Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches.This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias.A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups.CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC. For the majority of patients with LGC cure is not obtained with surgery alone . RecurreP = 0.5272) [Clinical trials have also directly compared postoperative CRT with CT alone for patients with LGC. A meta-analysis of four randomized clinical trials with patients submitted to D2 lymphadenectomy for LGC showed that CRT significantly reduced the risk of locoregional recurrence, but without significant improvement in distant relapse and OS . The ART 0.5272) . Based oInstituto do Cancer do Estado de Sao Paulo (ICESP), Sao Paulo, Brazil. The Ethics Committee of ICESP approved the study protocol. Patients were eligible for analysis if they were 18 years or older, had histological confirmation of gastric cancer, had curative gastrectomy with nodal dissection and had received adjuvant treatment. The choice of adjuvant treatment was based on physician preference. Exclusion criteria included the use of neoadjuvant treatment and metastatic disease at diagnosis.We retrospectively evaluated consecutive patients with LGC who received adjuvant treatment from January 2012 to November 2015 at 2 on day 1 every 3 weeks) or XP regimens .Adjuvant CRT was based on the INT 0116 trial , 8 with The primary endpoint of the study was to compare OS (measured from the first day of systemic treatment until death or last follow-up) for adjuvant CRT and CT alone. Secondary endpoints include treatment toxicity, loco-regional recurrence and distant recurrence.A propensity score-matched analysis was used in order to balance the two treatment groups. The subjects were matched 1:1 according to the following covariates: tumor histology, pathological staging (I-II and III), type of lymphadenectomy and surgical margin. After this adjustment, OS was estimated using Kaplan-Meier method and log-rank test.p values were two-sided.Data regarding treatment toxicity were recorded for each cycle of adjuvant treatment according to the National Cancer Institute - Common Toxicity Criteria  . FrequenPatterns of recurrence were analyzed in both groups. Loco-regional recurrence was defined as disease recurrence in the tumor bed, anastomosis, regional lymph nodes, radiation field and/or, for those patients submitted to partial gastrectomy, the remaining stomach. Distant recurrence was defined as recurrence in the liver, peritoneum, non-regional lymph nodes or any other extra abdominal site.p = 0.021), with more stage III patients in the CT group (68.3%) than in the CRT group (52.5%). Imbalances were also observed for type of lymphadenectomy and surgical margin since D2 dissections were more frequent in CT than in CRT group (79.3% vs. 73.1%) and more microscopic tumor infiltrated margins (R1 resections) were observed in CRT than in CT group (12.2 vs. 7.9%). However, these differences were not statistically significant .From January 2012 to November 2015, a total of 309 patients were eligible for the study, 227 in the CRT group and 82 in the CT group. Baseline characteristics are summarized in Table 7 regimen. In the CT group, 78 patients (95.1%) were treated with capecitabine and oxaliplatin and 4 patients (4.9%) received capecitabine and cisplatin.All 227 patients in the CRT group were treated with the INT-0116 trialp = 0.212)   in the CRT group and 20.6 months (range 0.2-52.6 months) in the CT group, the two-year OS was similar between groups (67.1% vs 71.9% for CRT and CT groups respectively). Median OS was 39.8 months for the CRT group and not reached in the CT group . Treatment delays for more than 7 days were similar between groups (29% vs 32.9% for CRT and CT group respectively), as well as treatment discontinuation rates (35.7% vs 35.4%). The most common cause of treatment discontinuation in the CRT group was toxicity (48.2%) followed by disease progression (19.7%) and