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The hypermucoviscosity involving hypervirulent K. pneumoniae confers to be able to avert neutrophil-mediated phagocytosis.
Weight loss alone may not explain the observed risk reduction, as improvements in diabetes, leptin, and ghrelin were associated with decreased cancer risk.PhD prepared nurse scientists within healthcare systems are uniquely positioned to advance nursing science through research and evidence-based practice (EBP) initiatives due to their ability to closely collaborate with nurses and other healthcare professionals in the clinical setting. The purpose of this paper is threefold 1) to describe the roles and contributions of Nurse Scientists, from their perspectives, in four different health care systems in the Greater Philadelphia area, three of which are Magnet® designated hospitals; 2) to highlight organizational approaches to increase nursing research and EBP capacity; and 3) to explore strategies that Nurse Scientists used to overcome barriers to build nursing research capacity. Nurse Scientists employed in these healthcare systems share many of the same essential roles and contributions focused on developing nursing research and EBP initiatives through education and mentorship of clinical nurses, conduct and oversight of independent research, and dissemination activities. With supportive executive nurse leadership, the Nurse Scientists within each healthcare system employed different strategies to overcome barriers in building nursing research and EBP capacity. Nurse scientists within healthcare settings have potentially powerful positions to generate and apply new knowledge to guide nursing practice and improve outcomes.Aim To describe the occurrence of opioid and benzodiazepine withdrawal symptoms in a cohort of pediatric intensive care unit (PICU) patients, the characteristics of this group, and patterns of withdrawal scoring observed during medication weaning. Background Patients in the PICU are a complex and vulnerable population. Opioids and benzodiazepines are routinely administered in this setting. Providers must be equipped to recognize and assess symptoms of narcotic and benzodiazepine withdrawal. Methods A retrospective chart review was conducted to describe all patients admitted to the medical intensive care unit who received continuous infusions of morphine and midazolam during a one-year period. Patient demographics, diagnosis, and presence of co-morbidities were abstracted. The number of days on continuous infusions was measured, along with Withdrawal Assessment Tool-1 (WAT-1) scores and documented symptoms that could be associated with withdrawal. WAT-1 scoring ranges from 0 to 12, a WAT-1 score of 3 or higher is considered to indicate clinically significant withdrawal symptoms. Descriptive statistics were utilized to summarize demographic and clinical variables. Results Among 60 cases, patient ages ranged 5 weeks to 29 years (median 3.5 years). Eighty percent of patients had a primary respiratory diagnosis and 88.3% had one or more co-morbidities. Forty-four patients (73.3%) had symptoms consistent with withdrawal. Thirty-one percent of patients had a maximum WAT-1 score between 3 and 8. The majority of patients (55%) had a history of opioid and/or benzodiazepine exposure. Conclusions The information learned highlights the need for ongoing conversation and continued study of how best to assess and manage withdrawal syndrome in pediatric critical care environments.Introduction and objectives Cardiac device-related infections (CDRI) may be life-threatening and require early and accurate diagnosis. The aims of this study were to analyze the performance of positron emission tomography-computed tomography (PET/CT) in suspected CDRI, to assess changes to the initial diagnosis, and to identify a clinical subgroup deriving the greatest benefit from this imaging modality. Methods Retrospective study including patients evaluated by PET/CT for suspected CDRI from 2011 to 2018. We assessed PET/CT performance and the agreement between the initial, post-PET and definitive diagnoses. We also assessed changes in the diagnosis, depending on initial clinical suspicion, to identify patients deriving the greatest benefit from PET/CT. Results We included 44 patients. The prevalence of endocarditis was 57%. The sensitivity and specificity of PET/CT for the diagnosis of infective endocarditis were 0.84 and 0.95, respectively. Post-PET diagnosis improved the initial diagnosis by 45%. PET/CT correctly reclassified 57% of patients with initial suspicion of generator pocket infection by detecting lead infection. Conclusions PET/CT showed high diagnostic performance in suspected of CDRI and significantly improved the conventional diagnostic approach, especially in patients with initial suspicion of focal infection.Opioids are widely used in clinical practice because of their strong analgesia. However, their use is restricted by such factors as tolerance and opioid-induced hyperalgesia (OIH), so it is critical to find ways to reduce the dosage of opioids to avoid the side effects. In this study, we demonstrated for the first time the regulatory role of A20 in morphine analgesia. By overexpressing and knocking down A20 in the spinal cord of mice, we found that A20 enhanced morphine analgesia rather than tolerance. Then, at the cellular level, different methods were used to confirm that A20 could not only strengthen the inhibition of cAMP induced by opioids drugs, but also affect μ opioid receptor (MOR) and ERK phosphorylation. In addition, we found that A20 interacted with MOR inhibitory protein β-arrestin2, which could be enhanced by MOR agonists. Furthermore, there was evidence that A20 could inhibit β-arrestin2 recruitment. Collectively, our results indicated that A20 in the spinal cord could enhance morphine analgesia and increase MOR function through