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IntroductionConsidering the large extent of the country's rangelands, studying their hydrology and soil erosion is important for choosing management scenarios. Rangeland exclosure is one of the watershed management methods that is used to improve vegetation and also control soil loss. Rangeland's exclosure of the Sanganeh Soil Conservation Research Site (SSCRS) started about 25 years ago, which has led to the improvement of vegetation in most of the slopes compared to the area under livestock grazing. However, vegetation has not been established on some slopes of the exclosure region. This research site has provided suitable conditions for soil erosion studies and assessment of rangeland management measures at the scale of the plot and small watersheds by having erosion plots of different lengths located on slopes with and without vegetation. In this regard, the present research is planned with the aim of determining the effect of rangelands exclosure 1) on soil loss in plots with and without vegetation, and 2) with different lengths. Material and MethodsIn this research, a comparison of soil erosion was made in th e area under free livestock grazing (E6) and exclosure watershed with similar conditions (E4). In this regard, six erosion plots with lengths of 5, 10, and 15 m (with areas of 10, 20, and 30 m2, respectively) in two vegetation situations (with and without vegetation cover) were selected in each study watershed. After collecting the soil erosion data under 24 natural rainfalls, the effect of plot length and vegetation situation were compared by paired t-test. Results and DiscussionThe results of data analysis indicated that the maximum intensity of 30 minutes is in the range of 2.4 to 32 mm per hour with an average of 0.9 mm per hour. It can be clearly understood from the distribution of precipitation data based on the seasons of the year that the average rainfall of three seasons, spring, autumn and winter, is almost equal. However, the average rain erosion index (EI30) in spring is 3.02 and 4.40 times higher th an the corresponding values in autumn and winter, respectively. The reason for this is the occurrence of heavy rains in spring. The comparison of two fields with cover and without cover in the areas of exclosure and under livestock grazing in terms of soil erosion showed that in both areas (with cover and with out cover) the amount of soil erosion in the plots under grazing is significantly higher than in exclosure area. So, in similar rainfalls in the region, the soil erosion in the watershed under grazing at different slopes is from a minimum of 282% to a maximum of 550% more than the exclosure watershed. By increasing the length of the plot, soil erosion per unit area decreases. The decreasing trend of specific sediment with the increase in the length of the flow path is mainly due to the decrease in the amount of specific runoff and as a result, it is not possible to move the eroded materials in the plot. In other words, due to the dominance of the surface erosion process and the lack of development of rill erosion in the investigated plots, the re-infiltration of runoff and the deposition of transported materials are the most important reasons for the decreasing relationship between the increase in the length of the plot and erosion per unit area. In both slopes (with and without vegetation), the effect of waterlogging on soil erosion has increased with the increase of the area of the plot. In other words, grazing pasture in 10 m2 plots has reduced soil erosion by 287.7 and 324.6 percent, respectively, in slopes without and with vegetation. Meanwhile, in the plots of 30 m2, the reduction of soil erosion was observed by 472.4 and 613.7 percent. On the other hand, in the slops with vegetation, grazing has a greater effect on reducing soil erosion. In this context, it can be stated that surface erosion and sheet currents are the dominant phenomena of erosion and sediment transport in the studied slopes, therefore, if the roughness and permeability of the soil increases due to the operation of pasture exclosure, it can be expected that the runoff flow in longer routes (from the slope 10 m2 to 20 and 30 m2) to increase the amount of material deposition. In this case, exclosure in the domain with a longer length has a greater effect on reducing soil erosion. ConclusionSSCRS with erosion plots in different conditions (length, vegetation conditions and pasture management) is a suitable place for scientific research in the field of pasture hydrology. In this research, the effect of plot length and vegetation status on erosion was evaluated using soil erosion data measured in two areas of exclosure and under livestock grazing. The results of this research showed that in both ranges (with and without vegetation), the amount of soil erosion in the plots under grazing is at a significant level of 1% higher than in exclosure region. So, in similar rains in the region, soil erosion in the watershed under grazing in different lengths is at least 282% more than the flooded watershed. Also, the results indicated that soil erosion per unit area decreases with increasing plot length. The decreasing trend of specific sediment with the increase in the length of the flow path is mainly due to the decrease in the amount of specific runoff and as a result, it is not possible to move the eroded materials in the plot. Finally, the results showed that in both fields with and without vegetation, the effect of waterlogging on soil erosion increased with increasing plot length. On the other hand, in the range with vegetation (compared to the range without cover), grazing has a greater effect on reducing soil erosion.The results of the surveys conducted at the SSCRS confirm the sensitivity and fragility of the dry grassland ecosystem in this region on behalf of the country's dry grasslands. In such a way that after a long period of flooding in the region, some slopes still lack vegetation. Therefore, the destruction of vegetation in some areas, especially steep slopes and sensitive formations, may not be easily returned to the original state, and great care must be taken in their management. Because these domains have high erosion and runoff production. Due to the existence of recorded information related to the ideal situation of the region (exclosure region), it is possible to create different grazing systems and evaluate its effects. Finally, it is possible to compare the information obtained from exclosure region, managed grazing and open grazing.

