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The cDNA library prepared from Lentinula edodes, Hokken 600 (H600), primordia was screened using cDNA expressed specifically in Dictyostelium discoideum prestalk as a probe. Twenty-one clones, Le-Dd1 ~ 21, were isolated from the L. edodes primordia cDNA library. Functional analysis of each gene was carried out by transformation into protoplast cells from L. edodes Mori 252 (M252) mycelia with the overexpression vector pLG-RasF1 of each gene because M252 protoplast cells were transformed with an 11-fold higher efficiency than H600 cells. Transformants with the overexpression vector of Le-Dd10 formed a fruiting body at almost the same time as H600, a positive control, although M252, a negative control, did not form a fruiting body under culture conditions. This suggested that Le-Dd10 is involved in the formation of fruiting bodies. Single-strand conformation polymorphism analysis revealed that Le-Dd10 is located on No. 4 linkage group of L. edodes. The properties of Le-Dd10 products were investigated by Western blotting analysis using polyclonal antibodies against GST:Le-Dd10 fusion proteins. As a result, 56-kDa, 27-kDa, and 14-kDa protein bands appeared in primordial and fruiting body stages, although the expected molecular weight of the Le-Dd10 product was 50 kDa. [ABSTRACT FROM AUTHOR]

Aims: Sleep-disordered breathing (SDB) is a well-known risk factor for cardiovascular outcomes. Studies of patients with SDB have identified frequent night-time urination as a manifestation related to SDB. We aimed to clarify whether night-time frequency of urination is independently associated with SDB in a general population. We also investigated whether night-time frequency of urination can help presumptive diagnose SDB.Methods: Study participants consisted of 7151 community residents. Oxygen saturation during sleep was measured for four nights using a pulse oximeter. SDB was defined as ≥15 events per hour in which oxygen desaturation exceeded or equal to 3% during an actigraphy-determined sleep period. Night-time frequency of urination was recorded for one week using a sleep diary.Results: Significant positive correlations were evident between night-time frequency of urination and SDB (none, 5.8%; once/night, 14.1%; twice/night, 20.1%; thrice/night, 28.7%; >thrice/night, 44.1%, P < 0.001). This association was independent of possible covariates, including sleep duration (adjusted odds ratio: once/night = 1.50, twice/night = 2.15, thrice/night = 3.07, >thrice/night = 3.73, P < 0.001). Other factors significantly associated with SDB were age, sex, obesity, observation of sleep apnea, and short sleep duration. The area under the curve of the risk score for SDB consisting of these conventional six items (0.834) significantly improved (0.842, P = 0.001) when night-time frequency of urination was considered as a risk score item.Conclusion: Night-time frequency of urination was associated with SDB. Our findings suggest that the urination frequency should be considered a manifestation of SDB even in a general population. [ABSTRACT FROM AUTHOR]

Severe post‐transplant hypoxemia, which is defined as <50 mm Hg of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) ratio, is a major post‐operative complication with high mortality rates in patients with hepatopulmonary syndrome (HPS). Non‐invasive positive pressure ventilation therapy and mechanical ventilation are options for respiratory support of patients with severe post‐transplant hypoxemia. However, these therapies are associated with several problems, such as compliance, ventilator‐associated pneumonia, and lung injury. We here firstly described two children with HPS who developed severe post‐transplant hypoxemia (lowest post‐operative P/F ratio, 49.7 and 34.0 mm Hg, respectively) that was successfully managed with high‐flow nasal cannula (HFNC) oxygen therapy and vasodilation drugs without adverse complications or necessity of reintubation. We consider that HFNC oxygen therapy could become a safe alternative respiratory therapy or be added to the other such as inhaled nitric oxide (iNO), methylene blue (MB), inhaled epoprostenol, embolization of abnormal pulmonary vessels, and combination of iNO and MB for severe post‐transplant hypoxemia in children with HPS. [ABSTRACT FROM AUTHOR]

We attempted to identify the total proteome in sesame lipid droplets. Results from two-dimensional electrophoresis showed 139 protein spots in lipid droplet samples. Each spot was isolated, digested with trypsin, and applied to liquid chromatography–tandem mass spectrometry (Q-Tof Premier). As a result, 103 spots were identified. Although oleosin, caleosin, and steroleosin are known major components of the lipid droplet, many other proteins were also found in the lipid droplet. In addition to the three major proteins, TAG factor protein, glyceraldehyde-3-phosphate dehydrogenase, F1 ATPase, 70-kDa heat shock protein, seed maturation protein PM24, and 11S globulin precursor isoforms 3 and 4 were found in the lipid droplet. Three types of oleosins, 15-, 15.5-, and 17-kDa were present in the sesame lipid droplet, and the 15.5-kDa oleosin had high homology with oleosin from Coffea canephora. It has been shown by acid phosphatase treatment that oleosin proteins contain phosphate groups. Protein disulfide-isomerase 2 precursor, calreticulin-1, and BiP, which are known as marker proteins of the endoplasmic reticulum, were found as the components of the lipid droplet. Immunoconfocal microscopy was used to show that 11S globulin precursor isoform 3 and 4 were indeed localized in the lipid droplet. The presence of 11S globulin in the lipid droplets suggested a new mechanism for the lipid droplet formation. [ABSTRACT FROM AUTHOR]

The airway epithelium acts as a frontline barrier against various environmental insults and its repair process after airway injury is critical for the lung homeostasis restoration. Recently, the role of intracellular reactive oxygen species (ROS) as transcription-independent damage signaling has been highlighted in the wound repair process. Both conditions of continuous hypoxia and intermittent hypoxia (IH) induce ROS. Although IH is important in clinical settings, the roles of IH-induced ROS in the airway repair process have not been investigated. In this study, we firstly showed that IH induced mitochondrial hydrogen peroxide (H 2 O 2 ) production and significantly decreased bronchial epithelial cell migration, prevented by catalase treatment in a wound scratch assay. RhoA activity was higher during repair process in the IH condition compared to in the normoxic condition, resulting in the cellular morphological changes shown by immunofluorescence staining: round cells, reduced central stress fiber numbers, pronounced cortical actin filament distributions, and punctate focal adhesions. These phenotypes were replicated by exogenous H 2 O 2 treatment under the normoxic condition. Our findings confirmed the transcription-independent role of IH-induced intracellular ROS in the bronchial epithelial cell repair process and might have significant implications for impaired bronchial epithelial cell regeneration. [ABSTRACT FROM AUTHOR]

Background: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA.Research Question: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP?Study Design and Methods: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline.Results: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity.Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm. [ABSTRACT FROM AUTHOR]

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we revealed that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane (PM). Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the PM and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1. [ABSTRACT FROM AUTHOR]

Remdesivir plays a key role in the treatment of coronavirus disease in 2019 (COVID-19). Haemodialysis is sometimes required for hospitalised patients with COVID-19, and patients undergoing haemodialysis are at an increased risk of severe COVID-19. In the present study, we report the serum concentrations of GS-441524, the active metabolite of remdesivir, in four patients undergoing continuous renal replacement therapy (CRRT). Patient 1, a male aged 70s, received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg remdesivir from day 2, according to the package insert as in non-haemodialysis patients. The mean trough serum concentration of GS-441524 was 783.5 ng/mL, which was approximately 7-fold higher than the mean for patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min. Patients 2-4 received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg once every 2 days from day 2. The mean trough serum concentrations of GS-441524 were 302.2 ng/mL, 585.8 ng/mL and 677.3 ng/mL, respectively. These were 3 to 6-fold higher than the mean for patients with eGFR ≥60 mL/min. The target doses for patients 1, 2, 3, and 4 receiving CRRT were 13.6 mL/kg/h, 6.0–12.5 mL/kg/h, 20.1 mL/kg/h, and 15.1 mL/kg/h, respectively, using a polysulphone membrane. The package insert dose of remdesivir is an overdose for CRRT patients with a target dose of 10–20 mL/kg/h. In low-intensity CRRT, as in Japan, it may be necessary to extend the interval between the doses of remdesivir. [ABSTRACT FROM AUTHOR]

Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment. [ABSTRACT FROM AUTHOR]

Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment. [ABSTRACT FROM AUTHOR]

