Global trends and scenarios for terrestrial biodiversity and ecosystem services from 1900 to 2050.

Based on an extensive model intercomparison, we assessed trends in biodiversity and ecosystem services from historical reconstructions and future scenarios of land-use and climate change. During the 20th century, biodiversity declined globally by 2 to 11%, as estimated by a range of indicators. Provisioning ecosystem services increased several fold, and regulating services decreased moderately. Going forward, policies toward sustainability have the potential to slow biodiversity loss resulting from land-use change and the demand for provisioning services while reducing or reversing declines in regulating services. However, negative impacts on biodiversity due to climate change appear poised to increase, particularly in the higher-emissions scenarios. Our assessment identifies remaining modeling uncertainties but also robustly shows that renewed policy efforts are needed to meet the goals of the Convention on Biological Diversity.

Risk Factors for Progression of Primary Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

INTRODUCTION: This study aimed to investigate intraocular pressure (IOP)-independent factors associated with the progression of primary open-angle glaucoma (POAG) with IOP ≤15 mm Hg. METHODS: POAG patients with maximum IOP ≤15 mm Hg at the Kyoto University Hospital between January 2011 and August 2021 were retrospectively enrolled. We evaluated effects of various factors on the rate of mean deviation (MD) changes in the visual field (VF) examinations using a linear mixed model. These factors included hypertension, diabetes mellitus (DM), hyperlipidemia (HL), cardiovascular disease, arrhythmia, disc hemorrhage, sleep apnea syndrome, orthopedic diseases, and malignant tumors. RESULTS: In total, 98 eyes from 68 patients were included. The baseline MD was -9.74 ± 7.85 dB. The mean rate of MD change and IOP during the observation period were -0.28 ± 0.04 dB/year and 11.8 ± 1.0 mm Hg, respectively. Comorbidity of DM or HL showed a significant positive association with the rate of MD change (ß = 0.35, p = 0.0006 and ß = 0.18, p = 0.036, respectively) in the model adjusted for age, sex, axial length, mean IOP, and standard deviation of IOP during the observation period. However, no significant association of DM or HL was found after adjusting for central corneal thickness. CONCLUSION: This study suggests that DM or HL is associated with VF deterioration in glaucoma with lower IOP, but the association may be due to differences in IOP characteristics.

Analytic and Clinical Validity of Myositis-Specific Antibodies by Line-Blot Immunoassay Is Essential.

OBJECTIVES: This study assessed the concordance between line blot (LB) and immunoprecipitation (IP) assays for detecting myositis-specific antibodies (MSAs) in idiopathic inflammatory myopathies (IIMs) and their association with IIM subtypes. METHODS: One hundred patients with IIM were enrolled, and MSA was detected using LB and IP. The IIM subtypes, including immune-mediated necrotizing myopathy-like, anti-tRNA synthetase syndrome-like, and clinically amyopathic dermatomyositis-like, were clinically diagnosed. The validity and reliability of the LB compared with the IP were evaluated. Optimal cutoff levels for LB were determined using various statistical methods including Cohen κ, Gwet's AC, diagnostic odds ratios, and receiver operating characteristic analysis. RESULTS: Line blot exhibited lower specificity and accuracy than IP in predicting IIM subtypes. Some MSAs performed better at higher LB cutoff values. Anti-signal recognition particle antibodies showed poor performance in predicting the immune-mediated necrotizing myopathy-like subtype using LB. Raising the cutoffs improved the reliability of anti-threonyl-tRNA synthetase and anti-signal recognition particle antibodies. Anti-histidyl-tRNA synthetase antibodies performed well at lower positivity, whereas diagnostic odds ratios increased for anti-transcription intermediary factor 1γ and anti-nuclear matrix protein 2 with higher cutoffs. CONCLUSIONS: Inconsistencies between LB and IP have been observed in patients with IIM. Individual optimal cutoffs for MSA by LB correlating with IP were determined. Rheumatologists should consider the differences between LB and IP results when classifying IIM subtypes.

Progression of retinitis pigmentosa on static perimetry, optical coherence tomography, and fundus autofluorescence.

In retinitis pigmentosa (RP), photoreceptor degeneration leads to progressive visual field loss and visual impairment. Several therapeutic trials are ongoing aiming to establish effective treatments. Although functional evaluations are commonly used in clinical trials, residual ellipsoid zone (EZ) measurement on optical coherence tomography has been shown to be more sensitive to detect disease progression. Establishment of sensitive outcome measurement is essential to develop new therapeutic strategies. In the current study, we evaluated the progression rates of the disease in 76 eyes of 76 patients with RP, using the residual EZ length, ring-shaped macular hyperautofluorescent (AF), and visual field. Decrease rates measured by the residual EZ area and by the hyper-AF ring area were strongly positively correlated (P < 0.0001, r = 0.71). The reduction rates of the residual EZ length and hyper-AF ring radius were constant regardless of their baseline measurements. Faster annual reduction rates of the hyper-AF ring area or radius were significantly correlated with faster visual field progression (P = 0.03, r = 0.25 and P = 0.004, r = 0.33, respectively). These findings support the usage of morphological measurements such as EZ or hyper-AF ring measurements as outcome measurement for future clinical trials for RP.

Characteristics of Eyes Requiring Trabeculotomy for Glaucoma With Steroid Treatment: Atopic Dermatitis and Factors Affecting Surgical Outcomes.

PURPOSE: The aim is to analyze the surgical outcomes of glaucomatous patients with steroid treatment and investigate the factors, including atopic dermatitis, associated with the surgical success rate. MATERIALS AND METHODS: We retrospectively enrolled participants who required first trabeculotomy for glaucoma with steroid treatment between May 2005 and February 2018 and then compared the postoperative outcomes according to the history of atopic dermatitis or surgical procedures. Surgical success was defined as postoperative IOP ≤ 21 mmHg, ≥20% reduction from baseline, and absence of reoperation. The factors influencing the surgical success rates were investigated using mixed-effects Cox regression. RESULTS: The study included 70 eyes of 46 patients (18 eyes of 12 patients with atopic dermatitis). Postoperative intraocular pressure was not significantly different between eyes with and without atopic dermatitis (12 months after the surgery: patients without atopic dermatitis, 15.4 ± 3.6 mmHg; patients with atopic dermatitis, 16.1 ± 3.9 mmHg; P = 0.65). Twelve months after the surgery, the number of postoperative medications was higher in patients with atopic dermatitis than in those without (2.8 ± 1.3 vs. 2.0 ± 1.7; P = 0.060). However, no significant differences were noted in surgical success rates between patients with atopic dermatitis and those without (P = 0.54). Mixed-effects Cox regression of surgical success rate indicated that only the number of preoperative medications significantly influenced surgical success (P = 0.03). CONCLUSIONS: Regardless of the presence of atopic dermatitis, patients taking many preoperative glaucomatous medications might require reoperation.

Influence of Trabeculectomy with Mitomycin C on Longitudinal Changes in the Visual Field in Glaucoma Patients with High Myopia.

Purpose: To evaluate the effect of trabeculectomy (Trab MMC) on visual field (VF) progression in eyes with glaucoma and high myopia. Patients and Methods: Patients diagnosed with primary open-angle glaucoma or exfoliation glaucoma who underwent Trab MMC as the first glaucoma surgery along with ≥3 VF tests preoperatively and postoperatively were enrolled. High myopia was defined as an axial length ≥26.5 mm. Postoperative reductions in intraocular pressure (IOP) were assessed by survival analysis using IOP measurements obtained preoperatively. The longitudinal trends of the outcome measures were evaluated using linear mixed models. Results: Thirty-five eyes of 32 patients were included in this study, including 22 eyes of 20 patients in non-highly myopic group and 13 eyes of 12 patients in highly myopic group. IOP decreased after Trab MMC, and the survival rate did not differ significantly in relation to axial length. Linear mixed-model analyses suggested that the inhibitory effects of Trab MMC on the rate of mean deviation (MD) changes were significant in the non-highly myopic group (-0.53 ± 0.15 dB/year preoperatively to -0.16 ± 0.13 dB/year postoperatively; P = 0.004), but not in the highly myopic group (-0.66 ± 0.19 dB/year preoperatively to -0.48 ± 0.18 dB/year postoperatively; P = 0.32). Conclusion: Trab MMC reduced IOP in both highly myopic and non-highly myopic eyes, and IOP reduction was very similar in both groups. The VF deterioration rate decreased in both groups, but the change was weaker and nonsignificant in the highly myopic group.