IntroductionSoil erosion by water is one of the most common environmental problems worldwide and is considered a serious risk for sustainability in developing countries. Water erosion on a global scale is one of the most critical types of soil and environmental degradation due to its geographical extent and ecological effects. In this regard, effectively controlling sediment load is an important component in watershed management. In the formulation of a watershed management strategy, the estimation of sediment delivery ratio (SDR) plays a significant role. SDR is defined as the sediment yield from an area divided by the gross erosion of that same area. SDR is expressed as a percentage and represents the efficiency of the watershed in moving soil particles from areas of erosion to the point where sediment yield is measured. One of the problems in estimating the SDR in watersheds is the lack of proper information on the amount of soil erosion and sediment yield. In this context, the Sanganeh soil conservation research station, having measured soil erosion and sediment yield of small watersheds, is a suitable place to evaluate the accuracy of the RUSLE model and estimate the ratio of sediment delivery on the scale of small watersheds. The current research aims to achieve two goals: a) determining the accuracy of the RUSLE model in estimating soil erosion based on the measurements in the erosion plots, and b) estimating the SDR using the estimated soil erosion values as well as the sediment yield measured at the outlet small watershed are planned. Materials and MethodsConsidering the importance of soil erosion and the study of sediment processes in semi-arid rangeland ecosystems, the Khorasan Razavi Agricultural and Natural Resources Research Center (KANRRC) assessed some micro-watersheds for the collection of storm-wise runoff and associated sediment. The Sanganeh research micro-watershed, located 100 km from Mashhad City (northeast Iran), is one of the watersheds selected for this study. The watershed area, the longest waterways, and the mean slope of the watershed are 1.2 ha, 145.0 m, and 31.2%, respectively. The study watershed consists of semi-arid rangeland dominated by Bromus tectorum and Artemisia diffusa, with a coverage of 50%. The soil is Entisol and Aridosol, young, with a maximum depth of 30 cm. The mean electrical soil conductivity (EC), soil organic matter (OM), clay, sand, silt, and surface rock fragments of soils are 1.81, 1.57, 10.6, 54.7, 34.7, and 5%, respectively. In this research, three experimental small watersheds with areas between 4300-12000 m2 were selected along with the erosion plots in them. Then, 24 rainfall events related to two periods of 2006-2009 and 2016-2018 were recorded along with the corresponding data of runoff and sediment in watersheds and plots. In this study, water flow and sediment yield were monitored at the main outlet of the micro-watersheds and plots. The runoff volume was calculated after each storm event by multiplying the depth of collected water, measured using an iron ruler at five points in the tank (corners and central), by the surface area of the collector. The collected runoff and sediment were then mixed thoroughly and one sample was taken to determine sediment concentration and sediment yield. Then, by collecting the required information (includeing rainfall erosivity, topography, conservation practice, soil erodibility, and cover-crop management factors), the RUSLE model was run and compared with the observation data of the plots. The storm-wise soil erosion predictions were compared with observed data based on the criteria of the coefficient of determination (R2) and relative estimation error (RE). In the following, by modifying the RUSLE model and observing the sedimentation data of the studied watersheds, the value of the SDR was estimated. Results and DiscussionAfter collecting the required information, the RUSLE model was implemented at the plot scale. The accuracy of the model was evaluated using erosion plot data, which was not confirmed due to huge overestimations of RUSLE. Next, to achieve more accurate results, regression types (linear, exponential, power, etc.) were used between the observed and estimated values of soil erosion (RUSLE). After applying the correction coefficient, this model was able to estimate the average erosion rate of the whole period are 12, 17, and 2% for E1, E4, and E6 watersheds, respectively, which is within the acceptable range of soil erosion modeling. Therefore, it can be said that the accuracy of the modified RUSLE model (by regression model) in estimating the average soil erosion during the period is higher than the event-based scale. Also, the prediction of maximum event estimation error for E1, E4, and E6 watersheds was 25.7, 35.8, and 21.6%, respectively. After evaluating the accuracy of the RUSLE model at the plot scale and in order to know the amount of soil erosion at the watershed scale, the values ​​of L, S, K, and C factors for the watersheds were calculated based on a weighted average and entered into the modified model. Therefore, the results of the RUSLE model were generalized to the watershed scale. In the final stage, by dividing the amount of erosion by the corresponding amounts of sediment yield measured at the outlet of watersheds, the ratio of sediment delivery was calculated. The average SDR of the entire period in the E1, E4, and E6 watersheds are 42.2, 41.5, and 39.7%, respectively, and in the maximum events, it is one or two percent higher. ConclusionOverall, the results of this research showed that using the modified RUSLE model, it is possible to estimate the average soil erosion in the Sangane soil conservation station and also estimate the SDR. Therefore, this approach can be used in executive programs in similar areas. According to the obtained results, the classification of rainfall data based on the rain erosive factor and then the evaluation of the RUSLE model can provide more accurate results. In addition, in this research, due to the small area of the watersheds, waterway processes did not play a role in the deposition and transfer of eroded soils. It is also suggested that similar research could be done in larger watersheds. Finally, considering the determination of the SDR in this area, it is recommended to evaluate the accuracy of the experimental methods for determining the SDR.

Undoubtedly, dust collection has negative effects and negative consequences for humans and may endanger their physical and mental health in various aspects. Regarding the general liability of the Islamic State against the citizens, the responsibility for coping with this phenomenon lies with the government and the Environmental Protection Agency. Due to the importance of coping with this issue, the legal jurisprudential analysis of the civil liability of the state against the harmful effects of dust on the health of citizens is of particular importance. This descriptive-analytical study analyzed the issue based on well-known jurisprudential and legal principles by examining Jurisprudential principles and mandatory rules and It has been concluded that the civil liability of the government for damages caused by dust can be justified on the basis of the rule of respect.

Identification and prioritization of critical sub-watershed is essential to sediment control at watershed scale. Many studies have been carried out on the topic of identifying and prioritizing the critical source areas (CSAs); however, only few researches have been conducted to prioritize sub-watersheds in terms of their contributions to the sediment yield of the main watershed outlet. In fact, observations alone are not enough for CSAs prioritization; hence, hydrological models may be applied for prioritization of sub-watershed. Therefore, in the present study, prioritization of sub-watershed was considered based on (1) on-site effects of soil erosion: specific sediment yield at sub-watershed scale (sediment yield/area), (2) offsite effect of soil erosion: sub-watershed contribution to the sediment yield of the main watershed outlet. In this study, Soil and Water Assessment Tool (SWAT) was applied for prediction of runoff and sediment load at sub-watershed scale and the main watershed outlet. The Unit Response Approach (URA) has also been applied to prioritize sub-watersheds in terms of their contributions to the sediment yield at the watershed outlet. The proposed model was applied in Mehran watershed, in West of Tehran (capital of Iran). The study watershed was divided into 37 sub-watersheds. The results showed that the contribution of sub-watershed No.14 and No. 17 had the largest sediment contribution into the main outlet of watershed. The results of this ranking can differ entirely from those based on single sub-watershed sediment production at the sub-watershed outlet. Targeting the placement of Best Management Practices, based on the CSAs concept, will assist sediment control in watersheds.

In addition to the well-known and explicit jurisprudential rules in the books of jurists, there are some general contents in verses, hadiths and jurisprudential fatwas from which new jurisprudential rules can be identified and applied. Among those cases is a jurisprudential rule entitled "Anything that hurts parents is forbidden" which, with the support of the verse "Tafif", can be considered as a general rule in the process of inference. Considering the necessity of organizing family relations and rulings, especially the correlation between children and parents based on jurisprudence, it seemed necessary to institute and prove such rules. this descriptive-analytical study has examined the sentence of harassment of parents from the perspective of jurists, research in issue, Its semantic scope, narrative and logical documents of this rule, Its conflict with other rules, It was concluded that this issue can be used as a general rule and the process of inferring the jurisprudential and related legal rulings.

Abstract Extensive impervious area and the man-made streams are the characteristics of urban areas. In recent years, rapid urbanization has led to change of rural areas into urban areas, and urban runoff will increase as the result of spread and growth of impervious areas. Land use changes, increasing urbanization, unauthorized construction, inefficiency of sewage system and increased impervious surface in urban areas have significant impacts on inundation hazard. Therefore, to manage urban areas and prioritize regions to inundation elimination problems, the area most affected by inundation should be determined. In this study, the Storm Water Management Model (SWMM) is used to simulate the rainfall-runoff in the study area. The simulated runoff in the SWMM model is used as input to the HEC-RAS model and determines inundation hazard zones in 5, 25 and 50 return periods. Then, six factors such as distance from the main channel, slope, land use, drainage density, the main channel slope and elevation were selected to determine inundation hazard map using Analytic Hierarchy Process (AHP). The results showed that the combined model (SWMM and HEC-RAS) was suitable to analyze urban inundation and determine inundation hazard zones on urban areas. Simulated results can be used to develop urban inundation hazard forecasts. In addition, the result of inundation hazard map indicates that 8.2% of the case study is determined as a high hazard zone.

