Background: Histone citrullination by PAD4 regulates tumor suppressor gene expression. Results:The novel PAD inhibitor YW3-56 inhibits cancerous growth by perturbing autophagy and regulating the SESN2-mTORC1 signaling axis. Conclusion: YW3-56 regulates the SESN2-mTORC1 autophagy pathway as one of its anticancer mechanisms. Significance: This study identifies a novel function of PAD4 in the autophagy pathway and developed potent PAD inhibitors for future cancer research.

The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.

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emic stroke. These trials may not have been blinded, but they were randomized and used death as a common outcome event, which cannot, of course, be affected by ascertainment bias. The nonrandomized studies of thrombolysis (which make up the majority of available reports in the literature) were included simply to highlight how unusable they are to obtain a true assessment of the effect of thrombolysis and also to show the totality of the evidence and how important it is to stop doing nonrandomized comparisons.With respect to large-scale trials of acute stroke treatment, it is important to remember that it has taken nearly 40 years for the myocardial infarction (MI) ResponseFisher and Zipseri measured the urinary excretion of thromboxane (TX) B2, the nonenzymatic hydrolysis product of TXA2. This is thought to reflect primarily the intrarenal synthesis of TXA2 (see Reference 2 for a review). In contrast, we reported measurements of the urinary excretion of 11-dehydro-TXB2, which derives from enzymatic degradation of TXB2 through the il-dehydro-dehydrogenase pathway and is considered to reflect primarily the extrarenal (largely platelet) synthesis of TXA2.With regard to the importance of gender, we found no statistically significant difference in thromboxane biosynthesis between men and women, the excretion rate being 356+963 (n=47) and 531+±857 (n=32), respectively (p=0.41), in the total study population and 485+ 1149 (n=32) and 790± 1042 pmol/mmol creatinine (n=19), respectively (p=0.35), in patients with cerebral ischemia. Thus, the apparent discrepancy between Dr. Fisher's earlier findings and our own is probably related to the different cellular sources of TXA2 being investigated in the two studies.

INTRODUCTION: Pulmonary sequestration (PS) is a rare congenital malformation where a nonfunctional lobe of lung tissue does not appropriately communicate with the tracheobronchial tree. The dysplastic lung tissue can have an anomalous vascular supply. Outside of incidental diagnosis on chest imaging, PS most commonly presents as recurrent localized pneumonia. CASE PRESENTATION:A 74-year-old female with a history of coronary artery disease, tobacco use, and chronic obstructive pulmonary disease was admitted frequently over four years for recurrent dyspnea and cough and repeatedly treated for community acquired pneumonia. The episodes appeared to resolve with antibiotics until she presented with hemoptysis in addition to her usual symptoms. Computed tomography (CT) chest revealed a right lower lobe abscess and bronchoscopy cultures grew Actinomyces Turicensis. She was discharged home on prolonged antibiotics with follow up at infectious disease (ID) and pulmonology. Interval CT chest was preformed to evaluate progression of the abscess with findings consistent with a sixcentimeter congenital PS in the right lower lobe extending into the subcarinal region with a feeding artery arising from the mid aortic arch. She completed the course of antibiotics with improvement in her dyspnea and functional status. Her CT images were reviewed at the multidisciplinary cardiothoracic surgery conference however, she was not an ideal candidate for lobectomy due to osteoporosis and kyphosis. She was medically optimized with trelegy, smoking cessation, and pulmonary rehabilitation and fortunately has had a significant reduction in the frequency of hospital admissions. DISCUSSION: Interestingly, this patient had two rare conditions: PS and pulmonary actinomycosis. As a congenital malformation, PS is usually diagnosed in childhood. It is incredibly rare for a malformation to be discovered in an adult older than 50 years old. The treatment of symptomatic lesions has historically been surgical resection, however transarterial embolization is emerging as a possible therapy. Recurrent pneumonia is a frequent presenting symptom of PS and the most commonly identified agent is Pseudomonas aeruginosa. The incidence of pulmonary actinomycosis is now incredibly rare with the frequent use of antibiotics. Actinomycosis has been noted in immunocompetent patients with structural lung disease, however the literature is limited.CONCLUSIONS: While the incidence of PS is quite rare, it is not unreasonable to include congenital lung malformations in the differential diagnosis of recurrent localized pneumonia or recurrent hemoptysis. Frequent admissions for either warrant additional investigation with advanced imaging or bronchoscopy.