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Abstract Introduction Dry eye can compromise corneal astigmatism measurement repeatability during preoperative cataract surgery examination. No previous studies have analyzed the effectiveness of long-acting 3% diquafosol sodium (LA-DQS) on astigmatism measurement repeatability. This research assessed the effect of LA-DQS on astigmatism measurement repeatability in preoperative patients with cataract and short tear break-up time (TBUT) type dry eyes in both eyes of the same patient. Correlations between repeatability and TBUT, corneal high-order aberrations (HOAs), and corneal astigmatism magnitude were also analyzed. Methods In total, 122 eyes (61 patients) with short TBUT-type dry eye were enrolled. Preoperatively, only one eye of all patients was treated with LA-DQS for 4 weeks. TBUT and corneal HOAs were checked using CASIA 2 before and 4 weeks post-treatment. The cylindrical power and meridian of astigmatism were measured at 3- and 4-week post-treatment using IOLMaster 700. Power vectors J0 and J45 were used for astigmatism calculations. Repeatability of astigmatism measurements was assessed as the within-subject standard deviation (Sw). The relative effects of TBUT and HOAs on J0 Sw and J45 Sw were also analyzed. Comparative changes in these variables were evaluated between treated and non-treated eyes, with additional analysis of their correlations. Results Treated eyes exhibited significant improvements in TBUT, HOAs, and post-treatment measurements of J0 Sw and J45 Sw at 3 and 4 weeks. In non-treated eyes, J0 Sw and J45 Sw showed significant correlation with TBUT and corneal HOAs. HOAs showed stronger relative associations with J0 Sw and J45 Sw than TBUT. In non-treated eyes, no significant correlation was found between cylindrical power and astigmatism measurement repeatability. Conclusions In short TBUT-type dry eye, preoperative treatment with LA-DQS significantly improved astigmatism measurement repeatability. This may improve the precision of intraocular lens (IOL) power calculations regardless of the magnitude of corneal astigmatism, especially when toric IOLs are used.

Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1–7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525.

Grape berry skin coloration is a key determinant of the commercial value of red wines. Global warming caused by climate change has inhibited anthocyanin biosynthesis in berry skins, leading to poor coloration. Through two-year field experiments, the endophyte che218 isolated from grape shoot xylem promoted anthocyanin accumulation in berry skins. The che218 enhanced anthocyanin biosynthesis in grapevine cultured cells. In the 2022 growing season, applying che218 to grape bunches enhanced anthocyanin accumulation in berry skins on day 20 post-treatment. However, the anthocyanin accumulation enhancing effect of che218 became negligible at harvest. In the 2023 growing season, che218 enhanced anthocyanin accumulation in berry skins on day 15 post-treatment and at harvest (day 30 post-treatment) and also upregulated the transcription of mybA1 and UFGT, two genes that regulate anthocyanin biosynthesis in berry skins. Whole genome sequencing demonstrated that che218 is an unidentified Microbacterium species. However, it remains unknown how che218 is involved in the biosynthesis of anthocyanin in berry skins. This study provides insights into the development of an eco-friendly endophyte-mediated technique for improving grape berry skin coloration, thereby mitigating the effects of global warming on berry skin coloration.

Background: Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. ATL, especially the aggressive type, is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent-type cases, that is, smoldering ATL, the average survival time is 55.0 months. Case Presentation: Five patients with ATL were followed up for their clinical course after amplified natural killer cell (ANK) therapy. Four patients who received ANK therapy as first-line therapy achieved complete remission and showed long-term survival without aggressive conversion or relapse for more than 5 years. One patient was treated with multiagent chemotherapy due to acute exacerbation but relapsed 2 months later. She was subsequently treated with radiation and ANK therapy and survived for more than 6 years. Furthermore, ANK therapy enhanced the immune function of ATL patients to a level higher than that of normal individuals. Conclusions: ANK therapy has great potential as first-line treatment for ATL.

Abstract Introduction Although uncommon, incomplete capsulotomy, anterior capsule tags and anterior capsule tears are still encountered during femtosecond laser-assisted cataract surgery (FLACS), resulting in surgical complications. This highlights the need to improve femtosecond laser-assisted capsulotomy technique to reduce capsulotomy-related complications. Therefore, the purpose of this study was to investigate the efficacy of a newly developed, modified technique of setting capsulotomy irradiation thickness in lowering the incidence of capsulotomy-related complications in FLACS. Methods This open-label prospective, comparative cohort study included 440 eyes (220 patients) treated with FLACS using the LenSx laser system (Alcon Laboratories, Inc. Fort Worth, TX, USA). Varying capsulotomy irradiation thicknesses were applied in each eye of the same patient. In Group 1, capsulotomy irradiation thickness was set between the upper edge of the highest point of the anterior capsule and the lower edge of the lowest point of the anterior capsule (modified technique). In Group 2, this was set between the center of the highest point of the anterior capsule and the center of the lowest part of the anterior capsule (conventional technique). Incidence rates of incomplete capsulotomy, anterior capsule tags and tears, and posterior capsule tears were compared. Results Preoperative baseline characteristics showed no significant differences. Mean total of the irradiation thicknesses was 877.1 ± 81.9 µm in Group 1 and 808.9 ± 80.0 in Group 2, with a statistically significant difference (P

Objectives: The mitochondrial DNA (mtDNA) is unique and circular with multiple copies of the genome. The lower mtDNA copy number (mtDNA-CN) in leukocytes is associated with the risk of all-cause mortality. However, its long-term association is unknown. Thus, the study examined the association between mtDNA-CN and the risk of all-cause mortality in a long-term follow-up study in the Japanese population. Design: This longitudinal study included the study cohort from an annual, population-based health checkup in the town of Yakumo, Hokkaido, Japan. Setting and Participants: 814 participants (baseline age range: 38–80 years, mean: 56.3 years) were included in this study in 1990. They were followed-up regarding mortality for about 30 years (median: 28.1 years) till 2019. Measures: The genomic DNA was extracted from peripheral blood mononuclear cells and the mtDNA-CN was measured using real-time polymerase chain reaction. The level of the mtDNA-CN was divided into tertiles (low, middle, and high). The participants were categorized based on their age into middle-aged (

Some food allergic patients who have undergone oral immunotherapy develop exercise-induced allergic reactions on desensitization (EIARDs). This study investigated basophil activation status during the exercise provocation test (EPT) performed to diagnose EIARD. EPT was performed on 20 participants, and in vivo basophil activation status was analyzed using activation markers CD203c and CD63. The results showed that there was no significant difference between EPT-positive and negative subjects for basophil activation status throughout EPT. Consequently, in vivo basophil activation after ingestion of the causative food may not be associated with EIARDs. New tests are desired for predicting EIARDs.

Abstract Background Differences between programmed capsulorhexis diameter and actual resulting capsulorhexis diameter (ARCD) are commonly encountered in femtosecond laser-assisted cataract surgery (FLACS). The purpose of this study was to identify the preoperative ophthalmic variables influencing capsulorhexis diameter index (CDI) in FLACS for adults and create a multiple linear regression model for obtaining a more accurate capsulorhexis diameter. Methods This retrospective study involved sixty-seven eyes of 44 patients who received FLACS and intraocular lens implantation. The ARCD was measured using anterior segment swept-source optical coherence tomography (CASIA 2). Keratometry (K1, K2 and average K), anterior chamber depth (ACD), lens thickness (LT), anterior chamber width (ACW), white-to-white (WTW), curvature radius of anterior lens capsule (Front R) and axial length (AL) were all measured preoperatively. Based on the derived data, LT/ACW, LT/AL, LT/ACD and LT/ACW/Front R were calculated. The ratio of the programmed capsulorhexis diameter and ARCD was defined as the CDI. Correlation analysis was conducted to examine the relationship between preoperative variables listed above and the CDI. Multiple linear regression analysis was applied to select the most influential preoperative variables on CDI. Results ACD, LT, ACW, Front R, AL, LT/ACW, LT/AL, LT/ACD, and LT/ACW/Front R showed significant correlation with CDI. Front R and LT/ACW/Front R were selected as constants in the multiple linear regression model using stepwise variable selection. The following equation represents the multiple linear regression model: CDI = 1.306–4.516 × LT/ACW/FrontR-0.011 × Front R, when P

Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative treatment for myelodysplastic syndromes (MDS), although predicting post-transplant outcomes remains inconclusive. This study evaluated patients who underwent allo-HCT for MDS to identify prognostic factors and develop a clinical risk model.Methods: We evaluated 55 patients between June 2000 and March 2015 to identify prognostic factors and develop a model for three-year overall survival (OS) and event-free survival (EFS). Cox regression analysis was performed on four factors: age ≥55 years; Hematopoietic Cell Transplant-Comorbidity Index >2; intermediate or worse cytogenetic status based on revised International Prognostic Scoring System; and unrelated donor status associated with poor OS in the univariate analysis. A clinical risk model was constructed using the sum of the regression coefficients and evaluated using receiver operating characteristic analysis and five-fold cross-validation.Results: Patient median age was 51 (range: 30–67) years. Median follow-up was 45.8 (range: 1.27–193) months; the three-year OS and EFS rates were 61.8% and 56.4%, respectively. The areas under the curves (AUCs) for OS and EFS were 0.738 and 0.778, respectively, and the average AUC for 50 times five-fold cross-validation were 0.711 and 0.723 for three-year OS and EFS, respectively.Conclusion: A four-clinical-risk-factor model that could effectively predict post-transplantation outcomes and help decision-making in MDS treatment was developed.

Medical illustrations represent a precious resource for learning surgical anatomy and surgical techniques, allowing preoperative and postoperative reviews. As traditional hand-drawn illustrations are difficult to use and expressing the area of neurointerventional surgery is time-consuming, we proposed methods for neurointerventional surgeons to create digital illustrations (DIs) for neurointerventional surgery using the iPad-exclusive Procreate application (Savage Interactive, Hobart, Australia). Dedicated "digital pens" were created and used for each endovascular device, creating straightforward representations of neurointerventional procedures and changes over time. DIs in neurointervention easily depict changes to highlighted surgical scenes for various devices with complex configurations and structures. DIs are also versatile, allowing easy intrainstitutional and interinstitutional sharing and discussion of technical tips on the manipulation of medical devices (coils, catheters, stents, etc.) among neurointerventional surgeons worldwide. DIs can be applied as educational tools not only in neurointerventional surgery, but also in craniotomy surgery and for surgical records from other specialties. [ABSTRACT FROM AUTHOR]

Purpose: Although stent-assisted technique is expected to help provide a scaffold for neointima formation at the orifice of the aneurysm, not all aneurysms treated with stent-assisted technique develop complete neointima formation. The white-collar sign (WCS) indicates neointimal tissue formation at the aneurysm neck that prevents aneurysm recanalization. The aim of this study was to explore factors related to WCS appearance after stent-assisted coil embolization of unruptured intracranial aneurysms (UIAs). Methods: A total of 59 UIAs treated with a Neuroform Atlas stent were retrospectively analyzed. The WCS was identified on digital subtraction angiography (DSA) 1 year after coil embolization. The cohort was divided into WCS-positive and WCS-negative groups, and possible predictors of the WCS were explored using logistic regression analysis. Results: The WCS appeared in 20 aneurysms (33.9%). In the WCS-positive group, neck size was significantly smaller (4.2 (interquartile range (IQR): 3.8–4.6) versus 5.4 (IQR: 4.2–6.8) mm, p =.006), the VER was significantly higher (31.8% (IQR: 28.6%–38.4%) versus 27.6% (IQR: 23.6%–33.8%), p =.02), and the rate of RROC class 1 immediately after treatment was significantly higher (70% vs 20.5%, p <.001) than in the WCS-negative group. On multivariate analysis, neck size (odds ratio (OR): 0.542, 95% confidence interval (CI): 0.308–0.954; p =.03) and RROC class 1 immediately after treatment (OR: 6.99, 95% CI: 1.769–27.55; p =.006) were independent predictors of WCS appearance. Conclusions: Smaller neck size and complete occlusion immediately after treatment were significant factors related to WCS appearance in stent-assisted coil embolization for UIAs using the Neuroform Atlas stent. [ABSTRACT FROM AUTHOR]

Grape berry skin coloration is a key determinant of the commercial value of red wines. Global warming caused by climate change has inhibited anthocyanin biosynthesis in berry skins, leading to poor coloration. Through two-year field experiments, the endophyte che218 isolated from grape shoot xylem promoted anthocyanin accumulation in berry skins. The che218 enhanced anthocyanin biosynthesis in grapevine cultured cells. In the 2022 growing season, applying che218 to grape bunches enhanced anthocyanin accumulation in berry skins on day 20 post-treatment. However, the anthocyanin accumulation enhancing effect of che218 became negligible at harvest. In the 2023 growing season, che218 enhanced anthocyanin accumulation in berry skins on day 15 post-treatment and at harvest (day 30 post-treatment) and also upregulated the transcription of mybA1 and UFGT, two genes that regulate anthocyanin biosynthesis in berry skins. Whole genome sequencing demonstrated that che218 is an unidentified Microbacterium species. However, it remains unknown how che218 is involved in the biosynthesis of anthocyanin in berry skins. This study provides insights into the development of an eco-friendly endophyte-mediated technique for improving grape berry skin coloration, thereby mitigating the effects of global warming on berry skin coloration. [ABSTRACT FROM AUTHOR]

Background: Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. ATL, especially the aggressive type, is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent-type cases, that is, smoldering ATL, the average survival time is 55.0 months. Case Presentation: Five patients with ATL were followed up for their clinical course after amplified natural killer cell (ANK) therapy. Four patients who received ANK therapy as first-line therapy achieved complete remission and showed long-term survival without aggressive conversion or relapse for more than 5 years. One patient was treated with multiagent chemotherapy due to acute exacerbation but relapsed 2 months later. She was subsequently treated with radiation and ANK therapy and survived for more than 6 years. Furthermore, ANK therapy enhanced the immune function of ATL patients to a level higher than that of normal individuals. Conclusions: ANK therapy has great potential as first-line treatment for ATL. [ABSTRACT FROM AUTHOR]

Takeshi Teshigawara,1– 3 Akira Meguro,3 Nobuhisa Mizuki3 1Department of Ophthalmology, Yokosuka Chuoh Eye Clinic, Yokosuka, Kanagawa, 238-0008, Japan; 2Tsurumi Chuoh Eye Clinic, Yokohama, Kanagawa, 230-0051, Japan; 3Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, 236-0004, JapanCorrespondence: Takeshi TeshigawaraDepartment of Ophthalmology, Yokosuka Chuoh Eye Clinic, 2-6 Odaki-cho, Yokosuka, Kanagawa, 238-0008, JapanTel +81 46 827 4001Fax +81 46 827 4141Email teshitake@gmail.comPurpose: Halos are a chief source of patient dissatisfaction after multifocal intraocular lens (IOL) implantation. The primary purpose of this study was to investigate the influence of age, postoperative refraction, and pre- and postoperative pupil size on postoperative halo size with a trifocal diffractive IOL (AcrySof IQ PanOptix) and extended depth-of-focus (EDOF) IOL (TECNIS Symfony) to determine whether these factors could predict postoperative halo size.Patients and Methods: This single-center, open-label study conducted between October 2018 and April 2020 in Yokosuka, Japan included 160 patients: 80 with PanOptix and 80 with Symfony IOLs. Size and intensity of the halos were examined binocularly using a computer-based simulator (Eyeland Design Network GmbH) and scored from 0 (minimum) to 10 (maximum) at 1, 3, and 6 months postoperatively, along with the change in each variable for both IOLs. The respective correlations of halo size with age, postoperative refraction, pre- and postoperative pupil size, and discomfort level due to the halo were also investigated 6 months postoperatively.Results: Halo size and intensity were significantly mitigated between 1, 3, and 6 months postoperatively. Throughout the observation period, halo size was significantly larger with PanOptix than with Symphony (P < 0.05), and halo intensity was significantly higher with Symphony than with PanOptix (P < 0.05). The pre- and postoperative pupil size correlated positively with halo size, while age and postoperative refraction were negatively correlated, for both IOLs.Conclusion: Understanding the features and predictive preoperative factors of halos in different types of multifocal IOLs may be useful in improving patient satisfaction.Keywords: halo size, multifocal intraocular lens, biometric predictable factors, trifocal intraocular lens, extended depth-of-focus intraocular lens, photic phenomena, halo