loss of follow up (18.5%). For the CT group, treatment discontinuation was due to toxicity (41.4%), followed by disease progression (20.7%) and patient preference (17.2%).p = 0.662). Systemic recurrence  was more common than locoregional recurrence  in both groups .Our study aimed to compare two distinct adjuvant strategies for the treatment of LGC: CRT and CT. Most of our patients had D2 lymph node dissection, which is the standard at our institution. Most patients with D1 lymph node dissection had surgery at outside institutions and were referred to our service for adjuvant treatment. Our results show no difference in OS between the two groups. Loco-regional recurrence rates were also similar between groups (17.6% vs 21.2%) and, as expected, systemic relapse was the most common site of recurrence for the majority of patients  [In the INT-0116 trial, only 10% of patients underwent D2 dissection . Therefop = 0.251) [P = 0.484). However, in a subgroup analysis of patients with pathologic lymph node involvement, the 3-year disease-free survival was prolonged in the CRT arm compared with the chemotherapy arm . A meta-analysis with a total of 960 Asian patients from four randomized clinical trials of D2-resected LGC also did not find an OS difference between CRT and CT alone (P = 0.34), despite adjuvant CRT significantly improving loco-regional recurrence-free survival  and disease-free survival  [p = 0.99) [p = 0.013). However, there were several imbalances in the study population and, after propensity score-matched analysis, the benefit remained significant, but much less remarkable  [In a retrospective study conducted in D2-dissected Chinese patients, adjuvant CRT INT-0116 regimen) and CT alone  had similar efficacy with a median OS of 51.0 vs 48.6 months respectively (= 0.251) . The ART= 0.251)  prospect6 regimen = 0.99) . Opposit= 0.033) .In our study, the most common grade 3-4 toxicities in the CRT group were neutropenia 37.8%) and gastrointestinal (approximately 10%), similar to data reported in the INT-0116 trial [.8% and gp = 0.021). This reflects the current practice at our institution of prioritizing more aggressive systemic therapy in case of extensive nodal disease and bulky primary tumors, which carry a higher risk for systemic recurrence. Moreover, the CT alone group had a slightly higher proportion of patients with D2-resected tumors (79.3% versus 73.1% for CT and CRT respectively), probably due to the fact that this population did not derive benefit from radiation in previous randomized trials [Our study has limitations. It is a retrospective study which leads to higher risk of selection bias. Indeed the two groups had different TNM pathological stage distributions, with more stage III patients in the CT group than in CRT group . Final results of the CRITICS trial (NCT00407186) are also awaited and a Chinese phase III trial is recruiting participants to compare adjuvant CT with S1 and oxaliplatin versus adjuvant CRT (NCT02648841). The TOPGEAR trial (NCT01924819) is currently evaluating the role of neoadjuvant CRT to increase treatment efficacy and compliance and reduce toxicity. Lastly, final results of FLOT4-AIO Trial NCT01216644) are eagerly awaited due to a survival and pathological complete response benefit of perioperative docetaxel, oxaliplatin and 5-FU (FLOT regimen) over standard platinum, fluoropyrimidine and anthracycline regimens , 21, whi6644 are Another field of active research is tumor biology. Data from the FLOT4 trial suggest that perioperative CT has limited activity for diffuse histology tumors  . In a reOur study shows that adjuvant CRT and CT alone present similar efficacy and manageable toxicity profile even though dose reductions and dose delays were more common in patients treated with CT alone. Therefore, in institutions where radiation therapy is a scarce resource, adjuvant CT alone is a reasonable treatment option. Research is ongoing to determine more effective treatment strategies and to improve patient selection.


