Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its ...reaction products are present in human atherosclerotic plaque, and it has been proposed that MPO oxidatively modifies targets in the artery wall. We have now generated MPO-deficient mice, and show here that neutrophils from homozygous mutants lack peroxidase and chlorination activity in vitro and fail to generate chlorotyrosine or to kill Candida albicans in vivo. To examine the potential role of MPO in atherosclerosis, we subjected LDL receptor-deficient mice to lethal irradiation, repopulated their marrow with MPO-deficient or wild-type cells, and provided them a high-fat, high-cholesterol diet for 14 weeks. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aorta indicated that lesions in MPO-deficient mice were about 50% larger than controls. Similar results were obtained in a genetic cross with LDL receptor-deficient mice. In contrast to advanced human atherosclerotic lesions, the chlorotyrosine content of aortic lesions from wild-type as well as MPO-deficient mice was essentially undetectable. These data suggest an unexpected, protective role for MPO-generated reactive intermediates in murine atherosclerosis. They also identify an important distinction between murine and human atherosclerosis with regard to the potential involvement of MPO in protein oxidation.
Personal protective equipment (PPE) is effective in preventing coronavirus disease (COVID-19) infection. Resident knowledge of proper use and effective training methods is unknown. We hypothesise ...that contamination decreases and knowledge increases after a formalised PPE educational session.
Participants included first year interns during their residency orientation in June 2020. Before training, participants took a knowledge test, donned PPE, performed a simulated resuscitation, and doffed. A standardised simulation-based PPE training of the donning and doffing protocol was conducted, and the process repeated. Topical non-toxic highlighter tracing fluid was applied to manikins prior to each simulation. After doffing, areas of contamination, defined as discrete fluorescent areas on participants' body, was evaluated by ultraviolet light. Donning and doffing were video recorded and asynchronously rated by two emergency medicine (EM) physicians using a modified Centers for Disease Control and Prevention (CDC) protocol. The primary outcome was PPE training effectiveness defined by contamination and adherence to CDC sequence.
Forty-eight residents participated: 24 internal medicine, 12 general surgery, 6 EM, 3 neurology, and 3 psychiatry. Before training, 81% of residents were contaminated after doffing; 17% were contaminated after training (P<0.001). The most common contamination area was the wrist (50% pre-training vs. 10% post-training, P<0.001). Donning sequence adherence improved (52% vs. 98%, P<0.001), as did doffing (46% vs. 85%, P<0.001). Participant knowledge improved (62%–87%, P <0.001). Participant confidence (P<0.001) and preparedness (P<0.001) regarding using PPE increased with training.
A simulation-based training improved resident knowledge and performance using PPE.
Background & AimCell therapy for patients with acute-on-chronic liver failure (ACLF), which is associated with high short-term mortality, is a promising strategy. We reasoned that administering ...stromal vascular cell (SVF) therapy to achieve cell-mediated microenvironment modulation for liver regeneration and hepatocyte replenishment in ACLF is an attractive alternative strategy to liver transplantation. We evaluated the perturbation of microenvironment by CD34+/CD34− SVF cells in hepatocyte cotransplantation in a rat model of ACLF regarding selected gene expression.Methods, Results & ConclusionDonor hepatocytes (1 × 107/1mL) and SVF cells (1 × 106/0.5mL) were isolated from Tg(UBC–emGFP) rats and human adipose tissues, respectively, and were intraportally transplanted into ACLF rats. SVF cells were divided into CD34+ and CD34− groups. The surviving animals were sacrificed at 1 and 2 weeks after the transplantation. Gene expression levels, measured by quantitative real-time RT-PCR, were normalized against endogenous glyceraldehyde-3-phosphatedehydrogenase control.Histologically, prominent biliary ductular proliferation and significantly progression of fibrosis (P = 0.005) were observed in the CD34− group than in the CD34+ group. Genes directly related to the end result of fibrosis (collagen type I, MMP9, and TIMP1) showed significantly higher expression in the CD34− group than in the CD34+ group at 1 week after cell transplantation (P < 0.05). These findings were consistent with histological changes. Moreover, TGFβ1 and IRF5 had the same expression pattern with significance (P < 0.05). Fibrosis-prone histopathology in the CD34− group was associated with TGFβ1 and IRF5. On the other side, significantly higher gene expression of vascular endothelial growth factor was found in the CD34+ group compared to the CD34- group (P = 0.032), suggesting transplanted CD34+ SVF cells are key components and might lead to liver repair by modulating angiogenesis.In conclusion, hepatic gene expression in the rat model of ACLF after cytotherapy of SVF cells and hepatocytes were differed with CD34 positivity. CD34+ SVF was instrumental in mediating hepatic repair.
Background
As a result of the COVID‐19 pandemic, patterns of patient presentations and medical education have changed, potentially resulting in fewer and different types of patient encounters. ...Procedural proficiency is a cornerstone of emergency medicine (EM) training, and residents must meet Accreditation Council for Graduate Medical Education (ACGME) requirements to graduate. It is feared there may have been a pandemic‐induced decrease in opportunities for residents to perform procedures. This study investigates the change in procedures performed by EM residents during the initial year of the pandemic.
Methods
This study utilized a multicenter retrospective design. Across three EM residency programs, logs of 14 ACGME‐required procedures performed by residents were reviewed. For each procedure, counts were compared prepandemic year (March 2019 to February 2020) to during pandemic year (March 2020 to February 2021). Procedures were further grouped into 4‐month periods: March to June, July to October, and November to February.
