Effect of Alpha-Glucosyl-Hesperidin Consumption on Lens Sclerosis and Presbyopia.

Presbyopia is characterized by a decline in the ability to accommodate the lens. The most commonly accepted theory for the onset of presbyopia is an age-related increase in the stiffness of the lens. However, the cause of lens sclerosis remains unclear.

Adding melphalan to fludarabine and a myeloablative dose of busulfan improved survival after allogeneic hematopoietic stem cell transplantation in a propensity score-matched cohort of hematological malignancies.

Fludarabine and a myeloablative dose of busulfan (Flu/Bu4) can improve prognosis after allogeneic hematopoietic stem cell transplantation (HSCT) with melphalan (Mel). We investigated the prognostic impact of adding Mel to Flu/Bu4 by comparing between Flu/Bu4/Mel and Flu/Bu4 groups. This study included 846 propensity score (PS)-matched patients who received either Flu/Bu4/Mel (n = 423) or Flu/Bu4 (n = 423) from 2394 patients enrolled in a multicenter prospective registry, from January 2010 to December 2016.

Irrigating Acetic Acid Solution During Colonoscopy for the Detection of Sessile Serrated Neoplasia: A Randomized Controlled Trial.

Background: Misdiagnosed sessile serrated lesions (SSLs) are important precursors for interval colorectal cancers.

Aims: We investigated the usage of acetic acid (AA) solution for improving the detection of SSLs in the right colon in a randomized controlled trial.

Methods: A tandem observation of the right colon was performed in 412 consecutive patients.

Multi-functionality of a tryptophan residue conserved in substrate-binding groove of GH19 chitinases.

GH19 and GH22 glycoside hydrolases belonging to the lysozyme superfamily have a related structure/function. A highly conserved tryptophan residue, Trp103, located in the binding groove of a GH19 chitinase from moss Bryum coronatum (BcChi-A) appears to have a function similar to that of well-known Trp62 in GH22 lysozymes. Here, we found that mutation of Trp103 to phenylalanine (W103F) or alanine (W103A) strongly reduced the enzymatic activity of BcChi-A.

Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis.

Objectives: This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM).

Methods: We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database.

Result: At the start of IRd, the median age was 72 years, 66.

A triplet combination of FOLFOXIRI plus cetuximab as first-line treatment in RAS wild-type, metastatic colorectal cancer: a dose-escalation phase Ib study.

Background: The triplet-agent (5-fluorouracil/leucovorin, oxaliplatin, and irinotecan; FOLFOXIRI) combined with an anti-epidermal growth factor receptor antibody as a first-line treatment of metastatic colorectal cancer (mCRC) has shown promising results in Western trials. This phase Ib study assessed the safety of FOLFOXIRI plus cetuximab in Japanese patients with RAS wild-type mCRC.

Methods: Patients with previously untreated RAS wild-type mCRC received weekly cetuximab (400 mg/m at week 1 and subsequently 250 mg/m) plus FOLFOXIRI that consisted of irinotecan (100, 120, and 150 mg/m defined as dose levels 0, 1, and 2), followed by oxaliplatin 85 mg/m and l-leucovorin 200 mg/m and then 5-fluorouracil 2400 mg/m.

Effect of Sensitivity Disparity Between the Two Eyes on Pointwise Monocular Sensitivity Under Binocular Viewing in Patients With Glaucoma.

Prcis: A difference between monocular sensitivities measured with and without occlusion was observed in glaucoma. Monocular sensitivity without occlusion could have been affected differently by binocular interaction due to the sensitivity disparity between both eyes.

Purpose: To investigate the influence of sensitivity disparity between both eyes on visual field results under binocular viewing in glaucoma.

Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study.

A previous dose-finding study has suggested that romiplostim is effective in patients with refractory aplastic anaemia (AA) and 10 µg/kg once weekly was recommended as a starting dose. In this Phase II/III, multicentre, open-label study, romiplostim was administered subcutaneously at a fixed dose of 10 µg/kg once weekly for 4 weeks (weeks 1-4) followed by weekly doses (5, 10, 15 and 20 µg/kg) titrated by platelet response for up to 52 weeks (weeks 5-52). A total of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and thrombocytopenia (platelet count of ≤30 × 10 /l) were enrolled.

Targeting Dormant Ovarian Cancer Cells and in an Mouse Model of Platinum Resistance.

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers.

AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B.

Imatinib is the gold standard in the conventional treatment of chronic myeloid leukemia (CML). However, some patients become resistant to imatinib therapy. To overcome this resistance, second‑generation (dasatinib, nilotinib, and bosutinib) and third‑generation (ponatinib) tyrosine kinase inhibitors (TKIs) have been developed and have been shown to be effective against refractory CML.

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset.

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety.

International severe asthma registry (ISAR): protocol for a global registry.

Background: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour.

Impact of climate and ambient air pollution on the epidemic growth during COVID-19 outbreak in Japan.

Coronavirus disease 2019 (COVID-19) rapidly spread worldwide in the first quarter of 2020 and resulted in a global crisis. Investigation of the potential association of the spread of the COVID-19 infection with climate or ambient air pollution could lead to the development of preventive strategies for disease control. To examine this association, we conducted a longitudinal cohort study of 28 geographical areas of Japan with documented outbreaks of COVID-19.

Functional role of phosphatidylcholine-specific phospholipase C in regulating leukotriene synthesis and degranulation in human eosinophils.

Phosphatidylinositol-specific phospholipase C (PI-PLC) and cytosolic phospholipase A (cPLA) regulate both eosinophil degranulation and leukotriene (LT) synthesis via PI-PLC-mediated calcium influx and cPLA activation. Phosphatidylcholine-specific phospholipase C (PC-PLC) likely plays a key role in cellular signaling, including the eosinophilic allergic inflammatory response. This study examined the role of PC-PLC in eosinophil LT synthesis and degranulation using tricyclodecan-9-yl-xanthogenate (D609), a PC-specific PLC inhibitor.

Chemical Defense of Yacón () Leaves against Phytophagous Insects: Insect Antifeedants from Yacón Leaf Trichomes.

Yacón is a perennial crop with high insect resistance. Its leaves have many glandular trichomes, which may be related to pest resistance. In order to collect the constituents of glandular trichomes, leaves were rinsed using dichloromethane (DCM) to obtain the rinsate, and the plant residues were subsequently extracted by DCM to obtain a DCM extract containing the internal constituents of yacón leaves.

A Simple Screening Method for Extra Virgin Olive Oil Adulteration by Determining Squalene and Tyrosol.

A simple screening method for discrimination between commercial extra virgin olive oils and their blends with other vegetable oils was developed. Squalene, which was contained relatively high amounts in virgin olive oil, was determined by HPLC after a simple pretreatment that was carried out by dilution of oil samples with 2-propanol. Tyrosol, which was contained at relatively high concentration in virgin olive oil among phenolic compounds, was determined by HPLC after a simple liquid-liquid extraction.

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer.

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.

Predictors of decline in vitamin D status in middle-aged and elderly individuals: a 5-year follow-up study.

Little is known about predictors of decline in vitamin D status (vitamin D decline) over time. We aimed to determine demographic and lifestyle variables associated with vitamin D decline by sufficiently controlling for seasonal effects of vitamin D uptake in a middle-aged to elderly population. Using a longitudinal study design within the larger framework of the Murakami Cohort Study, we examined 1044 individuals aged between 40 and 74 years, who provided blood samples at baseline and at 5-year follow-up, the latter of which were taken on a date near the baseline examination (±14 d).

Geranylated Coumarins From Thai Medicinal Plant With Testosterone 5α-Reductase Inhibitory Activity.

Geranylated coumarin constituents, kayeassamin I () and mammeasins E () and F () were newly isolated from the methanol extract of the flowers of (Calophyllaceae) originating in Thailand, along with five known isolates, such as mammea E/BC (), deacetylmammea E/AA cyclo D (), deacetylmammea E/BB cyclo D (), mammea A/AA cyclo F (), and mammea A/AC cyclo F (). These compounds (-) were obtained as an inseparable mixture (. 1:1 ratio) of the 3″ and 3″ forms, respectively.

Oral Administration System Based on Meloxicam Nanocrystals: Decreased Dose Due to High Bioavailability Attenuates Risk of Gastrointestinal Side Effects.

Meloxicam (MLX) is widely applied as a therapy for rheumatoid arthritis (RA); however, it takes far too long to reach its peak plasma concentration for a quick onset effect, and gastrointestinal toxicity has been observed in RA patients taking it. To solve these problems, we designed MLX solid nanoparticles (MLX-NPs) by the bead mill method and used them to prepare new oral formulations. The particle size of the MLX-NPs was approximately 20-180 nm, and they remained in the nano-size range for 1 month.

Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors.

HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or -mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting.