Differential silencing of STAT3 isoforms leads to changes in STAT3 activation.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in multiple fundamental biological processes and a key player in cancer development and progression. STAT3 is activated upon tyrosine phosphorylation and is constitutively active in various malignancies; therefore, the expression of pSTAT3 has been recognized as a predictor of poor survival. STAT3 encodes two alternatively-spliced STAT3 isoforms: the full-length STAT3α isoform and the truncated STAT3ß isoform. These isoforms have been suggested as the reason for the occasionally observed opposing roles of STAT3 in cancer: an oncogene, on one hand, and a tumor suppressor on the other. To investigate their roles in aggressive breast cancer, we separately silenced each isoform and found that they affect each other's activation, impacting cell viability, cytokine expression, and migration. Silencing specific isoforms can lead to a more favorable balance of activated STAT3 proteins in the cell. Distinguishing between the two isoforms and their active forms is crucial for STAT3-related cancer diagnosis and therapy.

miR-155: A Potential Biomarker for Predicting Mortality in COVID-19 Patients.

COVID-19, a pandemic of severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2), continues to pose diagnostic and therapeutic challenges due to its unpredictable clinical course. Prognostic biomarkers may improve care by enabling quick identification of patients who can be safely discharged home versus those who may need careful respiratory monitoring and support. MicroRNAs (miRNAs) have risen to prominence as biomarkers for many disease states and as tools to assist in medical decisions. In the present study, we aimed to examine circulating miRNAs in hospitalized COVID-19 patients and to explore their potential as biomarkers for disease severity. We studied, by quantitative PCR, the expressions of miR-21, miR-146a, miR-146b, miR-155, and miR-499 in peripheral blood. We found that mild COVID-19 patients had 2.5-fold less circulating miR-155 than healthy people, and patients with a severe COVID-19 disease had 5-fold less circulating miR-155 than healthy people. In addition, we found that miR-155 is a good predictor of COVID-19 mortality. We suggest that examining miR-155 levels in patients' blood, upon admission to hospital, will ameliorate the care given to COVID-19 patients.

[RESIDENCY EXAMINATIONS IN THE COURSE OF THE COVID-19 CRISIS: THE EFFORTS OF THE ISRAELI SCIENTIFIC COUNCIL TO EXECUTE THE FINAL BOARD ORAL EXAMINATIONS DURING A LOCAL AND A WORLDWIDE PANDEMIC].

INTRODUCTION: The Israeli Scientific Council is responsible for the physician's training process and the residency exams. These are performed in two phases: Stage A (written examination) and Stage B (the final Board oral examination). The COVID-19 pandemic started in Israel a few weeks before the scheduled spring 2020 Stage B exams and had a major impact, not only on the health and economic systems in Israel, but also on the residency exams. AIMS: To describe the efforts of the Israeli Scientific Council to execute the spring 2020 Stage B exams during the COVID-19 pandemic in comparison to the worldwide data, and to deduce the appropriate management during potential future crises. METHODS: We present a description of the activity of the Israeli Scientific Council since the start of the COVID-19 pandemic according to documents and other sources, An internet search was conducted on the destiny of residency examinations throughout the world, and a comparison between them. RESULTS: Due to rapid worsening in the restrictions enforced in Israel, the spring 2020 oral board exams were cancelled. However, a decision was made to execute them in the summer. This new schedule dictated a delay in the schedule of other residency examinations and forced condensation of 5 periods into 10 months instead of 14. The examination team prepared the new summer exams period under the assumption that heavy restrictions will still be implemented. Indeed, COVID-19 was still around and the restrictions were still enforced. Despite that, all oral Board examinations were perfectly executed. This contrasts with the rest of the world, in which most residency exams were cancelled, even without a solution or an alternative date. CONCLUSIONS: Recruitment of all involved and preparation for the worst-case scenario enabled the perfect execution of the previously cancelled exams, and will enable the execution of future residency exams under conditions of potential health or war crises. DISCUSSION: To the best of our knowledge, the Israeli Scientific Council is the only communal body in the world which organized an alternative period for the cancelled oral exams, only 4 months after the cancelled dates. Due to an enormous effort and rigorous preparations, Israel is also the only place in which oral exams were successfully executed, physically, under an active disease and very heavy restrictions.

