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Purpose To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. Design Retrospective, cross-sectional study. Participants Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April 2020. Methods All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. Main Outcome Measures To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. Results A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4% in the POAG group and 10.1% in the controls (P = 0.044); 6.4% of POAG patients and 3.4% of controls had more than 1 AiD (P = 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6%) and psoriasis (4.1%), which were also the most common in controls (2.8% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95% confidence interval, 1.27–5.36, P = 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P = 0.006), diabetes mellitus (OR, 2.31, P = 0.008), and non-White ethnicity (OR, 4.75, P 0.13, for both). Conclusions A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.

PURPOSE: Clinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought to identify whether pre-transplant levels of circulating proteins reporting on immune activation and inflammation are associated with incident PGD. METHODS: The study population consisted of 219 adult heart transplant recipients identified between 2016 and 2020 at Duke University Medical Center, randomly divided into derivation (n = 131) and validation (n = 88) sets. PGD was defined using modified ISHLT criteria. Proteomic profiling was performed using Olink panels (n = 354 proteins) with serum samples collected immediately prior to transplantation. Association between normalized relative protein expression and PGD was tested using univariate and multivariable (recipient age, creatinine, mechanical circulatory support, and sex; donor age; ischemic time) models. Significant proteins identified in the derivation set (p < 0.05 in univariate models), were then tested in the validation set. Pathway enrichment analysis was used to test candidate biological processes. The predictive performance of proteins was compared to that of the RADIAL score. RESULTS: Nine proteins were associated with PGD in univariate models in the derivation set. Of these, only CLEC4C remained associated with PGD in the validation set after Bonferroni correction (OR [95% CI] = 3.04 [1.74,5.82], p = 2.8×10(−4)). Patterns of association were consistent for CLEC4C in analyses stratified by biventricular/left ventricular and isolated right ventricular PGD. Pathway analysis identified interferon-alpha response and C-type lectin signaling as significantly enriched biologic processes. The RADIAL score was a poor predictor of PGD (AUC = 0.55). CLEC4C alone (AUC = 0.66, p = 0.048) and in combination with the clinical covariates from the multivariable model (AUC = 0.69, p = 0.018) improved discrimination for the primary outcome. CONCLUSIONS: Pre-transplantation circulating levels of CLEC4C, a protein marker of plasmacytoid dendritic cells (pDCs), may identify HT recipients at risk for PGD. Further studies are needed to better understand the potential role pDCs and the innate immune response in PGD.

Background Sensitized candidates with unacceptable antigens are a group that demands special attention in organ transplantation. Calculated panel reactive antigen (cPRA) is not used to modify allocation priorities in lung transplantation. The impact of cPRA on waiting list time and mortality is unknown. Methods We performed a retrospective review of candidates for lung transplantation listed from May 2005 to 2018. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing STAR (Standard Analysis and Research) dataset was paired with additional unacceptable human leukocyte antigen (UA-HLA) data, which were used to calculate the listing cPRA. Candidates were stratified based on the lack of UA-HLAs or cPRA level for candidates with unacceptable antigens reported. Unadjusted competing risks and adjusted subdistribution hazard models were fit. Results A total of 29,085 candidates met inclusion criteria for analysis. Of these, 23,562 (81%) with no UA-HLAs, 3472 (11.9%) with a cPRA less than 50, and 2051 with a cPRA greater than or equal to 50 (7.1%). On adjusted analysis, a cPRA greater than or equal to 50 was independently associated with increased waitlist mortality at 1 year (hazard ratio, 1.71; 95% confidence interval, 1.55-1.88; P Conclusions Further evaluation of organ allocation with consideration of a candidate's cPRA may be warranted in order to optimize equity in access to transplants.

Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell- mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4+ T-cell infiltration into the retina. Adoptive transfer of CD4+ T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-gamma-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.

BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. METHODS: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. RESULTS: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P

Massive MIMO system has attracted attention due to it’s significant improvement in system capacity and spectrum utilization. Pilot pollution greatly limited the performance of Massive MIMO system. To optimize the pilot pollution in Massive MIMO system. In this paper, a pilot allocation scheme based on machine learning algorithm and users’ angle of arrival is proposed. The scheme firstly classified all users according to whether the users’ angle of arrival overlaps with each other. It randomly assigned pilot sequences to users whose angle of arrival do not overlap with each other. Secondly, it used machine learning algorithm to classify users whose angle of arrival overlap with each other into interfering group and non-interfering groups based on users’ location information. We assign orthogonal pilots to users in the interfering group and randomly assign pilot sequences to users in the non-interfering group. Simulation results show that when the number of antenna reached 300, the pilot efficiency can be increased by about 11.67%. The pilot allocation scheme proposed in this paper can effectively suppress the impact of pilot pollution on the performance of Massive MIMO system, improve pilot efficiency and reduce pilot overhead.

