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A large body of research has demonstrated a synergistic anticancer effect between docosahexaenoic acid (DHA) and standard chemotherapy regimens against colorectal cancer (CRC). In this study, we investigated the chemotherapeutic potential of cotreatment with DHA and isoliquiritigenin (ISL) against CRC HCT-116 cells. Apoptosis was confirmed by Annexin V/PI staining and expression of apoptosis-associated proteins. The synergistic effect of DHA and ISL combination on apoptosis was detected using combination index approaches. Flow cytometry was carried out using fluorescent probes to measure the production of reactive oxygen species (ROS). PF-06882961 DHA and ISL in combination synergistically enhanced the decrease in cell viability versus the compounds used alone. Moreover, we demonstrated that the synergistic anti-CRC activity of cotreatment with these two compounds was achieved by inducing the apoptosis caspase-dependently mediated through augmented ROS generation followed by increased Fas ligand mRNA expression and cytochrome c release. Our data also demonstrated that cotreating with DHA and ISL strongly upregulated the phosphorylation of ERK and JNK, which are functionally associated with ROS induced by the two compounds in combination. Interestingly, further study revealed that inhibiting ERK phosphorylation strongly enhanced Fas ligand mRNA expression and the combination of the two compounds induced stronger cytotoxicity, whereas inhibiting JNK phosphorylation significantly reduced the apoptotic signals mediated by cotreatment with these two compounds. Excessive ROS-induced JNK activation and cytochrome c release from mitochondria played a key role in the synergistic anticancer activity of CRC cells by cotreating with DHA and ISL.

When child and adolescent psychiatry fellowship applicants are applying to programs, many will use fellowship websites to gather information. This study assesses the accessibility and content available on child and adolescent fellowship websites.

Using the Electronic Residency Application Service (ERAS) list of child and adolescent fellowship programs for 2020, 139 child and adolescent fellowship training websites were compiled. Information on websites was evaluated within the following three categories program overview, application information and recruitment, and educational opportunities. A total of 22 criteria were evaluated within these three categories. Descriptive statistics were used to analyze the websites.

A list provided by ERAS and a Google search identified child and adolescent fellowship program websites. Analysis of content revealed most websites included an overview of the program (97.8%), but fewer included information such as the number of fellowship spots (51.5%), salary (45.5%), application deadline (41.0%), and call responsibility (19.4%).

Results suggest there is room for improvement in the comprehensiveness and accessibility of child and adolescent fellowship websites. Especially during a time when much of the programmatic information will be obtained virtually due to COVID-19, it is critical that fellowship websites are uniformly curated so applicants can more easily find information about programs.

Results suggest there is room for improvement in the comprehensiveness and accessibility of child and adolescent fellowship websites. Especially during a time when much of the programmatic information will be obtained virtually due to COVID-19, it is critical that fellowship websites are uniformly curated so applicants can more easily find information about programs.We present the case of a 47-year-old man with a history of recurrent episodes of frontal headache, fever, and chest discomfort as well as longstanding, difficult to treat arterial hypertension. Clinical work-up revealed the unexpected finding of an underlying pheochromocytoma as well as recent "silent" myocardial infarction. Our case highlights the importance of paying attention to incidental cardiac findings on somatostatin receptor positron emission tomography/computed tomography, as routinely performed in patients with clinically suspected neuroendocrine tumors. These incidental cardiac findings cannot only indicate a primary or secondary (metastatic) neuroendocrine tumor, but also areas of myocardial inflammation, as somatostatin receptors cannot only be found on the majority of neuroendocrine tumors, but also among other tissues on the surface of activated macrophages and lymphocytes. The detection of myocardial inflammation is of clinical importance and its underlying etiology should be evaluated to prompt eventual necessary treatment, as it is a potential driving force for cardiac remodeling and poor prognosis.

The aims of this study were to investigate the application of a constant infusion (CI) to mitigate the issue of constantly changing Gd-DTPA contrast levels in a bolus injection for extracellular volume (ECV) measurements by (a) comparing a CI alone to a bolus alone and a bolus followed by CI in healthy myocardium, (b) evaluating the impact of glucose suppression using heparin on ECV.