The success of soil conservation and watershed management programs requires the understanding of individuals’ attitudes towards these programs. Therefore, the goal of the current study was evaluation of the attitude of the residents towards watershed management practices in the rural areas in the Khorasan Razavi Province using a cross sectional survey. The required data were collected from 60 respondents who were randomly selected in two watersheds through personal interviews by a questionnaire. Descriptive and factor analysis were used to analyze the data. Findings showed that the knowledge level of the respondents about watershed management practices were satisfactory. Also, the acceptance level of watershed residents was moderate. Factor analysis showed that priorities of the residents towards watershed management programs were the economic, social, and educational service items. Data analysis discovered that these factors explained 66% of the variation of reactions to the programs.

Suspended sediment (SS) resulted from distributed soil erosions facilitates soil organic matter and phosphorus (P) transportation and influences soil depletion and water quality. Organic matter (OM) in soil is the most important indicator of soil quality and productivity. P is one of the major nutrients controlling eutrophication of surface water. Irregular contaminant load pulsed by heavy rainfall may damage the ecological quality of downstream waters. Evaluation of OM and P, depleted by erosion processes in watershed scale, is necessary for better understanding the watershed system and should lead to appropriate management approaches. On the other hand, different behaviours of soil erosion as well as the necessity of regional studies have been proved. The present study was conducted in the Kojour watershed, Iran in order to (1) get some ideas about the storm-wise OM and P load in river, (2) evaluate the relationship between the peak of OM and P concentration and discharge during individual rainfall events, and (3) assess the applicability of rainfall and runoff variables of ten storm events in the prediction of storm-wise OM and P loss. The results showed that most of the OM and P peaks preceded the peak discharge, following a clockwise hysteretic loop that exhibited hysteresis with a greater OM and P concentration for a given discharge occurring on the rising limb rather than on the falling limb. The results also showed that regression models had good efficiency in estimation of storm-wise OM and P loss with coefficient of determination of 0.96 and 0.93, respectively.

Evaluation of soil erosion by existing models is needed as an important tool for managerial purposes in designation of proper water and soil conservation techniques. The present study aimed to assess the applicability of hillslope erosion model (HEM) as one of the newest erosion models for prediction of storm-wise sediment yield in Khosbijan rangeland with 20% slope steepness by using soil erosion standard plots. In order to run the model, runoff depth, land surface cover, soil texture, slope steepness and length were determined for 16 storm events. The results showed that the uncalibrated HEM did not simulate the observed sediment yields properly. Calibration of soil erodibility parameter and developing regression between observed and estimated data indicated that the model was capable of predicting sediment yield in plots by applying soil erodibility parameter of 0.15 with determination coefficient of 0.64 and estimate error of 40%.

Splash erosion is recognized as the first stage in a soil erosion process and results from the soil surface bombing by rain drops. At the moment when rain drops conflict with the soil surface, soil particles move and destruct the soil structure. Soil particles dispersed by rain drops and moved by runoff are two basic soil erosion processes. In this study, the effect of applying various amounts of polyacrylamide (PAM) (0, 0.2, 0.4 and 0.6 g/m2) on the quantity of splash erosion at three rainfall intensities of 65, 95 and 120 mm/h by using of FEL3 rainfall simulator was investigated in marly soil in a laboratory. Results indicated differences in the effects of various treatments with PAM at all rainfall intensities, such as 0.6 g/m2 PAM had the maximum effect on the splash erosion control by reducing soil erosion by about 28.93%. But statistical results showed that the use of various amounts of PAM (0.2, 0.4 and 0.6 g/m2) for controlling splash erosion at various rain intensities to decrease splash erosion did not reveal a statistically significant difference. Therefore, the application of 0.2, 0.4 and 0.6 g/m2 PAM reduced the splash erosion, however, there was no statistical difference among these application rates of PAM. Finally, the results of statistical analysis of different intensities showed that only at 120 mm/h there was a significant difference between PAM treatment and control treatment (0 g/m2 PAM) in the splash erosion control. At this intensity, the treatment with 0.4 g/m2 PAM produced a maximum effect on the splash erosion control with 40% in comparison with the control treatment.

Purpose: To compare modified viscotrabeculotomy (VCO-Tbo) to modified trabeculotomy (Tbo) in late-onset primary congenital, juvenile open-angle, steroid-induced, and pigmentary glaucoma., Methods: Patients were randomly assigned to VCO-Tbo and Tbo groups in this study. Intraocular pressure (IOP), antiglaucoma medications, and success/failure rates were assessed. A linear mixed model was used to compare the change trend at different follow-up times. Survival time was evaluated using the Kaplan-Meier graph and Log-Rank test., Results: The mean IOP at 1, 3, and 12 months in the VCO-Tbo group was 14.1 ± 3.1, 15.9 ± 3 and 17 ± 3.1 mmHg, respectively. The mean IOP at the same time points in the Tbo group was 15.9 ± 3.3, 17.6 ± 3.5 and 18.4 ± 3.2 mmHg (P = 0.051, 0.058, 0.088, respectively). The VCO-Tbo group had significantly lower IOP after six months (16.5 ± 4.1 mmHg vs. 18.7 ± 3.8 mmHg; p = 0.031) and by the last visit (16.8 ± 2.1 mmHg vs. 18.8 ± 2 mmHg; p = 0.013). The reduction in the number of medications was significant in both groups compared to baseline (P < 0.001), but there was no significant difference between groups (P = 0.450). The complete and qualified success rate was 43.9% and 34.1% in the VCO-Tbo group and 46.8% and 10.6% in the Tbo group at the final follow-up (p = 0.040, and 0.039, respectively)., Conclusion: Both procedures are effective in IOP and medication reduction. The survival time and efficacy of modified trabeculotomy can be augmented by injecting cohesive viscoelastic in the Schlemm's canal., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The purpose of this study is to describe a patient who experienced simultaneous central retinal vein and cilioretinal artery occlusions, as well as perifoveal hemorrhage in the Henle fiber., Case Presentation: A 67-year-old Iranian woman presented with a 3-day history of reduced vision in her left eye. Venous tortuosity and retinal hemorrhage were observed in the retina, together with whitened regions around the fovea, consistent with the diagnosis of central retinal vein occlusion in conjunction with cilioretinal artery occlusion. In structural and en face optical coherence tomography, star-shaped hemorrhages were observed around the fovea, which looked hyperreflective in the Henle fiber layer., Conclusions: We present a case of central retinal vein occlusion exacerbated by cilioretinal occlusion and hemorrhage in the Henle fiber layer. The hemorrhage is most likely the result of increased intraluminal pressure in the deep capillary plexus., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To review the concept of plateau iris and summarize the recent evidence on its diagnosis and management., Methods: This is a narrative review on the plateau iris. A literature review was conducted in PubMed, Google Scholar, and Scopus databases using keywords: angle-closure glaucoma, glaucoma, nonpupillary block glaucoma, plateau iris, and plateau iris management., Results: This review defined the current knowledge about plateau iris. First of all, the anatomy and epidemiology were discussed. Then, we outlined the available evidence on the diagnosis of plateau iris and its differential diagnosis. Conclusively, the treatment options were mentioned., Conclusions: Plateau iris is a condition in which nonpupillary block mechanisms are responsible for intraocular pressure elevation and angle closure attack when a patent peripheral iridotomy has removed the relative pupillary block. An anteriorly positioned ciliary body causes mechanical obstruction of trabecular meshwork in these patients. It is usually seen in younger patients with angle closure and is diagnosed by gonioscopic examination and imaging modalities such as Ultrasound biomicroscopy. Despite the known mechanism of plateau iris, there is no consensus over treatment. Low-dose pilocarpine and Argon laser peripheral iridoplasty are nonsurgical treatments for these patients, but their effects are short-term. Cataract extraction with/without endocyclophotocoagulation (ECP), endocycloplasty, excisional goniotomy, and transscleral cyclophotocoagulation are alternative treatments. Patients should be examined periodically for further progression or recurrence of plateau iris. In cases of glaucoma unresponsive to conventional medical treatments, surgical treatments such as trabeculectomy and drainage devices should be considered., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Current Ophthalmology.)

Introduction:   activity tracker device usage can help analyze the impact of disease state and therapy on patients in clinical practice.  factors such as age, race, and gender may contribute to difficulties with using such technology.  Objective: we evaluated the effect of age, race, and gender on the usability of the Fitbit OneTM activity tracking device in sarcoidosis patients and the impact of device on sarcoidosis patients' activity., Method: patients participated in a six-month prospective study where were asked to wear a Fitbit OneTM activity tracker daily. device usage education was provided at study enrollment.  weekly data download and submission reports to participating centers was required. patients were asked to complete a post-study questionnaire reviewing the motivation of the activity tracker on daily activity., Results: at three centers, 91 patients completed all study visits and the post study questionnaire with a mean age of 55 and 75% were female and 34% african american. accurate downloads occurred >75% of the time, regardless of age, race, or sex. results of the post-study questionnaire did not show a correlation between the likelihood of wearing the device and motivation to increase activity., Conclusion: using an activity tracking device to evaluate and/or correlated with quality of life (QOL) instruments may prove beneficial for gathering more data on patients.  age, race, and gender did not contribute to differences in usability among sarcoidosis patients.

Background: Sarcoidosis, a multi-systemic granulomatous disease, is a predominantly T-cell disease but evidence for a role for humoral immunity in disease pathogenesis is growing. Utilizing samples from the Genomic Research in Alpha-1 anti-trypsin Deficiency and Sarcoidosis (GRADS) study, we examined the prevalence of autoantibodies in sarcoidosis patients with pulmonary-only and extra-pulmonary organ involvement compared to normal controls., Study Design and Methods: We analyzed serum samples from sarcoidosis patients who participated in the GRADS study utilizing an autoantigen microarray platform for both IgM and IgG antibodies. The cohort included sarcoidosis patients with pulmonary-only disease (POS, n = 106), sarcoidosis patients with extra-pulmonary disease (EPS, n = 120) and a normal control cohort (NC, n = 101). Organ involvement was assessed following a standardized format across all GRADS participating centers., Results: Sarcoidosis patients overall had increased levels of IgM and IgG autoantibodies compared to normal controls. In addition, several autoantibodies were elevated in the POS and EPS cohorts compared to the NC cohort. Differences in autoantibody levels were also noted between the POS and the EPS cohorts. When comparing organ involvement with sarcoidosis, bone, spleen and ear, nose and throat involvement had higher IgM expression than other organs., Conclusion: Sarcoidosis patients have elevated IgM and IgG autoantibody levels compared to normal controls. In addition, individuals with pulmonary as well as additional organ involvement had higher IgM expression. Further research is needed focusing on specific organ-autoantibody pairs and role of autoantibodies in disease pathogenesis., Competing Interests: The authors have declared that no competing interests exist in relationship to this work.

Introduction: The impact of common measures to assess sarcoidosis have not been compared longitudinally to outcomes that are meaningful to patients. We prospectively examined the relationship of baseline measurements of sarcoidosis status to outcomes of interest to patients longitudinally over 6 months., Methods: Sarcoidosis patients cared for at 6 US medical centers were "phenotyped" at baseline with measurements of pulmonary function, organ involvement, health related quality of life (HRQoL) instruments, and their anti-sarcoidosis treatment history. These patients were followed for 6 months by monitoring outcomes of interest to patients (OIPs) including steps walked, calories expended, sleep, HRQoL measures, workdays missed and health care utilization. For each baseline phenotypic measurement, patients were dichotomized into two groups above and below a specified cutoff value. The area under the OIP versus time curve was compared between these two groups., Results: The cutoff values for many baseline phenotypic measures distinguished the patients into groups with significantly different 6-month OIPs. The chosen cutoff for the patient global estimate of health status distinguished the most OIPs (13/15). The 6-min walk distance cutoff was associated with more OIPs than spirometric measures. All of the HRQOL measure cutoffs were associated with many OIPs, although most of them were other HRQOL measures., Interpretation: Cutoffs for most of the phenotypic measures used to assess sarcoidosis distinguished groups of sarcoidosis patients with differing OIPs over the subsequent 6 months. The patients' global assessment of their disease was the most accurate of these measures., Clinical Trial Registration Number: NCT04342403., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Most phenotyping paradigms in sarcoidosis are based on expert opinion; however, no paradigm has been widely adopted because of the subjectivity in classification. We hypothesized that cluster analysis could be performed on common clinical variables to define more objective sarcoidosis phenotypes., Methods: We performed a retrospective cohort study of 554 sarcoidosis cases to identify distinct phenotypes of sarcoidosis based on 29 clinical features. Model-based clustering was performed using the VarSelLCM R package and the Integrated Completed Likelihood (ICL) criteria were used to estimate number of clusters. To identify features associated with cluster membership, features were ranked based on variable importance scores from the VarSelLCM model, and additional univariate tests (Fisher's exact test and one-way ANOVA) were performed using q-values correcting for multiple testing. The Wasfi severity score was also compared between clusters., Results: Cluster analysis resulted in 6 sarcoidosis phenotypes. Salient characteristics for each cluster are as follows: Phenotype (1) supranormal lung function and majority Scadding stage 2/3; phenotype (2) supranormal lung function and majority Scadding stage 0/1; phenotype (3) normal lung function and split Scadding stages between 0/1 and 2/3; phenotype (4) obstructive lung function and majority Scadding stage 2/3; phenotype (5) restrictive lung function and majority Scadding stage 2/3; phenotype (6) mixed obstructive and restrictive lung function and mostly Scadding stage 4. Although there were differences in the percentages, all Scadding stages were encompassed by all of the phenotypes, except for phenotype 1, in which none were Scadding stage 4. Clusters 4, 5, 6 were significantly more likely to have ever been on immunosuppressive treatment and had higher Wasfi disease severity scores., Conclusions: Cluster analysis produced 6 sarcoidosis phenotypes that demonstrated less severe and severe phenotypes. Phenotypes 1, 2, 3 have less lung function abnormalities, a lower percentage on immunosuppressive treatment and lower Wasfi severity scores. Phenotypes 4, 5, 6 were characterized by lung function abnormalities, more parenchymal abnormalities, an increased percentage on immunosuppressive treatment and higher Wasfi severity scores. These data support using cluster analysis as an objective and clinically useful way to phenotype sarcoidosis subjects and to empower clinicians to identify those with more severe disease versus those who have less severe disease, independent of Scadding stage., (© 2022. The Author(s).)

