricular arrhythmia.The procedures were performed 4.3 days after ECMO. Inoue balloon size was 24-27 mm. LA septostomy were successfully created in 14 patients. Procedure time on average was 36.8 min (range, 15-85 min). There were no procedure-related complications.Radiography on the next day showed rapid resolution of pulmonary edema. CONCLUSIONS: Trans-septal LA decompression by Inoue balloon catheter is a feasible alternative method for adult patients with refractory pulmonary edema under ECMO.

Clinical Outcomes of Polytetrafluoroethylene-Covered Stents for Coronary Artery Perforation in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) is associated with increased mortality. Polytetrafluoroethylene covered stents (CS) are an effective approach to treat CAP, but data regarding elderly patients requiring CS implantation for CAP are limited. The aim of this study is to report clinical data for elderly CAP patients undergoing CS implantation during PCI. METHODS: Nineteen consecutive elderly patients (≥ 65 years) undergoing CS implantation due to PCI-induced CAP in a tertiary referral center from July 2003 to April 2016 were retrospectively examined. RESULTS: There were 13 men and six women, with a mean age of 75.3 ± 5.6 years (range: 65-86 years). Perforation grade was Ellis type II in five patients (26.3%), and Ellis type III in 14 patients (73.7%). Cardiac tamponade developed in six patients (31.6%), and intra-aortic balloon pumping was needed in four patients (21.1%). The overall success rate for CS implantation rate was 94.7%. The overall in-hospital mortality rate was 15.8%; the in-hospital myocardial infarction rate was 63.2%. Among 16 survival-to-discharge cases, dual antiplatelet therapy (DAPT) was prescribed in 14 cases (87.5%) for a mean duration of 14 months. Overall, there were five angiogram- proven CS failures among 18 patients receiving successful CS implantation. The 1, 2 and 4 years of actuarial freedom from the CS failure were 78%, 65%, and 43% in the angiogram follow-up patients. CONCLUSIONS: CS implantation for CAP is feasible and effective in elderly patients, while CS failure remains a major concern that encourages regular angiographic follow-up in these case.

Thumb-pads up-a new species of thick-thumbed bat from Sumatra (Chiroptera: Vespertilionidae: Glischropus).

To date, three species of the genus Glischropus are recognized from the Indomalayan zoogeographic region-G. bucephalus from the Indochinese subregion, G. tylopus from the Sundaic subregion (Peninsular Thailand and Malaysia, Borneo, Sumatra, Moluccas) and G. javanus, restricted to Java. The investigation of the holotype and three topotype specimens of G. batjanus supported the view that the name was previously correctly regarded as the junior subjective synonym of G. tylopus. During review of material recently collected in southwestern Sumatra, Indonesia, one specimen of a yet undescribed species of Thick-thumbed bat was identified. G. aquilus n. sp. markedly differs from its congeners by its dark brown pelage, nearly black ear and tragus, and in skull proportions. The phylogenetic analysis based on cytb sequences also supports the specific distinctness of G. aquilus n. sp. Its discovery brings the count to 88 species of bats known from Sumatra.

MicroRNA-146a decreases high glucose/thrombin-induced endothelial inflammation by inhibiting NAPDH oxidase 4 expression.

Diabetes is associated with hyperglycemia and increased thrombin production. However, it is unknown whether a combination of high glucose and thrombin can modulate the expression of NAPDH oxidase (Nox) subtypes in human aortic endothelial cells (HAECs). Moreover, we investigated the role of a diabetes-associated microRNA (miR-146a) in a diabetic atherothrombosis model. We showed that high glucose (HG) exerted a synergistic effect with thrombin to induce a 10.69-fold increase in Nox4 mRNA level in HAECs. Increased Nox4 mRNA expression was associated with increased Nox4 protein expression and ROS production. Inflammatory cytokine kit identified that the treatment increased IL-8 and IL-6 levels. Moreover, HG/thrombin treatment caused an 11.43-fold increase of THP-1 adhesion to HAECs. In silico analysis identified the homology between miR-146a and the 3'-untranslated region of the Nox4 mRNA, and a luciferase reporter assay confirmed that the miR-146a mimic bound to this Nox4 regulatory region. Additionally, miR-146a expression was decreased to 58% of that in the control, indicating impaired feedback restraint of HG/thrombin-induced endothelial inflammation. In contrast, miR-146a mimic transfection attenuated HG/thrombin-induced upregulation of Nox4 expression, ROS generation, and inflammatory phenotypes. In conclusion, miR-146a is involved in the regulation of endothelial inflammation via modulation of Nox4 expression in a diabetic atherothrombosis model.

