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SIRT1 is an NAD+-dependent protein deacetylase that has been shown to play a significant role in many biological pathways, such as insulin secretion, tumor formation, lipid metabolism, and neurodegeneration. There is great interest in understanding the regulation of SIRT1 to better understand SIRT1-related diseases and to better design therapeutic approaches that target SIRT1. There are many known protein and small molecule activators and inhibitors of SIRT1. One well-studied SIRT1 regulator, resveratrol, has historically been regarded as a SIRT1 activator, however, recent studies have shown that it can also act as an inhibitor depending on the identity of the peptide substrate. The inhibitory nature of resveratrol has yet to be studied in detail. Understanding the mechanism behind this dual behavior is crucial for assessing the potential side effects of STAC-based therapeutics. Here, we investigate the detailed mechanism of substrate-dependent SIRT1 regulation by resveratrol. We demonstrate that resveratrol alters the substrate recognition of SIRT1 by affecting the KM values without significantly impacting the catalytic rate (kcat). Furthermore, resveratrol destabilizes SIRT1 and extends its conformation, but the conformational changes differ between the activation and inhibition scenarios. We propose that resveratrol renders SIRT1 more flexible in the activation scenario, leading to increased activity, while in the inhibition scenario, it unravels the SIRT1 structure, compromising substrate recognition. Our findings highlight the importance of substrate identity in resveratrol-mediated SIRT1 regulation and provide insights into the allosteric control of SIRT1. This knowledge can guide the development of targeted therapeutics for diseases associated with dysregulated SIRT1 activity.

Introduction: Blood pressure measurement is important for treating patients. It is known that there is a discrepancy between cuff blood pressure vs arterial blood pressure measurement. However few studies have explored the clinical significance of discrepancies between cuff (CPB) vs arterial blood pressure (ABP). Our study investigated whether differences in CBP and ABP led to change in management for patients with hypertensive emergencies and factors associated with this change. Methods: This prospective observational study included adult patients admitted between January 2019–May 2021 to a resuscitation unit with hypertensive emergencies. We defined clinical significance of discrepancies as a discrepancy between CBP and ABP that resulted in change of clinical management. We used stepwise multivariable logistic regression to measure associations between clinical factors and outcomes. Results: Of 212 patients we analyzed, 88 (42%) had change in management. Mean difference between CBP and ABP was 17 milligrams of mercury (SD 14). Increasing the existing rate of antihypertensive infusion occurred in 38 (44%) patients. Higher body mass index (odds ratio [OR] 1.04, 95% confidence Interval [CI] 1.0001–1.08, P-value

Introduction: Blood pressure (BP) monitoring is an essential component of sepsis management. The Surviving Sepsis Guidelines recommend invasive arterial BP (IABP) monitoring, although the benefits over non-invasive BP (NIBP) monitoring are unclear. This study investigated discrepancies between IABP and NIBP measurement and their clinical significance. We hypothesized that IABP monitoring would be associated with changes in management among patients with sepsis requiring vasopressors. Methods: We performed a retrospective study of adult patients admitted to the critical care resuscitation unit at a quaternary medical center between January 1–December 31, 2017. We included patients with sepsis conditions AND IABP monitoring. We defined a clinically significant BP discrepancy (BPD) between NIBP and IABP measurement as a difference of > 10 millimeters of mercury (mm Hg) AND change of BP management to maintain mean arterial pressure ≥ 65 mm Hg. Results: We analyzed 127 patients. Among 57 (45%) requiring vasopressors, 9 (16%) patients had a clinically significant BPD vs 2 patients (3% odds ratio [OR] 6.4; 95% CI: 1.2–30; P = 0.01) without vasopressors. In multivariable logistic regression, higher Sequential Organ Failure Assessment (SOFA) score (OR 1.33; 95% CI: 1.02–1.73; P = 0.03) and serum lactate (OR 1.27; 95% CI: 1.003–1.60, P = 0.04) were associated with increased likelihood of clinically significant BPD. There were no complications (95% CI: 0–0.02) from arterial catheter insertions. Conclusion: Among our population of septic patients, the use of vasopressors was associated with increased odds of a clinically significant blood pressure discrepancy between IABP and NIBP measurement. Additionally, higher SOFA score and serum lactate were associated with higher likelihood of clinically significant blood pressure discrepancy. Further studies are needed to confirm our observations and investigate the benefits vs the risk of harm of IABP monitoring in patients with sepsis.

Abstract Introduction Breast cancer is a significant public health concern in Jordan. It is the most common cancer among Jordanian women. Despite its high incidence and advanced stage at time of diagnosis, the uptake of breast cancer screening in Jordan is low. This study aims to compare clinical outcomes of both screening and diagnostic mammogram among women in Jordan. Methods A retrospective cohort of 1005 women who underwent mammography in breast imaging unit in a tertiary hospital in Jordan. It aimed to investigate outcomes of screening and diagnostic mammography. recall rates, clinical manifestations and cancer rates were investigated. Results A total of 1005 participants were involved and divided into screening group (n = 634) and diagnostic group (n = 371). Women in the diagnostic group were more likely to be younger, premenopausal, smokers with higher BMI. Among the screening group, 22.3% were labeled with abnormal mammogram, 26% recalled for ultrasound, 46 patients underwent tissue biopsy and a total of 12 patients had a diagnosis of breast carcinoma. Among the diagnostic group, the most commonly reported symptoms were a feeling of breast mass, mastalgia and nipple discharge. Abnormal mammogram was reported in 50.4% of women, a complementary ultrasound was performed for 205 patients. A diagnostic Tru-cut biopsy for 144 patients and diagnostic excisional biopsy for 17 patients were performed. A total of 131 had a diagnosis of carcinoma. Conclusion With the high possibility of identifying a carcinoma in mammography among symptomatic women and low uptake of screening mammogram, efforts to increase awareness and improve access to screening services are crucial in reducing the burden of breast cancer in Jordan.

Background: Use of Electronic Health Records is increasing. Copy-and-paste function is frequently used with higher rates of documentation errors. Studies to determine the nature of such errors are needed.Objectives: Determination of the effect of implementing a dictation system for completing notes on the quality of clinical documentation. We hypothesized that implementation of the dictation system for note writing would decrease the rate of errors in the progress notes as well as decrease the rate of copying and pasting. Design/Methods: A prospective interventional study in inpatient medical service for six months’ duration starting in July 2016. Resident physicians’ charts were reviewed by the attending physician on a daily basis. This study was done in a community based hospital affiliated to a university program. Residents’ physicians included Internal Medicine, Transitional year and Combined Internal Medicine Pediatrics residents. Charts reviewed for hospitalized patients. A total of 54 residents were offered a pre-intervention survey indicating their subjective use of copy/paste function. Response rate of 85.18%. Progress notes were reviewed on a daily basis for residents on their inpatient rotation. A total of 621 notes were reviewed. Results: Percentage of notes copied prior to the intervention was 92.73% which decreased to 49.71% post-intervention (RR of 0.54, 95% CI 0.48 0.60 Z statistic 11.005 with p-value