Hepatitis C virus (HCV) is a major global health issue and successful treatment has been associated with a reduction of risk of all-cause mortality. Advancements have been made in HCV treatment through the use of interferon-free regimens. Most trials have been conducted in HCV genotype (GT) 1 and data for interferon-free regimens in GT4 patients are limited. The aim of this study was to evaluate the safety and efficacy of sofosbuvir plus simeprevir in a real-world cohort of HCV GT4 patients with advanced fibrosis.Eighty-seven GT4 treatment-naïve or –Interferon (IFN) ribavirin (RBV) experienced patients treated with sofosbuvir and simeprevir +/- ribavirin (RBV) were enrolled in this cohort study .Patients were 51.7% male, 78.2% IFN/RBV treatment-experienced, and 37.9% received RBV treatment. The overall sustained virologic response at least 12 weeks after treatment (SVR12) rate was 87.4% while patients treated with and without RBV had rates of 87.9% and 87% (p = 0.593), respectively, and patients with advanced fibrosis (F3) and patients with cirrhosis had SVR12 rates of 94.4% and 82.4% (p = 0.087), respectively. SVR12 rates in treatment-naïve patients and in IFN/RBV -experienced patients were 78.9% and 89.7% (p = 0.191), respectively. Treatment failure occurred most commonly in patients with cirrhosis and severe disease. The treatment was well tolerated and no patient died or discontinued treatment due to adverse events.Sofosbuvir in combination with simeprevir +/- ribavirin in GT 4 HCV patients with advanced fibrosis achieved high SVR12 rates and was well tolerated. RBV did not appear to increase the rate of SVR12. Hepatitis C virus (HCV) is a major global health issue affecting 170 million patients worldwide ,3 and suHCV GT 4 accounts for 20% of HCV infections worldwide  and is mGT4- treatment naïve or –IFN/RBV experienced patients from 15 referral centers in Belgium treated with sofosbuvir and simeprevir +/- ribavirin were enrolled between January and September 2015 in this observational study. Reference centers allowed to prescribe DAAs were included in the study. All patients had advanced fibrosis (F3-F4) as required by national reimbursement criteria. Degree of fibrosis was defined at the beginning of treatment by histology or by combination of an elastography test and a biological fibrosis score with a maximum age of laboratory values of 1 year. The cut-offs for F3-F4 chronic HCV fibrosis assessment for transient elastography were for Fibroscan® : F3 ≥9.5 kPA and F4 ≥12.5 kPA, and for shear wave elastography: F3 ≥8.7 kPA and F4 ≥10.4 kPA ,28. The Sofosbuvir + simeprevir treatment was considered as standard of care treatment for participants as recommended by Belgian and EASL guidelines ,30.The uData collection included demographic data, history of previous HCV treatment, laboratory data including levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin, creatinine, hemoglobin, platelet count, International Normalized Ratio (INR), and HCV RNA. Severity of cirrhosis was assessed by Child-Pugh and MELD scores. These different parameters were also assessed at week 4 (W4) and week 12 (W12) of treatment when available.Treatment efficacy was measured as sustained virologic response (SVR)12 defined as HCV RNA level below level of quantification at least 12 weeks after the end of treatment (EOT). For patients who did not achieve SVR12, the frequency of relapse, and non-response was reported. The numbers of patient lost-to-follow-up was also reported.The primary endpoint was SVR12. Other efficacy endpoints were virological response at W4 and HCV RNA at the end of treatment. The primary analysis was done in the intention-to-treat (ITT) population including all patients who received at least one dose of treatment. An additional analysis of the primary endpoint was performed that excluded patients who did not have SVR12 values due to missing data, or lost to follow-up. The demographic data were compared between groups using Student’s t-test or the Mann-Whitney U test as appropriate. Categorical variables were studied using the two-sided Chi-square test. A p value <0.05 was considered statistically significant. Calculations were performed with SPSS 18.0 software .Eighty-seven patients with HCV GT 4 were included between January 2015 and September 2015. Thirty-six patients (41.4%) had severe fibrosis (F3) and 51 (58.6%) were patients with cirrhosis. The study population included 46 (51.7%) male and 68 (78.2%) IFN/RBV-experienced patients. The majority of patients were black Africans (58.6%). Median age was 61 (30–81) years and 9 patients were HCV/HIV co-infected. Thirty-three (37.9%) patients received ribavirin treatment, 12 (33%) of patients with advanced fibrosis and 21 (41.2%) of patients with cirrhosis. In patients with cirrhosis, median MELD score and Child-Pugh score were 8 (6–19) (range) and 5 (5–9) (range), respectively, 43.7% patients had platelet counts below 100 000/mm³, 28.2% had albumin <35g/L and 13 patients had a history of liver decompensation. At baseline, the clinical and demographic characteristics of patients who received ribavirin were similar to those who did not receive ribavirin, except for ALT levels which were higher in patients treated with ribavirin. The majority of patients received 12 weeks of treatment. Demographic and baseline characteristics are shown in In an ITT analysis, SVR12 rate was 87.4% (76/87). Among the patients who failed to achieve SVR12, 5 had post treatment relapse, 1 patient had lack of