Angiotensin-(1-7) decreases glycated albumin-induced endothelial interleukin-6 expression via modulation of miR-146a.

The presence of glycated albumin (GA) is associated with increased diabetic complications. This study investigated the effect of angiotensin-(1-7) on the expression of GA-induced endothelial interleukin-6 (IL-6) in human aortic endothelial cells (HAECs). We also evaluated whether miR-146a is involved in the post-transcriptional regulation of angiotensin-(1-7). HAECs were stimulated with GA with or without angiotensin-(1-7) pretreatment. Inflammatory cytokine screening approach identified that angiotensin-(1-7) (10(-7) M) potently inhibited GA (200 µg/mL)-stimulated endothelial IL-6 expression in conditioned medium. ELISA confirmed this finding. Real-time PCR showed that angiotensin-(1-7) decreased GA-induced intracellular IL-6 mRNA expression and western blotting showed that angiotensin-(1-7) decreased GA-induced intracellular IL-6 protein expression. Bioinformatics' miR target analysis identified homology between miR-146a and the 3'-UTR of the human IL-6 mRNA, suggesting a potential regulation of IL-6 by miR-146a. Treatment with GA decreased endothelial miR-146a expression to 37.2% of the albumin control, while angiotensin-(1-7) increased endothelial miR-146a expression to 1.9-times that of the medium control. Pretreatment with angiotensin-(1-7) inhibited the GA-mediated downregulation of miR-146a to 78.9% of the albumin control levels. Furthermore, the inhibitory effect of angiotensin-(1-7) on IL-6 expression was abolished in GA-treated, miR-146a inhibitor-transfected HAECs. In conclusion, these results suggest that angiotensin-(1-7) exerted an endothelial protective effect through IL-6 downregulation, and miR-146a modulation is involved in this protective effect.

Prognostic significance of reciprocal ST-segment depression in patients with acute STEMI undergoing immediate invasive intervention.

PURPOSES: Reciprocal changes are frequent in patients with acute ST-segment elevation myocardial infarction (STEMI). However, their prognostic significance is not clear in patients undergoing immediate invasive intervention. BASIC PROCEDURE: We retrospectively examined 165 consecutive patients with STEMI receiving immediate invasive intervention. The first electrocardiography taken in the emergency department was analyzed. Patients were assigned to 2 groups: with a reciprocal change (group I, n = 100) and without a reciprocal change (group II, n = 65). MAIN FINDINGS: Electrocardiographs revealed that more anterolateral and inferior STEMI occurred in group I and more anterior STEMI occurred in group II. In the emergency department, group I had lower systolic and diastolic blood pressures, higher ventricular tachycardia and fibrillation rates, and higher cardiopulmonary resuscitation rates than did group II. Upon admission, peak troponin I levels were significantly higher in group I, and more group I patients required intra-aortic balloon pumping support. This unstable hemodynamic condition in group I patients was reflected by their higher in-hospital mortality rate. Multivariate analysis showed that age (odds ratio [OR], 1.103; 95% confidence interval [CI], 1.022-1.190; P = .012), Killip class (OR, 2.785; 95% CI, 1.049-7.400; P = .040), and reciprocal change (OR, 9.553; 95% CI, 1.146-79.608; P = .037) remained as independent predictors of in-hospital mortality. Actuarial freedom from all-cause mortality was worse in group I (P = .046). PRINCIPAL CONCLUSIONS: The data suggest that patients with STEMI with reciprocal electrocardiographic changes have unstable hemodynamic status and poorer outcomes. Further prospective studies using a larger patient population are needed.

ChiroVox: a public library of bat calls.