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora., National Institutes of Health (U.S.) (Grant EY025913), National Institutes of Health (U.S.) (Grant EY027067), National Institutes of Health (U.S.) (Grant EY025259), National Institutes of Health (U.S.) (Grant NS038253), National Institutes of Health (U.S.) (Grant AI69208)

Most immunosuppressive regimens used in clinical vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)-based. As such, most recipients have experienced CNI-related side effects. Costimulation blockade, specifically CD28/B7 inhibition with belatacept, has emerged as a clinical replacement for CNI-based immunosuppression in kidney transplantation. We have previously shown that belatacept can be used as a centerpiece immunosuppressant for VCA in nonhuman primates, and subsequently reported successful conversion from a CNI-based regimen to a belatacept-based regimen after clinical hand transplantation. We now report on the case of a hand transplant recipient, whom we have successfully treated with a de novo belatacept-based regimen, transitioned to a CNI-free regimen. This case demonstrates that belatacept can provide sufficient prophylaxis from rejection without chronic CNI-associated side effects, a particularly important goal in nonlifesaving solid organ transplants such as VCA.

Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i.e., normal tension glaucoma (NTG). Interestingly, patients who carry the gain-of-function mutation of the pro-inflammatory gene TBK1 - tumor necrosis factor (TNF) receptor associated factor NF-κB activator (TANK) binding kinase 1 - are at increased risk to develop NTG. This finding suggests a causal link between neuroinflammatory processes and glaucoma. Various studies have reported the presence of neuroinflammatory responses by microglia, astrocytes and other blood-born immune cells in the optic nerve head (ONH) at early stages of experimental glaucoma. Inhibition of certain pro-inflammatory pathways, particularly those associated with microglial activation, appears to be neuroprotective. In this review, we will focus on the inflammatory responses, in particular the proposed roles of microglia, in the pathogenesis of glaucoma.

The human leukocyte antigen (HLA) system is an important immunologic barrier that must be considered for successful solid organ transplantation. Formation of donor-specific HLA antibodies in solid organ transplantation is an important cause of allograft injury and may contribute to recipient morbidity and mortality. Therapeutic plasma exchange is often requested to lower HLA antibody levels prior to or after transplantation and for management of HLA antibodies in the context of organ rejection. In this review, we summarize the current terminology, laboratory testing, and clinical significance of HLA sensitization in the solid organ transplant population. Furthermore, to illustrate applications of HLA testing in clinical practice, we summarize our own lung and kidney institutional protocols for managing HLA antibodies in the peri-transplant setting.

Background To date, it has repeatedly been demonstrated that infusing bone marrow-derived stem cells (BMSCs) into acellular nerve scaffolds can promote and support axon regeneration through a peripheral nerve defect. However, harvesting BMSCs is an invasive and painful process fraught with a low cellular yield. Methods In pursuit of alternative stem cell sources, we isolated stem cells from the inguinal subcutaneous adipose tissue of adult Sprague–Dawley rats (adipose-derived stem cells, ADSCs). We used a co-culture system that allows isolated adult mesenchymal stem cells (MSCs) and Schwann cells (SCs) to grow in the same culture medium but without direct cellular contact. We verified SC phenotype in vitro by cell marker analysis and used red fluorescent protein-tagged ADSCs to detect their fate after being injected into a chemically extracted acellular nerve allograft (CEANA). To compare the regenerative effects of CEANA containing either BMSCs or ADSCs with an autograft and CEANA only on the sciatic nerve defect in vivo, we performed histological and functional assessments up to 16 weeks after grafting. Results In vitro, we observed reciprocal beneficial effects of ADSCs and SCs in the ADSC–SC co-culture system. Moreover, ADSCs were able to survive in CEANA for 5 days after in vitro implantation. Sixteen weeks after grafting, all results consistently showed that CEANA infused with BMSCs or ADSCs enhanced injured sciatic nerve repair compared to the acellular CEANA-only treatment. Furthermore, their beneficial effects on sciatic injury regeneration were comparable as histological and functional parameters evaluated showed no statistically significant differences. However, the autograft group was roundly superior to both the BMSC- or ADSC-loaded CEANA groups. Conclusion The results of the present study show that ADSCs are a viable alternative stem cell source for treating sciatic nerve injury in lieu of BMSCs.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P < .0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P < .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.

