Design, synthesis, and evaluation of new benzimidazole thiourea derivatives as antitumor agents.

Novel benzimidazole thiourea derivatives were designed and synthesized based on sorafenib as a lead compound. The benzimidazole moiety was traded by the pyridine ring to enhance the hydrophobic interaction and retain hydrogen bonding in the hinge region, while lipophilic moieties with different bulkiness were employed in the deep hydrophobic pocket for better hydrophobic interactions. Thiourea as a urea bioisostere was also utilized. Substantial activity was demonstrated against a leukemia subpanel in an in vitro antitumor screening at the NCI. In the single-dose assay, compounds 7i, 7j, and 7l had a GI%) higher than sorafenib against most leukemia cell lines (GI% = 86.2%-137.1%), while in the five-dose assay, compound 7l outperformed sorafenib against the HL-60(TB) and SR leukemia cell lines in terms of GI50 , TGI, and LC50 . Compound 7l also caused cycle arrest at the G0-G1 and S phases in the HL-60(TB) leukemia cell line and induced apoptosis via elevating the Bax/Bcl-2 ratio and increasing caspases 3, 7, and 9 by 5.1-, 3.2-, and 5.2-fold, respectively. Compounds 7i, 7j, and 7l also inhibited the vascular endothelial growth factor receptor-2 (VEGFR-2), B-Raf(V600E) , and platelet-derived growth factor receptor beta (PDGFR-ß) enzymes with an IC50 range of 0.063-0.44 µM. COMPARE analysis and a molecular docking study were also performed to predict the possible mechanism of action and binding mode, respectively.

An Enhanced Method for Full-Inversion-Based Ultrasound Elastography of the Liver.

Similar to many other types of cancer, liver cancer is associated with biological changes that lead to tissue stiffening. An effective imaging technique that can be used for liver cancer detection through visualizing tissue stiffness is ultrasound elastography. In this paper, we show the effectiveness of an enhanced method of quasi-static ultrasound elastography for liver cancer assessment. The method utilizes initial estimates of axial and lateral displacement fields obtained using conventional time delay estimation (TDE) methods in conjunction with a recently proposed strain refinement algorithm to generate enhanced versions of the axial and lateral strain images. Another primary objective of this work is to investigate the sensitivity of the proposed method to the quality of these initial displacement estimates. The strain refinement algorithm is founded on the tissue mechanics principles of incompressibility and strain compatibility. Tissue strain images can serve as input for full-inversion-based elasticity image reconstruction algorithm. In this work, we use strain images generated by the proposed method with an iterative elasticity reconstruction algorithm. Ultrasound RF data collected from a tissue-mimicking phantom and in-vivo data of a liver cancer patient were used to evaluate the proposed method. Results show that while there is some sensitivity to the displacement field initial estimates, overall, the proposed method is robust to the quality of the initial estimates. Clinical Relevance- Improved elasticity images of the liver can aid in achieving more reliable diagnosis of liver cancer.

Gastroenterology manifestations and COVID-19 outcomes: A meta-analysis of 25,252 cohorts among the first and second waves.

A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random-effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup-analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta-analysis suggests an association between GI symptoms in COVID-19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID-19 patients during the second wave compared to the first wave of the outbreak.

Broken Kirschner Wires Can Migrate: A Case Report and Review of Literature.

INTRODUCTION: Kirschner wires are in use in orthopedic and trauma surgery since the past 80 years. These wires can break due to metal fatigue and migrate which can cause lethal complications. CASE REPORT: A 27-year-old female sickle cell patient with avascular necrosis of the head of femur, drilling, and injection of the osteoblasts in the head of femur was being performed. A 2 cm of 2.0 mm proximal tip of the guide wire broke. Discussion started whether to leave the wire and the young decided to leave the broken wire, but the wisdom directed us to remove it. CONCLUSION: Migration of wires does occur, we believe not only broken wires should be removed but also even the unbroken wire to be removed once the purpose of use is achieved.