efficacy during treatment with detectable HCV RNA but below lower limit of quantification (LLOQ) at the end of treatment and a relapse after, 1 patient was lost to follow up during the treatment but had a positive HCV viral load after the end of treatment (no compliance data is available for this patient) and 4 patients were lost to follow-up after completing treatment. SVR12 in patients treated with and without RBV were 87.9% (29/33) and 87% (47/54) (p = 0.593), respectively, and among patients with cirrhosis, SVR12 in patients treated with and without RBV were 81% (17/21) and 83.3%(25/30) (p = 0.555), respectively. SVR12 in patients with advanced fibrosis (F3) and in patients with cirrhosis were 94.4% (34/36) and 82.4% (42/51) (p = 0.087), respectively. Moreover, SVR12 in treatment-naïve patients and in IFN/RBV-experienced patients were 78.9% (15/19) and 89.7% (61/68) (p = 0.191), respectively. HCV RNA at the end of treatment was undetectable in 69 patients (79.3%). HCV RNA was detectable but below LLOQ in 12 patients and data were missing for 6. However, among the 12 patients with detectable HCV RNA but below LLOQ at the EOT, 10 achieved SVR12 (1 failure of treatment and 1 lost to follow-up). The number of patients with undetectable HCV RNA at the EOT was higher in patients treated with RBV (93.9%) than in patients without RBV (70.4%) (p = 0.007) . An addiFinally, HCV RNA was measured at week 4 of treatment in 67 patients. HCV viral load was undetected in 22 patients (32.8%), 14/28 (50%) in patients treated with RBV and 8/39 (20.5%) in patients without RBV (p = 0.012). There was no SVR12 rate difference between patients with undetectable HCV RNA at W4  and patients with positive HCV RNA at W4  (p = 0.534).During the treatment, SAE were observed in 3 patients. One patient was hospitalized for anemia due to rectal blood loss resolved after transfusion and not related to the treatment, 1 patient was hospitalized for encephalopathy not considered to be related to the treatment and 1 patient developed hepatorenal syndrome possibly related to the treatment. No patient died or discontinued treatment due to adverse events. Among patients treated with and without ribavirin, 5/33 (15.2%) and 3/51 (5.9%) had hemoglobin<10g/dl (p = 0.132) during the treatment and ribavirin dose was decreased in 3 of the 33 RBV-treated patients and stopped in 3 patients. The 6 patients who modified RBV dosage during treatment all had cirrhosis. The median baseline haemoglobin level for the 6 patients who modified their ribavirin dosage was 13.5 [11.5–15.3] g/dL compared with 14.4 [11.5–17.7] g/dL for the 27 patients who had no modifications to their ribavirin dosage during the study (p = 0.190) and the median baseline RBV dosage was 900 [800–1200] mg in patients who modified RBV dosage and 1200 [400–1200] mg in patients without modification of RBV dosage (p = 0.189).In this Belgian real-world cohort of HCV GT4 patients with advanced fibrosis, we showed that the combination of SOF + SMV achieved in ITT analysis an SVR12 rate of 87.4%, 87.9% for patients treated with RBV and 87% for patients treated without RBV. After exclusion of patients who did not achieve SVR12 for reasons other than virologic failure, we observed an SVR rate of 91.6%. These results showed that the combination of SOF+SMV is efficacious in HCV GT4 patients with advanced fibrosis and that the addition of RBV did not appear to increase the rate of SVR12 although patients treated with RBV seemed to have a faster decrease of their viral load with a higher rate of negative viral load at week 4 and at the EOT. Interestingly, some patients had detectable HCV RNA but below LLOQ at the EOT but achieved SVR12. We did not observe a significant difference in SVR12 between patients with severe fibrosis F3 and patients with cirrhosis. This may be due to the small size of the cohort. However, all but one patient who failed to achieve SVR12 were patients with cirrhosis and advanced disease. This observation is consistent with results observed previously in other studies . After eLimited data are currently available to guide treatment in chronic HCV GT4 patients especially with advanced fibrosis. However it is important to develop optimal treatment strategies for HCV GT4 patients because this genotype is highly endemic in non-Western parts of the world and its prevalence has increased in several European countries –21 MoreoOur study is subject to several limitations. First, ribavirin treatment was not given after randomization but only at the discretion of the treating clinician and the number of patients with cirrhosis receiving RBV is probably too small to show a potential benefit of RBV treatment in this population. It is thus difficult to make definitive conclusions concerning the role of ribavirin in the efficacy of treatment in our cohort of patients. Moreover, we had no data about resistance associated variants (RAV) which might influence the treatment response. Indeed, in the COSMOS study, the viral relapse rate was mainly correlated with mutations that have previously been associated with simeprevir resistance . HoweverIn conclusion, we showed in this real-world cohort of GT4 patients with severe fibrosis and cirrhosis that the combination of SOF and SMV is efficacious and well tolerated and represents a good therapeutic option in HCV GT4 patients with advanced fibrosis and compensated cirrhosis. In patients with decompensated cirrhosis, second-generation IFN-free combinations would be better suited.