BackgroundSystemic allergic reaction is characterized by vasodilation and vascular leakage, which causes a rapid, precipitous and sustained decrease in arterial blood pressure with a concomitant decrease of cardiac output. Histamine is a major mediator released by mast cells in allergic inflammation and response. It causes a cascade of inflammation and strongly increases vascular permeability within minutes through its four G-protein-coupled receptors (GPCRs) on endothelial cells. High mobility group box-1 (HMGB1), a nonhistone chromatin-binding nuclear protein, can be actively secreted into the extracellular space by endothelial cells. HMGB1 has been reported to exert pro-inflammatory effects on endothelial cells and to increase vascular endothelial permeability. However, the relationship between histamine and HMGB1-mediated signaling in vascular endothelial cells and the role of HMGB1 in anaphylactic-induced hypotension have never been studied.Methods and resultsEA.hy 926 cells were treated with different concentrations of histamine for the indicated periods. The results showed that histamine induced HMGB1 translocation and release from the endothelial cells in a concentration- and time-dependent manner. These effects of histamine were concentration-dependently inhibited by d-chlorpheniramine, a specific H1 receptor antagonist, but not by H2 or H3/4 receptor antagonists. Moreover, an H1-specific agonist, 2-pyridylethylamine, mimicked the effects of histamine, whereas an H2-receptor agonist, 4-methylhistamine, did not. Adrenaline and noradrenaline, which are commonly used in the clinical treatment of anaphylactic shock, also inhibited the histamine-induced HMGB1 translocation in endothelial cells. We therefore established a rat model of allergic shock by i.v. injection of compound 48/80, a potent histamine-releasing agent. The plasma HMGB1 levels in compound 48/80-injected rats were higher than those in controls. Moreover, the treatment with anti-HMGB1 antibody successfully facilitated the recovery from compound 48/80-induced hypotension.ConclusionHistamine induces HMGB1 release from vascular endothelial cells solely through H1 receptor stimulation. Anti-HMGB1 therapy may provide a novel treatment for life-threatening systemic anaphylaxis.

Abstract Treatment of recurrent ruptured aneurysms incorporating a branch vessel arising from the dome is challenging. Here, we attempted horizontal stent‐assisted coil embolization via a retrograde route from the contralateral internal carotid artery to treat a small ruptured posterior communicating artery aneurysm incorporating a fetal variant posterior cerebral artery after clipping.

Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.

We previously reported that maternal fructose consumption increases blood corticosterone levels in rat offspring. However, the underlying mechanism of action remains unclear. In the present study, we aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring (GC; corticosterone in rodents and cortisol in humans). Female Sprague Dawley rats received HFCS solution during gestation and lactation. The male offspring were fed distilled water from weaning to 60 days of age. We investigated the activities of GC-metabolizing enzymes (11β-Hsd1 and 11β-Hsd2) in various tissues (i.e., liver, kidney, adrenal glands, muscle, and white adipose tissue) and epigenetic modification. 11β-Hsd2 activity decreased in the kidney of the HFCS-fed dams. Moreover, the epigenetic analysis suggested that miR-27a reduced Hsd11b2 mRNA expression in the kidney of offspring. Maternal HFCS-induced elevation of circulating GC levels in offspring may be explained by a decrease in 11β-Hsd2 activity via renal miR-27a expression. The present study may allow us to determine one of the mechanisms of GC elevation in rat offspring that is often observed in the developmental origins of the health and disease (DOHaD) phenomenon.