Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans.

Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects.     

'Good prognosis tumours' in breast cancer screening.

The Forrest Report led to the introduction of the breast screening programme with the aim of reducing mortality from breast cancer. In 1989 a breast screening programme was introduced to the South Bucks District and now two cycles have been completed. The findings are of a high yield of good prognosis tumours 71% and 72%, respectively. These encouraging figures are reflected in a high response rate and with a fall in the incidence of non-screen-detected tumours.     

Major complications of operative gynecologic laparoscopy in southern Taiwan: a follow-up study

STUDY OBJECTIVES: This follow-up study examined the major complications among 4307 operative gynecologic laparoscopies. The overall complication rate and each individual category were compared with those of our previous study period. The clinical outcome and salvage procedures were correlated with the time of recognition and the severity of initial procedures in the individual injury type. DESIGN: Retrospective, comparative study based on medical record reviewing (Canadian Task Force classification II-3). SETTING: Tertiary teaching hospital, Chi Mei Foundation Hospital in southern Taiwan. PATIENTS: Records of women (n = 4307) aged 40.5 +/- 11.7 years (mean +/- SD [95% CI 40.1-40.5]) who underwent operative gynecologic laparoscopies from January 2000 through February 2006 were reviewed in this study. The complications were compared with those of our previous study based on 1507 laparoscopies performed between December 1992 and November 1999 for follow-up comparison. INTERVENTIONS: Gynecologic laparoscopic surgeries. MEASUREMENTS AND MAIN RESULTS: Thirty-four complications occurred in 31 patients requiring repair procedures, 3 of whom had multiple complications, with an overall complication rate of 0.72% (31/4307). There were 13 bladder injuries (0.30%), 7 bowel injuries (0.16%), 3 cases of internal bleeding (0.07%), 4 vaginal stump hematomas or abscesses (0.09%), 3 ureteral injuries (0.07%), 3 major vessel injuries (0.07%), and 1 trocar site hematoma (0.02%). In addition, there were 125 (2.88%) postoperative blood transfusions without additional operative intervention. The major complication rate decreased compared with that of the previous study (0.72% [95% CI 0.51%-1.02%] vs 1.59% [95% CI 1.07%-2.36%]; p = .005). The overall complication rates were not significantly different between laparoscopic hysterectomy (LH) group and non-LH group. However, bladder injury happened more frequently in the LH group, whereas bowel injury was more common in the non-LH group. In addition, the severity of the original injury, timing of recognition, and accompanying salvage procedures correlated with the clinical outcomes. CONCLUSION: The significantly decreased major complication rate, as compared with that of our previous study period, confirms the importance of experience accumulation and use of preventive maneuvers in reducing the complication rate. There were no significant differences among the individual injury category during these 2 study periods. The manifestations of bowel injury were highly variable and individualized. The accumulation of surgical experience with the aid of preventive maneuvers is helpful to reduce the complication rate significantly.     

Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts.

Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery.