Optimisation of composite flour comprising pearl millet, kidney beans and tigernut with xanthan gum was evaluated for rheological evaluations. The functional properties of the composite flour were optimized using optimal design of response surface methodology. The optimum blends, defined as blends with overall best functional characteristics were run 3 , run 7  and run 13 . The pasting characteristics and rheological evaluation of the optimized blends were further evaluated in rapid visco units (RVU). Run 7 had the overall best pasting characteristics; peak viscosity (462 RVU), trough (442 RVU), breakdown viscosity (20 RVU), final viscosity (975 RVU), setback (533 RVU), peak time (5.47 min) and pasting temperature (89.60 °C). These values were found to be better than several composite flours consisting mixture of wheat and non-wheat crops. In addition, the rheological characteristics (measured by Mixolab) showed that run 7 is the best in terms of dough stability, swelling, water absorption and shelf stability. Composite flour with 85% pearl millet flour in addition to kidney beans and tigernut flours could therefore serve as a viable alternative to 100% wheat flour in bread production. PartialPearl millet is a species of millet widely grown in Nigeria; Nigeria being the world’s third largest producer after India and Niger . MilletsKidney beans is an underutilized tropical legume rich in protein, ash, soluble and insoluble fibres, and linoleic acid . It has Mixolab measures dough development behaviour during mixing and heating, thereby enabling determination of contribution of protein and starch to dough rheology . It helpCurrently, there is little or no work on the pearl millet-kidney beans composite flour. In addition to utilizing pearl millet-kidney bean, this work further added tigernut flour and carry out the optimization of the functional, pasting and rheological properties of pearl millet-based composite flour as viable alternative to wheat flour in bread production.22.1(pennisetum glaucuml) was obtained from Mile 12 market, Lagos State; Xanthan gum was obtained from Payless Chemical Store, Ojota, Lagos, Nigeria; Tigernut (Cyperus esculentus) was obtained from Iddo market, Lagos; Kidney bean (Phaseolus vulgans) was purchased at Iddo market, Lagos State;Pearl Millet 2.2The method of 2.3Tigernut flour was produced using the method of 2.4The method of 2.5The experimental design was carried out using optimal mixture design of response surface methodology . The independent variables were pearl millet flour (75.00–85.00 g/100 g), kidney beans flour (10.00–20.00 g/100 g), and tigernut flour (5.00–10.00 g/100 g). Xanthan gum (0.5 g/100 g) was added to all the samples in order to enhance its viscoelastic characteristics. The dependent variables are the functional characteristics.2.63) was calculated using the formula:The method described by 2.7This was determined by the method described by 2.8Water absorption capacity (WAC) of sample was determined using the method outlined by 2.90) was weighed into pre-weighed 15 ml centrifuge tubes and thoroughly mixed with 10 ml (V1) of refined pure groundnut oil using vortex mixer. Samples were allowed to stand for 30 min. The sample-oil mixture was centrifuged at 3000 rpm for 20 min. Immediately after centrifugation, the supernatant was carefully poured into a 10 ml graduated cylinder, and the volume was recorded (V2). Oil absorption capacity (milliliter of oil per gram of sample) was calculated.Oil absorption capacity (OAC) was determined using the method of 2.101) of concentrate suspension was blended for 3 min using a high speed blender, poured into a 250 ml graduated cylinder, and the volume of foam (VF) was immediately recorded. Foaming capacity was calculated using;Foaming capacity (FC) was determined in triplicate using the method described by 2.11The method of 2.12The gel obtained from swelling index was used in calculating swelling capacity (SC) thus:2.13The pasting properties of the samples were assessed using the Rapid Visco-Analyser . A 3 g sample was dispersed in an aluminum canister containing 25 ml of distilled water. The samples were tested according to Standard Profile 1, where the flour-water suspension was held at 50 °C for 1 min and then heated to 95 °C, held for 10 min, and then cooled to 50 °C and held for another 2 min. The starch viscosity parameters measured were pasting temperature, peak viscosity, breakdown viscosity, final viscosity, trough viscosity setback viscosity and peak time. The results were expressed as RVU for all of the parameters with the exception of pasting temperature, which is expressed in °C.2.14Mixolab  was used according to standard methods (AACC 54–60.01). Mixolab consisted of heating/cooling cycle after constant mixing at 80 rpm. The cooling temperature was 50 °C while the maximum temperature was 90 °C at one heating/cooling cycle. The analyses were carried out at constant water absorption according to 2.15Statistical analyses were carried out using the Response Surface Methodology so as to fit the quadratic polynomial equation generated by the Design-Expert software version 8.0.3.1 . In order to correlate the response variable to the independent variables, multiple regressions was used to fit the coefficient of the polynomial model of the response. The quality of the fit of model was evaluated using analysis of variance (ANOVA).33.12 and adjusted R2 values of 0.6170 and 0.1792 respectively obtained buttressed the assertion. The results of the functional properties of the composite flour are presented in 2 and adjusted R2 values were 0.9230 and 0.8075 respectively, while the p-value (0.9733) the for lack of fit was not significant (p ≥ 0.05). A high adjusted R2 is an indication of less variations between the dependent and independent variables, hence, it is desirable (The dispersibility of the composite flour ranged from 71–80%. Kidney beans significantly (p ≤ 0.05) increase the dispersibility. The Resirable . In addiesirable . The p-vesirable  shows th2BC, AB2C, ABC2) were significant (p ≤ 0.05). The R2 and adjusted R2 values were 0.9753 and 0.9470 respectively. The WAC values obtained were higher than the values obtained for Wheat flour, Wheat-plantain-tigernut composite flour (The WAC ranged from 126–145%. Kidney beans significantly (p ≤ 0.05) increased the WAC. However, the ANOVA showed that the model  and model terms . The contour plot  were significant (P ≤ 0.05).The foaming capacity (0.96–2.95%) is very low. The combine effect of the raw materials must have been responsible for this. 2 and the adjusted R2 values were 0.9881 and 0.9703 respectively.The swelling capacity ranged between 4.93 and 5.69 g/g. Pearl millet and kidney beans flours conspicuously increased the swelling capacity of composite flour as shown in 3.2Three best blends based on the optimization of functional properties were run 3 , run 7 , and run 13 . There are 38 optimization results. The choice is subjective, based on individuals objectives. In this case, the three best combinations selected from the 38 possible combinations were based on high or low WAC, high OAC, high foaming (≥ 1.70%) and high swelling capacity.3.3The results of the pasting characteristics of the optimized composite flour samples  and the control are presented in The trough ranged from 354–442 RVU for the composite flour while it is 936 RVU for the control. The trend followed that of peak viscosity. Trough, which measures the ability of paste to withstand breakdown during cooling. The values obtained in this work are better than the values obtained by The breakdown viscosity had been shown to reflect the stability of the peak viscosity during processing . Starch The Final viscosity ranged from 782–940 RVU for the composite flour sample, while the final viscosity value for the control is 1906 RVU. Increased pearl millet content (as in run 7) had the increased the final viscosity of the composite flour. Final viscosity defines the particular quality of starch and stability of cooked paste. Lower final viscosity signifies reduced ability to form viscous pastes. The final viscosity obtained in this work is better than what were obtained by toasted maize-based composite flour  and wheaPasting temperature was lowest in the control (100% wheat), closely followed by composite flour with 85% pearl millet (run 7). The sample with highest pearl millet flour (run 7) has consistently displayed better pasting characteristics, though, unlike 100% wheat flour. Pasting temperature is defined as the minimum temperature at which starch granules in the composite flour swells. In addition, run 7 had the best pasting time.3.4The results of mixolab of the composite flours (runs 7 and 13) are presented in Stage one (C1) is the dough development which corresponds to farinograph curve . The water absorption for run 7  and run 13  were 51.3% and 46.3% respectively. Water absorption indicates the potential of protein molecules to absorb water, hence, an indicator of baking quality . In addiThe dough development time (DDT) which is the time the dough have optimum viscoelastic properties for gas retention  were 19.97 and 26.22 mins for runs 7 and 13 respectively. Run 7, therefore, had a faster dough development time. The stability time for runs 7 and 13 were 9.18 and 1.57 mins respectively. The longer stability period is an indication of better protein quality. Since the stage one had been shown to correspond to farinograph curve, run 7 therefore had better dough quality for bread making than run 13.et al., 2015). Wheat flour has C2 of 0.4Nm. So run 7 has C2 value close to wheat flour. High C2 value has been reported to indicate good protein quality.In stage two, the protein network weakening rate (α) was −0.064 and −0.026 Nm/min for runs 7 and 13 respectively. In addition, the minimum consistency (C2), which is the minimum values of torque produced as the dough was subjected to mechanical and thermal stress were 0.43 and 2.73 Nm for runs 7 and 13 respectively. Run 13 therefore had a better resistance to thermal and mechanical stresses. A C2 of 0.36 Nm was reported for wheat cassava flour (Ibidapo In the third stage (C3), the gelatinization rates (β) were 0.728 and 0.014 Nm/min for runs 7 and 13 respectively. The availability of dough heating and water from thermal denaturation of protein must have resulted in starch gelatinization . The maxIn stage four (C4), the cooking stability (γ) were −0.532 and −0.018 Nm/min respectively. Run 13 had better cooking stability. The breakdown torques (difference between C3 and C4) were 0.70 and 0.20 Nm. The last stage (C5) is the setback stage (retrogradation of starch molecules), which resulted from decrease in temperature. The setback torque (difference between C5 and C4) were 2.4 Nm and 1.7 Nm in runs 7 and 13 respectively. Run 7 was therefore better shelf stable. Mixolab characteristics were better in run 7 than in run 13. The presence of pearl millet could account for this.The Mixolab profiler indicating absorption, mixing index, gluten plus, viscosity, amylose and retrogradation for run 7 were one, six, four, one, nine and six respectively. Run 13 with 75% pearl millet had no result, indicating further that run 7 (85% pearl millet) sample had better Mixolab, hence, rheological behaviour. In comparison with 100% wheat flour, the results were absorption (2), mixing index (6), gluten plus (5), viscosity (8), amylose (6) and retrogradation (5) as reported by 4Pearl millet-based composite flour offered a viable alternative to wheat-based composite flour for bread production. The results of the functional, pasting and rheological properties confirmed it. While the functional properties of pearl millet – based composite flour was better than 100% wheat flour, the 100% wheat flour had better pasting and rheological characteristics. On the other hand, pearl millet – kidney beans – tigernut composite flour (85%:10%:5%) had excellent rheological behaviour comparable with 100% wheat flour.Olugbenga O. Awolu: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data.The authors declare no conflict of interest.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.No additional information is available for this paper.


To report on radiation-related side effects and complications after ruthenium-106 plaque brachytherapy of uveal melanomas.Medical records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy between 1997 and 2012 at a single center, were analyzed.We evaluated the occurrence of radiation-related side effects on the anterior and posterior segment of the eye. The influence of patient, tumor and treatment parameters on outcome was analyzed by multivariate time to event analysis considering competing risks.The median overall follow-up was 37.9 months.After treatment, the estimated risk at 12, 24 and 48 months for developing anterior segment complications was 25.3%, 37.5% and 50.3% for cataract formation and 5.4%, 6.4% and 8.1% for secondary glaucoma, respectively.The estimated risk for the occurrence of posterior segment complications 12, 24 and 48 months after treatment was 3.1%, 6.7% and 18.3% for radiation retinopathy, 18.3%, 27.1% and 42.6% for radiation maculopathy and 16.5%, 21.0% and 32.8% for radiation neuropathy, respectively. The risk of an increase in retinal detachment after treatment was 14.7%, 14.7% and 17.4% at 12, 24 and 48 months, respectively. The risk of vitreous hemorrhage occurring after treatment was 6.2%, 8.1% and 12.7%, and the risk of tumor vasculopathy was 15.4%, 17.4% and 19.0%. Scleral necrosis was observed in one patient.Radiation-related side effects and complications are common among patients treated with ruthenium brachytherapy for uveal melanoma. However, the risk for those largely depends on individual tumor parameters.Before treatment, patients should be informed of their specific risks to develop various side effects.Patient information before treatment should cover not only general information about the treatment and possible complications and side effects but should also give details on the specific risks of the patient in her individual situation. This also includes elucidating the patient's individual resources and expectations and her willingness for long-term regular follow-up examinations and secondary adjunct treatments. Since eye-conserving radiation therapies have largely replaced enucleation in the treatment of uveal melanoma, the impact of radiation-related side effects, their occurrence and their management have become a main point of interest.Commonly described side effects include anterior segment complications such as cataract formation, the development of iris neovascularization and secondary glaucoma. Complications affecting the posterior segment of the eye are commonly related to ischemic events of the retina, mainly induced by endothelial cell loss and capillary closure, leading to the formation of teleangiectatic-like channels, capillary collaterals, retinal oedema, microaneurysms and vitreoretinal neovascularizations.  These foWe analyzed the occurrence of radiation-related side effects and complications of the anterior and posterior segment of the eye after ruthenium-106 plaque brachytherapy for uveal melanoma, comprising cataract formation, secondary glaucoma, retino-, maculo- and optic neuropathies, retinal detachments and/or retinal detachment increases, as well as vitreous hemorrhages.This retrospective analysis comprises the medical records of 143 eyes of 143 patients, out of a total of 172 patients treated with ruthenium (Ru-106) brachytherapy between June 1997 and July 2012 at the Department of Ophthalmology, Medical University of Graz. All data had prospectively been recorded in an electronic database  at our department. This study was approved by the local institutional review board .Eye preserving treatment by ruthenium plaque brachytherapy was offered to patients if they gave informed consent and agreed in regularly planned follow up examinations. Further, local tumor characteristics  had to enable for focal brachytherapy. Relative contraindications comprised large tumor size  and a close distance of posterior tumor margin to the optic disc or the center of the fovea (within 1.5mm).Twelve patients had previously been treated by transpupillary thermo-therapy  or gamma knife radiosurgery  and were therefore excluded, as were cases with isolated iris melanomas (n = 11) and incomplete medical records (n = 6). Among the included 143 patients, 24 patients (16.8%) had planned combined adjunct TTT (“sandwich-therapy”) 3 months before or after plaque brachytherapy.The inclusion and exclusion criteria, pre-irradiation assessment, collected descriptive data on tumor, treatment and patient parameters, patient demographics, past medical and family history and the treatment protocol have been described previously.  The locaAt the first presentation, each patient received a full ophthalmic exam including visual acuity, slit lamp and indirect fundus examination. Moreover, fundus photographs were taken. For accurate determination of the tumor characteristics standardized echography (A/B-scan) was used in all cases. If necessary for diagnosis and/or monitoring of posterior segment complications (e.g. macular edema) during follow-up, ocular angiography (fluorescein and indocyanine green) and optical coherent tomography were performed. Further patient demographics, past medical and family history were evaluated.Follow-up examinations were planned approximately one month after the removal of the plaque and thereafter scheduled every three months for the first two years and every six months up to five years after irradiation. Thereafter patients were followed annually.  Those fouveal intraocular melanomas (excluding isolated iris melanomas) were treated using local ruthenium-106 plaque brachytherapy. According to the wide spectrum of melanomas in study population  we used different plaque types, depending on the basal diameter. The following plaques were used: CCA (up to 15.3mm), CCB (up to 20.2mm), CCC (up to 24.8mm), CIB (up to 20.2mm), CCX (up to 11.6mm), COB (up to 19.8mm), manufactured by BEBIG, Berlin, Germany. The treatment was planned to deliver a minimum irradiation dose to the tumor apex of at least 100 Gy but not to exceed a maximum dose to the outer scleral surface of 1000 Gy.The plaque insertion and positioning surgery was usually done in general anesthesia, the plaque removal usually in local retrobulbar anesthesia. To achieve a proper position of the radioactive plaque on the globe a non-radioactive transparent plastic template of the same size (dummy applicator) was used. Indirect ophthalmoscopy with scleral indentation and transpupillary transillumination were used to visualize the tumor and outline the tumor borders on the scleral surface with a surgical pen. Extraocular muscles (rectus and oblique muscles) were removed and reinserted if necessary. The applicator was positioned on the sclera with minimal safety margin of one millimeter around the tumor margins.The primary outcome measures were complications of the anterior and posterior segment of the eye.All complications were analyzed considering pre-irradiation tumor parameters and treatment parameters. A Kaplan-Meier analysis was used to estimate the event rate in case of unequal follow up times. Competing risk regression (Fine-Gray method) was done to include competing and censoring events into the risk calculation. The end of follow-up was defined as the day of the last presentation of the patient at our department or as the day of enucleation of the affected eye regardless of causality.Cataract formation due to radiotherapy was defined as any asymmetrical increase in lens opacity on the treated eye. Secondary glaucoma was defined as any unilateral increase in the previously normal intraocular pressure (IOP) on the treated eye if the IOP of the other eye stayed within normal ranges. Radiation retinopathy was defined as any occurrence of occlusions and changes of the retinal vessels, such as microinfarcts, hemorrhages, microaneurysms, retinal edema and lipid exudations. A radiation maculopathy was defined as showing the same features within a 1.5 disc diameter of the foveola. Optic neuropathy was defined as partial or complete atrophy of the optic nerve head with or without bleeding at the optic disc. Isolated tumor vasculopathy was defined as bleeding or exudation on the tumor surface.Statistical analysis was performed using Stata 13.0 . The values of continuous variables are presented as the median, range and interquartile range (IQR) or standard deviation (SD). Categorical variables are presented as relative and absolute frequencies. Follow-up was calculated by the inverse Kaplan-Meier method.  The occuCompeting risk regression was used to calculate the cumulative incidence function (CIF) for each complication and to perform a uni- and multivariate risk factor analysis as described previously.  