Purpose Models to identify those at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are lacking and the pathophysiology remains poorly understood. We sought to identify whether proteins reporting on immune activation and inflammation were associated with incident PGD. Methods Using the Olink platform, we performed proteomic profiling of pre-transplant serum samples from HT recipients. PGD was defined using modified ISHLT criteria. We tested the association between PGD and protein levels using logistic regression with adjustment for clinical covariates (recipient age, creatinine, MCS, and sex; donor age; ischemic time). Significant proteins (p Results The derivation cohort consisted of 157 adult HT recipients, among whom 47 had PGD. Eleven of 368 proteins were associated with PGD in unadjusted and adjusted models and were tested in a validation cohort of 62 patients. The strongest association in the derivation cohort was with CLEC4C (OR [95%CI] = 2.0 [1.4,3.1], p=5.4 × 10−4), which remained the most significant tested protein in the validation set (OR [95%CI] = 1.8 [0.9,3.8], p=0.10; p Conclusion CLEC4C, a marker of plasmacytoid dendritic cells (PDC) which play a pro-inflammatory role via IFN-α signaling, may identify HT recipients at the highest risk for PGD. Further studies are needed to better understand the potential role of PDCs in PGD.

Background: The community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut–brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models. Methods: Dextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut–brain axis. Results: Colitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats. Conclusions: The administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut–brain axis.

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision.

The monochromator for the new residual stress diffractometer at China Advanced Research Reactor (CARR) was simulated and optimized using SIMRES software. Objected the Fe (211) diffraction peak, the effect of horizontal and vertical curvature of Si (400) monochromator on Figure of Merit was studied to optimize the focusing parameters. With the optimal focusing condition, the influence of wafer thickness, number of wafers, packet height and gap of packets on performance of instrument was calculated consequently and the corresponding geometrical size was fixed. Finally, the design of the monochromator for the new residual stress diffractometer at CARR was completed.

Purpose We previously reported that heart transplant (HTx) recipients with pre-formed, anti-HLA antibodies at low titer had one-year survival that was comparable to patients without any anti-HLA antibodies. As a result, we defined unacceptable HLA antigens by MFI>1000 in serum at 1:16 dilution. The current study evaluates how pre-formed, low-titer, donor-specific antibodies (DSA) and positive crossmatch affect long term survival of HTx recipients. Methods Total 495 adult recipients transplanted at our center between Jan. 2007 and Dec. 2016 were studied. Prior to HTx, recipients had HLA antibody screening (FlowPRA) and specificity testing (LABScreen). Unacceptable HLA antigens were defined by MFI>1000 in serum at 1:16 dilution. Acceptable donors were selected by virtual crossmatch using the criteria above, and flow cytometry crossmatch (FCXM) was performed peri- or post-HTx. Recipients transplanted across low titer DSA, positive in undiluted serum but negative at 1:16 dilution, received peri-operative plasmapheresis. We used log-rank testing to evaluate survival in the following groups compared to their controls: (1) presence of any pre-formed HLA antibodies; (2) presence of pre-formed DSA; and (3) positive FCXM. Results Of 495 HTx recipients, 179 (36%) had pre-existing HLA antibodies, and their overall survival was not different from patients without HLA antibodies (p=0.883). However, median survival time was reduced in patients with pre-formed DSA (n=62), compared to DSA-negative recipients (n=117): 9.1 years (95% CI 3.52 to 14.65) vs. 10.9 years (95% CI 6.13 to 15.70); p=0.02. The survival rates for 1-, 3-, 5-year of DSA-negative recipients were 91.5%, 85.4% and 79.5%, and the DSA-positive recipients were 83.9%, 66.1% and 61.7%, respectively. Total 62 recipients had pre-HTx DSA. Among them, 26 had a positive FCXM (46%). The survival rates of FCXM-positive cases were lower than FCXM-negative cases (n=36) at 1, 3, and 5 years: 80.8%, 57.9%, 52.1% vs. 86.1%, 71.4%, 67.6%. Conclusion Our findings suggest that pre-formed DSA, even at low titer, negatively impacted HTx survival. Cases with positive FXCM had the worst outcomes. Avoiding all pre-formed DSA may improve survival for HTx patients, but may increase waitlist mortality. To improve the HTx survival, close post-transplant monitoring and proactive immunological management may be required when pre-formed DSA are present.

In order to make best use of the neutron flux, a polarized neutron reflectometry with vertical sample geometry is simulated by Vitess package based on Monte Carlo method. The results prove that the neutron flux gain up to a factor reaches 4.3 and the vertical neutron angle divergence is proved, when the optimal tilting angle of the vertically focusing geranium monochromator is 1.3°. At last the optimal separations of horizontal blades of slit packages are optimized. The parameters can be an instruction for polarized neutron reflectometry construction or project analysis in the future.

As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multi-modal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000-10,000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort.

China Advanced Research Reactor (CARR) is a 60 MW tank-in-pool inverse neutron trap type reactor at CIAE. In order to use the non-destructive analytical techniques for phase specific residual stresses research, the new materials science diffractometer RSD was designed at CARR, which is one of the first commissioned instruments to meet the demand of industrial applications. The system comprises two types of monochromator, mosaic flat copper (220) and perfect double focusing silicon (311). The take-off angle of monochromator could change continuously from 41 to 109 degree. Therefore the neutron wavelength varies from 0.895 and 2.666 angstrom. The detector is a one dimension position sensitive detector. Various affiliated equipments enable it to do texture and tensional experiments. The best resolution could reach 0.2% using double focusing Si (311) monochromator. When RSD is available for routine operation, some research work in the field of nuclear industrial and aviatic engineering materials will be carried out using the beam of CARR.

Neutron Texture Diffractometer at CARR is the first neutron instrument for texture measurement in China. It was built through modifying a Four-Circle Diffractometer relocated from Juelich Center for Neutron Science and equipping with some necessary new components. Currently, the adjustment and calibration with neutrons for this instrument has been finished. The detailed characteristics of this instrument are described and the preliminary results of quantitative texture analysis for a warm-rolled Zircaloy-4 plate are presented. The results show good quality and small statistical errors.

Neutron velocity selector is widely used on neutron scattering instruments as key component. To calibrate it (wavelength and wavelength-resolution-rate measurement), it is necessary to design calibration instrument and develop calibration technique. Based on small angle neutron scattering instrument (SANS) at China Advanced Research Reactor (CARR), instrument structure was designed and instrument parameters were determined. Count loss influence on measurement of wavelength resolution rate (WRR) was studied for the first time. Measurement error of WRR is decided by product of dead time and Gauss peak count rate (GPCR) and increases with increasing GPCR for the same dead time. In order to ensure WRR measurement error less than 0.9%, upper limits of GPCR for detector adjoining chopper and detector far away from chopper are less than 10000[s-1] and 2500[s-1] respectively. According to upper limits of GPCR, floor limit of total measurement time for each spectrum is calculated to be 6.66 minutes.

In China, because it is difficult to pay the high electricity, resulting in a large number of highway tunnel illuminations is insufficient. In order to solve remote highway tunnel lighting power supply problem, we use the solar photovoltaic system, developed and built a solar lighting system in highway tunnel. This paper introduces the design and application process of this system.

Background Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes. Methods A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods. The prevalence of and predictors for HLA antibodies were determined. The impact of HLA antibodies on survival after transplant and the development of BOS were determined using Cox models. Results Of the 441 recipients, 139 (32%) had detectable antibodies to HLA. Of these 139, 54 (39%) developed antibodies specific to donor HLA. The detection of posttransplant HLA antibodies was associated with BOS (HR, 1.54; P = .04) and death (HR, 1.53; P = .02) in multivariable models. The detection of donor-specific HLA antibodies was associated with death (HR, 2.42; P Conclusions Approximately one-third of lung transplant recipients have detectable HLA antibodies, which are associated with a worse prognosis regarding graft function and patient survival.

AIM To characterize whether a glaucoma model with chronic elevation of the intraocular pressure (IOP) was able to be induced by anterior chamber injection of microbeads in rabbits. METHODS In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 µL, 25 µL, 50 µL or 100 µL microbeads (5×106 beads/mL; n=6/group) in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 µL microbeads or phosphate buffer saline (PBS) were made respectively at days 0 and 21 (n=24/group). The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy (TEM) were used to assess the changes in the retina. The expression of glial fibrillary acidic protein (GFAP) in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of microbeads. RESULTS Following a single intracameral injection of 10 µL, 25 µL, 50 µL or 100 µL microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 µL and 25 µL groups (17.13±1.25 mm Hg vs 17.63±0.74 mm Hg; P=0.346). The peak value of IOP from 50 µL group (23.25±1.16 mm Hg) was significantly higher than 10 µL and 25 µL groups (all P

Irreversible vision loss is often caused by the loss of retinal neurons, and one reason that retinal degenerative diseases are devastating is that, once retinal neurons are lost, they do not grow back. Stem cell-based neuron replacement strategy for retinal degenerative diseases are leading the way in clinical trials of transplantation therapy, and the exciting findings in both human and animal models point to the possibility of restoring vision through a cell replacement approach. Presumably, a less invasive method of retinal regeneration by mobilizing endogenous stem cells to replace those lost is highly desirable and promising for restoring vision. However, many obstacles remain, including mobilization of endogenous stem cells for restoration of lost cells, directed differentiation of progenitor cells, and establishment of functional connectivity in order to regain vision. The field of retinal self-repair is progressing at a rapid pace and encouraging outcomes.

In the application of intuitionistic fuzzy sets(IFSs), distances and similarity measures play very important roles. In this paper, firstly, the modified definition of normalized distance and degree of similarity between IFSs are introduced, which are proved to be more reasonable than some existing definitions. Then, the relations between normalized distance and degree of similarity are analyzed. New distances and similarity measures between IFSs are proposed and corresponding proofs are given. Finally, a comparison of application to pattern recognitions is made to show the proposed distances and similarity measures are more reasonable than some existing methods.

The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse-related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84 adults with high-risk hematologic malignancies receiving reduced intensity conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical related donors. In this clinical model, freedom from RRM is dependent on GVL effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy groups. KIR-ligand and ligand-ligand models were studied in both GVH and rejection directions and statistically correlated with outcome measures. In the myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1 missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028). There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1, although sample sizes were too small to provide inferential statistics. Findings in lymphoid malignancy patients should be further studied. These results suggest that the absence of appropriate HLA ligands in the recipient to donor iKIR may induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC transplants.

Acute cellular rejection affects greater than a third of lung transplant recipients. Alloreactive T lymphocytes, responding directly or indirectly to donor antigen, constitute the basis of lung allograft rejection, as diagnosed by well-established histopathological criteria that reflect the severity of perivascular or peribronchial inflammation in the lung allograft. Recent evidence supports a more complex immune response to the allograft with involvement of humoral mechanisms, characterized by circulating antibody to donor HLA and specific patterns of lung injury, occurring in parallel with T cell-based rejection. Emerging evidence further suggests that the interaction between recipient genetics, immunosuppression therapies, and allograft environmental exposures, including pulmonary infection, contributes to high rejection rates after lung transplantation. A greater understanding of the heterogeneous mechanisms of lung rejection is critical to developing effective therapies that target the precise pathophysiology of the disease and ultimately improve long-term lung transplant outcomes.

Aim Although lymph nodes are preferred resources for isolation of lymphocytes for crossmatches, the nodes may not be available at the time of crossmatching. An unusual case led us to revisit 39 deceased donor’s crossmatch results to see if enough B cell events were acquired in flow crossmatching. Methods Cells were isolated using Density Gradient of Ficoll-Hypaque from pronase-treated PBL, and/or from lymph nodes. Flow crossmatches (FCXM) were performed on a BD FACSCalibur. In FCXM, anti-CD3 was used to mark T-cells, anti-CD19 was used to mark B-cells and goat anti-human IgG was used as a secondary antibody for detection of donor specific antibody. Results A 38 years old Caucasian female suffered a severe injury from a car accident was evaluated as the potential deceased donor for three kidney recipients. Three tubes of PBL were received for initial FCXM. The crossmatch failed due to lower B cell events ( Conclusions Our findings suggest the PBLs, as the resources of cells for crossmatch, most of the times (94%) could result in successful crossmatches.

The originally published version of this Article contained an error in Figure 4. The bar chart in panel f was inadvertently replaced with a duplicate of the bar chart in panel e. This error has now corrected in both the PDF and HTML versions of the Article.

The role of esophageal hypersensitivity in functional heartburn (FH) with negative pH test, negative symptom index, and the proton pump inhibitor (PPI) failure has not been established. The aim of this study was to investigate the characterization of visceral hyperalgesia evoked by esophageal balloon distention and acid perfusion in patients with FH, nonerosive reflux disease, and erosive esophagitis and further characterize the pathophysiologic mechanism of FH.A total of 21 FH patients (with esophageal acid exposure3.1% and a symptom index50% and nonresponse to a therapeutic trial with proton pump inhibitors, 25 Nonerosive reflux disease (NERD) patients (with esophageal acid exposure4%), 23 erosive esophagitis (EE) patients (LA grade B to D), and 18 healthy controls were recruited in the study. Mechanosensitivity including the initial perception threshold (IPT) and pain threshold (PT) was evaluated by using a Barostat with a double-random staircase distension protocol. Chemosensitivity was graded along a visual analog scale after perfusion of saline and 0.1 N HCl.The baseline IPTs and PTs were all lower in patients with FH, NERD, and EE than in the controls (all P0.01). In addition, the baseline PT in FH patients was significantly lower than those in NERD (P=0.015) and EE patients (P0.001). After acid perfusion, the mean symptom intensity scores were significantly greater in patients with FH, NERD, and EE than those in the controls (all P0.001). The postacid perfusion IPTs in patients with FH, NERD, and EE were all significantly lower than the corresponding baseline values (all P0.01). The PTs in FH (P=0.026) and EE patients (P0.001) were significantly lower than the corresponding baseline values. Moreover, the postacid perfusion PT was significantly lower in FH patients than in NERD patients (P0.001).FH patients are more sensitive to mechanical or chemical stimuli than NERD patients. Sensitization of esophageal acid-sensitive chemoreceptors may exert a significant influence on the pressure-sensitive mechanoreceptors, and there is the cooperative interaction in the process of esophageal visceral hyperalgesia.

Study design A histologic study of recombinant human bone morphogenetic protein-2/calcium phosphate cement (rhBMP-2/CPC) using adult rhesus monkeys in vivo. Objective To evaluate the histologic changes of rhBMP-2/CPC in vertebroplasty and determine the feasibility of this bone substitution instead of polymethylmethacrylate (PMMA). Summary of background data Previous studies have shown that the new rhBMP-2/nanoscale CPC has a suitable strength and injection for vertebroplasty. However, the osteoinductive properties and biodegradable characteristics are still unclear. Methods Percutaneous vertebroplasty (PVP) was performed in 4 adult rhesus monkeys of 2 groups. Ten vertebral bodies (VBs) from T10-L7 of each rhesus were selected, and the 20 VBs in each group were randomly divided into 3 subgroups. Subgroup A (rhBMP-2/CPC): 8 VBs, filled with rhBMP-2/CPC; Subgroup B (PMMA): 6 VBs, filled with injectable PMMA; Subgroup C (control): 6 VBs, filled with normal saline. The 2 rhesus monkeys from each of the groups were killed at 2 and 6 months after operation, respectively. Individual specimens from the 40 VBs were collected for histologic observation. Results In subgroup A, radiographic and histologic observations showed that the part of the rhBMP-2/CPC cement degraded with new bone and new vessel ingrowths, into the material, after 2 months. In addition, gaps, fibrous hyperplasia, or sclerotic callus were not found in the interface. After 6 months, the cement was nearly all replaced by mature bone tissue. In subgroup B, the inflammatory cell infiltration and fibrous membrane gapping were found after 2 months, and subsided partly at 6 months. But no new bone formation and material degradation were discovered. In subgroup C, the tunnels were filled with irregular new trabeculae after 2 months and unrecognizable from the surrounding mature bone after 6 months. Conclusion It is confirmed that the rhBMP-2/CPC is an osteoinductive and biodegradable material (in animal trials). It may also be an alternative to PMMA in order to achieve biostabilization in a vertebroplasty.

Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.

The persistence of transplacentally transferred maternal T cells is common in infants with severe combined immunodeficiency (SCID), occurring in more than half of patients with SCID undergoing transplantation at our institution. These T cells respond poorly to mitogens in vitro but can cause cutaneous graft-versus-host disease; however, other effects of these cells are unknown. We describe 2 infants with SCID who had unusual problems associated with transplacentally transferred maternal T cells. Patient 1 was a 5-month-old girl with Janus kinase 3-deficient SCID who had 4% circulating CD3(+) T cells but no lymphocyte proliferative response to mitogens. Although the number of T cells increased after 2 nonchemoablated, T cell-depleted, haploidentical, paternal bone marrow transplantations, T-cell function failed to develop, and she became pancytopenic. Restriction fragment length polymorphism studies of flow cytometry-sorted blood T cells revealed all to be of maternal origin. A subsequent nonchemoablated, T cell-depleted maternal transplantation resulted in normal T-cell function and marrow recovery. Patient 2 was a 9-month-old girl with IL-7Ralpha-deficient SCID who presented with autoimmune pancytopenia. She had 8% blood T cells (all CD45RO(+)) but no response to mitogens. High-resolution HLA sequence-specific priming typing detected both maternal haplotypes, indicating the presence of maternal cells. Her pancytopenia resolved after treatment with rituximab and was thought to be due to host B-cell activation by transplacentally acquired maternal T cells. Persistent transplacentally acquired maternal T cells in infants with SCID can mediate immunologic functions despite failing to respond to mitogens in vitro. We present evidence that these cells can cause allograft rejection and immune cytopenias.