Purpose: To compare the accuracy of anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in localizing rectus muscle insertions., Methods: The study was performed on 27 patients (39 rectus muscles) who required primary or secondary surgery. Using caliper function in the AS-OCT and UBM software, the distance from the insertion site to the anterior chamber angle was measured. The actual muscle insertion distance from limbus was considered as the measured distance plus 1 mm. The measurements by UBM and AS-OCT were compared with intraoperative measurements and with each other., Results: AS-OCT and UBM were performed on 13 medial rectus, 24 lateral rectus, and 2 superior rectus muscles. Ninety two percent of UBM measurements (36 muscles) were within 1 mm, one was within 1-1.5 mm, and 2 were within 1.5-2 mm of surgery measurements. Eighty five percent of AS-OCT measurements (33 muscles) were within 1 mm, 5 were within 1-1.5 mm, and one was within 1.5-2 mm of surgery measurements. In all cases, the mean absolute error of the UBM (0.54 ± 0.44) and AS-OCT (0.51 ± 0.36) showed no significant difference (p = .76)., Conclusion: AS-OCT and UBM can be used interchangeably to localize rectus muscle insertions and showed good agreement with intraoperative measurements.

Purpose: To evaluate the superficial vascular density of the optic nerve head in different stages of pseudoexfoliation disease using optical coherence tomography angiography (OCTA)., Methods: In this cross-sectional study, 57 normal eyes, 41 eyes with pseudoexfoliation syndrome (PXS), 82 eyes with pseudoexfoliation glaucoma (PXG) and 27 non-glaucomatous fellow eyes of PXG (NL-PXG) that had OCTA were included. Circumpapillary RNFL (cpRNFL) thickness and circumpapillary capillary density (cpCD) were compared among the groups after adjusting for confounders using linear-mixed model., Results: PXG eyes had thinner global RNFL and lower cpCD (74.2±14.3 µm and 36.7±10.0%) than control (103.3±8.6 µm and 52.5±2.3%), PXS (96.8±8.8 µm and 51.5±2.3%), and NL-PXG eyes (96.3±11.1 µm and 50.1±3.9%) (p<0.001). After adjustment for age, gender and signal strength index, global cpRNFL thickness was comparable among control, PXS and NL-PXG. NL-PXG had the lowest cpCD (p=0.045) and sectoral cpCD compared to PXS and control eyes. Although cpCD was comparable between control and PXS (p=0.425) eyes, sectoral differences (p=0.009 and 0.004, for inferonasal and temporal-inferior cpCD, respectively) were detectable between the two groups. AUROC for differentiating NL-PXG eyes from normal were better for cpCD (0.78) compared to cpRNLF (0.69)., Conclusions: OCTA can detect reduced capillary density before significant changes in cpRNFL in fellow eyes of PXG patients. This can enable earlier detection of glaucomatous loss in pseudoexfoliation disease and enhance management of the disease., Competing Interests: Competing interests: Weinreb: Aerie Pharmaceuticals (C), Alcon (C), Allergan (C), Bausch & Lomb (C), Eyenovia (C), Unity (C), Heidelberg Engineering (F), Carl Zeiss Meditec (F), Genentech (F), Konan (F), OptoVue (F), Topcon (F), Optos (F), Centervue (F). Rao HL: Santen (C), Carl Zeiss Meditec (C), Allergan (C). Others: none., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes. We then performed logistic regression modeling and generated ROC curves to determine which genes could most accurately differentiate: 1) CBD versus sarcoidosis 2) CBD versus BeS 3) sarcoidosis versus controls 4) non-progressive versus progressive sarcoidosis. Results CD55 and TNFα were significantly upregulated, while CXCL9 was significantly downregulated in CBD compared to sarcoidosis (p < 0.05). The ROC curve from the logistic regression model demonstrated high discriminatory ability of the combination of CD55, TNFα, and CXCL9 to distinguish between CBD and sarcoidosis with an AUC of 0.98. CD55 and TNFα were significantly downregulated in sarcoidosis compared to controls (p < 0.05). The ROC curve from the model showed a reasonable discriminatory ability of CD55 and TNFα to distinguish between sarcoidosis and controls with an AUC of 0.86. There was no combination of genes that could accurately differentiate between CBD and BeS or sarcoidosis phenotypes. Interpretation CD55, TNFα and CXCL9 expression levels can accurately differentiate between CBD and sarcoidosis, while CD55 and TNFα expression levels can accurately differentiate sarcoidosis and controls., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Sarcoidosis is an immune-mediated disease. Cardiac involvement, a granulomatous form of myocarditis, is under-recognized and prognostically relevant. Anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in nonsarcoidosis myocarditis forms., Objective: The aim was to assess serum AHAs and AIDAs as autoimmune markers in cardiac sarcoidosis., Methods: This is a cross-sectional study on AHA and AIDA frequency in: 29 patients (aged 46 ± 12, 20 male) with biopsy-proven extracardiac sarcoidosis and biopsy-proven or clinically suspected and confirmed by 18-fluorodeoxyglucose positron emission tomography and/or cardiovascular magnetic resonance (CMR) cardiac involvement; 30 patients (aged 44 ± 11, 12 male) with biopsy-proven extracardiac sarcoidosis without cardiac involvement (no cardiac symptoms, normal 12-lead electrocardiogram, echocardiography and CMR), and control patients with noninflammatory cardiac disease (NICD) ( n = 160), ischemic heart failure (IHF) ( n = 141) and normal blood donors (NBDs) ( n = 270). Sarcoidosis patients were recruited in two recruiting tertiary centers in the USA and Italy. AHAs and AIDAs were detected by indirect immunofluorescence on the human myocardium and skeletal muscle., Results: AHA and AIDA frequencies were higher in sarcoidosis with cardiac involvement (86%; 62%) than in sarcoidosis without cardiac involvement (0%; 0%), NICD (8%; 4%), IHF (7%; 2%) and NBD (9%; 0%) ( p = 0.0001; p = 0.0001, respectively). Sensitivity and specificity for cardiac sarcoidosis were 86% and 92% for positive AHAs and 62% and 98% for positive AIDAs, respectively. AIDAs in cardiac sarcoidosis were associated with a higher number of involved organs ( p = 0.04)., Conclusions: Serum AHAs and AIDAs provide novel noninvasive diagnostic autoimmune markers for cardiac sarcoidosis.