Recordings of bat echolocation and social calls are used for many research purposes from ecological studies to taxonomy. Effective use of these relies on identification of species from the recordings, but comparative recordings or detailed call descriptions to support identification are often lacking for areas with high biodiversity. The ChiroVox website (https://www.chirovox.org) was created to facilitate the sharing of bat sound recordings together with their metadata, including biodiversity data and recording circumstances. To date, more than 30 researchers have contributed over 3,900 recordings of nearly 200 species, making ChiroVox the largest open-access bat call library currently available. Each recording has a unique identifier that can be cited in publications; hence the acoustic analyses are repeatable. Most of the recordings available through the website are from bats whose species identities are confirmed, so they can be used to determine species in recordings where the bats were not captured or could not be identified. We hope that with the help of the bat researcher community, the website will grow rapidly and will serve as a solid source for bat acoustic research and monitoring.

Sampling flying bats with thermal and near-infrared imaging and ultrasound recording: hardware and workflow for bat point counts.

Bat communities can usually only be comprehensively monitored by combining ultrasound recording and trapping techniques. Here, we propose bat point counts, a novel, single method to sample all flying bats. We designed a sampling rig that combines a thermal scope to detect flying bats and their flight patterns, an ultrasound recorder to identify echolocating bat calls, and a near-infrared camera and LED illuminator to photograph bat morphology. We evaluated the usefulness of the flight pattern information, echolocation call recordings, and near-infrared photographs produced by our sampling rig to determine a workflow to process these heterogenous data types. We present a conservative workflow to enable taxonomic discrimination and identification of bat detections. Our sampling rig and workflow allowed us to detect both echolocating and non-echolocating bats and we could assign 84% of the detections to a guild. Subsequent identification can be carried out with established methods such as identification keys and call libraries, based on the visible morphological features and echolocation calls. Currently, a higher near-infrared picture quality is required to resolve more detailed diagnostic morphology, but there is considerable potential to extract more information with higher-intensity illumination. This is the first proof-of-concept for bat point counts, a method that can passively sample all flying bats in their natural environment.

Bat point counts: A novel sampling method shines light on flying bat communities.

Emerging technologies based on the detection of electro-magnetic energy offer promising opportunities for sampling biodiversity. We exploit their potential by showing here how they can be used in bat point counts-a novel method to sample flying bats-to overcome shortcomings of traditional sampling methods, and to maximize sampling coverage and taxonomic resolution of this elusive taxon with minimal sampling bias. We conducted bat point counts with a sampling rig combining a thermal scope to detect bats, an ultrasound recorder to obtain echolocation calls, and a near-infrared camera to capture bat morphology. We identified bats with a dedicated identification key combining acoustic and morphological features, and compared bat point counts with the standard bat sampling methods of mist-netting and automated ultrasound recording in three oil palm plantation sites in Indonesia, over nine survey nights. Based on rarefaction and extrapolation sampling curves, bat point counts were similarly effective but more time-efficient than the established methods for sampling the oil palm species pool in our study. Point counts sampled species that tend to avoid nets and those that are not echolocating, and thus cannot be detected acoustically. We identified some bat sonotypes with near-infrared imagery, and bat point counts revealed strong sampling biases in previous studies using capture-based methods, suggesting similar biases in other regions might exist. Our method should be tested in a wider range of habitats and regions to assess its performance. However, while capture-based methods allow to identify bats with absolute and internal morphometry, and unattended ultrasound recorders can effectively sample echolocating bats, bat point counts are a promising, non-invasive, and potentially competitive new tool for sampling all flying bats without bias and observing their behavior in the wild.

Flower-visiting insects of genus Melastoma (Myrtales: Melastomataceae) at the Fushan Botanical Garden, Taiwan.

