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Atherosclerotic cardiovascular diseases remain the leading causes of morbidity and mortality worldwide. Cholesterol crystals in atherosclerotic plaques play an essential role in atherosclerosis progression. However, no clinical drugs have been used for removing cholesterol crystals from plaque to counter atherosclerosis. Previous studies identified the hydrophobic domain of lipid bilayer in liposomes acted as sinks for solubilizing hydrophobic cholesterol. Moreover, adjusting the composition of the lipid bilayer in liposomes can enhance its hydrophobic molecule loading capacity. Therefore, in this study, ginsenosides Rb1 (Rb1), one of main active components of ginseng which has a similar structure to cholesterol, is anchored into soy phospholipids bilayer with its hydrophobic region to prepare nano-sponge-like liposomes (Rb1-LPs), aiming to amplify the solubilization of cholesterol in lipid bilayer. For targeting delivery to atherosclerotic plaques, Annexin V (AnxV), a protein that can specifically recognize phosphatidylserine upregulated in atherosclerotic plaques, is applied to decorate the surface of Rb1-LPs by click reaction to obtain the final preparation of AnxV-Rb1-LPs. The in vitro studies showed that incorporating Rb1 into lipid bilayer remarkably increased the affinity of the lipid bilayer to free cholesterol and the solubilization of cholesterol crystals. Additionally, nano-sponge-like liposomes could efficiently reduce the accumulation of cholesterol crystals and improve cholesterol efflux, finally inhibiting inflammation and apoptosis in cholesterol-laden cells. Furthermore, AnxV-Rb1-LPs could efficiently accumulate in atherosclerotic plaques after intravenous injection, exert nano-sponge-like functions to remove intra- and extracellular cholesterol crystals, ultimately alleviating inflammation and apoptosis in atherosclerotic plaques for antiatherosclerosis. Therefore, AnxV-Rb1-LPs provide a potential strategy for removing cholesterol crystals in atherosclerotic plaques and can be further utilized in other diseases with excessive cholesterol accumulation.

Immune cells stand as a critical component of the immune system to maintain the internal environment homeostasis. The dysfunction of immune cells can result in various life-threatening diseases, including refractory infection, diabetes, cardiovascular disease, and cancer. Therefore, strategies to standardize or even enhance the function of immune cells are critical. Recently, nanotechnology has been highly researched and extensively applied for enhancing the cytoplasmic delivery of bioactive molecules to immune cells, providing efficient approaches to correct in vivo and in vitro dysfunction of immune cells. This review focuses on the technologies and challenges involved in improving endo-lysosomal escape, cytoplasmic release and organelle targeted delivery of different bioactive molecules in immune cells. Furthermore, it will elaborate on the broader vision of applying nanotechnology for treating immune cell-related diseases and constructing immune therapies and cytopharmaceuticals as potential treatments for diseases.

The Social Relationship Coping Efficacy scale (SRCE) was designed to assess cancer patients' efficacy for maintaining social support and social relationships. The purpose of the study was to confirm the psychometric quality and utility of a Greek-language version of the (SRCE) scale. The study included 116 women with breast cancer, who underwent surgery at a public hospital In Greece. The SRCE scale was translated using standard procedures and then culturally adapted for use in Greece. Psychometric evaluation of the SRCE-Greek scale included reliability, structural validity and convergent validity analyses. The SRCE-Greek scale demonstrated strong internal consistency (Cronbach a 0.87), and split-half reliability (Spearman-Brown, 0.747; Guttman, 0.742). The structural construct validity was confirmed with factor analysis using principal axis factor analysis. Construct validity was further supported with convergent validity with the Family Crisis Oriented Personal Evaluation Scales (F-COPES) (Acquiring Social Support, Reframing) and Family Support scale. The Greek language SRCE has strong internal consistency reliability and construct validity, as well as satisfactory convergent validity. Results provide support for the use of the SRCE-GR as a research and clinical instrument for the assessment of breast cancer patient's self-efficacy with regard to maintaining and enhancing close social relationships and social support.