Purpose: To evaluate the effects of subconjunctival bevacizumab injection on intraocular pressure (IOP), hypertensive phase, and failure and success rates of Ahmed Glaucoma Valve (AGV) implantation., Methods: A total of 63 eyes of 63 patients (30 cases in control and 33 cases in bevacizumab group) were included in this randomized masked prospective clinical trial. Pre- and postoperative BCVA, IOP, number of medications, complications and success rates were compared between AGV + bevacizumab and AGV alone group., Results: Both groups showed statistically significant reductions in IOP in all their follow-up visits (P < 0.05). The mean IOP was lower in the AGV + Bevacizumab group than AGV group in all follow-up visits. However, the difference was only significant at the 3rd month (17.3 ± 6.2 vs. 20.7 ± 4.6, p = 0.04). The number of medications was not differed significantly between the two groups at their last visit (p value = 0.84) Complete success rate was higher in AGV + Bevacizumab. However, the difference was not significant (p = 0.73). The qualified and overall success rate, failure rate and the need for second tube were not statistically different between the two groups. The hypertensive phase was not statistically significant between the 2 groups (33.3% in AGV + Bevacizumab group and 50% in AGV group, p = 0.06) CONCLUSION: Adjunctive use of Bevacizumab during AGV implantation is beneficial in controlling hypertensive phase and IOP control and may lead to higher success rates and lower failure rates after AGV implantation. However, whether it's clearly beneficial or its exact role remains to be investigated.

Rationale: Improvement of quality of life (QoL) in patients with sarcoidosis is an important goal of management. The King's Sarcoidosis Questionnaire (KSQ) and Patient Global Assessment (PGA) are instruments that have been used in sarcoidosis. Objectives: We defined the minimal clinically important difference (MCID) as the within-patient clinically meaningful change threshold and determined the MCID of KSQ general health (KSQ GH), KSQ lung, and PGA using both anchor and distribution methods. The discriminatory properties of these MCIDs relative to other QoL instruments were then determined. Methods: Patients with sarcoidosis recruited from six centers in the United States were prospectively studied. Initially and at 6 months, patients completed a series of QoL questionnaires, including the St. George's Respiratory Questionnaire (SGRQ), Short Form 36 (SF-36), Fatigue Assessment Scale (FAS), Sarcoidosis Assessment Tool (SAT), KSQ, and PGA, and spirometry. For the anchor method, receiver operator characteristic curves were used to determine the MCID for improvement or worsening. The distribution method using half of the standard deviation was calculated for KSQ GH, KSQ lung, and PGA. Results: Of the 325 patients enrolled in the study, 271 completed the 6-month evaluation. At 6 months, approximately half of patients were worse and 30% were improved based on previously established MCID values for the SGRQ, SF-36, and FAS. There were no discordant cases. There were significant correlations between the KSQ GH, KSQ lung, and PGA and most parameters assessed. The best correlations were with the SGRQ, SF-36, and FAS, which have established MCID values. Using anchor analysis, we found that most of the domains of SGRQ and SF-36 were able to determine the significant MCIDs for all three variables. These MCIDs were similar to those determined by the half least square method. We propose an MCID of 8 for the KSQ GH, an MCID of 4 for the KSQ lung, and an MCID of 2 for the PGA because these values captured >90% of parameters studied. These MCID values discriminated between changes in other QoL instruments. Conclusions: The determination of MCID values for KSQ lung, KSQ GH, and PGA may prove useful for clinical practice as well as clinical trials.

Background: Interprofessional communication using Facebook ® , Snapchat ® , Instagram ® , and WhatsApp ® has become a reality that is shaping our future. However, studies evaluating the dimensions of this use in the medical field are scarce and proper guidelines have not yet been established. This highlights the importance of exploring the wide range of using such common communication tools in the medical field. Objective: The aim of this study is to investigate the prevalence of WhatsApp use as an interprofessional communication tool among Lebanese physicians and explore the dimensions of its use. Materials and Methods: This cross-sectional study was conducted by using LimeSurvey through an e-mail-based questionnaire sent to 5,329 physicians enrolled in the Lebanese Order of Physicians. Results: Four hundred twenty-nine physicians completed the survey with a response rate of 8%. Most respondents (96.5%) were WhatsApp users, where 72.7% stated being consulted by colleagues via WhatsApp, and about 50% reported being members of professional WhatsApp groups that mainly share medical cases and patients' updates. Further, most physicians made sure that the shared information contained no patient identifier and kept it for future referencing without the patient's permission or consent before consulting their colleagues. Almost 75% of the respondents agreed that guidelines are needed to illustrate the medico-legal and ethical aspects of WhatsApp use by physicians and recommended using WhatsApp specifically for inter-physician communication. Conclusion: The findings of this study illustrate the high prevalence of WhatsApp Messenger use among Lebanese physicians. Utilizing such digital platforms is highly demanded to enhance interprofessional communication between physicians in the medical field.

Rationale: A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients. Objectives: To measure ABC-like cell percentages in patients with lung granulomatous diseases. Methods: Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet. Measurements and Main Results: ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood. Conclusions: Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure. Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability. Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality. Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Purpose: To evaluate the effect of postoperative latanoprost administration on central macular thickness (CMT) after uneventful cataract surgery in glaucoma patients., Setting: Farabi Eye Hospital, Tehran, Iran., Design: Prospective randomized clinical trial., Methods: In this single-masked trial, glaucoma patients treated with latanoprost who had no other risk factor for the development of pseudophakic macular edema were randomly allocated to continuation of latanoprost or discontinuation of the drop after uneventful cataract surgery. At baseline and postoperatively at 1 month and 3 months, patients had complete ocular examinations and CMT measurements using optical coherence tomography. The main outcome measure was the change in the CMT between baseline measurements and postoperative measurements at 1 month and 3 months., Results: One hundred fifty-six eyes (latanoprost 76; discontinuation 80) finished the trial. There were no differences in baseline patient demographics or characteristics, including the CMT, between the two groups. There was transient increase in the mean CMT by 12 μm ± 49 (SD) in the latanoprost group at 1 month (P = .03); however, the value returned to baseline by 3 months (6 ± 55 μm; P = .27). The between-group difference in the mean change in the CMT from baseline was -3.1 μm (95% confidence interval [CI], -18.4 to 12.0; P = .68) after 1 month and -10.5 μm (95% CI, -26.6 to 5.5; P = .19) after 3 months; the differences were not significant., Conclusion: Latanoprost administration after cataract surgery had no measurable effect on macular thickness., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Introduction: Pulmonary sarcoidosis is a rare heterogeneous lung disease of unknown aetiology, with limited treatment options. Phenotyping relies on clinical testing including visual scoring of chest radiographs. Objective radiomic measures from high-resolution computed tomography (HRCT) may provide additional information to assess disease status. As the first radiomics analysis in sarcoidosis, we investigate the potential of radiomic measures as biomarkers for sarcoidosis, by assessing 1) differences in HRCT between sarcoidosis subjects and healthy controls, 2) associations between radiomic measures and spirometry, and 3) trends between Scadding stages., Methods: Radiomic features were computed on HRCT in three anatomical planes. Linear regression compared global radiomic features between sarcoidosis subjects (n=73) and healthy controls (n=78), and identified associations with spirometry. Spatial differences in associations across the lung were investigated using functional data analysis. A subanalysis compared radiomic features between Scadding stages., Results: Global radiomic measures differed significantly between sarcoidosis subjects and controls (p<0.001 for skewness, kurtosis, fractal dimension and Geary's C ), with differences in spatial radiomics most apparent in superior and lateral regions. In sarcoidosis subjects, there were significant associations between radiomic measures and spirometry, with a large association found between Geary's C and forced vital capacity (FVC) (p=0.008). Global radiomic measures differed significantly between Scadding stages (p<0.032), albeit nonlinearly, with stage IV having more extreme radiomic values. Radiomics explained 71.1% of the variability in FVC compared with 51.4% by Scadding staging alone., Conclusions: Radiomic HRCT measures objectively differentiate disease abnormalities, associate with lung function and identify trends in Scadding stage, showing promise as quantitative biomarkers for pulmonary sarcoidosis., Competing Interests: Conflict of interest: S.M. Ryan has nothing to disclose. Conflict of interest: T.E. Fingerlin has nothing to disclose. Conflict of interest: M. Mroz has nothing to disclose. Conflict of interest: B. Barkes has nothing to disclose. Conflict of interest: N. Hamzeh has nothing to disclose. Conflict of interest: L.A. Maier reports grants from NIH/NHLBI during the conduct of the study, and grants from NIH/NHLBI, aTYR and Mallinckrodt ARD, Inc., outside the submitted work. Conflict of interest: N.E. Carlson has nothing to disclose., (Copyright ©ERS 2019.)