Advanced systemic sclerosis-associated interstitial lung disease (SSc-ILD) can be treated with lung transplantation. There is limited data on lung transplantation outcomes in patients with SSc-ILD, in non-Western populations.We assessed survival data of patients with SSc-ILD, on the lung transplant (LT) waiting list, and evaluated post-transplant outcomes in patients from an Asian LT center. In this single-center retrospective study, 29 patients with SSc-ILD, registered for deceased LT at Kyoto University Hospital, between 2010 and 2022, were identified. We investigated post-transplant outcomes in recipients who underwent LT for SSc-ILD, between February 2002 and April 2022. Ten patients received deceased-donor LT (34%), two received living-donor LT (7%), seven died waiting for LT (24%), and ten survived on the waiting list (34%). Median duration from registration to deceased-donor LT was 28.9 months and that from registration to living-donor LT or death was 6.5 months. Analysis of 15 recipients showed improved forced vital capacity with a median of 55.1% at baseline, 65.8% at 6 months, and 80.3% at 12 months post-transplant. The 5-year survival rate for post-transplant patients with SSc-ILD was 86.2%. The higher post-transplant survival rate at our institute than previously reported suggests that lung transplantation is acceptable in Asian patients with SSc-ILD. [ABSTRACT FROM AUTHOR]

Summary: Recently an association between blood glucose dysregulation and sleep disruption was suggested. The association between sleep disordered breathing, most of which is due to obstructive sleep apnea (OSA) in the general population, and diabetic severity, as well as the impact of antidiabetic treatment, remains unclear. This study aimed to investigate these associations as well as age and sex differences. This cross‐sectional study evaluated 7,680 community participants as the main cohort (population‐based cohort). OSA was assessed by the 3% oxygen desaturation index from pulse oximetry, which was corrected for sleep duration obtained by wrist actigraphy. For arguing the limitations for using pulse oximetry, 597 hospitalised patients, who were assessed by the apnea–hypopnea index from attended polysomnography, were also evaluated as the validation cohort (hospital‐based cohort). Moderate‐to‐severe OSA was more prevalent as haemoglobin A1c (HbA1c) levels increased (<5.6%/5.6%–<6.5%/6.5%–<7.5%/≥7.5%, respectively) in both cohorts (p < 0.001), but only in those without antidiabetic treatment. The HbA1c level was an independent factor for moderate‐to‐severe OSA (population‐based cohort, odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10–1.45; hospital‐based cohort, OR 1.69, 95% CI 1.22–2.33, per 1% increase). These associations were more prominent in the middle‐aged (aged <60 years) than in the elderly (aged ≥60 years) and in women than in men in both cohorts. The prevalence of moderate‐to‐severe OSA in patients with antidiabetic treatment in the hospital‐based cohort was ≥75% regardless of HbA1c levels. In conclusion, an association between the prevalence of OSA and HbA1c level even within or over the normal range was found only in patients without antidiabetic treatment and was more prominent in the middle‐aged and in women. [ABSTRACT FROM AUTHOR]

Living-donor lobar lung transplantation (LDLLT) remains a life-saving option for pediatric patients with respiratory failure. However, the long-term survival and post-transplant quality of adult lobar grafts transplanted into children are unknown. Therefore, this study aimed to evaluate the outcomes of pediatric LDLLT and post-transplant graft growth. We retrospectively reviewed the prospectively collected clinical data of 25 living-donor lung transplantations performed in 24 pediatric recipients aged ≤17 years. The annual pulmonary function test data and computed tomography scans of 12 recipients, followed up for >5 years without significant complications, were used to evaluate growth in height, graft function, and radiological changes. The Kaplan–Meier method and simple linear regression were performed for analysis. Bilateral lower lobe transplantation was performed in 12 patients, unilateral lower lobe transplantation in 12, and bilateral middle lobe transplantation in 1. The median volumetric size matching at transplantation was 142% (range, 54%-457%). The 5- and 10-year overall survival rates were 87.7% and 75.1༅, respectively. Chronic lung allograft dysfunction occurred in 2 patients. During a median follow-up of 6 years, the median increases in height and vital capacity were 14.4% (range, 0.80%-43.5%) and 58.5% (range, 6.7%-322%), respectively. Graft weight was positively correlated with graft volume (r2=0.622, p <0.001) after the graft volume exceeded the original lobar volume in the donor. This study shows that pediatric LDLLT offers satisfactory long-term survival, with the growth of mature adult lobes transplanted into growing children. [ABSTRACT FROM AUTHOR]