Aim The purpose of this study is to investigate conflicts and identify the factors that cause the creation of conflicts in the operating room as well as coping strategies for conflict resolution. Background The operating room is a special and changeable working environment, which is constantly evolving and requires interdisciplinary team collaboration. Therefore, it is an environment that may cause conflict among employees METHOD: The study was conducted at three Public Hospitals of Athens, during the period from 1/4/2018 to 15/6/2018. The research tool used to conduct the research was the questionnaire of Kontogianni et al. (2011). The questionnaire consisted of four sections dealing with conflict issues and their management. The sample consisted of 185 nurses and medical staff. The level of statistical significance was set equal to 0.05. The questions were analyzed through the statistical package SPSS 20. Results Τhe majority of participants had conflicts with colleagues (79%), with doctors (69.5%) and with nurses (43.7%). Τhe majority of the sample was unaware of conflict management strategies (60%). One of the important factors that intensify the conflicts is the burdensome workload in combination with the unsatisfactory salary. Avoidance is the preferred conflict management strategy (64.7%), followed by mutual benefit trading (55.4%.) Acceptance is the least appropriate strategy (10.9%). Conclusions In order to deal with conflicts in the operating room effectively, it is necessary for nurses and physicians to be trained in conflict management. Implications for nursing management Nursing managers should support the training of nurses in conflict management in order to create a climate of cooperation and reduce conflicts.

The aims of this study were to evaluate health outcomes and the economic burden of hospitalized COVID-19 patients in the United States. Hospitalized patients with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) from 1 April to 31 October 2020 were identified in the Premier Healthcare COVID-19 Database. Patient demographics, hospitalization characteristics, and concomitant medical conditions were assessed. Hospital length of stay (LOS), in-hospital mortality, hospital charges, and hospital costs were evaluated overall and stratified by age groups, insurance types, and 4 COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage. Of the 173,942 hospitalized COVID-19 patients, the median age was 63 years, 51.0% were male, and 48.5% were covered by Medicare. The most prevalent concomitant medical conditions were cardiovascular disease (73.5%), hypertension (64.8%), diabetes (40.7%), obesity (27.0%), and chronic kidney disease (24.2%). Approximately one-fifth (21.9%) of the hospitalized COVID-19 patients were admitted to the ICU and 16.9% received IMV; most patients (73.6%) did not require ICU admission or IMV, and 12.4% required both. The median hospital LOS was 5 days, in-hospital mortality was 13.6%, median hospital charges were $43,986, and median hospital costs were $12,046. Hospital LOS and in-hospital mortality increased with ICU and/or IMV usage and age; hospital charges and costs increased with ICU and/or IMV usage. Patients with both ICU and IMV usage had the longest median hospital LOS (15 days), highest in-hospital mortality (53.8%), and highest hospital charges ($198,394) and hospital costs ($54,402). This retrospective administrative database analysis relied on coding accuracy and a subset of admissions with validated/reconciled hospital costs. This study summarizes the severe health outcomes and substantial hospital costs of hospitalized COVID-19 patients in the US. The findings support the urgent need for rapid implementation of effective interventions, including safe and efficacious vaccines.