Morocco has recently developed a plan of reducing sugar consumption to reinforce prevention of non-communicable diseases and to contribute to the achievement of global voluntary targets for non-communicable diseases set by ICN2 by 2025. The objective of the present study was to assess acceptance of yogurts with different percentage reduction of sugar by the Moroccan population.A total of 201 participants (age > 15 y.) were recruited to determine the level of sugar reduction in yogurt. Sucrose was added to a plain yoghurt in the following different concentrations 166.5; 149.8; 133.2; 116.5; 99; 83.2 mM/l, corresponding to the reduction of sugar of 0%, -10%, -20%, -30%, -40% and -50%, respectively, compared available yogurt in local market. Overall, the acceptability scores of the different yoghurts were based on liking, “Just About Right” (JAR) and purchase intent scales was used to score the different yoghurts.Yogurts containing -20% and -30% added sugar were highly accepted by 81% and 74% of respondents. Based on JAR score, yoghurt with 20% (133.2mM/l) and 30% (116.5 mM/l) reduction were considered as “Just about right” by 42.7% and 44.3% respectively. Best average score of purchase intent was obtained for sucrose concentration of 149.8 mM/l. 35.8% and 40.3% for yoghurt with sucrose concentration of 133.2 mM/l and 116.5 mM/l respectively.The finding from this study indicated that yogurts containing -20% and -30% added sugar were most accepted by respondents. Advocacy before dairy industry to have them commit towards sugar reduction in yogurt is needed, in order to help achieving the national sugar reduction strategy in Morocco. Morocco has recently developed a plan of reducing sugar consumption in order to reinforce prevention of non-communicable diseases. This action has been taken to contribute to the achievement of global voluntary targets for non-communicable diseases set by the Second International Conference on Nutrition ICN2 by 2025 . In factSubjects: A total of 201 participants (age > 15 years) were recruited to determine the level of sugar reduction in yogurt. Males constituted 48.3% and females 51.7%. Information on age (years), gender and frequency of consumption of yogurt were collected using a valid questionnaire [ionnaire . IndividSample preparation: Plain yoghurt  was chosen as reference for 0% added sucrose, while the sweet yogurt  was chosen as the reference of 100% added sugar, as this is the usual concentration of sugar in yogurt available in Moroccan local market. Sucrose was added to a plain yoghurt in the following different concentrations 166.5; 149.8; 133.2; 116.5; 99; 83.2 mM/l, which corresponded to the reduction of sugar to obtain different sweetness levels corresponding to a reduction of 0%, -10%, -20%, -30%, -40% and -50%, respectively. The mixtures were homogenized and then cooled at 5°C for 5 to 7 days until descriptive sensory analysis were conducted [Sensory analysis: Participants were requested to taste the yogurts and evaluated their overall liking based on taste scale. It consisted a 9-points hedonic scale (1 = I extreme dislike to 9 = I extreme like). The 9 points were grouped into 3 categories: 1 = I dislike, 2 = I either like nor dislike and 3 = I like. Sweetness intensity was assessed using the JAR (Just About Right) 9-points scale . Purchase intent was scored on a 5-point scale . Weekly frequency of yogurt consumption was also determined. Each participant evaluated 7 yogurt samples, which were presented in 3-digits coded [ts coded . Three sts coded -18. Rinsts coded .Statistical analysis: Statistical analysis was performed using SPSS (version 21). The data were analyzed using ANOVA, at a p-value ≤0.05, mean values were further compared using FISHER test. Scores distribution frequency was calculated for the 3 used scales . The percentage (%) of scores in each category was calculated and Freidman's Chi2 test was applied to assess the significance between the different categories.Overall liking: Sweetness liking: 72.6% of participant indicated that yoghurt with a concentration of 166.5 mM sucrose/l (0% reduction) was too sweet versus 96.5% who reported that 0mM/l (100% reduction) was not sweet enough. 20% (133.2mM/l) and 30% reduction were considered as “Just about right” by 42.7% and 44.3% respectively .First study at national level aiming to reduce sugar consumption in food;Currently available yoghurt in Moroccan market is considered as very sweet by Moroccan consumers;Yoghurts with sugar reduction of 20% and 30% were highly liked by participants.The authors declare no competing interest.