BACKGROUND: We investigated the diversity and behaviour of insects that visit flowers of four native Melastoma (Family Melastomataceae) species of Taiwan and a horticultural hybrid Melastoma species at the Fushan Botanical Garden, Taiwan biweekly from May to August 2020. Visits of flower-visiting insects were classified into seven behavioural categories, based on the insects' behaviour and positions on the flower. The data are further assigned into four insect-flower interactions, namely pollination, herbivory, commensalism and neutralism. Our goal is to provide baseline data of insect-plant interactions of Melastoma, which is a common, but understudied plant genus in the country. NEW INFORMATION: A total of 1,289 visits to flowers were recorded by at least 63 insect morphospecies belonging to seven orders. The number of insect species recorded per Melastoma species ranged from 9 to 39. Visiting, sonication and passing were the three most frequently recorded types of behaviour, collectively accounting for 90.2% (n = 1,240) of the total observations. Pollination was the most dominant insect-flower interaction, accounting for 70.2% of the total observations, followed by neutralism (20.0%), herbivory (6.3%) and commensalism (3.5%). Sweat bees of the genera Lasioglossum and Maculonomia (Hymenoptera: Halictidae) are considered key pollinators to Melastoma species in Fushan Botanical Garden, based on their high number of visits and sonication behaviour. Our study provides the first list of insects that visit the flowers of all Taiwan's known Melastoma species and description of their interactions with the plants.

(-)-Epigallocatechin-3-gallate decreases thrombin/paclitaxel-induced endothelial tissue factor expression via the inhibition of c-Jun terminal NH2 kinase phosphorylation.

Patients with paclitaxel-eluting stents are concerned with stent thrombosis caused by premature discontinuation of dual antiplatelet therapy or clopidogrel resistance. This study investigates the effect of (-)-epigallocatechin-3-gallate (EGCG) on the expression of thrombin/paclitaxel-induced endothelial tissue factor (TF) expressions in human aortic endothelial cells (HAECs). EGCG was nontoxic to HAECs at 6h up to a concentration of 25 micromol/L. At a concentration of 25 micromol/L, EGCG pretreatment potently inhibited both thrombin-stimulated and thrombin/paclitaxel-stimulated endothelial TF protein expression. Thrombin and thrombin/paclitaxel-induced 2.6-fold and 2.9-fold increases in TF activity compared with the control. EGCG pretreatment caused a 29% and 38% decrease in TF activity on thrombin and thrombin/paclitaxel treatment, respectively. Real-time polymerase chain reaction (PCR) showed that thrombin and thrombin/paclitaxel-induced 3.0-fold and 4.6-fold TF mRNA expressions compared with the control. EGCG pretreatment caused an 82% and 72% decrease in TF mRNA expression on thrombin and thrombin/paclitaxel treatment, respectively. The c-Jun terminal NH2 kinase (JNK) inhibitor SP600125 reduced thrombin/paclitaxel-induced TF expression. Furthermore, EGCG significantly inhibited the phosphorylation of JNK to 49% of thrombin/paclitaxel-stimulated HAECs at 60min. Immunofluorescence assay did not show an inhibitory effect of EGCG on P65 NF-kappaB nuclear translocation in the thrombin/paclitaxel-stimulated endothelial cells. In conclusion, EGCG can inhibit TF expression in thrombin/paclitaxel-stimulated endothelial cells via the inhibition of JNK phosphorylation. The unique property of EGCG may be used to develop a new drug-eluting stent by co-coating EGCG and paclitaxel.

Hispolon promotes MDM2 downregulation through chaperone-mediated autophagy.

Amplification and overexpression of murine double minute (MDM2) has been observed in several human cancers. Some chemotherapeutic agents cause MDM2 ubiquitination and degradation in a proteasome-dependent system. In addition to the proteasome system, chaperone-mediated autophagy (CMA) is a lysosomal pathway for selective misfolded protein degradation. Molecular chaperone heat shock cognate 70 protein (Hsc70) recognizes the misfolded proteins, which are then delivered to lysosome-associated membrane protein type 2A (LAMP2A) for lysosomal degradation. Our previous study reported that hispolon was able to induce cell apoptosis and downregulate MDM2 expression. In this study, our results showed that the proteasome inhibitor, MG132, could not inhibit hispolon-induced MDM2 downregulation. In contrast, both inhibition of lysosomes with NH(4)Cl and inhibition of LAMP2A using siRNA partially attenuated hispolon-induced MDM2 downregulation. To determine whether Hsc70 recognizes MDM2 on amino acids 135-141, SMP14 antibody was used to compete with Hsc70 for interaction with MDM2. After Hsc70 knockdown, SMP14 antibody immunoprecipitated increased MDM2. We also found that hispolon induced increased association of Hsp70, Hsc70, Hsp90 and LAMP2A with MDM2. This association was inhibited in cells pretreated with geldanamycin (GA), an Hsp90 inhibitor. GA also attenuated hispolon-induced MDM2 downregulation. Meanwhile, inhibition of Hsc70 using siRNA attenuated hispolon-induced MDM2 downregulation. Our study provides the first example of the ability of hispolon to mediate MDM2 downregulation in lysosomes through the CMA pathway.