Effects of work-family life support program on the work-family interface and mental health among Japanese dual-earner couples with a preschool child: A randomized controlled trial.

OBJECTIVES: This study examined the effectiveness of a newly developed work-family life support program on the work-family interface and mental health indicators among Japanese dual-earner couples with a preschool child(/ren) using a randomized controlled trial with a waitlist. METHODS: Participants who met the inclusion criteria were randomly allocated to the intervention or the control groups (n = 79 and n = 85, respectively). The program comprised two 3-h sessions with a 1-month interval between them and provided comprehensive skills by including self-management, couple management, and parenting management components. The program sessions were conducted on weekends in a community center room with 3-10 participants. Outcomes were assessed at baseline, 1-month, and 3-month follow-ups. Primary outcomes were work-family balance self-efficacy (WFBSE), four types of work-family spillovers (i.e., work-to-family conflict, family-to-work conflict, work-to-family facilitation, and family-to-work facilitation), psychological distress, and work engagement reported by the participants. RESULTS: The program had significantly pooled intervention effects on WFBSE (P = .031) and psychological distress (P = .014). The effect sizes (Cohen's d) were small, with values of 0.22 at the 1-month follow-up and 0.24 at the 3-month follow-up for WFBSE, and -0.36 at the 3-month follow-up for psychological distress. However, the program had nonsignificant pooled effects on four types of work-family spillovers and work engagement. CONCLUSIONS: The program effectively increased WFBSE and decreased psychological distress among Japanese dual-earner couples with a preschool child(/ren).

Clinical significance of serum autoantibodies in patients with sarcoidosis.

BACKGROUND: The association between sarcoidosis and autoimmunity has been reported for years. However, the significance of autoantibodies in the pathophysiology and clinical management of sarcoidosis is not well understood. No autoantibodies that can be used as serologic biomarkers to diagnose the disease, monitor the state of the disease, and predict the prognosis of patients are established. METHODS: We performed a comprehensive analysis of serum autoantibodies and analyzed their associations with clinical features of sarcoidosis. RESULTS: Patients with systemic autoimmune rheumatic diseases-associated autoantibodies had a higher prevalence of advanced radiographic stage and consolidations in high-resolution computed tomography than patients without autoantibodies (p < .05). Age, sex, clinical history, pulmonary function tests, serum angiotensin-converting enzyme levels, rheumatoid factor, and the number of involved organs were not significantly different between the two groups. CONCLUSIONS: There may be an association between autoantibodies and more advanced pulmonary lesions in patients with sarcoidosis. Further investigations are needed to establish the significance of autoantibodies.

A cell-based assay for detection of anti-fibrillarin autoantibodies with performance equivalent to immunoprecipitation.