All statFrom 143 records reviewed, 81 (56.6%) patients were female and 62 (43.4%) patients were male gender. The age at the first presentation was 62.5 years  see .11.2% (n = 16) of patients suffered from systemic diabetes, 42% (n = 60) from systemic hypertension, 9.8% (n = 14) from a coronary artery disease and 9.1% (n = 13) from another systemic cancer.The right eye was affected in 49.7% (n = 71) of the patients, the left eye in 50.3% (n = 72) of the patients.A concurrent retinal detachment was diagnosed in 47.5% (n = 68) of the patients, an age related macular degeneration in 4.9% (n = 7) and a concurrent diabetic retinopathy in one patient (0.7%) at time of diagnosis.41.2% (n = 59) of patients had a pre-existing cataract and 9.1% (n = 13) of patients were pseudophacic at the initial presentation. A further 2.8% (n = 4) showed to have pre-existing glaucoma. Three patients (2.1%) had another choroidal nevus in the affected eye.The initial visual acuity before treatment was at least 20/40 in 73.4% (n = 105) of cases, in 96.5% (n = 138) at least 20/200 and in 98.6% (n = 141) at least counting fingers (CF).The median tumor height was 4.5 mm (IQR: 3.8–6.6 mm) and the longest basal diameter of the lesions examined was 11.0 mm . The median distance of the tumor to the optic disc was 6 mm (IQR: 3.7–9.9) and to the center of the macula region 7.5 mm . All patients were categorized into TNM7 groups [The anterior tumor margin of the most melanomas examined was located anterior to the equator ; In 36 (25.2%) cases posterior to the equator and in 28 (19.6%) anteriorly at the ciliary body. The posterior margin of the lesions evaluated was within 1.5 mm from the optic disc or the center of the macula in 11.2% (n = 16), in 21.7% (n = 31) between 1.6 and 3.0 mm from the optic disc or fovea, in 58.7% (n = 84) posterior to equator (≥ 3mm to optic disc or fovea) and in 8.4% (n = 12) anterior to equator of the eye. [The median delivered dose to the external scleral surface was 689.8 Gy (IQR: 488.7–922.8) and the median delivered dose to the tumor apex was 89.8 Gy (IQR: 59.3–120.8). The applied dose to the tumor apex was < 80 Gy in 60 (42%) cases, 80–110 Gy in 37 (26%) cases and > 110 Gy in 46 (32%) cases. The dose to the scleral surface was < 200Gy in 1 (0.7%) case, 200–500 Gy in 37 (26%) cases, 500–800 Gy in 47 (33%) cases and >800 Gy in 58 (41%) cases. Twenty-four patients received an adjunct sandwich therapy, which was planned and performed in case of uncertain irradiation sufficiency, mainly in case of extended tumor height. The first application was performed in April 1997. [An overview about the performed post irradiation adjunct treatments is summarized in The median overall follow-up time, calculated by the inverese Kaplan-Meier method, was 37.88 months .The majority of patients 76.9% (n = 110) developed at least one side effect or complication after treatment see . The meaOverall, we observed 58 (40.6%) patients who developed a secondary cataract after treatment. The estimated risk of cataract formation 12, 24 and 48 months after irradiation was 25.3% (CI 95%: 18.5–34.0%), 37.5% (CI 95%: 29.2–47.2%), and 50.3% (CI 95%: 39.6–62.1), respectively.Risk factors found in the uni- and multivariate analysis are shown in After treatment, in total 15 (10.5%) patients developed a secondary glaucoma. The estimated risk of an increase of IOP was 5.4% (CI 95%: 2.6–10.9%), 6.4% (CI 95%: 3.2–12.5%), and 8.1% (CI 95%: 4.1–15.6%) at 12, 24, and 48 months after irradiation. Uni- and multivariate risk factors are shown in After treatment, we observed 24 (16.8%) patients to develop a radiation retinopathy, 55 (38.5%) patients to develop a radiation maculopathy and 36 (25.2%) patients to develop a radiation related optic neuropathy, respectively. The estimated risk 12, 24 and 48 months after irradiation of the development of radiation retinopathy was 3.1% (CI 95%: 1.2–8.1%), 6.9% (CI 95%: 3.5–13.4%) and 18.3% (CI 95%: 11.0–29.5%), respectively. The risk of radiation maculopathy was 18.3% (CI 95%: 12.5–26.2%), 27.1% (CI 95%: 19.9–36.2%), and 42.6% (CI 95%: 32.9–53.8%), and the risk of a radiation optic neuropathy was 16.5% (CI 95%: 11.1–23.9%), 21.0% (CI 95%: 14.9–29.2%) and 32.8% (CI 95%: 24.4–43.1%), respectively.The risk factors found in the univariate and multivariate analysis are shown in In total we observed 27 (18.9%) patients, who developed a retinal detachment, or retinal detachment increase and 25 (17.5%) patients, who developed a vitreous hemorrhage after treatment. The estimated risk 12, 24 and 48 months after irradiation of the development of a retinal detachment or an increase in retinal detachment was 14.7% (CI 95%: 9.7–21.8%), 14.7% (CI 95%: 9.7–21.8%), and 17.4% (CI 95%: 11.6–25.5%) and for a vitreous hemorrhage was 6.2% (CI 95%: 3.2–12.1%), 8.1% (CI 95%: 4.4–14.6%), and 12.7% (CI 95%: 7.3–21.6%).The risk factors found in the univariate and multivariate risk factor analysis are shown in During follow-up, we observed 30 (21.0%) patients showing a tumor vasculopathy. The estimated risk of the development of postoperative tumor vasculopathy at 12, 24 and 48 months after irradiation was 15.4% (CI 95%: 10.2–22.9%), 17.4% (CI 95%: 11.8–25.4%) and 19.0% (CI 95%: 12.9–27.5), respectively. No statistically significant risk factors could be found.In this study, we describe anterior and posterior segment complications after ruthenium-106 brachytherapy.Due to the small number of studies evaluating the side effects after ruthenium-106 plaque brachytherapy and the differences in the inclusion criteria and definition of the complications, a valid comparison between these studies and our study is difficult.For the evaluation and calculation of the side effects, several factors had to be considered. First, we corrected for unequal follow-up times. Second, the occurrence of one complication or its treatment can hinder the identification of another. For that reason, such situations were considered “censoring events” and taken into account in our analysis. At the time point of the necessary subsequent surgical intervention, the analysis of the respective complications was stopped and the patient considered “censored”. Finally, secondary enucleation after treatment also defines the end of follow-up and was regarded as a “competing risk”.Cataract formation: The most frequent complication, occurring in 40.6% n = 58) of our study population with an estimated risk of 50.3% after 4 years is secondary cataract formation. Other authors also identified cataract formation as one of the most frequent complications after ruthenium-106 brachytherapy, occurring in up to 37%  of cases8 of our The higher rate of irradiation-induced cataracts in our series might be explained by the difficulty of differentiation between age-related cataract formation and irradiation-induced cataract formation due to the retrospective study design.Secondary glaucoma: The estimated risk of the occurrence of secondary glaucoma 12, 24 and 48 months after irradiation was 5.4%, 6.4%, and 8.1%, respectively. The most important risk factors for post-irradiation IOP increase were a mushroom-like tumor shape and a higher tumor distance to the disc (p = 0.032), with a 4-fold increase in risk if the tumor was ≥ 10 mm away from the optic disc.Other authors found similar results for IOP increase after irradiation, at 7%  or 3.9% Radiation retinopathy: In our population, the estimated risk of the development of a radiation-induced retinopathy was 18.3% as of four years after treatment.We could not find any clinically relevant risk factors for the development of a radiation retinopathy. The main risk factor was a reduced tumor size and, correspondingly, an elevated irradiation dose to the tumor apex. This surprising result might be explained by the higher number of adjunct treatments in the case of larger tumors, which might have influenced the results of the statistical analysis (as those cases were considered to be censored) but also might have affected the occurrence of radiation retinopathy, as the result remained unchanged even if those cases were retained in the analyses . InRadiation maculopathy: In our retrospective data analysis, we evaluated radiation-induced maculopathies separately. The estimated occurrence 1, 2 and 4 years after treatment was 18.3%, 27.1% and 42.6%, respectively.Other authors described similar rates. Summanen et al. found this complication in 15% of cases at two years and 30% at three years after treatment . Others The risk factors found in our evaluation comprised a mushroom-like tumor shape, a reduced tumor distance to the disc or fovea, and pre-existing retinal detachment . SummaneOptic neuropathy: We found radiation induced optic neuropathies in 16.5%, 21.0% and 32.8% 12, 24, and 48 months after irradiation. The rate of optic neuropathies reported in the literature varies widely.Accordingly, Summanen et al. reported incidence rates of 10% and 12% at two and three years after treatment . AnotherSimilarly, in our analysis, the most important risk factors were a small tumor distance to the disc (<1.5 mm) and, in association, an elevated longest basal diameter of the tumor.Vitreous hemorrhage and retinal detachment: The risk of developing a vitreous hemorrhage was 12.7%, and the risk of a retinal detachment (RD) or an increase in a pre-existing RD was 17.4% as of four years after irradiation. Other authors describe similar rates, with RD developing or increasing in 26% of cases by five years after treatment, primarily in large tumors. [We found pre-existing retinal detachments (4-fold risk elevation) and the treatment dose rate to be the most important statistically significant risk factors in the multivariate analysis.Limitations of our study: As with all retrospective studies we cannot prove a causal association between the identified risk factors and the respective complication. In addition, our study covers a long time span. Though data have been recorded in a prospective manner in a clinical database with defined criteria, the possibility remains that some of these have been applied differently over time. Using the available photographs, ultrasounds and angiographic images, we checked for correctness to keep this risk as small as possible. Finally, due to the relatively small number of cases some risk factors might not have been detected.Comparison of iodine-125 and ruthenium-106 plaque brachytherapy Iodine (I-125) is the most commonly used radionuclide for the brachytherapy of uveal melanomas. We assume that the treatment of uveal melanomas by Ru-106 plaques is less frequent because this nuclide is limited in penetration depth and therefore commonly considered suitable for uveal melanomas up to a maximal height of 6 mm. However, it has also been used for significantly higher tumors by some authors.  A furtheAnterior and posterior segment complications are common after the irradiation of choroidal and ciliary body melanomas by ruthenium brachytherapy. The most important risk factors for radiation-induced side effects seem to be the tumor size and localization, influencing the irradiation dose to important vulnerable structures.As complications might occur years after initial treatment, long-term follow-up must be ensured.Before treatment, patients should be informed of their specific risks to develop various side effects.Patient information before treatment should cover not only general information about the treatment and possible complications and side effects but should also give details on the specific risks of the patient in her individual situation. This also includes elucidating the patients individual resources and expectations and her willingness for long term regular follow-up examinations and secondary adjunct treatments.S1 File(TXT)Click here for additional data file.


Men had higher mortality rates compared to women, 6.7 per 100 person-years (p-y), (95% CI: 5.8–7.8) vs. 4.4 per 100 p-y, (95% CI: 3.8–5.0); mortality rate ratio: 1.54, (95% CI: 1.27–1.87), p <0.001. Age-standardised mortality rate was 7.9 per 100 p-y (95% CI: 4.1–11.7) for men and 5.7 per 100 p-y (95% CI: 2.7 to 8.6) for women ). Mean CD4+ cell count increases post-ART initiation were lower in men at all follow-up time points. Men presented later in the course of their HIV disease for ART initiation with more advanced disease and experienced a higher mortality rate compared to women.In attaining UNAIDS targets of 90-90-90 to achieve epidemic control, understanding who the current utilizers of HIV treatment services are will inform efforts aimed at reaching those not being reached. A retrospective chart review of CAPRISA AIDS Treatment Program (CAT) patients between 2004 and 2013 was undertaken. Of the 4043 HIV-infected patients initiated on ART, 2586 (64.0%) were women. At ART initiation, men, compared to women, had significantly lower median CD4+ cell counts (113 vs 131 cells/mm In South Africa, an estimated 6.2 million people are currently living with HIV infection . South AIn order to achieve the UNAIDS 90-90-90 goals for epidemic control and enhance individual and population level impact of public access anti-retroviral therapy (ART), detailed understanding of gaps in access to treatment services and factors that contribute to poor HIV treatment outcomes including ongoing mortality, is imperative. Data from other countries are inconsistent and contradictory, with some studies demonstrating gender imbalances in access to HIV treatment services and in clinical outcomes among patients on ART ,5, and oNotwithstanding the higher burden in women and 5–7 year earlier acquisition of HIV infection in adolescent girls and young women between the ages of 15–24 years , men areA South African study assessing the sustainability of task shifting in a rural primary care clinic demonstrated that 68.8% of those accessing ART services between 2004 and 2010 (p < 0.05) were women , and thoIn a country with the largest ART rollout program, it is important to understand who the current utilizers of HIV treatment services are, as this will help inform efforts aimed at reaching those currently not being reached. This study sought to investigate whether there were gender and age differences in those accessing HIV care services and clinical outcomes in those initiated on ART among urban and rural patients utilizing a free HIV treatment program in KwaZulu-Natal, South Africa.We undertook a retrospective chart review of ambulant HIV infected, ART naïve adult patients enrolled into the PEPFAR-funded CAPRISA AIDS Treatment Programme (CAT) between June 2004 and August 2013. Patients were enrolled from two different catchment populations in KwaZulu-Natal; a TB clinic in the urban eThekwini district and a rural primary health care clinic in Vulindlela, rural KwaZulu-Natal. ART eligibility criteria, and definitions of immunologic and virological response to ART, defined as <400 copies/ml was as per current South African Government HIV/AIDS treatment guidelines . FollowiRoutine demographic and clinical data were recorded at baseline and at follow-up visits. Laboratory safety assessments and CD4+ cell counts and viral loads were conducted at baseline and every 6 months or as clinically indicated. Patients were regarded as lost to follow-up if they missed 3 consecutive scheduled visits and if all attempts to track them telephonically and physically had failed. No lost to follow-up patients re-engaged in care. Patients provided written informed consent for participation in the CAT programme and for the use of their medical records. Approval for data collection and analysis was obtained from the University of KwaZulu-Natal, Biomedical Research Ethics Committee (Ref: E248/05).We used unpaired t-test, and Wilcoxon rank sum test for continuous data and Fisher’s exact test for categorical data to compare demographics and clinical characteristics between men and women. Data was censored at 72 months of follow-up. Kaplan-Meier was used to construct survival curves and compare them using the log-rank test. Poisson approximations and F-tests were used to construct 95% confidence intervals (CI) for mortality rate, TB incidence rate and rate ratios, respectively. We calculated age-standardised mortality rates using 5-year age band. The province of KwaZulu-Natal was used as a standard population. Predictors of mortality were assessed through both univariate and multivariate proportional hazards regression. Proportionality was assessed by fitting time dependent covariates in a model created by interacting baseline variables with survival time.The association between gender and CD4+ cell count was determined through linear mixed models. All models were adjusted for baseline covariates such as clinic site, age, tuberculosis status at baseline, past history of TB, WHO stage, CD4+ cell count and viral load. We conducted sensitivity analysis evaluating the impact of ART programme maturity on the effect of gender on mortality during ART initiation periods of 2004–2008 and 2009–2013.We calculated attributable risk in order to assess the relative contribution and impact of specific covariates on mortality. The effect of loss to follow-up on mortality was determined through sensitivity analysis. P values less than 0.05 were considered statistically significant. All analyses were conducted using SAS, version 9.4  and R version 3.2.2.The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.3), p <0.001, a lower median body mass index (BMI) (21.0 vs 24.2 kg/m2), p<0.001 and higher mean log viral loads (5.0 vs 4.9 copies/ml), p<0.001  men and 2586 women (64%), 14 years and older, were initiated on ART between June 2004 and August 2013. Baseline clinical characteristics are presented in  p<0.001 . The ove p<0.001 .Deaths occurred among 173 men and 239 women, over 8033.71 person-years of follow-up, (median of 16.3 months ), . Overall3, p = 0.098; 5.4 (95% CI 4.3–6.7) and 3.8 (95% CI 3.2–4.6) for baseline CD4+ cell counts of 50–200 cells/mm3, p = 0.012 and 5.2 (95% CI 2.8–8.9) and 2.1 (95% CI 1.2–3.3). Mortality rate ratio stratified by baseline CD4+ cell count comparing men and women was 1.31 (95% CI 0.95–1.8) for baseline CD4+ cell counts < 50 cells/mm3, p = 0.098; 1.42 (95% CI 1.08–1.87) for baseline CD4+ cell counts of 50–200 cells/mm3, p = 0.012 and 2.1 (95% CI 1.22–5.26) for baseline CD4+ cell counts of > 200 cells/mm3  vs 3.9 per 100 p-y (95% CI: 2.4–5.9) in women of the same age, mortality rate ratio: 3.06 (95% CI: 1.45–6.46), p = 0.003 . Among tells/mm3 .3 and 556.6 cells/mm3, p = 0.001 among men and women respectively , p<0.0001, and a two-fold higher risk of death among patients with a baseline CD4+ cell count between 50–200 cells/mm3, , p = 0.001, : 1.29, 95% CI: 1.05–1.58, p = 0.016 . Risk of= 0.001, .In addition, patients presenting with no TB at ART initiation or a higher mean log viral load or WHO stage 4 disease had significantly higher risk of death .We found that the attributable risk of death among patients initiating ART was 24.3% (95% CI 17.3–30.5) for patients with a low baseline CD4+ cell count and 10.2% (95% CI 2.7–16.9) for male patients .Of note, sensitivity analysis evaluating the impact of ART programme maturity on the effect of gender on mortality showed that mortality rates between men and women was consistently two-fold higher and significantly different at all follow-up time-points between 2009–2013. This finding did not hold for the period 2004–2008 during the period of ART initiation .We provide evidence of gender disparities between HIV infected men and women in access and response to antiretroviral therapy. Clinical outcomes differed by gender; with men demonstrating higher overall mortality rates and suboptimal immunologic recovery.The bulk of deaths in both men and women occurred in the first 24 months of follow-up concurring with findings from other studies ,19. DespAfter removing the confounding effect of age, mortality rates observed in men and women in our study was lower than the age-standardised mortality rates. Interestingly, mortality rates among men and women in the study population closely approximated age-standardised mortality when we assumed that patients who were loss to follow-up within 6 months of ART initiation died.In contrast to the epidemiological data of the evolving epidemic in southern Africa wherein HIV acquisition does not occur in men until their late twenties ,21 and wConversely, studies from developed countries show differing results, finding no gender differences in clinical, virological and immunological outcomes among HIV infected men and women initiating ART ,23. A muPoor prognostic markers of ART response were apparent in men at baseline, who were older, had lower CD4+ cell counts and higher viral loads compared to women. This finding concurs with published South African literature demonstrating that compared to men, women were more likely to access HIV testing, and among those testing HIV positive, women were younger with higher CD4+ cell counts than their male counterparts .This study also showed that the late presentation of men was associated with poor immunological response to ART with higher risk of morbidity and mortality . Our fin3 in comparison with those patients that presented with baseline CD4+ cell counts of less than 50 cells/mm3. Furthermore, we found that the mortality risk among patients initiating ART was attributable to both low baseline CD4+ cell count and male gender, corroborating published literature showing that baseline CD4+ cell count is an important factor impacting CD4+ cell count increase and recovery on treatment [We show that during follow up overall mortality rate halved among men and women with baseline CD4+ cell counts of 50–200 cells/mmreatment . In settOur findings demonstrate that the absence of a diagnosis of prevalent TB increased risk of mortality. Published literature has cited that undiagnosed TB is higher among patients accessing ART than in the general population; with the majority of incident TB diagnosed in the early weeks of ART initiation being TB prevalent but missed at baseline screening ,31,32. IMen had higher lost to follow-up rates in our cohort in keeping with reports from published literature ,34. AdveAs this was a secondary analysis of routinely collected programme data, missing data limited our ability to comment on various correlations e.g. the impact of socio-economic and demographic variables on clinical outcomes. Treatment adherence was not measured and its impact on outcomes could be underestimated. We have not investigated other biological and behavioural factors that may have contributed to poor ART outcomes in men. While the vast majority of patients enrolled into this cohort were women, we had very few pregnancies and are therefore unable to comment on the impact of pregnancy in women on mortality in this cohort. Additional studies that explore potential barriers that South African men experience when seeking HIV care, and optimal strategies to link and engage men in ART services, is warranted.While heterosexual transmission is the primary mode of HIV transmission in sub Saharan Africa, the impact of free ART provision on access and clinical outcomes in men and women is unequal. Men presented late for ART initiation with more advanced disease and a higher mortality rate compared to women in this six-year ART program. The increased feminization of the HIV epidemic in sub Saharan Africa has rightfully demanded that greater focus be given to women with respect to HIV prevention, transmission, treatment and care. However, in a predominantly heterosexual epidemic, greater programmatic effort should be directed toward encouraging men to test early and frequently. As we prepare to scale-up “Test and Treat” in all HIV infected patients, innovative strategies are needed to ensure that men and women that test HIV positive have access to effective linkage to care for early ART initiation to achieve the goal of reducing mortality and increasing AIDS free survival.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


During that period, daily counts of ERVs for respiratory, cardiovascular and ocular diseases were obtained from a Level-3A hospital in Beijing from 1 December 2012 to 28 February 2013, and associations of which with PM2.5 and BC were estimated by time-stratified case-crossover analysis in single- and two-pollutant models. We found a 27.5% : 13.0, 43.9%) increase in respiratory ERV (lag02), a 19.4%  increase in cardiovascular ERV (lag0), and a 12.6%  increase in ocular ERV (lag0) along with an interquartile range (IQR) increase in the PM2.5. An IQR increase of BC was associated with 27.6%  (lag02), 18.8%  (lag0) and 11.8%  (lag0) increases for changes in these same health outcomes respectively. Estimated associations were consistent after adjusting SO2 or NO2 in two-pollutant models. This study provides evidence that improving air quality and reducing haze days would greatly benefit the population health.In January 2013, severe haze events over northeastern China sparked substantial health concerns. This study explores the associations of fine particulate matter less than 2.5 μm (PM January 2013 was a month when significantly high periods of PM2.5 concentration occurred in Beijing, with a monthly mean concentration of 240 μg/m3 [Beijing, the capital of China, experienced several severe haze episodes in January 2013 that focused attention on the issues of poor air quality. There has been a growing concern in this region that poor air quality is affecting both human health and the environment. Haze events mainly occur during winter months due to stable meteorological conditions and emissions from coal-fired power plants and residential heating [2.5 and adverse health effects worldwide, including increased cause-specific hospitalization and mortality [2.5 on endocrine dysfunction [2.5 exposure and conjunctivitis morbidity were reported in Canada [2.5 was associated with the decrease in tear osmolality, which indicated that exposure to PM2.5 may also affect human ocular adnexal . Currently, studies on the ocular hazardous effects of PM2.5 are still very limited, especially in China. On the other hand, premature death counts and the economic cost of death due to PM2.5 exposure attributed to haze pollution events have been reported [2.5 exposure and its related health effect at high concentrations  have not been well-characterized because pollutant and health data from places with such conditions as China are seldom available. Thus, while considerable evidence links PM2.5 to the occurrence and development of various diseases, there still remain challenges and opportunities for studies of PM2.5 associated health effects in China.Previous studies have reported associations between exposure to PMortality ,7 and reortality  or immunortality . There afunction  and advefunction . Saxena function  reportedn Canada  and Japan Canada ; Torricen Canada  in Brazireported ,17; howe2.5 [2.5 and BC were associated with total emergency-room visits in Shanghai. Janssen et al. [2.5 mass, but their measured effects on all-cause and cardiovascular mortality of an interquartile range (IQR) increase were similar. Thus, BC may play an important role in PM2.5 related health risks, which need more epidemiological evidences. However, BC data is not widely available since it is not included in routine air monitoring programs.One important aerosol component of haze is combustion-derived black carbon (BC). As a component of PM2.5 , it has 2.5 , elevate2.5 , decreas2.5 . Previou2.5  and bloo2.5 . Gold et2.5  found th2.5  reportedn et al.  performe2.5 and BC with cause-specific hospital emergency room visits (ERVs) during extreme haze events in Beijing using a time-stratified case-crossover strategy. Different lag periods were included to detect the potential delayed or cumulative effects of exposure. Data from other available gaseous pollutants were also included. Stratification analyses for age and gender were performed to determine whether these subgroups demonstrated differing responses.This study was conducted to explore the links of PMDaily hospital emergency room visits from 1 December 2012 to 28 February 2013 were collected from the Peking University Third Hospital, the emergency center that serves unscheduled cases living around it and other areas in Beijing. As one of the top-level hospitals, over 10 thousand emergency visits were recorded every month. During the clinical process, the information of each visit was recorded on a standardized form, including an identification number, gender, age and primary diagnoses. Then a database was built based on these cases. The primary diagnosis were coded by medically trained researchers according to the International Classification of Diseases, 10th Revision (ICD-10) . Respira2.5, sulfur dioxide (SO2), and nitrogen dioxide (NO2) data from 12 ambient air quality monitoring sites were obtained from China Municipal Environmental Monitoring Center and processed to produce 24 h daily records from 27 November 2012 to 28 February 2013. Daily mean temperature (Tem.) and relative humidity (RH) from one station  during the study period were obtained from the China Meteorological Data Sharing Service System. PM2.5 and BC was highly correlated (correlation coefficient = 0.92) in our study period, we built a simple regression model to fill in missing data for BC. The regression and fitted parameters were provided as follows:2.5 values of the corresponding day that BC is missing.Black Carbon (BC) monitoring was conducted using an Aethalometer  at one site only located on the campus of Health Science Center of Peking University, which is about 450 m away from Peking University Third Hospital. This monitor was the only source of BC data available for this study. The machine uses a continuous filtration and optical measurement method to give real-time data of BC. In this study, we used 5-min average values and computed the daily average concentration for data analysis. There were 11.7% daily BC values missing during this period. As daily average PM2.5, BC and meteorological monitors are shown in Locations of Peking University Third Hospital, PM2.5 as well as BC and hospital emergency admissions during a haze season were estimated using conditional logistic regression model in SAS . The case period was from 1 December 2012 to 28 February 2013  and the days with the same day-of-week in the same calendar month as the case days were chosen as the control. In single-pollutant models, public holiday, temperature, and relative humidity were adjusted. In the case of temperature, previous research has shown that the 15-day moving average (lag0–14) temperature had larger effects on human health [2 or NO2 were added in two-pollutant models, respectively, to avoid the multicollinearity between them. In these models, the percentage increases in cause-specific ERVs for an interquartile range (IQR) increase in PM2.5 and BC in the single lag models were estimated. Lag days ranging from 0 to 4 and moving average from 2 days (01) up to 5 days (04) were evaluated.The case-crossover design with a time-stratified approach was used to estimate the impacts of short exposures on the acute health outcomes. Each subject served as their own control. Exposure levels at a time period just before hospital emergency visits were compared with those at other times when he or she was not hospitalized, thus time trend and unvarying factors such as age, sex, smoking, nutrition status, and socio-economic conditions were controlled by this design ,29. In tn health ,31. Thus2.5, SO2, and NO2 from all 12 monitors in the Beijing region shown instead of just the monitors near the hospital. Analyses were performed to find the lag period with the largest associations between SO2 and NO2 and ERVs to minimize the bias introduced by them. Both SO2 and NO2 showed a largest association with ERVs at lag2 in single-pollutant models. Our study was conducted during the winter season in Beijing, thus pollen was not likely to be an important factor that would bias the associations between PM2.5 and BC and ERVs, especially for ocular diseases, so pollen levels were not considered in the models.The hospital serves the entire region, so in this study we used the averaged concentration levels of PM2.5 levels in single-pollutant models. The lag period at which the associations between PM2.5 and BC and cause-specific ERVs were largest and also significant in the unstratified models were chosen as the lag day of pollutants in this analysis. If no significant associations were found, the largest ones were chosen. We also did stratification analysis of age, gender and PM2.5 or BC to evaluate the adequacy of using linear pollutant terms in the single-pollutant models. Combined effects of linear, quadratic and cubic terms for an IQR increase in PM2.5 or BC were calculated and compared with the associations estimated with only linear terms in the models.To evaluate the sensitivity of imputing missing BC data, we compared the results obtained using the original dataset with missing values to those from the imputed dataset. Based on Winquist’s  study, w2.5 and BC were 119.8 and 5.2 μg/m3 respectively. Time-series plots for PM2.5, BC and ERV counts during the study period are shown in 2.5. High daily concentrations of PM2.5 of 53 days exceed secondary daily standard of NAAQS (75 μg/m3).There were 2323, 541, and 1007 respiratory, cardiovascular, and ocular disease case admissions collected and analyzed the during study period, respectively. The male proportion for respiratory, cardiovascular and ocular ERV cases were 39.3%, 48.3% and 44.4% respectively; 91.4%, 56.0% and 91.9% of the cases were younger than 65 years old, respectively. 2.5 and BC , SO2 (lag2) and NO2 (lag2) . Both PM2.5 and BC were positively correlated with daily respiratory and cardiovascular ERVs counts and weakly negatively correlated with ocular ERVs counts  with no statistical significance found (p > 0.05).Spearman correlation coefficients (r) between air pollutants, meteorological variables and daily respiratory, cardiovascular and ocular diseases ERV counts are shown in 2.5 (121.6 μg/m3) and BC (5.4 μg/m3) from lag0 to lag4 and moving average from lag01 to lag04 with respiratory, cardiovascular, and ocular ERVs. Significant associations were found between both PM2.5 and BC and respiratory ERVs on lag0, lag1, lag01–02, with a largest one at lag02, even after adjusting for SO2 and NO2. For an IQR increase in PM2.5, the largest estimated percent increases in respiratory ERVs were observed at lag02 with a value of 27.5% : 13.0, 43.9%) in the single-pollutant model and values of 25.0%  and 26.2% , respectively, after adjusting SO2 and NO2; for an IQR increase in BC, the largest estimated percent increases in respiratory ERVs also appeared at lag02, which were 27.6% , 21.4% , and 26.6% , respectively in the single- and two-pollutant models. Both PM2.5 and BC were significantly and positively associated with cardiovascular ERVs occurred at lag0, which were 19.4% , 20.2%  and 20.9% , respectively, for PM2.5 before and after adjusting SO2 and NO2, and 18.8% , 20.5%  and 23.3% , respectively, for BC. The associations between PM2.5 and ocular ERVs were positive and significant at lag0 in both single- and two-pollutant models, which were 12.6 , 13.2  and 15.3 , respectively. A significant association was found between BC and ocular ERVs at lag0 after adjusting NO2 ) (p < 0.05).2.5 and BC and respiratory ERVs at lag02, cardiovascular and ocular ERVs at lag0 were selected in the modified effects analysis. No significant differences were found between age groups for the associations in the three cause-specific ERVs, and larger 95% CIs were observed in elders (older than 65) than that in younger subjects (younger than 65)  and 28.9% , respectively; a smaller association between BC and respiratory ERVs was seen in elders, which was 13.5%  compared to 29.0%  in youngers individuals. Both PM2.5 and BC were associated with larger increments in cardiovascular ERVs in elders  and 22.2% , respectively) than that in youngers individuals  and 15.8% , respectively); however, they were negatively associated with ocular ERVs in elders  and −7.6% , respectively) compared to positive associations of 12.8%  and 12.1% , respectively, in younger subjects. Associations between PMthan 65) . The est2.5 and BC concentrations and increments of respiratory and ocular ERVs were larger in females, whereas that was larger in males between PM2.5 and cardiovascular ERVs, though all these differences are not statistically significant. An IQR increase in PM2.5 was associated with 13.2%  and 39.0%  increases among males and females in respiratory ERVs, respectively, 20.5%  and 14.7%  increases in cardiovascular diseases, respectively, and 6.0%  and 16.5%  increases in ocular ERVs, respectively. Similar results were seen for associations between BC and ERVs, except that the estimated percentage increase in male ERVs of cardiovascular disease was slightly lower than that in female ERVs with an IQR increase in BC, which was 17.6%  compared to 19.3% .When examining effect modification by gender , we foun2.5 or BC that no significant differences were observed for the estimated associations without and with quadratic and cubic terms of PM2.5 or BC fitted in the single-pollutant models.Sensitivity analysis on associations between ERVs and BC before and after daily missing data imputed were shown in 2.5 and BC and hospital emergency visits for three specific health outcomes, including respiratory, cardiovascular and ocular diseases during a winter haze season in Beijing, China. To our knowledge, this is one of a few studies to investigate associations between PM2.5 and BC and hospital ERVs during the periods with high ambient pollutant levels, and the first study to explore particulate air pollutant links to ERVs related to ocular diseases in China. By using a time-stratified case-crossover method, potential confounders, such as age, sex, microenvironment, socioeconomic status, nutritional status, and personal habit were controlled. As China’s emergency departments in hospitals give timely service to patients with sudden and life-threatening diseases or excruciating symptoms, the observed occurrences of ERVs associated with PM2.5 or BC exposure were equivalent to the excess morbidity seen in the corresponding diseases. In this study, we observed significant associations between PM2.5 concentration during the study period was 119.8 μg/m3, which was much higher than the national secondary ambient air quality standard in China (daily 75 μg/m3). However, for BC ambient pollution, no standard levels have been set either in China or elsewhere in the world. Compared with other studies conducted to estimate the associations of PM2.5 or BC with hospital emergency visits outside of China [2.5 and BC levels were fairly high during the study period, with IQRs of 121.6 μg/m3 and 5.5 μg/m3, respectively. In the St. Louis metropolitan area of the U.S., an IQR increase in PM2.5 (11.1 μg/m3) and elemental carbon (0.42 μg/m3) were associated −0.1%  and 1.6%  increases of cardiovascular ERVs, respectively [2.5 and BC. Baseline air pollution levels  as well as factors such as ambient pollutant levels and population sensitivity and chemical composition of particulate matter may contribute to the large differences between these two studies. Smaller associations of PM2.5 were also reported in Beijing with ERVs in the same hospital as our study during 2007 to 2008, an IQR increase in PM2.5 (68 μg/m3) was associated with 3.1%  increment of cardiovascular ERVs in winter [2.5 may lead to the increases of hospital ERVs in Beijing.The 24 h average PMof China , PM2.5 aectively , whereas2.5, especially for cardiovascular effects. Zanobetti’s study [2.5 (16.3 μg/m3) and BC (1.7 μg/m3) were associated with an 8.6%  increase and an 8.3%  increase in emergency myocardial infarction hospitalization, respectively. Wang et al. [2.5 and BC  were associated with a 1.88%  and a 1.33%  increase in emergency room visits, respectively in Shanghai. In our study, estimated ERVs associations with an IQR increase in exposure were similar for PM2.5 and BC , which was consistent with the studies that PM2.5 significantly associated with outpatient attendance for allergic conjunctivitis  in non-pollen season in Tokyo [2 concentrations. Currently, limited information is available on the associations of PM density ,35. In oin Tokyo  and conjin Tokyo . Though 2.5 and BC with hospital ERVs appeared not to be confounded by NO2 or SO2; they varied little after adjusting 2-day lag concentration of SO2 or NO2. Compared to non-haze days, the increase of particulate matter was much more significant than that of SO2 and NO2 during haze days [2.5 and BC with cause-specific ERVs in the highly polluted period of the study. We found the estimated associations between PM2.5 and BC and cardiovascular ERVs were larger in subjects older than 65 years. Similar results were seen where both PM2.5 mass and its chemical constituents are associated with ERVs for ischemic stroke among patients older than 65 years in Taiwan [2.5 and BC and ocular ERVs were only found in younger subjects. The toxic actions of air pollutants on different parts of human body system and different age groups may differ. This may lead to the differences in response to PM2.5 or BC among age groups. Besides, the small number of elder subjects contribute to larger 95% CIs of associations. Further studies with more cases may help to detect clearer differences between age groups. The observations that females had stronger associations of PM2.5 or BC exposure with ERVs than males in our study with the exception of PM2.5 and cardiovascular ERVs suggests that factors such as hormonal levels, household duties and time spent in outdoor air may contribute to observed differences in response.In our study, associations of PMaze days , which sn Taiwan . This gr2.5 data representing a wide range of monitoring sites and BC data representing only one site. This may contribute to unknown degrees of exposure misclassification. Thirdly, a small portion of BC data was missing and an imputing method was used. Although results of sensitivity analysis suggest the estimation of the associations was not significantly affected by the imputation method . This work will also attempt to locate and include data collected by others for BC in Beijing. With the continued improvement in the health data collection system and the expanding availability of air pollutants data, this study can be extended both temporally and spatially and the additional health effects due to severe haze exposure may be calculated. Further studies on non-linear associations of air pollution with ERVs and distinguishing PM2.5 and BC health effects are also proposed.Our future work will focus on comparing the associations between ERVs and exposure of air pollutants by using varied methodologies (e.g., introducing techniques such as imputation modeling to estimate PM2.5 as well as BC are associated with increases in hospital ERVs for respiratory, cardiovascular, and ocular diseases during severe haze in Beijing. It is possible that the findings of this study may be viewed as suggesting that BC contributes to the associations of PM2.5 with related health outcomes. To the extent that this is true, it may be health protective to establish regulations for BC. Our findings suggested that improving air quality and reducing haze days would benefit the population health. In conclusion, our study found that elevated levels of ambient PM


P ≤ 0.05) in oocytes exposed to VS3  than those exposed to VS1  and VS2 . Although recovery rates were significantly lower (P ≤ 0.05) in SSV and Cryotop vitrified oocytes (66.9% to 71.1%) than those vitrified by straws with VS1 or VS2 solutions (86.3% to 91.0%), survival rates were higher in the SSV and Cryotop groups (90.7% to 94.8%) than in the straw and OPS groups (68.2% to 86.5%). Among vitrified groups, maturation and fertilization rates were the highest in the Cryotop-VS2 group . These values were comparable to those seen in the controls . Cleavage (22.5% to 27.9%), morula (13.2% to 14.5%), and blastocyst (6.4% to 8.5%) rates were significantly higher (P ≤ 0.05) in SSV and Cryotop groups than in straws. No significant differences were observed in these parameters between the Cryotop and control groups. We report for the first time that dromedary oocytes vitrified at the GV-stage have the ability to be matured, fertilized and subsequently develop in vitro to produce blastocysts at frequencies comparable to those obtained using fresh oocytes.Cryopreservation of oocytes would serve as an alternative to overcome the limited availability of dromedary camel oocytes and facilitate improvements in IVP techniques in this species. Our goal was to develop a protocol for the vitrification of camel oocytes at the germinal vesicle (GV) stage using different cryoprotectant combinations: 20% EG and 20% DMSO (VS1), 25% EG plus 25% DMSO (VS2) or 25% EG and 25% glycerol (VS3) and various cryo-carriers; straws or open pulled-straw (OPS) or solid surface vitrification (SSV); and Cryotop. Viable oocytes were cultured in vitro for 30 h. Matured oocytes were fertilized with epididymal spermatozoa and then cultured in vitro in modified KSOMaa medium for 7 days. Survival and nuclear maturation rates were significantly lower ( Oocyte cryopreservation has potential applications in human and animal reproduction, such as fertility preservation in cancer patients, preservation of genetic materials in livestock and conservation of endangered species , 2. HoweCamelus dromedarius, is an important livestock species with high productivity of meat and milk. However, the reproductive efficiency in camelids is low, partly due to the late onset of puberty, early embryonic mortality, seasonality and the length of the gestation period (13 months). Although recent reproductive technologies such as IVF [The dromedary camel, h as IVF , 35 and h as IVF  have beeh as IVF , 37, in Unless stated otherwise, all chemicals and reagents were purchased from Sigma–Aldrich .Dromedary camel ovaries were collected from a local slaughterhouse  over the period of November 2016 to April 2017 and kept in a thermos flask filled with pre-warmed (30 °C), sterile, normal saline solution  until processing. COCs were aspirated from 2 to 8 mm follicles using a 20-gauge needle attached to a 20-mL syringe , 35. TheTo evaluate the effects of exposure of COCs to different vitrification solutions (VS) on survival and nuclear maturation, selected COCs were equilibrated in a solution of 10% EG and 0.25 M trehalose (ES) for 3 min at 37 °C. Following equilibration, COCs were exposed for 60 sec to VS1 (20% EG plus 20% DMSO), VS2 (25% EG plus 25% DMSO) or VS3 (25% EG plus 25% glycerol). After exposure, dilution of the cryoprotectants was performed by transferring the COCs into 1 M trehalose solution, where they were maintained for 3 min at 37 °C. COCs were then transferred into decreasing concentrations of trehalose solution (0.5 and 0.25 M) for 3 min each at room temperature. All vitrification and dilution solutions were prepared in H-TCM 199 medium supplemented with 10% (v/v) fetal calf serum (FCS) as a base medium (BM). Following cryoprotectant dilution, COCs were morphologically examined according to a previously described method [2. Then, the thin strip was covered with a hard plastic cover (3 cm long) on top of the Cryotop sheet to protect it during storage in the liquid nitrogen containers. Warming was performed according to the method described by [After equilibration in ES as mentioned above, COCs were transferred to either VS1 or VS2 in BM, at room temperature, for 60 sec before being loaded into the cryodevice . Vitrification of oocytes by straws, OPS or SSV was performed according to the methods previously described , 10, 24.ribed by IVM of COCs was performed as previously described , 35. Bri2 in air for 10 minutes before being transferred to a 15-mL centrifuge tube. After centrifugation and removal of the supernatant, the sperm pellet was re-suspended in 1 mL of sperm-TALP medium supplemented with 5 mM caffeine. Following swimming for 1 hour at 39 °C, sperm motility was evaluated. For IVF, in vitro mature oocytes were washed three times in fertilization medium  and then inseminated with motile spermatozoa at concentration of 2 x 106 spermatozoa/mL. Oocytes and spermatozoa were co-incubated for 18 h at 39 °C in 5% CO2 air. Following gamete co-incubation, the fertilization status was determined by fixation and staining of oocytes using aceto-orcein staining as described above. Inseminated oocytes were categorized as fertilized when a spermatozoon, swollen sperm head, or a male and/or female pronucleus was detected in the ooplasm.Mature oocytes were fertilized in vitro using epididymal spermatozoa according to the method described previously , 35, 38.2, 5% O2, and 90% N2 until Day 7 (Day 0 = day of insemination). Cleavage, morula and blastocyst development were recorded on Days 2, 4 and 7 pi, respectively.Eighteen hours post-insemination (pi), presumptive zygotes were washed three times in H-TCM 199 supplemented with 5% FCS and then twice in embryo culture medium  andt-test was used to evaluate the differences in blastocyst development among the experimental groups. Statistical analysis was performed using GraphPad Prism 5 software. The results were considered to be statistically significant at P ≤ 0.05.At least three replicates were used for each experimental group. Data were presented as the means ± S.E.M. and analyzed by one-way ANOVA followed by Tukey's multiple comparisons test. Student’s P ≤ 0.05) reduced the percentages of morphologically intact oocytes compared to those exposed to VS1 or VS2  (P ≤ 0.05) lower in the VS3 group compared with those in the VS1 and VS2 groups . These values were significantly (P ≤ 0.05) lower than those seen in the controls (64.5%) (Exposure of COCs to VS3 significantly (ctively) . Further (64.5%) .P ≤ 0.05) lower in the Cryotop vitrified groups  compared with those vitrified in straws  and with those vitrified in OPS . The recovery rates were also reduced in SSV vitrified groups  compared with those vitrified in traditional-straws (P ≤ 0.05) of morphologically intact oocytes were found in the SSV and Cryotop groups, with the values ranging from 90.7% to 94.8%, compared to those obtained after vitrification and warming using traditional straws  or to those obtained after OPS vitrification using the VS1 solution  in the groups vitrified by traditional straws  compared to those vitrified with Cryotop  and to those in the control group (64.5%). No significant differences were observed in cumulus cell expansion between Cryotop and OPS, with both vitrification solutions and the control group (P ≤ 0.05) in COCs vitrified by Cryotop using the VS2 solution (51.8%) compared to those vitrified using traditional straws  and OPS . Vitrification of COCs with traditional straws and OPS in both VS1 and VS2 or with SSV in VS1 significantly decreased (P ≤ 0.05) the maturation rates compared with the controls (59.2%). No significant differences were recorded in nuclear maturation rates between Cryotop vitrified groups and the controls  fertilization rates  compared to those obtained in the other vitrified groups. Fertilization rates were significantly (P ≤ 0.05) lower in the OPS vitrified groups  compared with those vitrified by Cryotop using VS1 solution and the controls. No significant differences were observed among the Cryotop-vitrified oocytes , the SSV-VS2 vitrified group (37.3%) and the control group (44.6%).As shown in P ≤ 0.05) in traditional straws , OPS  and SSV-VS1 (22.5%) vitrified oocytes than the control group (32.2%). Vitrification of COCs in traditional straws using VS1 or VS2 or with OPS using VS1 significantly (P ≤ 0.05) reduced cleavage rates compared with those vitrified by the Cryotop . No significant differences were observed in cleavage rates between Cryotop-vitrified oocytes and the control group. Development to the morula stage (day 4 pi) did not significantly differ in COCs vitrified by OPS, SSV or Cryotop using both vitrification solutions  and the control group (16.9%). Vitrification of COCs by using traditional straws significantly (P ≤ 0.05) reduced morula development  compared to the control. Blastocyst development was significantly (P ≤ 0.05) lower in COCs vitrified with traditional straws using VS1 or VS2 solutions (1.7%) compared with those vitrified by OPS in VS2 solution (6.1%), SSV (6.4% and 8.5% in VS1 and VS2 respectively), Cryotop  and the control (9.0%). Vitrification of COCs using OPS in a solution composed of 20% EG and 20% DMSO (VS1) resulted in significantly lower (P ≤ 0.05) blastocyst formation rates (3.1%) compared to the control. No significant differences were identified in blastocyst rates between SSV, Cryotop-vitrified groups and the control (Cleavage rates (48 hpi) were significantly lower  oocytes. We also showed that both vitrification solutions and cryo-carriers affect the viability and developmental competence of vitrified/warmed dromedary camel oocytes. Furthermore, we revealed that both the survival and nuclear maturation of dromedary camel COCs were affected by the types and concentrations of the cryoprotectants used for vitrification with the lowest values seen in groups exposed to a combination of 25% EG plus 25% glycerol (VS3). Among the different vitrification solutions, the highest percentages of intact and mature oocytes were achieved in the VS2 group , indicatOocyte loss during vitrification and warming procedures has been reported in buffaloes , goats , sheep , 20, andIn vitro maturation, fertilization and development of oocytes after cryopreservation are imperative requirements in the success of oocyte cryopreservation. The effects of vitrification and warming of COCs at the GV-stage on cumulus cell expansion after IVM have been reported across different species, and the results are still controversial and dependent on the individual species. For example, recent studies in buffalo showed that the percentages of oocytes with expanded cumulus cells after IVM did not significantly differ between the vitrified and the control groups (74.9% versus 88.1%) . On the Oocyte vitrification has been reported to decrease in vitro fertilization rates in different species such as cattle , sheep , and pigPerturbations resulting from oocyte cryodamage may also appear during cleavage and early embryo development . Many stTaken together, our results demonstrate that SSV and Cryotop vitrification methods are equally effective for the cryopreservation of dromedary camel COCs at the GV stage; both methods resulted in high survival, maturation, fertilization, cleavage and preimplantation embryo development. Indeed, both of the techniques can be recommended for the cryopreservation of dromedary camel oocytes. The choice between the two methods may depend on the advantages and availability of each method, as well as on the number of oocytes undergoing cryopreservation. Although SSV is a cheaper method by which large numbers of oocytes can be preserved in a short time, it is hard to control the size of the droplet, and thus, the chances for losing the oocytes are high. However, with Cryotop vitrification, the volume of the solution and oocyte number can be controlled. However, the number of oocytes that can be preserved with each Cryotop is limited, and it takes a long time to preserve large numbers of oocytes. In conclusion, we show that both the vitrification solution and cryodevice affect the survival and developmental competence of vitrified/warmed dromedary camel oocytes. We report for the first time that dromedary camel oocytes vitrified at the germinal vesicle stage have the ability to be matured, fertilized and subsequently cultured in vitro to produce blastocysts at frequencies comparable to those obtained using fresh oocytes. Both SSV and Cryotop as cryo-carriers in combination with VS2 (25% EG plus 25% DMSO) could be used effectively for the vitrification of dromedary camel GV-oocytes. However, further studies are warranted to assess the ability of in vitro-produced blastocysts to develop in vivo, establish pregnancy and produce live offspring when transferred to surrogate mothers.