Frailty in Chronic Obstructive Pulmonary Disease and Risk of Exacerbations and Hospitalizations.

Background: Frailty is a complex clinical syndrome associated with vulnerability to adverse health outcomes. While frailty is thought to be common in chronic obstructive pulmonary disease (COPD), the relationship between frailty and COPD-related outcomes such as risk of acute exacerbations of COPD (AE-COPD) and hospitalizations is unclear. Purpose: To examine the association between physical frailty and risk of acute exacerbations, hospitalizations, and mortality in patients with COPD. Methods: A longitudinal analysis of data from a cohort of 280 participants was performed. Baseline frailty measures included exhaustion, weakness, low activity, slowness, and undernutrition. Outcome measures included AE-COPD, hospitalizations, and mortality over 2 years. Negative binomial regression and Cox proportional hazard modeling were used. Results: Sixty-two percent of the study population met criteria for pre-frail and 23% were frail. In adjusted analyses, the frailty syndrome was not associated with COPD exacerbations. However, among the individual components of the frailty syndrome, weakness measured by handgrip strength was associated with increased risk of COPD exacerbations (IRR 1.46, 95% CI 1.09-1.97). The frailty phenotype was not associated with all-cause hospitalizations but was associated with increased risk of non-COPD-related hospitalizations. Conclusion: This longitudinal cohort study shows that a high proportion of patients with COPD are pre-frail or frail. The frailty phenotype was associated with an increased risk of non-COPD hospitalizations but not with all-cause hospitalizations or COPD exacerbations. Among the individual frailty components, low handgrip strength was associated with increased risk of COPD exacerbations over a 2-year period. Measuring handgrip strength may identify COPD patients who could benefit from programs to reduce COPD exacerbations.

Non-canonical Interaction Between O-Linked N-Acetylglucosamine Transferase and miR-146a-5p Aggravates High Glucose-Induced Endothelial Inflammation.

Background and Aims: Increased O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification is linked with diabetic complications. MicroRNA-146a-5p (miR-146a-5p) is a negative inflammatory regulator and is downregulated in diabetes. Here, we investigated the interaction between miR-146a-5p and OGT. Methods: Human aortic endothelial cells (HAECs) were stimulated with high glucose (25 mM) and glucosamine (25 mM) for 24 h. Western blot, real time PCR, bioinformatics analysis, luciferase reporter assay, miR-146a-5p mimic/inhibitor transfection, siRNA OGT transfection, miR-200a/200b mimic transfection, and OGT pharmacological inhibition (ST045849) were performed. The aorta from miR-146a-5p mimic-treated db/db mice were examined by immunohistochemistry staining. Results: HG and glucosamine upregulated OGT mRNA and protein expression, protein O-GlcNAcylation, and IL-6 mRNA and protein expression. Real time PCR analysis found that miR-146a-5p was decreased in HG- and glucosamine-stimulated HAECs. This suggested that OGT-induced protein O-GlcNAcylation as a mechanism to downregulate miR-146a-5p. Bioinformatic miR target analysis excluded miR-146a-5p as a post-transcriptional regulator of OGT. However, a luciferase reporter assay confirmed that miR-146a-5p mimic bound to 3'-UTR of human OGT mRNA, indicating that OGT is a non-canonical target of miR-146a-5p. Transfection with miR-146a-5p mimic and inhibitor confirmed that miR-146a-5p regulated OGT/protein O-GlcNAcylation/IL-6 expression levels. Furthermore, OGT siRNA transfection, miR-200a/miR-200b mimic transfection, and ST045849 increased HG-induced miR-146a-5p expression levels, indicating that HG-induced miR-146a-5p downregulation is partially mediated through OGT-mediated protein O-GlcNAcylation. In vivo, intravenous injections of miR-146a mimic decreased endothelial OGT and IL6 expression in db/db mice. Conclusion: A non-canonical positive feedback interaction between miR-146a-5p and OGT is involved in a vicious cycle to aggravate HG-induced vascular complications.

BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.

Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guérin (BCG) vaccination can reduce mortality from neonatal sepsis in human newborns, but the underlying mechanism for this rapid protection is unknown. We found that BCG was also protective in a mouse model of neonatal polymicrobial sepsis, where it induced granulocyte colony-stimulating factor (G-CSF) within hours of administration. This was necessary and sufficient to drive emergency granulopoiesis (EG), resulting in a marked increase in neutrophils. This increase in neutrophils was directly and quantitatively responsible for protection from sepsis. Rapid induction of EG after BCG administration also occurred in three independent cohorts of human neonates.

A comparison between standard and high density Resilient AneuRx in reducing aneurysm sac pressure in a chronic canine model.

OBJECTIVES: Low intra-aneurysm sac pressure has been shown to correlate with sac shrinkage following endovascular aneurysm repair (EVAR) whereas high pressure results in sac enlargement. The Resilient AneuRx (RSA) has higher density Dacron compared with the standard AneuRx (STA) and was developed in an attempt to reduce type 4 and 5 endoleaks, thereby more effectively reducing sac pressure. The purpose of this study is to compare the ability of RSA and STA in reducing sac pressure in a chronic canine aneurysm model. MATERIALS AND METHODS: Artificial polytetrafluoroethylene (PTFE) aneurysm (26 x 50 mm) with an Endosure wireless pressure sensor (CardioMEMS, Atlanta, Ga) attached to the inner surface was implanted in the abdominal aorta of 10 mongrel dogs. Two weeks after creation of the aneurysm, each animal underwent EVAR with either STA (n = 5) or RSA (n = 5). Following EVAR, intra-sac pressure was measured with the implanted wireless pressure sensor up to 3 months postoperatively when the animals were sacrificed. RESULTS: EVAR was successful with no signs of an endoleak in all 10 dogs. Pressure sensing with the wireless sensor was also successful in each animal until the end of the study. Systolic intra-sac pressure remained at a high level in the STA group, whereas it gradually lowered over time in the RSA group. This difference reached statistical significance at 2 months and lasted to 3 months. No endoleak was detected in either group at the time of sacrifice. Gross analysis confirmed that all the aneurysm sacs were thrombosed without any flow inside the sac. CONCLUSION: Despite absence of an endoleak, intra-sac pressure remained high in the STA group. RSA effectively reduced sac pressure over time. Graft porosity appears to be an important factor that may determine the outcome of EVAR. These findings may be useful in designing improved endograft.

Paclitaxel induces up-regulation of tissue factor in human aortic endothelial cells.

Patients who underwent paclitaxel-eluting stent implantation are at a risk of developing late stent thrombosis. However, it is unclear whether paclitaxel alone can modulate tissue factor (TF) expression in human aortic endothelial cells (HAEC). HAEC were stimulated with paclitaxel. Western blotting, real-time PCR, and a chromogenic TF activity assay were done. In HAEC, while paclitaxel (10 (-5) mol/L to 10 (-9) mol/L) treatment for 5 h up-regulated the expression of TF in a dose-dependent manner, paclitaxel cotreatment with thrombin further enhanced it. While paclitaxel (10 (-5) mol/L) itself induced a 3.7-fold enhancement in TF activity, its cotreatment along with thrombin elicited a 7.6-fold increase in TF activity. Paclitaxel also caused an 8.1-fold increase in TF mRNA expression, and paclitaxel cotreatment with thrombin caused a 13.6-fold enhancement in TF mRNA expression. In summary, paclitaxel alone can up-regulate endothelial TF expression. These findings are significant for the patients receiving paclitaxel-eluting stents, and they may provide opportunities to develop novel therapeutic strategies for DES thrombosis.