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Hierarchical mechanical metamaterials built with scalable tristable elements regarding ternary logic function and amplitude modulation.
involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).Background Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer. Methods In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 21 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. Secondary end points included overall survival, response duration, progressimonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group. Conclusions Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects. (Funded by Daiichi Sankyo; DESTINY-Gastric01 ClinicalTrials.gov number, NCT03329690.).This corrects the article on p. 633 in vol. 59, PMID 29869461.Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults with known risk factors of prothrombotic conditions, pregnancy, infection, malignancy, and drugs. Dutasteride is a 5α-reductase inhibitor that is used for benign prostate hypertrophy and androgenetic alopecia. To date, CVT caused by dutasteride use has not been reported. A 25-year-old male presented with headache and diplopia. He had taken 0.5 mg of dutasteride every other day for 9 months to treat alopecia. A headache developed 7 months after he started taking medication, and horizontal diplopia occurred 1 month after the onset of headache. Fundus examination showed bilateral papilledema. Brain magnetic resonance imaging showed thrombosis in the left sigmoid and transverse sinuses. Headache and diplopia improved after discontinuing dutasteride and starting anticoagulation. The results from this case report indicated dutasteride as a potential cause of CVT. Presumably, the increased estrogen level due to dutasteride use caused the formation of a thrombus.Fascicular involvement of the median nerve trunk in the upper arm is uncommon in cases of peripheral neuropathy, and its symptoms are consistent with those of anterior interosseous nerve (AIN) syndrome. We report three cases of focal anterior interosseous fascicular involvement in the median nerve trunk presenting as AIN palsy. Our report emphasizes the unique ultrasonographic and magnetic resonance imaging (MRI) features of swelling, hourglass-like constriction and torsion, and entwinement of the nerve fascicle of the dorsal region of the median nerve, which were confirmed surgically. On MRI, all patients showed denervation changes in the AIN territory, as well as in the median nerve territory, without compressing structures.Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8-7.5) at a dose of 2.6-3.6 mg/m². Two patients who needed high-dose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332-799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163-346 mg/dL) (p less then 0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. Selleck Nutlin-3a We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.Purpose Ethanol elicits several inflammatory responses and affects the innate immune response. The aim of this study was to identify the mechanism by which ethanol affects uric acid-induced NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation by regulation of aryl hydrocarbon receptor (AhR) and thioredoxin-interacting protein (TXNIP). Materials and methods Human myeloid leukemia cells (U937 cells) were used to assess the role of ethanol in NLRP3 inflammasome activation induced by monosodium urate (MSU) crystals. Expression of target molecules, such as NLRP3 inflammasome components, AhR, and TXNIP, were measured using quantitative real-time PCR and Western blot analyses. The effect of ethanol-induced TXNIP on the NLRP3 inflammasome was assessed in human macrophages transfected with TXNIP siRNA. Results U937 cells treated with 100 mM ethanol for 24 h induced NLRP3 and interleukin (IL)-1β expression. Ethanol increased reactive oxygen species generation in a time- and dose-dependent manner. AhR mRNA expression was downregulated in U937 cells treated with 100 mM ethanol, whereas CYP1A1 mRNA expression increased.
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