A global effort to develop vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began early in 2020. In mid-December, the U.S. Food and Drug Administration approved emergency use authorization for two vaccines that successfully concluded their phase 3 trials ([ 1 ][1]), and vaccine distribution in the United States began shortly afterwards. As vaccinations progress, the public must continue to social distance, limit large gatherings, wear masks, and engage in other non-pharmaceutical interventions (NPIs) to curb the spread of COVID-19. Both the Pfizer/BioNTech and Moderna vaccines use mRNA technology and require two doses administered 3 and 4 weeks apart, respectively, to reach the full 90 to 95% efficacy ([ 2 ][2]). In light of limited supply, the Centers for Disease Control and Prevention has provided preliminary guidance indicating that vaccination should be prioritized first for health care workers and long-term care facility residents, then for other essential workers, and next for people at higher risk for severe illness ([ 3 ][3]). Subsequently, vaccination will reach most sectors of the population, though inoculation of children under 16 has yet to be recommended. Globally, vaccination uptake over the coming year could prevent disease for the sizeable portion of the population that has yet to be infected with SARS-CoV-2 and move the world to a post-pandemic phase; however, this potential benefit of averted infections, hospitalizations, and deaths depends considerably on societal maintenance of NPIs during vaccine deployment. Relaxing NPIs before attaining adequate distribution would enable infection of many more people before their vaccination than would occur if NPIs were to be maintained or increased. Locally, relaxation of NPIs increases the reproduction number, Rt , which enables greater transmission of the virus and a larger overall attack rate. These changes lead to a faster and larger accumulation of infections that could greatly outpace vaccination distribution efforts. Thus, maintaining NPIs throughout the upcoming SARS-CoV-2 vaccination campaign is essential for maximizing the health benefit. In the coming months, public health messaging is critically needed to encourage continued compliance with NPI control measures. 1. [↵][4]U.S. Food and Drug Administration, “COVID-19 vaccines” (2020); [www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines][5]. 2. [↵][6]1. C. Zimmer, 2. J. Corum, 3. S.-L. Wee , “Coronavirus vaccine tracker,” The New York Times (2020). 3. [↵][7]Centers for Disease Control and Prevention, “How CDC is making COVID-19 vaccine recommendations” (2020); [www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations-process.html][8]. Pfizer Inc. reviewed this manuscript and approved the decision to submit the manuscript for publication. F.J.A., A.C., and D.L.S. own Pfizer stock. J.S. and Columbia University disclose partial ownership of SK Analytics. J.S. has done paid consulting work for Business Network International and receives funding from Pfizer Inc., National Science Foundation grant DMS-2027369, and a gift from the Morris-Singer Foundation. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #xref-ref-1-1 "View reference 1 in text" [5]: http://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines [6]: #xref-ref-2-1 "View reference 2 in text" [7]: #xref-ref-3-1 "View reference 3 in text" [8]: http://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations-process.html

©2016 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ajcc2016625 Teri M. Kozik is a nurse researcher and George S. Charos is an electrophysiologist and director of Cardiology at St. Joseph’s Medical Center, Stockton, California. Salah S. Al-Zaiti is an assistant professor at the Department of Acute and Tertiary Care Nursing, University of Pittsburgh, Pennsylvania. Mary G. Carey is associate director for clinical nursing research, Strong Memorial Hospital, Rochester, New York and Michele M. Pelter is an assistant professor at the the Department of Physiological Nursing at University of California, San Francisco, California. ECG Puzzler

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

OBJECTIVES: To evaluate potential costs and savings from implementing an evaluation tool that uses bedside review of antibiotic use and infection management to assess whether patients with infections in acute medical and surgical wards could have their antibiotic regimen changed and be safely managed out of hospital. METHODS: The tool was implemented in 30 acute wards in five UK hospital trusts. Data were collected on demographic variables, diagnosis, social situation, hospital stay and all current antibiotic prescribing for 291 patients. A physician and pharmacist assessed antibiotic therapy and feasibility of discharge. Resource use was measured for each patient, unit costs attached, and mean and total costs of implementing recommendations were calculated. RESULTS: Implementation of these recommendations could reduce total inpatient days by 494 at a saving of £186 731, and save £20 215 from adjustment of antibiotic therapy. Additional costs were associated with implementation of the assessment (£2468), community support (£6227) and outpatient parenteral antimicrobial therapy (£5616). As a result, the net potential savings would be £192 635 in total or £662 (95% CI: £393, £930) for every patient assessed. Excluding eight patients with the highest potentially avoidable inpatient stays (>15 days), mean savings would fall to £363 per patient assessed but remain highly significant (95% CI: £261, £465). CONCLUSIONS: Careful assessment of antibiotic use in acute wards has the potential to reduce the use and cost of antibiotics, and length of stay. Added costs of assessment and out-of-hospital support services would offset a small proportion of these potential savings. Randomized studies are now needed to test these results.