Results
A total of 113 EM resident physicians were included in this study. Procedures performed by EM residents tended to decrease during the COVID‐19 pandemic. There were statistically significant decreases in number of annual cricothyrotomies (2.4 vs. 0.9, p < 0.001) and pediatric trauma resuscitations (5.7 vs. 3.9, p = 0.024). Comparing the first 4‐month periods of each year, there were significant decreases in cardiac pacing (6.3 vs. 5.4, p = 0.038), chest tubes (2.2 vs. 1.0, p < 0.001), cricothyrotomies (0.6 vs. 0.1, p = 0.001), intubations (8.2 vs. 4.4, p = 0.002), and pericardiocenteses (1.7 vs. 0.2, p < 0.001).
Conclusions
The COVID‐19 pandemic has led to a decrease in the number of procedures performed per EM resident in many of the domains required by the ACGME. Although only some procedures had statically significant decreases, it remains to be seen if this will lead to decreased resident procedural competency. Further research may be required in this area to determine any such effect.
In 2014 the Geriatric Emergency Department (GED) Guidelines were published and endorsed by four major medical organizations. The multidisciplinary GED Guidelines characterize the complex needs of the ...older emergency department (ED) patient and current best practices with the goal of promoting more cost‐effective and patient‐centered care. The recommendations are extensive and the vast majority of EDs then and now do not have either the resources nor hospital administrative support to provide this additional service. At the 2021 American Academy of Emergency Medicine's Scientific Assembly, a panel of emergency medicine physicians and geriatricians discussed the GED Guidelines and the current realities of EDs' capacity to provide best practice and guideline recommended care of GED patients. This article is a synthesis of the panel's presentation and discussion. With the substantial challenges in providing guideline recommended care in EDs, this article will explore three high impact GED clinical conditions to highlight guideline recommendations, challenges and opportunities, and discuss realistically achievable expectations for non‐Geriatric ED accredited institutions. In 2014 the Geriatric Emergency Department Guidelines were published describing the current best practices for geriatric ED patients. Unfortunately, the vast majority of EDs worldwide do not provide the level of service recommended by the GED guidelines. The GED Guidelines can best be termed aspirational for U.S. EDs at the present time.
Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting ...using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.
The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.
The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.
•HB-EGF antisense oligonucleotide suppressed hepatic VLDL production leading to a remarkable downregulation of circulatory lipid levels.•HB-EGF antisense also induced an effective suppression of atherosclerosis development.•Newly we observed that the HB-EGF antisense significantly improved systemic insulin sensitivity.
Minority carrier lifetime in p-HgCdTe KINCH, M. A; AQARIDEN, F; CHANDRA, D ...
Journal of electronic materials,
06/2005, Letnik:
34, Številka:
6
Conference Proceeding, Journal Article
Recenzirano
High operating temperature (HOT) detector concepts using midwave infrared (MWIR) (x ~ 0.3) p-type HgCdTe operating at temperatures within the thermo-electric cooler range are of significant interest ...at the present time. However, it is apparent that much work remains to be done in the areas of material, diode passivation, and diode formation technologies before the "holy grail" of photon detection at room temperature for all infrared wavelengths is achieved. Over the years, at DRS, we have developed a technology base for both n- and p-type HgCdTe materials parameters that are relevant to photodiode design and fabrication. This paper will discuss data that we have taken recently on minority carrier lifetime in MWIR and long wave infrared (LWIR) HgCdTe, particularly p type, and how it compares to current theories of Auger 7, radiative, and Shockley-Read recombination in this material. Extrinsic group IB (Cu, Au) and group V (arsenic) p-type dopants were used, together with group III (In) for n-type. The impact of the data on future HOT detector work is discussed. PUBLICATION ABSTRACT
BackgroundAntiplatelet agents are increasingly used in cardiovascular treatment. Limited research has been performed into risks of acute and delayed traumatic intracranial hemorrhage (ICH) in these ...patients who sustain head injuries. Our goal was to assess the overall odds and identify factors associated with ICH in patients on antiplatelet therapy.MethodsA retrospective observational study was conducted at two level I trauma centers. Adult patients with head injuries on antiplatelet agents were enrolled from the hospitals’ trauma registries. Acute ICH was diagnosed by head CT. Observation and repeat CT to evaluate for delayed ICH was performed at clinicians’ discretion. Patients were stratified by antiplatelet type and analyzed by ICH outcome.ResultsOf 327 patients on antiplatelets who presented with blunt head trauma, 133 (40.7%) had acute ICH. Three (0.9%) had delayed ICH on repeat CT, were asymptomatic and did not require neurosurgical intervention. One with delayed ICH was on clopidogrel and two were on both clopidogrel and aspirin. Patients with delayed ICH compared with no ICH were older (94 vs 74 years) with higher injury severity scores (15.7 vs 4.4) and trended towards lower platelet counts (141 vs 216). Patients on aspirin had a higher acute ICH rate compared with patients on P2Y12 inhibitors (48% vs 30%, 18% difference, 95% CI 4 to 33; OR 2.18, 95% CI 1.15 to 4.13). No other group comparison had significant differences in ICH rate.ConclusionsPatients on antiplatelet agents with head trauma have a high rate of ICH. Routine head CT is recommended. Patients infrequently developed delayed ICH. Routine repeat CT imaging does not appear to be necessary for all patients.Level of evidenceLevel III, prognostic.
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