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. AstraZeneca. ClinicalTrials.gov identifier, NCT01757275.

The presence of specific antibodies and T cells that are specific in patients with glaucoma supports the idea that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy, at least in some patients. At present, our understanding regarding immunological mechanisms associated with glaucomatous optic neuropathy is far from satisfactory. In this review, we examined evidence suggesting involvement of autoimmune responses in the pathogenesis of glaucoma. These include detection of autoantibodies and T cells and expression of cytokines and stress proteins in patients with glaucoma. Although immune responses are thought to be detrimental, some responses may exert a protective effect against neurodegenerative damage. Likely, the balance between positive and negative regulators determines the survival or demise of cells. It is vital that research continues to elucidate the roles of the immune system in glaucomatous neurodegeneration and the possibility of alternative modalities of treatment. These studies may also provide valuable molecular biomarkers for the diagnosis and identification of a specific cohort of patients with glaucoma, that is, those with normal-tension glaucoma.

Aim Our transplant center has used virtual crossmatch (vXM) for donor selection for heart and lung transplantation for over 10 years with great success. The UNET match run for kidney transplant is used to select potential donor for final prospective crossmatches (fXM). Therefore, the match run can also be considered as a vXM process. A question has been raised if the vXM can be used for final donor selection to replace the fXM for kidney transplants. Routinely typing all of HLA gens including DQA1, DPB1 and DPA1 has become a standard practice in many HLA labs in the past a couple of years which may reduce the rate of unexpected positive fXM. This study was to retrospectively review fXMs performed in 2016 for kidney transplantation and to determine if a positive fXM could be predicated by the vXM. Methods 358 fXMs performed for kidney transplantation in 2016 were included in the study. Their fXMs were performed by flow cytometry. The donor cells were routinely treated with pronase to reduce background bindings. vXMs were performed either based UNET match run or by manually checking presence/absence of DSA detected in patients. Results Among these 358 fXMs, 19 (5%) fXMs were positive. Of these 19 positive fXMs, 14 positive could be predicated by vXM because of presence of DSA. The other 5 positive fXMs were non-HLA specific because of absence of detectable DSA. One (1) of the 5 non-specific positive fXMs was T cell positive and B cell negative caused by pronase treatment and it became negative with cells without pronase treatment. Another (1) T cell positive and B cell negative fXM might have been caused by presence of non-HLA antibodies because of absence of detectable DSA. fXM with non-pronase treated cells remained T cell positive and B cell negative. The other 3 positive fXMs were from the same patient who was HIV positive with no detectable DSA. It is well known that non-specific positive crossmatches occurred in HIV positive patients. Conclusions Based on the findings of our study, we can conclude that performing vXM can avoid positive fXMs caused by HLA antibodies and can be safely used for donor selection for kidney transplantation without performing a fXM.