Remdesivir, a prodrug of the nucleoside analog GS‐441524, plays a key role in the treatment of coronavirus disease 2019 (COVID‐19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID‐19 with special characteristics. In this study, we aimed to measure serum GS‐441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS‐441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd) of GS‐441524. A one‐compartment model described serum GS‐441524 concentration data. The CL and Vd of GS‐441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS‐441524 using retrospectively obtained serum GS‐441524 concentrations in Japanese patients with COVID‐19, which would be helpful for optimal individualized therapy of remdesivir. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is frequently complicated by sleep disordered breathing (SDB), and previous studies have largely focused on hypoxemic SDB. Even though nocturnal hypercapnia was shown to exacerbate pulmonary hypertension, the clinical significance of nocturnal hypercapnia among PAH patients has been scarcely investigated. Method: Seventeen patients with PAH were identified from 246 consecutive patients referred to Kyoto University Hospital for the evaluation of lung transplant registration from January 2010 to December 2017. Included in this study were 13 patients whose nocturnal transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring data were available. Nocturnal hypercapnia was diagnosed according to the guidelines of the American Academy of Sleep Medicine. Associations of nocturnal PtcCO2 measurements with clinical features, the findings of right heart catheterization and pulmonary function parameters were evaluated. Results: Nocturnal hypercapnia was diagnosed in six patients (46.2%), while no patient had daytime hypercapnia. Of note, nocturnal hypercapnia was found for 5 out of 6 patients with idiopathic PAH (83.3%). Mean nocturnal PtcCO2 levels correlated negatively with the percentage of predicted total lung capacity (TLC), and positively with cardiac output and cardiac index. Conclusion: Nocturnal hypercapnia was prevalent among advanced PAH patients who were waiting for lung transplantation, and associated with %TLC. Nocturnal hypercapnia was associated with the increase in cardiac output, which might potentially worsen pulmonary hypertension especially during sleep. Further studies are needed to investigate hemodynamics during sleep and to clarify whether nocturnal hypercapnia can be a therapeutic target for PAH patients. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is an established factor in the pathogenesis and exacerbation of fatty liver disease. However, randomized controlled trials have failed to demonstrate decreases in liver fat content in OSA patients by continuous positive airway pressure (CPAP) performed for several months. The aim of this study is to investigate the impact of long-term CPAP therapy on liver fat content in OSA patients with fatty liver. Liver fat content in 61 male OSA patients was evaluated by computed tomography performed because of abdominal obesity before and after CPAP initiation. At baseline, there were 25 participants with fatty liver. Their apnea-hypopnea index and percent sleep time with oxygen saturation < 90% were greater than those in the 36 participants who did not have fatty liver (52.3 vs. 41.8/h and 30.4 vs. 14.8%, respectively). The average therapy duration was 31 months. In the analysis of the entire participant group, liver fat content did not change after CPAP therapy. In those without fatty liver, liver fat content increased accompanied by increases in BMI, whereas in the participants with fatty liver, liver fat content decreased despite stable BMI, abdominal fat distribution, and insulin resistance. In male OSA patients with abdominal obesity, decreases in liver fat content were observed after long-term CPAP therapy only when fatty liver was present at baseline. This implies that there are some conditions, such as OSA-related hypoxemia and others, which may exacerbate fatty liver and that fatty liver may improve with CPAP therapy. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionisation (MALDI) imaging mass spectrometry (IMS) allows for the simultaneous detection and imaging of several molecules in brain tissue. However, the detection of glycerolipids such as diacylglycerol (DAG) and triacylglycerol (TAG) in brain tissues is hindered inMALDI-IMS because of the ion suppression effect from excessive ion yields of phosphatidylcholine (PC). In this study, we describe an approach that employs a homogeneously deposited metal nanoparticle layer (or film) for the detection of glycerolipids in rat brain tissue sections using IMS. Surface-assisted laser desorption/ionisation IMS with sputter-deposited Pt film (Pt-SALDI-IMS) for lipid analysis was performed as a solvent-free and organic matrix-free method. Pt-SALDI produced a homogenous layer of nanoparticles over the