Anti-fibrillarin autoantibodies are useful for the diagnosis and prognosis of systemic sclerosis (SSc). Anti-fibrillarin produces a clumpy nucleolar pattern in indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA). Here we develop and validate a reliable cell-based anti-fibrillarin assay (Fibrillarin/CBA) for use in clinical diagnostic laboratories. A TransMembrane Signal was fused to the human fibrillarin gene (TMS-fibrillarin). HEp-2 cells overexpressing transgenic TMS-fibrillarin at the cytoplasmic membrane were used as IFA substrate in the Fibrillarin/CBA. Sixty-two serum samples with nucleolar pattern in the HEp-2 IFA (41 clumpy; 21 homogeneous/punctate) were tested for anti-fibrillarin using Fibrillarin/CBA, immunoprecipitation (IP), line-blot and ELISA. In addition, samples from 106 SSc-patients were evaluated with Fibrillarin/CBA and the results were correlated with disease phenotypes. Thirty-eight of 41 samples with the clumpy nucleolar pattern (92.7%) were positive in the Fibrillarin/CBA, while all 21 samples with other nucleolar patterns were negative. Fibrillarin/CBA results agreed 100% with IP results. Among the 38 Fibrillarin/CBA-positive samples, only 15 (39.5%) and 11 (29%) were positive for anti-fibrillarin in line-blot and ELISA, respectively. Higher frequency of diffuse cutaneous SSc (dcSSc) phenotype (72.7% vs 36.8%; p=0.022), cardiac involvement (36.4% vs 6.5%; p=0.001) and scleroderma renal crisis (18.2% vs 3.3% p = 0.028) was observed in SSc patients with positive compared to negative Fibrillarin/CBA result. Performance of Fibrillarin/CBA in the detection of anti-fibrillarin autoantibodies was comparable to the gold standard IP. Positive Fibrillarin/CBA results correlated with disease phenotypes known to be associated with anti-fibrillarin autoantibodies, underscoring the clinical validation of this novel assay.

Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage.

We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-D-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions.

Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters.

Purpose: We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production. Methods: Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs. Results: BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time. Conclusions: BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.

Clinical characteristics of idiopathic interstitial pneumonias with anti-Ro52/tripartite motif-containing 21 antibodies.

Antibodies to Ro52/tripartite motif-containing 21 (TRIM21), referred to as anti-Ro52, are found in patients diagnosed with diverse systemic autoimmune rheumatic disease and associated with interstitial lung diseases. However, little is known about the clinical characteristics of anti-Ro52 in patients with idiopathic interstitial pneumonias (IIPs). We aimed to analyze the prevalence, co-existent autoantibodies, and clinical characteristics of anti-Ro52 in patients with IIP. The study enrolled 288 patients diagnosed with IIP. Clinical, laboratory and radiographic findings of IIP patients were compared between anti-Ro52 positives and negatives. Anti-Ro52 (20/288; 6.9%), anti-ARS (18/288; 6.3%), and anti-Ro60/SS-A (16/288; 5.6%) were the most common autoantibodies detected in IIP patients. Among 20 IIP patients who had anti-Ro52, anti-ARS was present in 8 (40%) patients. The criteria for interstitial pneumonia with autoimmune features (IPAF) were significantly better fulfilled by patients with anti-Ro52 than those without (P = 0.001). Meeting serological domain (P < 0.001) and Raynaud's phenomenon (P = 0.009) were significantly more common in the anti-Ro52-positive patients. Anti-Ro52-positive IIP patients have clinical features consistent with IPAF. Anti-Ro52 may have an important role in detecting the autoimmune phenotype in IIP patients.

Clinical Significance of Antinucleolar Antibodies: Biomarkers for Autoimmune Diseases, Malignancies, and others.

Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5-9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90. ANoA has been classically known to be associated with scleroderma (SSc) and the characterization of nucleolar antigens identified several autoantigens recognized by SSc autoantibodies. The clinical association of anti-Th/To, PM-Scl, fibrillarin/U3RNP, and RNA polymerase I with SSc or SSc-overlap syndrome is well established, and commercial assays are developed. Anti-hUBF/NOR90, nucleophosmin/B23, and nucleolin/C23 are known for decades and reported in systemic autoimmune rheumatic diseases (SARDs), malignancies, graft versus host disease (GVHD), and others; however, their clinical significance remains to be established.

Association between topical ß-blocker use and asthma attacks in glaucoma patients with asthma: a cohort study using a claims database.

