Efficacy of Mineral Trioxide Aggregate (MTA) as a Reparative Material in Iatrogenic Furcal Perforations in Mandibular Molars.

BACKGROUND/OBJECTIVES:  Mineral trioxide aggregate (MTA) is widely recognized as one of the most biocompatible materials for perforation repairs during root canal treatment (RCT). Experimental evidence has consistently demonstrated MTA's superior sealing ability and biocompatibility compared to various dental materials, including amalgam, intermediate restorative material, zinc oxide eugenol cement, and resin-modified glass ionomer cement. This study aimed to assess the efficacy of MTA as a reparative material in iatrogenic furcal perforations during RCT. MATERIALS & METHODS: A descriptive cross-sectional study was conducted from May 18, 2021, to November 17, 2021, at the Department of Operative Dentistry, Nishtar Institute of Dentistry, Multan, Pakistan. Seventy-six patients aged 18-60 years, of both genders, who developed iatrogenic furcal perforations during procedures were included. Patients with fractures or endo-perio lesions identified during clinical and radiographic examinations were excluded. Isolation was achieved using a rubber dam. The perforation site was cleaned and irrigated with 1% sodium hypochlorite to control hemorrhage and enhance visualization. Following the manufacturer's recommendations, the perforation site was sealed with MTA mixed with sterile saline. RESULTS: The age range in this study was 18 to 60 years, with a mean age of 42.09 ± 9.69 years. Most patients (56.78%) were between 41-60 years old. Out of the 76 patients, 46 (60.53%) were male, and 30 (39.47%) were female, resulting in a male-to-female ratio of 1.5:1. The study found that MTA's efficacy as a reparative material in iatrogenic furcal perforations was observed in 61 (80.26%) patients. A 6-month follow-up revealed no periodontal ligament breakdown, demonstrating the efficacy of MTA as a reparative material in iatrogenic furcal perforations. CONCLUSION: This study concludes that the efficacy of MTA as a reparative material in iatrogenic furcal perforations is remarkable and significant.

Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors.

To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.

Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations.

From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy.

Prolonged Cardiac Monitoring to Detect Atrial Fibrillation after Cryptogenic Stroke or Transient Ischemic Attack: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The cause of ischemic stroke or transient ischemic attack (TIA) remains unclear after initial cardiac monitoring in approximately one-third of patients. Randomized controlled trials (RCTs) showed that the prolonged cardiac monitoring of patients with cryptogenic stroke or TIA increased detection of atrial fibrillation (AF). We aimed to perform a meta-analysis of all RCTs that evaluated the prolonged monitoring ≥7 days in patients with cryptogenic stroke or TIA. METHODS: We searched PubMed, EMBASE, Cochrane CENTRAL, and relevant references for RCTs without language restriction (inception through December 2014) and performed meta-analysis using random effects model. Detection of AF, use of anticoagulation at follow-up, recurrent stroke or TIA, and mortality were major outcomes. RESULTS: Four RCTs with 1149 total patients were included in the meta-analysis. Prolonged cardiac monitoring ≥7 days compared to shorter cardiac monitoring of ≤48 hours duration increased the detection of AF (≥30 seconds duration) in patients after cryptogenic stroke or TIA (13.8% vs. 2.5%; odds ratio [OR], 6.4; 95% confidence interval [CI], 3.50-11.73; P < 0.00001; I(2) , 0%]. It also increased the odds of AF detection of any duration (22.6% vs. 5.2%; 5.68[3.3-9.77]; P < 0.00001; I(2) , 0%). The patients who underwent prolonged monitoring were more likely to be on anticoagulation at follow-up (2.21[1.52-3.21]; P < 0.0001; I(2) , 0%). No differences in recurrent stroke or TIA (0.78[0.40-1.55]; P = 0.48; I(2) , 0%) and mortality (1.33[0.29-6.00]; P = 0.71; I(2) , 0%] were observed between two strategies. CONCLUSION: Prolonged cardiac monitoring improves detection of atrial fibrillation and anti-coagulation use after cryptogenic stroke or TIA and therefore should be considered instead of shorter duration of cardiac monitoring.