Previously we showed that alveolar macrophages (AMs) from patients with chronic beryllium disease (CBD) and beryllium sensitization (BeS) demonstrated significantly greater cell surface CD16 (encoded by the FCGR3A gene) than controls. We hypothesized that these differences were related to polymorphisms in the FCGR3A gene. This study was to determine the association between FCGR3A polymorphisms in CBD, BeS versus controls as well as clinical data, providing potential information about disease pathogenesis, risk, and activity. A total of 189 CBD/154 BeS/150 controls (92 Be-exposed non-diseased and 58 healthy controls) were included in this study. Sequence-specific primers polymerase chain reaction (PCR-SSP) was used to determine FCGR3A 158V/F polymorphisms. We found significantly higher frequencies of the 158V allele (OR: 1.60 (CI: 1.17-2.19), p = 0.004) and 158VV homozygotes (OR: 2.97 (CI: 1.48-5.97) p = 0.007) in CBD versus controls. No differences were found in the frequencies of FCGR3A alleles or genotypes between BeS versus controls and CBD versus BeS. Average changes in exercise testing maximum workload (Wlm), maximum oxygen consumption (VO 2 m), and diffusion capacity of carbon monoxide (DLCO) demonstrated greater decline over time in those CBD cases with the 158VV gene, modeled between 10 and 40 years from first beryllium exposure. The FCGR3A V158F polymorphism is associated with CBD compared to BeS and controls and may impact lung function in CBD.

Sarcoidosis is a multisystemic granulomatous disease that affects individuals worldwide. The lungs are most commonly involved but any organ can be involved. It has variable manifestations and clinical course. Diagnosis of sarcoidosis is based on clinicopathologic findings and the exclusion of other causes of granulomatous disease. Its hallmark is the formation of granulomas in affected organs. Immunosuppressive therapy is the cornerstone of the management of sarcoidosis and is indicated when there is evidence of symptomatic or progressive disease or when critical organs (ocular, cardiac, nervous system) are involved., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and sarcoidosis in lung cells obtained by BAL. BAL cells from CBD (n = 8), beryllium-sensitized (n = 8), sarcoidosis (n = 8), and additional progressive sarcoidosis (n = 9) and remitting (n = 15) sarcoidosis were profiled on the Illumina 450k methylation and Affymetrix/Agilent gene expression microarrays. Statistical analyses were performed to identify DNA methylation and gene expression changes associated with CBD, sarcoidosis, and disease progression in sarcoidosis. DNA methylation array findings were validated by pyrosequencing. We identified 52,860 significant (P < 0.005 and q < 0.05) CpGs associated with CBD; 2,726 CpGs near 1,944 unique genes have greater than 25% methylation change. A total of 69% of differentially methylated genes are significantly (q < 0.05) differentially expressed in CBD, with many canonical inverse relationships of methylation and expression in genes critical to T-helper cell type 1 differentiation, chemokines and their receptors, and other genes involved in immunity. Testing of these CBD-associated CpGs in sarcoidosis reveals that methylation changes only approach significance, but are methylated in the same direction, suggesting similarities between the two diseases with more heterogeneity in sarcoidosis that limits power with the current sample size. Analysis of progressive versus remitting sarcoidosis identified 15,215 CpGs (P < 0.005 and q < 0.05), but only 801 of them have greater than 5% methylation change, demonstrating that DNA methylation marks of disease progression changes are more subtle. Our study highlights the significance of epigenetic marks in lung immune response in granulomatous lung disease.

In this review, we argue for the use of high-resolution computed tomography (HRCT) over chest X-ray in the initial evaluation of patients with sarcoidosis. Chest X-ray, which has long been used to classify disease severity and offer prognostication in sarcoidosis, has clear limitations compared with HRCT, including wider interobserver variability, a looser association with lung function, and poorer sensitivity to detect important lung manifestations of sarcoidosis. In addition, HRCT offers a diagnostic advantage, as it better depicts targets for biopsy, such as mediastinal/hilar lymphadenopathy and focal parenchymal disease. Newer data suggest that specific HRCT findings may be associated with important prognostic outcomes, such as increased mortality. As we elaborate in this update, we strongly recommend the use of HRCT in the initial evaluation of the patient with sarcoidosis., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Purpose: To compare outcomes of phacoemulsification combined with viscocanalostomy, endocyclophotocoagulation (ECP), or ab interno trabulectomy for intraocular pressure (IOP) control and safety in eyes with open-angle glaucoma and visually significant cataract., Setting: Farabi Eye Hospital, Tehran, Iran., Design: Retrospective case series., Methods: Medical records of patients who had combined surgery and were followed for at least 1 year were reviewed. Complete success, postoperative IOP, number of medications at each visit, and complications were evaluated and compared before and after adjustments for confounders., Results: Forty-six eyes had combined phacoviscocanalostomy, 35 had phaco-ECP, and 28 eyes phaco-ab interno trabulectomy. The groups were matched for baseline IOP (P = .24). At the final follow-up (mean 17.2 months ± 5.5 [SD]), the phacoviscocanalostomy group had the lowest mean IOP (13.5 ± 4.7 mm Hg, 29% decrease) (P = .01). There was no significant difference in the final IOP between phaco-ECP and phaco-ab interno trabulectomy (16.4 ± 3.9 mm Hg, 20% decrease versus 15.8 ± 4.2 mm Hg, 15% decrease) (P = .88). The reduction in the number of medications was greater with phacoviscocanalostomy (77%) than with phaco-ECP (40%) and phaco-ab interno trabulectomy (44%) (P = .01). Phacoemulsification-ab interno trabulectomy had the fewest complications. Intraocular pressure spikes were more frequent in the phaco-ECP group (20%) than in the other groups (4%) (P = .05)., Conclusions: All procedures significantly lowered IOP. Phacoemulsification-ab interno trabulectomy resulted in fewest complications and phacoviscocanalostomy led to the largest IOP drop and largest reduction of medications., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Ichthyosis Follicularis, Atrichia, and Photophobia (IFAP) is a severe rare genetic disorder caused by mutations in the gene encoding the Membrane-Bound Transcription Factor Peptidase, Site 2 (MBTPS2). Olmsted syndrome is another rare genetic disease with overlapping clinical features caused by mutations in the gene encoding the Transient Receptor Potential Cation Channel, subfamily V (TRPV3). Mutations in MBTPS2 have been recently reported in Olmsted syndrome, underscoring the overlap and the confusion in separating Olmsted from IFAP syndrome. We studied a Lebanese family with IFAP syndrome both, clinically and molecularly, and investigated whether there is a cross relation between TRPV3 and MBTPS2. We identified a recurrent mutation designated p.F475S in MBTPS2 in the affected individuals. This mutation was not found in 100 control individuals from the same population. We determined that TRPV3 regulatory region is a target for MBTPS2. In addition, there was an increased cell death in the cells transfected with the mutant versus the wild-type MBTPS2. In conclusion, we identified a direct regulatory effect of MBTPS2 on TRPV3 which can partially contribute to the overlapping clinical features of IFAP and Olmsted syndromes under a common signaling pathway.