CDDPHANG) is prepared for effective delivery of doxorubicin (DOX) to treat osteosarcoma. Importantly, both DOX and CDDP have led clinically used antitumor drugs, and CDDP acts as a crosslinker and ancillary anticarcinogen to prevent the premature release of DOX and to achieve synergistic therapeutic performance. Because of the enhanced stability of the nanogel, this CDDP‐crosslinked DOX‐loaded nanomedicine (CDDPHANG/DOX) exhibits an obviously prolonged circulation time compared to free drugs. Moreover, after valid tumor accumulation, DOX and CDDP are synergistically delivered into the tumor cells and synchronously released into the intracellular acidic environment. Based on the synergistic apoptosis‐inducing effects of DOX and CDDP, CDDPHANG/DOX reveals an evidently enhanced antitumor efficacy compared to free drugs and their combination, indicating its great prospects for the chemotherapy of osteosarcoma.Osteosarcoma is one of the most serious bone malignancies with rapid speed of deterioration and low survival rate in children and teenagers. Chemotherapy is an important treatment for osteosarcoma, while the conventional small‐molecule therapeutics exhibit low efficacies and severe side effects in the clinic. Drug‐delivery platforms based on nanotechnology, particularly for self‐stabilized delivery platforms with prolonged blood circulation, enhanced intratumoral accumulation, improved antitumor efficacy, and diminished side effects, may break the deadlock on osteosarcoma chemotherapy. Here, a cisplatin (CDDP)‐crosslinked hyaluronic acid (HA) nanogel ( Substantially, structural stability was one of the most crucial properties of nanomedicine, which helps avoid the untimely drug leakage dilemma via their delivery procedure.In this study, a biodegradable, in situ crosslinked nanogel based on hyaluronic acid (HA), a biocompatible polysaccharide, was designed to stride the multiple barriers mentioned above. Compared to other drug delivery systems, HA offers better security for in vivo study and clinical translation due to its excellent biocompatibility and biodegradability. Herein, doxorubicin (DOX) and cisplatin (CDDP), two of the most widely clinically used chemotherapy drugs with proved synergistic effects for many malignancies,To be specific, cationic DOX was incorporated into the nanoparticle through the electronic interaction with anionic HA, obtaining HA/DOX. Meanwhile, besides the acquainted antitumor activity, CDDP was also used as a crosslinker, which chelated to the side carboxyl groups (COOH) of HA, to stabilize the drug‐loaded nanogel, avoid its premature release during circulation, prolong its circulation time, and reduce its associated side effects.22.1SchemeMn) and polydispersity indices (PDI) of HA determined by gel permeation chromatography (GPC) was 16 060 g mol−1 and 1.7, respectively. The procedure of DOX loading was performed first by hybridizing DOX with HA in an aqueous medium with the weight ratio of 10:1. Afterward, CDDP was introduced to the solution as a crosslinker to accomplish the in situ crosslinking with three different molar ratios  of COOH in HA to CDDP. These three different molar ratios were chosen based on our pilot studies. We found that further decrease of the molar ratio would induce the destabilization and precipitation of nanoparticles. On the other hand, further increase of the molar ratio would result in inadequate crosslinking, leading to the insufficient stability of the nanoparticles. Finally, the lyophilized powder