Introduction Avoidance of previous donor mismatched HLA antigens is often considered for lung re-transplant due to concerns of potential HLA sensitization and memory responses. However, this approach may result in the exclusion of a large number of potential donors from consideration. Recently, we successfully performed a re-transplant with a history of multiple repeated mismatches. Patient/method A 30+ year old male with a past medical history of cystic fibrosis underwent two previous bilateral lung transplants in August 2004 and in November 2010. Both allografts failed due to CLAD/BOS that developed after respiratory viral infections. The patient also subsequently developed detectable class I and II HLA antibodies with a cPRA > 88% in May 2016. Among these antibodies, strong anti-A1, B7 and DQ2 were first donor HLA specific. The second donor shared an A3-B18-DR4 haplotype with the first donor but not the recipient. No HLA antibodies specific to this A3-B18-DR4 haplotype antigens or to any other mismatched HLA antigens of the second donor were detected. A third lung transplant became urgently necessary in October 2016. Adding his previous donors’ mismatched HLA antigens to the unacceptable HLA list resulted in a cPRA > 96%. Therefore, a personalized listing strategy was developed based on discussions between the HLA lab and the transplant program. Results A deceased donor became available in November 2016. The virtual crossmatch revealed that the donor had no unacceptable HLA antigens based on HLA antibody detection. However, this donor carried the A3-B18-DR4 haplotype which was a repeated mismatch haplotype of the previous two donors. Based on a risk and benefit assessment, this donor was accepted as the source of lungs for the third transplant. The patient received 5 plasmapheresis sessions post-transplant to prevent antibody mediated rejection. Frequent post-transplant HLA antibody monitoring has not detected development of donor specific antibodies to the third donor and the new allograft functions well. Conclusion Lung re-transplant can be performed with a cross of a repeated HLA mismatch provided that the recipient has no detectable HLA antibodies specific to the current donor. Our preliminary findings obtained from our study conducted on UNOS lung transplant data supports this conclusion. An assessment of risk and benefit of crossing the repeated mismatch HLA antigens should be done on a case-by-case basis.

Purpose There is a need for automated retinal optical coherence tomography (OCT) image analysis tools for quantitative measurements in small animals. Some image processing techniques for retinal layer analysis have been developed, but reports about how useful those techniques are in actual animal studies are rare. This paper presents the use of a retinal layer detection method we developed in an actual mouse study that involves wild type and mutated mice carrying photoreceptor degeneration. Methods Spectral domain OCT scanning was performed by four experimenters over 12 months on 45 mouse eyes that were wild-type, deficient for ephrin-A2 and ephrin-A3, deficient for rhodopsin, or deficient for rhodopsin, ephrin-A2 and ephrin-A3. The thickness of photoreceptor complex between the outer plexiform layer and retinal pigment epithelium was measured on two sides of the optic disc as the biomarker of retinal degeneration. All the layer detection results were visually confirmed. Results Overall, 96% (8519 out of 9000) of the half-side images were successfully processed using our technique in a semi-automatic manner. There was no significant difference in success rate between mouse lines (p = 0.91). Based on a human observer's rating of image quality for images successfully and unsuccessfully processed, the odds ratios for ‘easily visible’ images and ‘not clear’ images to be successfully processed is 62 and 4, respectively, against ‘indistinguishable’ images. Thickness of photoreceptor complex was significantly different across the quadrants compared (p

The optic nerve is the only nerve pathway that relays visual information from the retina to the brain. These nerve fibers are highly vulnerable when injury or diseases occur to the nerve. Optic neuropathy is a generic name for optic nerve diseases. Isolated optic nerve injury can happen in two ways: (1) diseases that selectively attack the optic nerve and (2) cranial trauma and ischemia that injure the optic nerve. Diseases that commonly injure the optic nerve include, most importantly, glaucoma and ischemic optic neuropathies. Other major categories of optic nerve damage also include those induced by trauma and hereditary and inflammatory conditions. These conditions are characterized by progressive damage to the optic nerve and loss of retinal ganglion cells (RGCs). Deciphering the cellular and molecular events that are responsible for triggering the cell death cascades in RGCs and control axon degeneration and regeneration may lead to novel targets for therapeutic interventions.

Because retinal tissue normally excised during retinal reattachment repair is usually discarded, safe methods for the removal of retinal tissue from the eye were developed. Two methods are described for the removal of retinal tissue fragments otherwise discarded during vitrectomy for retinal detachment repair: (1) the removal of small oval pieces of retinal tissue associated with horseshoe retinal tears and (2) the removal of larger rectangular pieces of retinal tissue associated with relaxing retinotomies or giant retinal tears. These methods provide the retinal surgeon with some simple and safe methods for the extraction of retinal tissue fragments that would otherwise be discarded at the end of surgery. [Ophthalmic Surg Lasers Imaging 2005;36:76–78.]

In developing countries, household air pollution (HAP) resulting from the inefficient burning of coal and biomass (wood, charcoal, animal dung and crop residues) for cooking and heating has been linked to a number of negative health outcomes, mostly notably respiratory diseases and cancers. While ocular irritation has been associated with HAP, there are sparse data on adverse ocular outcomes that may result from acute and chronic exposures. We consider that there is suggestive evidence, and biological plausibility, to hypothesize that HAP is associated with some of the major blinding, and painful, eye conditions seen worldwide. Further research on this environmental risk factor for eye diseases is warranted.