The incidence and prevalence of obesity are fast increasing worldwide. Various indices have been used to measure and assess obesity. The body mass index (BMI) is the most common and practical of these indices. Overweight and obesity exert considerable adverse effects on the cardiovascular system. These effects are mediated through various neurohormonal and cytokine pathways, most of which are inflammatory mediators. Systolic and / or diastolic heart failure is more prevalent among obese and overweight individuals than among normal weight people. The concept of the "obesity paradox" has been proposed by some previously published studies, in which the prognosis of obese patients with established cardiovascular diseases, especially heart failure, is better than that of their leaner counterparts. In this review, we discuss the obesity paradox and its possible pathophysiologic mechanisms.

Background: Sarcoidosis is a disease that is associated with occupational and environmental antigens, in the setting of a susceptible host. The aim of this study was to examine the association between sarcoidosis mortality and previously reported occupational exposures based on sex and race., Methods: The decedents enrolled in this study were derived from United States death certificates from 1988-1999. Cause of death was coded according to ICD-9 and ICD-10. The usual occupation was coded with Bureau of the Census Occupation Codes. Mortality odds ratio (MOR) were determined and multiple Poisson regression were performed to evaluate the independent exposure effects after adjustment for age, sex, race and other occupational exposures., Results: Of the 7,118,535 decedents in our study, 3,393 were identified as sarcoidosis-related, including 1,579 identified as sarcoidosis being the underlying cause of death. The sarcoidosis-related MOR of any occupational exposure was 1.52 (95% CI, 1.35-1.71). Women with any exposure demonstrated an increased MOR compared to women without (MOR 1.65, 95% CI, 1.45-1.89). The mortality risk was significantly elevated in those with employment involving metal working, health care, teaching, sales, banking, and administration. Higher sarcoidosis-related mortality risks associated with specific exposures were noted in women vs men and blacks vs whites., Conclusions: Findings of prior occupations and risk of sarcoidosis were verified using sarcoidosis mortality rates. There were significant differences in risk for sarcoidosis mortality by occupational exposures based on sex and race., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate different mechanisms of primary angle closure (PAC) and to quantify anterior chamber (AC) parameters in different subtypes of angle closure disease using anterior segment optical coherence tomography (AS-OCT)., Methods: In this prospective study, 115 eyes of 115 patients with angle closure disease were included and categorized into three groups: 1) fellow eyes of acute angle closure (AAC; 40 eyes); 2) primary angle closure glaucoma (PACG; 39 eyes); and 3) primary angle closure suspect (PACS; 36 eyes). Complete ophthalmic examination including gonioscopy, A-scan biometry, and AS-OCT were performed. Based on the AS-OCT images, 4 mechanisms of PAC including pupillary block, plateau iris configuration, thick peripheral iris roll (PIR), and exaggerated lens vault were evaluated. Angle, AC, and lens parameter variables were also evaluated among the three subtypes., Results: There was a statistically significant difference in the mechanism of angle closure among the three groups (p = 0.03). While the majority of fellow eyes of AAC and of PACS eyes had pupillary block mechanism (77.5% and 75%, respectively), only 48.7% of PACG eyes had dominant pupillary block mechanism (p = 0.03). The percentage of exaggerated lens vault and plateau iris mechanisms was higher in PACG eyes (25.5% and 15.4%, respectively). Fellow eyes of AAC had the shallowest AC (p = 0.01), greater iris curvature (p = 0.01), and lens vault (p = 0.02) than PACS and PACG eyes. Iris thickness was not significantly different among the three groups (p = 0.45)., Conclusion: Using AS-OCT, we found that there was a statistically significant difference in the underlying PAC mechanisms and quantitative AC parameters among the three subtypes of angle closure disease.

A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine-cytokine receptor interactions, and Toll-like receptor, chemokine and JAK-STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways., Competing Interests: can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2016.)

Background: Oxidative stress (OS) has been shown to play a role in the pathogenesis of sarcoidosis and previous studies have shown that anti-oxidants can reduce markers of oxidative stress and inflammation in the peripheral blood of sarcoidosis subjects. We investigated the effect of N-Acetyl-Cysteine (NAC) on oxidative stress and inflammatory markers in the lungs of sarcoidosis patients., Methods: We randomized 11 sarcoidosis subjects to active therapy and 3 to placebo for 8 weeks in a double blinded study. Bronchoscopy with bronchoalveolar lavage was performed pre and post therapy. Our primary endpoint was TNF-α production from stimulated and unstimulated BAL cells. Secondary outcomes included measures of oxidative stress (GSH, 8-OHdG) levels in the BAL. In-vitro studies were also performed to assess the effect of NAC on lipopolysaccharide stimulated BAL cell production of TNF-α., Results: Eight subjects in the active group and 2 in the placebo group completed the study protocol. Eight weeks of oral NAC did not have a significant impact on TNF-α levels from BAL cells in-vivo in spite of a 59% increase in BAL GSH levels. Our in vitro studies showed a significant decline in TNF-α production from LPS stimulated BAL cells treated with 5 and 10 mM of NAC., Conclusions: Oral NAC increased GSH levels but failed to suppress in-vivo TNF-α production in contrast to effects in-vitro. Anti-oxidant therapy may still play a role in the management of sarcoidosis but therapy with better bioavailability or potency is needed to suppress the lung inflammatory response., (Copyright © 2016 Elsevier Ltd. All rights reserved.)