Energy drink consumption has increased significantly over the past decade and is associated with greater than 20,000 emergency department visits per year. Most often these visits are due to cardiovascular complaints ranging from palpitations to cardiac arrest.To determine if energy drinks alter; blood pressure, electrolytes, activated bleeding time (ACT), and/or cardiac responses measured with a 12-lead electrocardiographic (ECG) Holter.Continuous ECG data was collected for five hours (30 minutes baseline and 4 hours post consumption [PC]). Subjects consumed 32 ounces of energy drink within one hour and data (vital signs and blood samples) was collected throughout the study period. Paired students t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data.Fourteen healthy young subjects were recruited (mean age 28.6 years). Systolic blood pressure (baseline=132, ±7.83; PC=151, ±11.21; P=.001); QTc interval (baseline=423, ±22.74; PC=503, ±24.56; P.001); magnesium level (baseline 2.04, ± 0.09; PC=2.13, ±0.15; P=.05); and calcium level (baseline=9.31, ±.28; PC=9.52, ±.22; P=.018) significantly increased from baseline. While potassium and ACT fluctuated (some subjects increased their levels while others decreased) these changes were not significant. Eight of the fourteen subjects (57%) developed a QTc500 milliseconds PC. Other T-wave changes were noted in 9/14 (64.3%) subjects PC.Energy drinks increased systolic blood pressure, altered electrolytes, and resulted in repolarization abnormalities. These physiological responses can lead to arrhythmias and other abnormal cardiac responses highlighting the importance that emergency room personnel assess for energy drink consumption and potential toxicity.

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome., National Human Genome Research Institute (U.S.), National Institutes of Health (U.S.)

PPARGC1A is a transcriptional coactivator that binds to and coactivates a variety of transcription factors (TFs) to regulate the expression of target genes. PPARGC1A plays a pivotal role in regulating energy metabolism and has been implicated in several human diseases, most notably type II diabetes. Previous studies have focused on the interplay between PPARGC1A and individual TFs, but little is known about how PPARGC1A combines with all of its partners across the genome to regulate transcriptional dynamics. In this study, we describe a core PPARGC1A transcriptional regulatory network operating in HepG2 cells treated with forskolin. We first mapped the genome-wide binding sites of PPARGC1A using chromatin-IP followed by high-throughput sequencing (ChIP-seq) and uncovered overrepresented DNA sequence motifs corresponding to known and novel PPARGC1A network partners. We then profiled six of these site-specific TF partners using ChIP-seq and examined their network connectivity and combinatorial binding patterns with PPARGC1A. Our analysis revealed extensive overlap of targets including a novel link between PPARGC1A and HSF1, a TF regulating the conserved heat shock response pathway that is misregulated in diabetes. Importantly, we found that different combinations of TFs bound to distinct functional sets of genes, thereby helping to reveal the combinatorial regulatory code for metabolic and other cellular processes. In addition, the different TFs often bound near the promoters and coding regions of each other's genes suggesting an intricate network of interdependent regulation. Overall, our study provides an important framework for understanding the systems-level control of metabolic gene expression in humans.

The sterol regulatory element-binding protein (SREBP) family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding partners NFY and SP1 in a human hepatocyte cell line using chromatin immunoprecipitation combined with genome tiling arrays (ChIP-chip). We find that SREBP1 occupies the promoters of 1,141 target genes involved in diverse biological pathways, including novel targets with roles in lipid metabolism and insulin signaling. We also identify a conserved SREBP1 DNA-binding motif in SREBP1 target promoters, and we demonstrate that many SREBP1 target genes are transcriptionally activated by treatment with insulin and glucose using gene expression microarrays. Finally, we show that SREBP1 cooperates extensively with NFY and SP1 throughout the genome and that unique combinations of these factors target distinct functional pathways. Our results provide insight into the regulatory circuitry in which SREBP1 and its network partners coordinate a complex transcriptional response in the liver with cues from the diet., Author Summary Transcription factors (TFs) are DNA-binding proteins that regulate the transcription of their target genes. TFs typically bind in proximity to the transcription start sites of their target genes in a region called the promoter. SREBP1 is a TF that increases the transcription of numerous genes involved in cholesterol and fat metabolism and has been linked to diet-related diseases such as insulin resistance and type 2 diabetes. Using microarray technology, we identified all of the promoters in the human genome that are bound by SREBP1 and two associated TFs called NFY and SP1 in a human liver cell line. Our findings greatly expand the number of genes and biological pathways that may be regulated by SREBP1 and reveal that different combinations of SREBP1 and its partners preferentially target genes involved in different pathways. Thus, in contrast to traditional studies that focus on individual genes, we have used a genomics approach to provide a novel global view of the regulatory circuitry in which SREBP1 and its partners coordinate a transcriptional response in the liver with cues from the diet.