Five healthy canine subjects were imaged to compare three different protocols for injecting Gd-DTPA and FDG bolus alone, CI alone, bolus followed by CI. Suppression of myocardial glucose uptake was induced using a continuous infusion of 20% lipid at a rate of 0.25mL·min

·kg

as well as 2000 units of intravenous heparin injected 20 minutes prior to FDG/Gd-DTPA injection.

There was no significant effect on ECV measurement when heparin was used for glucose suppression at equilibrium irrespective of infusion protocol). Measurements of ECV in myocardium, regardless of infusion protocol showed no significant difference at all time points (P = 0.21) prior to washout.

The suppression of myocardial uptake of [

F]FDG with heparin did not alter the determination of myocardial ECV though a larger sample size may show differences. Further, the infusion protocol (bolus or constant infusion) had no effect on the calculated ECV.

The suppression of myocardial uptake of [18F]FDG with heparin did not alter the determination of myocardial ECV though a larger sample size may show differences. Further, the infusion protocol (bolus or constant infusion) had no effect on the calculated ECV.This review summarizes key imaging studies that were presented at the American Heart Association Scientific Sessions 2020, which occurred virtually this year due to the pandemic, related to the fields of single-photon emission computed tomography, positron emission tomography, cardiac computed tomography, cardiac magnetic resonance, and echocardiography. The aim of this bird's eye view is to inform readers of the various studies discussed at the meeting from these imaging modalities. Since there was no physical attendance this year, we find that a general overview of imaging will be especially useful. Further, we hope that the presentation of multiple imaging studies in a single synthesized review will stimulate new ideas for future research in imaging.

Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using

I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging.

The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers.

In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance.

These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.

These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.Pectus excavatum is a chest wall malformation with a strong psychological and aesthetic impact. Rarely, pectus excavatum patients can show respiratory or cardiac symptoms occurring mainly during physical exertion. We report a case of a 34-year-old pregnant woman with a severe degree of pectus excavatum who developed serious cardiovascular disease resulting in spontaneous twin abortion at the twenty-first week of gestation. Cardiovascular disease was resolved after open surgical correction of pectus excavatum. This case shows how a tardive diagnosis and a delayed surgical approach for pectus excavatum can lead to severe consequences.

Micro- and macrovascular complications of diabetes are leading morbidities in the world population. They are responsible not only for increased mortality but also severe disabilities, which jeopardize quality of life (e.g., blindness, walking limitations, and renal failure requiring dialysis). The new antidiabetic agents (e.g., glucagon-like peptide1 receptor agonists and sodium-glucose cotransporter inhibitors) are increasingly recognized as breakthrough agents in the treatment of diabetes and prevention of diabetic complications. However, drugs effective in preventing and treating diabetic disabilities are still needed and sulodexide could be one of those able to address the unmet clinical needs of the new antidiabetic agents.

We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings, and journal suppomplications of diabetes without increasing the risk of AEs.

Sulodexide has a beneficial effect on the ocular, peripheral arterial disease, trophic ulcers, and renal complications of diabetes without increasing the risk of AEs.An elevated plasma low-density lipoprotein cholesterol (LDL-C) level is a well-established atherosclerotic cardiovascular disease (ACSVD) risk factor. Randomized studies with statins (alone or in combination with other lipid-lowering drugs) have demonstrated their clinical efficacy in lowering LDL-C. Several classes of new, non-statin agents have been successfully studied and used (e.g., ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 [i-PSCK9]). However, many high ACSVD risk patients remain at a high residual cardiovascular risk, with at least 10% being statin intolerant. Bempedoic acid (ETC-1002) is a new inhibitor of cholesterol synthesis that targets ATP citrate lyase (ACL). Importantly, ETC-1002 is only converted into an active form in the liver and is free of muscle side effects.Area Covered Mechanism of action of ETC-1002, clinical pharmacology, completed clinical studies with bempedoic acid, lipid-lowering efficacy/safety issues, and recent meta-analyses of trials with ETC-1002.