β-arrestin2. Upregulating A20 expression may be a potential strategy to improve the therapeutic profile of opioids and reduce their side effects.Necroptosis represents a newly defined form of regulated necrosis and participates in various human inflammatory diseases. It remains unclear whether necroptosis is presented in heatstroke-induced lung injury. We show that heat stress(HS) triggered an significant upregulation of receptor-interacting protein 1 (RIP1) and mixed lineage kinase domain-like protein (MLKL) expression in a time-dependent manner, without a significant change of receptor-interacting protein 3 (RIP3). Furthermore, co-immunoprecipitation assays showed that RIP1 binds to RIP3 to form the necrosome in heat stress-induced PMVECs. In vitro, necrostatin-1 (Nec-1) pre-treatment reduced heat stress-induced PMVECs necroptosis, which also inhibited HMGB1 translocation from the nucleus into the cytoplasm. Similarly, inhibition for ERK (PD98059), NF-κB (BAY11-7082) and c-Jun (c-Jun peptide), respectively, also suppressed the HMGB1 cytoplasm translocation. Furthermore, siRNA-mediated RIP1/RIP3 knockdown negatively regulated the release of HMGB1 in HS-induced necroptosis through the ERK, NF-κB, and c-Jun signaling pathways. Our study reveals that HS induces RIP1/RIP3-dependent necroptosis through the MAPK, NF-κB, and c-Jun signaling pathways in PMVECs.Lens epithelial cells (LECs) apoptosis induced by oxidative stress is a major factor in age-related-cataract (ARC) pathogenesis, but there are still many blind nodes in this progress. This study aimed to investigate the effects of MDM2 phosphorylation in ARC and H2O2-induced lens epithelial cells apoptosis. Our results confirmed that the levels of p-MDM2 (Ser166) and p-MDM2 (Ser186) in the anterior lens capsules of human cataracts were reduced compared to that in normal capsules. Similarly, in naturally aging cataract mice, the level of MDM2 phosphorylation also decreased. Oxidative stress-induced apoptosis model was constructed by cultivating HLE-B3 cells with 200 μM H2O2. It was confirmed that MDM2 could regulate lens epithelial cell apoptosis, and MDM2 inhibitors could partly inhibited AKT's role in suppressing apoptosis induced by H2O2. Besides, we examed the decreased level of p-AKT(Ser473) in apoptosis of lens epithelial cells and ARC. Our study revealed that MDM2 phosphorylation mediated H2O2-induced lens epithelial cells apoptosis and ARC, which could provide new ideas for the clinical treatment of ARC.O-GlcNAcylation was first found by Torres and Hart in monocytes. It is a dynamic and reversible post-translational modification catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation is increased in diabetic cardiomyopathy (DCM) patients and it has been reported that OGT plays an important role in the regulation of cardiac gene transcription, cell cycle and calcium homeostasis. The purpose of this study is to investigate the effects of OGT on signal transduction and function of β1-adrenoceptor (β1AR) in adult rat cardiomyocytes. We found that after overexpressing OGT by adenovirus vector in adult rat cardiomyocytes, cAMP formation and phosphorylation of phospholamban (PLB) at Ser16 (p16-PLB) were decreased under isoprenaline (ISO) stimulation. Over expression of OGT increased the intracellular [Ca2+]i and deteriorated the death of cardiomyocytes induced by prolonged stimulation with ISO. β1-adrenoceptor was overexpressed using a plasmid vector and then co-immunoprecipitation (co-IP) followed by Western blot was employed to define the O-GlcNAcylation of β1-adrenoceptor. The results showed that O-GlcNAcylation of β1-adrenoceptor was increased in OGT overexpressed cells, and there was no significant change in the formation of cAMP and phosphorylation of PLB after β1-adrenoceptor was blocked by CGP20712A. Given that OGT affects the signal transduction of β1-adrenoceptor in adult rat cardiomyocytes by increasing the O-GlcNAcylation of β1-adrenoceptor, the mechanism revealed in this study indicates that OGT and β1AR may be therapeutic targets in patients undergoing diabetic cardiomyopathy.Background Calcified coronary lesions still represent a challenge for coronary angioplasty, with sub-optimal acute PCI results causing more frequent late stent failure. Purpose The study aimed at the evaluation of the immediate procedural outcome in a real-world consecutive population of a selective use of lithotripsy based on the intravascular imaging assessment with IVUS or OCT. Methods and results Thirty-one calcified stenoses (28 patients) out of a total of 455 lesions (370 patients) treated between November 2018 and May 2019 received IVL under intravascular imaging guidance. The majority of the IVL lesions had angiographically severe calcifications and were selected after intravascular imaging. A smaller group was identified by poor expansion after high-pressure balloon dilatation, in one case despite preliminary small burr Rotablation. After IVL, when OCT was performed calcium fractures were observed in 71% of cases. After OCT/IVUS guided stent optimization a satisfactory lumen enlargement (minimal stenration DES expansion delivers excellent immediate lumen expansion and patient outcome, both in concentric and eccentric calcifications.The number of cases of the coronavirus-induced disease-2019 (COVID-19) continues to increase exponentially worldwide. In this crisis situation, the management of ST-segment elevation myocardial infarction (STEMI) is challenging. In this review, we outline the risk and benefits of primary PCI vs. thrombolysis for STEMI. While thrombolysis may seem like a good choice, many patients have a contraindication and could end-up using more resources. Also, with a high probability of the angiogram showing non-obstructed coronary arteries during acute infections, primary PCI should be the preferred strategy.
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