The follow-up period was 1-55 months (median 12 months). The local control rate (LC) of 3, 6, 12, 24 and 36 months was 93.3%, 77.7%, 58.9%, 38.7% and 19.3%, respectively. Patients with tumor size ≤ 4cm  and actual D90 between 110 to 130Gy  had better LC. The 1, 2 and 3 years of overall survival (OS) was 79.3%, 63.0% and 52.5%, respectively. The poor performance status , concurrent distant metastasis  and large postoperative residual tumor size  were closely correlated with a poor OS. Our data indicate thatCT-guided 125I brachytherapy is an effective and safe modality for the local treatment of recurrent ovarian cancer.This retrospective study was to evaluate the local control and survival of  Ovarian cancer (OC) remains the fifth most common cause of cancer death in women . Despite125I brachytherapy has been accepted as a useful and minimally invasive treatment for different tumors with significant efficacy. The most common application of 125I interstitial irradiation has been in the treatment of prostatic malignancies [125I brachytherapy combines the advantages of delivering a high dose of irradiation to the tumor with a very sharp fall-off outside the implanted volume; thus, sparing nearby normal tissues [125I brachytherapy with its unique characters may address this clinical problem.gnancies , althouggnancies –12. 125I tissues . This is125I brachytherapy has been employed for salvage or supportive treatment of gynecological cancer in dedicated brachytherapy suits since 2010. The purpose of this study was to review and update our experience and to evaluate the significance of local treatment with 125I interstitial brachytherapy among patients with recurrent ovarian cancer.In our institution, 125I brachytherapy procedures were performed in 47 patients with 51 recurrent ovarian cancer lesions. Of 47 patients, 42 (89.4%) met the treatment planning system criteria after the first procedure. Five patients did not reach the treatment planning system criteria, followed by additional implantations. The final 125I brachytherapy achieved rate was 100%. The actuarial D90 (dose delivered to 90% of the target volume) ranged from 95-162 (mean 126Gy). The V100 (the percentage of the target volume receiving at least 100% of the prescription dose) of each patient was more than 95%, and the V150 (the percentage of the target volume receiving at least 150% of the prescription dose) for all cases was less than 50%. The D2cc for organs at risk was less than 70-75Gy. The total number of implanted seeds was 1775, with an average of 35.6±12.9 seeds per lesion .A total of 52 125I brachytherapy resolved the symptoms associated with tumor infiltration including pain (5/5), frequent and urgent urination (4/5), tenesmus caused by rectum pressure (8/9), rectum or vaginal bleeding (3/4). The local control rate of 3, 6, 12, 24, and 36 months was 93.3%, 77.7%, 58.9%, 38.7%, 19.3%, respectively , tumor diameter ≤4cm , no distant metastasis before the procedure  and actual D90 between 110-130Gy  had significant association to better results in the univariate analysis. However, multivariate analysis identified only tumor diameter , and actual DVH parameter D90  as independent prognostic factors associated with local control rate (Table The follow-up period was 1-55 months median 12 months). In patients with symptoms, the symptomatic relief was obtained in 86.95% 20/23) of patients.  months. rination /5, tenes of patie125I brachytherapy (P = 0.016), good performance status (P = 0.006) and small postoperative residual tumor size (P = 0.049) , good performance status  and small postoperative residual tumor size  were still the independent predictors of better OS. The results are shown in Table The mean OS of this study group was 14.6 months Figure . In 12 p125I brachytherapy, including liver metastasis in 12 patients, spleen metastasis in 2 patients, liver and spleen metastasis in 1 patient, bone metastasis in 1 patient, and the other 2 patients with inguinal lymph node metastasis. In this study, the patients who had distant metastasis when received the 125I brachytherapy were correlated with poor OS (P = 0.010). Besides that, three patients developed distant metastases after the procedure. There had two liver metastasis (8 months and 14 months) and one lung metastasis (16 months) from the time of brachytherapy. The afterward metastasis had no association with OS (P = 0.894).Distant metastases were present in eighteen patients prior to 125I brachytherapy were observed  and low photon energy (27-35 KeV), 125I brachytherapy has increasingly been used for gynecological malignant tumors [125I brachytherapy for (recurrent) ovarian cancer.In this study, we demonstrated that me cases . Chemothme cases . Repeateadiation , 19. Braadiation  proved tt tumors –23. Howe125I brachytherapy has several dosimetric advantages when compared to the other kind of radiotherapy [125I seeds closer together [125I brachytherapy in the treatment of OC. In our series, the local control rate of 3, 6, 12 and 24 months was 93.3%, 77.7%, 58.9%, 38.7%, respectively, and the patients released the symptom very quickly. Besides that, we found that patients with tumor size > 4 cm had significantly lower LC (P = 0.037). This is consistent with the other kind of radiotherapy [125I brachytherapy is a local treatment and we have shown that performance status can not influence the LC. That indicates that the patient's condition does not affect the efficacy of 125I brachytherapy, and the symptoms associated with tumor infiltration are resolved significantly after 125I seed implantation.With the recurrent rates of 70% or more, many OC patients will require further salvage therapies. For recurrent pelvic malignancies without evidence of systemic disease, the decision to add radiation to the salvage regimen should be considered –26. As ootherapy , 22, 23.together . Despiteotherapy . Howeverotherapy . In our 125I implantation monotherapy from 160 to144Gy [125I brachytherapy for each patient and repeat DVH with close observation should be applied during the procedure.Another important finding in our study is the dose-effect relationship in recurrent OC. With an actual D90 of 110-130Gy, a better LC rate was obtained. This is corresponding to the AAPM (American Association of Physicists in Medicine) recommendation that clinics reduce the prescribed dose for  to144Gy . It can  to144Gy . With th125I seed local treatment can reduce the tumor burden, relieve local symptoms and improve quality of life of patients. But some patients had distant metastases before 125I seed implantation. Although distant metastases had been treated with other therapies, it still had an important influence on prognosis. The mean OS in this study was14.6 months. The overall survival rates of patients with distant metastases before the procedure were significantly lower 55.6% (10/18) than those with no distant metastasis 89.3% (25/28) (P = 0.010). By the time of writing this paper, the two patients who had longest OS were 55 and 48 months, respectively. All of them didn't have distant metastasis before the procedure. For the 12 death, 66.7% (8/12) patients had distant metastases prior to 125I brachytherapy. Furthermore, good performance status (P = 0.010) and small postoperative residual tumor size (P = 0.014) were closely correlated with a better OS. So, this reminds us that postoperative residual tumor size is an important predictor for the prognosis of patients with 125I brachytherapy.125I brachytherapy for recurrent OC is dependent on the accurate placement of radioactive seeds [The success of ve seeds . The bigve seeds  found thve seeds . Althoug125I brachytherapy appears more tolerable. Adverse events of adjuvant 125I implantation are generally related to puncture process, but are generally mild and manageable, such as pain of the puncture site and small amount of vaginal bleeding. Moreover, some patients will feel intestinal uncomfortable when we need to pass through the bowel during 125I implantation. But, the recovery of bowel function is quickly, and no serious damage to the intestinal. No procedure-related deaths or major complications occurred. Based on these results, 125I brachytherapy is an effective and safe modality for the treatment of recurrent ovarian cancer.Although it is difficult to compare differences in treatment techniques and subsequent outcomes, the patients received limited whole-pelvis or electr125I brachytherapy may be suitable for patients with isolated recurrences after resection and resistant to conventional chemotherapy. Fortunately, in this study, we found a good local control rate and patients tolerance of 125I brachytherapy. However, large-scale multicentre studies with long-term follow-up will be designed to confirm the efficacy and safety of 125I seeds for recurrent ovarian cancer in the future.However, there are some limitations concerning the present study. This study was limited by its retrospective nature, and relatively small sample size from a single institution. More than 60% of the patients were within the recent two years and the follow up period were relatively short. Given the propensity of ovarian cancer to recur in the abdomen, 125I brachytherapy is an effective and safe salvage therapy for patients in poor general condition with a previous history of various types of therapy, and may be the most appropriate treatment for recurrent tumors of small size (tumor volume of < 4cm) located within the pelvic. In a word, 125I brachytherapy for recurrent ovarian cancer is a promising area of investigation to improve local disease control and quality of life.In conclusion, This study was approved by institutional review board and was performed in compliance with hospital ethics and clinical practice guidelines. The study included patients who with recurrent ovarian cancer. In addition, all patients were medically inoperable or patients and their families refused surgery and failed to respond to one or more chemotherapeutic regimens. Patients were excluded from the study if they had (1) uncorrectable coagulopathy , (2) thrombocytopenia , (3) severe history of mental disease, (4) severe renal or hepatic function impairment.125I brachy therapy from March 2011 to August 2015 were enrolled in this study. The patients distribution in 2011 to 2015 was 6, 6, 5, 17, 13; respectively. 74.5% (35/47) were FIGO stage III-IV; the mean size of the lesions was 5.14 cm ± 1.65  in the largest diameter. As to the recurrent sites, 27.5%(14/51) were at the vaginal stump, 9.8% (5/51) were para-aortic, 33.3% (17/51) were around the rectum, 29.4% (15/51) were irregular masses extended laterally to the pelvis. The mean value of CA125 was 546.13u/ml . All patients had received surgical cytoreduction and 29.78 % (14/47) had more than one times of surgery. The mean time of the lesions were seen on images was 29.1 months  after the last resection of the primary cancer. The diagnosis of recurrent OC was confirmed with pathologic proof at CT-guided needle biopsy in all patients. In all patients, 72.3% (34/47) were serous carcinoma, 14.9% (7/47) were endometrioid carcinoma, 4.3% (2/47) were mucinous carcinoma, 6.4% (3/47) were clear cell carcinoma and 2.1% (1/47) were granular cell carcinoma. The patients had previously been treated with a median of 3 chemotherapeutic agents  over a median of 12 treatment cycles . Patient characteristics are listed in Table A total of 47 patients  with 51 recurrent OC lesions received 125I implant was 90-150Gy, which was adjusted according to the adjacent structures. PTV edge was covered by isodose curve from 80% to 90%  was performed under CT guidance according to the plan  was used to create implant plans based on patients’ CT images Figure . The pre% Figure . Dose-vo% Figure . Implantn Figure .125I seeds implantation was performed in a standard CT room under local anesthesia and CT imaging was taken at intervals of 5 mm. With CT fluoroscopic guidance, 18 G implantation needles were inserted into target lesions avoiding puncture of large blood vessels and nearby important organs, a turntable gun was then used to place 125I seeds into recurrent tumors and seeds were released 0.5-1cm apart upon withdrawing the needles. However, those close to critical structures such as vital blood vessels, intestine and bladder, 125I seeds must be kept at least one centimeter away. The evaluation of post plan was routinely obtained for each patient. For tumors showing insufficient radioactivity, more 125I seeds were implanted.All the 125I brachytherapy was calculated according to the Response Evaluation Criteria in Solid Tumors (RECIST) [Follow-up consisted of record of symptoms improvement, routine physical examinations and appropriate imaging examination. A CT scan was undertaken 1 and 3 months after the procedure, and then at 3-month intervals after implantation, or as necessary. The objective response rate of (RECIST) . Local c(RECIST) .P < 0.05 was considered statistical significant.Data collected were analyzed using SPSS version 16.0 . The probabilities of LC and OS were calculated using the Kaplan-Meier product-limit method. Possible predictive factors were analyzed for impact on LC and on OS with univariate analyses using the classical log-rank test. Cox proportional hazards model was used for multivariate analysis. A two-sided