PURPOSE: To investigate the association between the use of topical ß-blockers and subsequent asthma attacks in glaucoma patients with asthma. METHODS: This was a retrospective longitudinal cohort study using an administrative claims database. All patients aged 20 years or older who were registered in the health insurance claims database updated and managed by JMDC Inc. (Tokyo, Japan). Patients who were newly prescribed eye drops for glaucoma treatment were identified between 2011 and 2017. The patients with glaucoma were divided into two groups: ß-blocker users and non-ß-blocker users, based on the presence of a ß-blocker in the prescribed eye drops. We investigated whether the incidence of asthma attacks in patients with previously treated asthma differed between the two groups. RESULTS: We categorized 17,666 patients in the ß-blocker-user group and 12,609 patients in the non-ß-blocker-user group. A total of 580 patients in the ß-blocker group (3.28%) and 847 in the non-ß-blocker group (6.72%) underwent asthma treatment before the prescription of anti-glaucoma eye drops (P < 0.001). Furthermore, 94 patients in the ß-blocker-user group (0.53%) and 278 in the non-ß-blocker user group (2.20%) were undergoing current treatment for asthma (P < 0.001). The adjusted hazard ratios of asthma attacks were 0.73 (95% confidence interval, 0.46-1.16, P = 0.18) in patients with a history of asthma treatment and 1.22 (95% confidence interval, 0.56-2.70, P = 0.62) in patients with current asthma treatment, compared to the non-ß-blocker-user group. CONCLUSION: Our results clarified that several patients with asthma were prescribed topical ß-blockers for glaucoma treatment. However, asthma attacks may not be significantly attributed to topical ß-blockers, even in glaucoma patients under current asthma treatment. The administration of topical ß-blockers to asthma patients could be a treatment option in the absence of other treatment options, if adequate informed consent is obtained. Further studies are needed to draw a firm conclusion on this clinical question.

Evaluation of outer nuclear layer overshadowed by retinal vessels in retinitis pigmentosa.

OBJECTIVES: We investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images. METHODS: We retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. As a control, we measured adjacent ONL thickness 100 µm superior and inferior from the vessel. Same measurements were performed in healthy subjects. We calculated the ratio of ONL thickness under vessel divided by the average of adjacent ONL thickness and defined as ONL preservation ratio. In patients with RP, the length of ellipsoid zone (EZ) from the fovea was also measured with SD-OCT vertical scans. RESULTS: Thirty EYS-associated RP patients and 25 healthy subjects were included. In both groups, ONL thickness overshadowed by retinal vessels was not significantly different from that of adjacent area. However, ONL preservation ratio of RP was larger than that of healthy control in both superior and inferior retina (1.03 vs 0.97; p < 0.01, 1.15 vs 0.95; p < 0.01, respectively). In RP, ONL preservation ratio was significantly larger in the inferior retina than superior retina (p < 0.01). Furthermore, in RP patients, the EZ length from the fovea was always shorter in the inferior than superior retina and there was a significant difference (p < 0.01). CONCLUSIONS: Patients with EYS-associated RP exhibited inferior-dominant photoreceptor death and the relative ONL preservation under retinal vessels. These results suggest that longitudinal environment light exposure may be correlated with the photoreceptor death.

Land-based climate change mitigation measures can affect agricultural markets and food security.

Earlier studies have noted potential adverse impacts of land-related emissions mitigation strategies on food security, particularly due to food price increases-but without distinguishing these strategies' individual effects under different conditions. Using six global agroeconomic models, we show the extent to which three factors-non-CO2 emissions reduction, bioenergy production and afforestation-may change food security and agricultural market conditions under 2 °C climate-stabilization scenarios. Results show that afforestation (often simulated in the models by imposing carbon prices on land carbon stocks) could have a large impact on food security relative to non-CO2 emissions policies (generally implemented as emissions taxes). Respectively, these measures put an additional 41.9 million and 26.7 million people at risk of hunger in 2050 compared with the current trend scenario baseline. This highlights the need for better coordination in emissions reduction and agricultural market management policies as well as better representation of land use and associated greenhouse gas emissions in modelling.