The efficacy and safety of a new antitachycardia pacing technique, self-adapting decremental overdrive pacing, was assessed in patients with clinical ventricular tachyarrhythmias who underwent programmed ventricular stimulation and serial drug testing. The three phases of this study involved a learning/experience phase, followed by intrapatient comparison of decremental overdrive pacing with conventional antitachycardia pacing modalities of overdrive burst ventricular pacing, and diastolic scanning with single (S2) and double (S2S3) ventricular extrastimuli. The final phase involved an intrapatient comparison of automated decremental overdrive pacing with overdrive burst ventricular pacing in patients with ventricular tachycardia (VT) cycle lengths of 280 msec or greater. Decremental overdrive pacing was superior to overdrive burst pacing and diastolic scanning (S2S3 and S2) (83% vs 38%, 50%, 9%) in patients with VT cycle lengths of 280 msec or greater. Automated decremental overdrive pacing as applied in the final phase was the most efficacious modality, terminating 92% of VT episodes compared with 56% for overdrive burst pacing in the same patients.

Atrial fibrillation (AF) is a difficult arrhythmia to manage with antiarrhythmic agents. Amiodarone is highly effective in restoring and maintaining normal sinus rhythm in patients with AF. However, the mechanism and predictors of efficacy for amiodarone in treating AF have not been adequately addressed. Various measures of success or failure of amiodarone therapy were examined in 68 patients who had paroxysmal or chronic, established AF refractory to conventional antiarrhythmic agents. The patients were 25 to 75 years old (mean 59) and mean follow-up was 21 months (range 3 to 56). Maintenance amiodarone dosages were 200 to 400 mg/day. Overall, amiodarone therapy was effective long term in 54 of the 68 patients (79%). Left atrial diameter, age, gender and origin of AF were not helpful in predicting success or failure of amiodarone therapy. The presence of chronic AF for longer than 1 year was an adverse factor in maintaining normal sinus rhythm (p = 0.007), although the success rate even in this group was relatively high (57%). Thirty-five percent of the patients had adverse effects, which precluded long-term therapy with amiodarone in 10%.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. The Consortium is funded by grants from the NHGRI as follows: production grants: U54HG004570 (B. E. Bernstein); U01HG004695 (E. Birney); U54HG004563 (G. E. Crawford); U54HG004557 (T. R. Gingeras); U54HG004555 (T. J. Hubbard); U41HG004568 /n(W. J. Kent); U54HG004576 (R. M. Myers); U54HG004558 (M. Snyder);/nU54HG004592 (J. A. Stamatoyannopoulos). Pilot grants: R01HG003143 (J. Dekker); RC2HG005591 and R01HG003700 (M. C. Giddings); R01HG004456-03 (Y. Ruan); U01HG004571 (S. A. Tenenbaum); U01HG004561 (Z. Weng); RC2HG005679 (K. P. White). This project was supported in part by American Recovery and/nReinvestment Act (ARRA) funds from the NHGRI through grants U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591,R01HG003541, U01HG004561, RC2HG005679andR01HG003988(L. Pennacchio). In addition, work from NHGRI Groups was supported by the Intramural Research/nProgram of the NHGRI (L. Elnitski, ZIAHG200323; E. H. Margulies, ZIAHG200341). Research in the Pennachio laboratory was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute, Department of Energy Contract DE-AC02-05CH11231, University of California.