surface of the rat brain tissue section. Highly selective detection of lipids was possible by MALDI-IMS and Pt-SALDI-IMS; MALDI-IMS detected the dominant ion peak of PC in the tissue section, and there were no ion peaks representing glycerolipids such as DAG and TAG. In contrast, Pt-SALDI-IMS allowed the detection of these glycerolipids, but not PC. Therefore, using a hybrid method combining MALDI and Pt-SALDI (i.e., matrix-enhanced [ME]-Pt-SALDI-IMS), we achieved the simultaneous detection of PC, PE and DAG in rat brain tissue sections, and the sensitivity for the detection of these molecules was better than that of MALDI-IMS or Pt-SALDI alone. The present simple ME-Pt-SALDI approach for the simultaneous detection of PC and DAG using two matrices (sputter-deposited Pt film and DHB matrix) would be useful in imaging analyses of biological tissue sections. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the usefulness of indocyanine green angiography (ICGA) to detect leaking spots and the effectiveness of ICGA-guided focal laser photocoagulation in eyes with diabetic macular edema (DME). Methods: Ten eyes (8 patients) with diffuse DME diagnosed using fluorescein angiography (FA) and refractory to a sub-Tenon injection of triamcinolone acetonide (STTA), grid laser photocoagulation, or both were enrolled. FA and ICGA were performed using the Heidelberg Retina Angiograph 2. Hyperfluorescent spots on early-phase FA and on early- and late-phase ICGA were superimposed onto the macular thickness map measured by optical coherence tomography (OCT) and counted to calculate the spot density in the area with or without macular edema (ME). ICGA-guided focal laser photocoagulation was carried out. In 7 eyes, STTA was simultaneously performed. The central macular thickness (CRT) and macular volume (MV) were measured by OCT. Results: On early-phase FA, 4.8 ± 2.3 and 2.3 ± 1.5 hyperfluorescent spots/disk area were observed inside and outside the ME, respectively. In contrast, the spot density was significantly decreased to 1.8 ± 0.9 inside the ME and was only 0.3 ± 0.4 outside the ME on late-phase ICGA (p < 0.01). The mean follow-up period after ICGA-guided photocoagulation was 19.0 months. The mean best-corrected visual acuity improved significantly from 0.77 ± 0.34 logarithm of the minimum angle of resolution at baseline to 0.52 ± 0.37 at the last visit (p < 0.01). Both CRT and MV significantly decreased (p < 0.01). Recurrence of DME was observed in 4 eyes: 3 eyes were treatable only with STTA and 1 required additional ICGA-guided laser photocoagulation. Conclusions: ICGA may be useful to detect leaking spots responsible for DME, enabling less invasive focal laser photocoagulation even in some of the eyes with diffuse DME. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background No studies have addressed the relationship between obstructive sleep apnea (OSA) and abdominal aortic calcification (AAC), a marker for subclinical atherosclerosis and future cardiovascular events. Objectives To investigate 1) the association between OSA severity and AAC, and 2) whether OSA can impact the extent of AAC independent of comorbid atherogenic risk factors. Methods 390 participants aged 40–70 years underwent polysomnography and abdominal computed tomography. AAC was separately quantified in the upper and lower abdominal aorta using the modified Agatston scoring method, and the total AAC score was calculated as a sum of the two scores. OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 87), moderate (AHI 15–30, n = 129), and severe (AHI ≥30, n = 174). Results Log-transformed total AAC score adjusted for age and body mass index (BMI) was greater in participants with an elevated AHI (3.4 for none/mild OSA, 3.7 for moderate OSA, and 4.2 for severe OSA, p = 0.04). Multivariate linear regression analysis including age and BMI as covariates showed that severe OSA was associated with higher scores for the lower and total AAC (β = 0.15 and 0.14, p = 0.01 and 0.01, respectively). The association did not persist after additionally adjusting for traditional atherogenic risk factors including visceral fat, smoking, hypertension, dyslipidemia, and diabetes. Conclusions Severe OSA was associated with a greater extent of AAC, which was dependent on coexisting atherogenic risk factors. Comorbid cardiometabolic disorders may largely mediate the association of OSA with subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Rationale: Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. Objectives: To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. Methods: Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. Results: Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m2 or visceral fat area ≥100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R2 = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent. Conclusions: Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation. [ABSTRACT FROM AUTHOR]