[POSTGRADUATE MEDICAL EDUCATION DURING COVID-19 PANDEMIC IN ISRAEL].

BACKGROUND: The Covid-19 pandemic has posed significant challenges to many aspects of life, including work processes to which we have become accustomed. Health systems world-wide have been affected in numerous ways and face epic and unprecedented challenges. Medical education, both in Israel and around the world, has been deeply impacted. It is no surprise that the institutions responsible for medical education, as well as many other institutions, have had to deal with uncertainty and unrest. In this article, we review the processes adopted by the Scientific Council of the Israel Medical Association, the body responsible for postgraduate medical training in the various medical specialties. The article reviews the actions taken by the Council during the first few months of the pandemic, March-July 2020, in order to maintain the quality of training.

Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery.

Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.

[SURGICAL RESIDENCY IN THE ERA OF RESTRICTED WORKING HOURS].

INTRODUCTION: Post-Graduate Medical Education in the surgical professions, as in other medical professions as well, has gone through an organizational revolution during the past 10-15 years. Catalyzers of this change were the information revolution, technological changes, life-work balance needs of residents, legalization of the medical system and different duty hours' restrictions that followed. These changes require rethinking traditional Post-Graduate Medical Education and adaptation of teaching methods, quality measurement methods, new definition of program director's role and more. In this article we review these changes as they appear in updated literature and the significance of the changes in the Israeli health system since the last physicians' bargaining agreement of 2011.

MiRNA-208a as a Sensitive Early Biomarker for the Postoperative Course Following Congenital Heart Defect Surgery.

Current clinical risk assessment strategies have poor accuracy for identifying patients who will suffer adverse perioperative events. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome after pediatric heart surgery. We tested the hypothesis that miRNAs-208a, -208b, and -499 can serve as noninvasive biomarkers for the extent of myocardial damage and the postoperative clinical course of pediatric patients with congenital heart defects (CHDs) at an early time point following surgery. Serum samples were obtained from 79 pediatric patients before and 6, 12, and 24 h after surgery. MiRNAs-208a, -208b, and -499 were quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Our results show that the levels of the three miRNAs were elevated at 6 h after surgery, remained high at 12 h and declined at 24 h after the operation. The amount of all three miRNAs at 6 h after surgery correlated with surgical and laboratory parameters. Their amount at 12 h after surgery correlated with the length of stay at the hospital. Expression levels of miRNA-208a at 6 h were related to the appearance of cardiac complications, and could predict whether a patient will sustain complications or will be ventilated for more than 48 h after surgery. Circulating miRNA-208a is a predictor for the risk of developing cardiac complications during the postoperative course as early as 6 h after heart surgery for CHD in pediatric patients.

New Role for Interleukin-13 Receptor α1 in Myocardial Homeostasis and Heart Failure.

BACKGROUND: The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins-4 and -13 are anti-inflammatory type-2 cytokines, signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor α1 in the heart is unknown. METHODS AND RESULTS: We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 receptor α1 is present in the myocardium and, together with the complementary type-2 interleukin-4 receptor chain Il4ra, is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1-deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild-type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P=0.004, left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; P=0.03). A bioinformatic analysis of mouse hearts indicated that interleukin-13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=-2.36; false discovery rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure-overload conditions. CONCLUSIONS: The results of our studies in humans and mice indicate, for the first time, a role of interleukin-13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease.

Neonatal Cervical Osteomyelitis With Bilateral Upper Limb Paresis.

Neonatal cervical osteomyelitis is extremely rare, with only a few cases having been reported. We report a neonate with cervical osteomyelitis and extensive inflammation of the surrounded tissues that caused nerve root compression and upper limb paresis.