of CDDP‐crosslinked DOX‐loaded nanomedicine (CDDPHANG/DOX) was achieved by a sequential process of dialyzing and lyophilized in darkness. It is worthy of note that all the synthetic processes were performed in an aqueous medium, thus representing a green chemistry approach.In our study, HA, a natural polysaccharide that has been demonstrated as one of the most promising biomaterials,FigureRh) of CDDPHANG/DOX decreased with the increased feeding molar ratio of CDDP from 1/90 (86.4 nm) to 1/50 (72.6 nm) and 1/10 (57.4 nm). This size shrinkage might be attributed to the enhanced crosslinking degree caused by the increased amount of CDDP. These consistent transmission electron microscopy (TEM) images also confirmed the regular changes in the particle sizes with different extents of crosslinking  and drug‐loading efficiency (DLE) of 2.2CDDPHANG/DOX were verified by monitoring the changes of Rh in phosphate‐buffered saline (PBS) at different pH values. To simulate the microenvironments with various acidities in vivo, we chose pH 7.4, 6.8, and 5.5 for our study, which correspond to the pH values of the normal physiological environment, acidic tumor tissue, and intracellular endo/lysosome, respectively.CDDP3.3HANG/DOX5.4 was taken as an example for this test. As shown in Figure CDDPHANG/DOX kept a stable status without significant size change at physiological pH. However, noticeable swelling and dissociation were detected at acidic pH 6.8 and 5.5. Specifically, CDDPHANG/DOX swelled from 56.9 ± 2.7 to 386.7 ± 56.3 nm within 24 h at pH 6.8, and the light‐scattering signal was not detectable owing to the particle dissociation after 36 h. Analogously, at a lower pH 5.5, the swelling and dissociation of the nanoparticle were even significant. The Rh of CDDPHANG/DOX at pH 5.5 was 57.5 ± 1.3 nm at the initial state, while it rose to 473.2 ± 129.9 nm rapidly in 12 h. Due to the disassembly of CDDPHANG/DOX at acidic pH, no light‐scattering signals of the particles could be detected after 12 h. The size and morphology changes of the nanogel were further confirmed by TEM . Notably, because of the prolonged incubation time of CDDPHANG/DOX in acidic environment with pH values of 6.8 or 5.5, especially for pH 5.5, its uniform spherical structure rapidly swelled and disintegrated. Finally, the nanogel disassembled and only chaotic structure was observed by TEM. Taken together, CDDPHANG/DOX revealed great physiological stability, and displayed fast expansion and rupture in acidic environments corresponding to the tumor tissue and intracellular endo/lysosome.The stability and pH‐sensitivity of CDDP3.3HANG/DOX5.4, CDDP1.0HANG/DOX5.8, and CDDP0.6HANG/DOX6.3) were evaluated in PBS at pH 7.4, 6.8, and 5.5  at pH 7.4 after 72 h compared to CDDP1.0HANG/DOX5.8 (46.6% ± 6.7%) and CDDP0.6HANG/DOX6.3 (52.0% ± 6.5%). Thus, as the content of CDDP increased, the DOX release rate decreased. Then, CDDP3.3HANG/DOX5.4 was employed to illuminate pH‐dependent CDDP release profiles. As shown in Figure CDDP3.3HANG/DOX5.4 was chosen for further studies.Moreover, CDDP crosslinking could largely enhance the stability of the nanomedicine and might effectively prevent premature drug release following intravenous injection. The crosslinking degree of DOX‐loaded nanoparticles was correlated to the drug release kinetics. Specifically, 2.3FigureCDDP3.3HANG/DOX5.4 group was located in the nucleus, which is the same site observed for free DOX. Therefore, the drug‐encapsulated nanogel was able to release DOX intracellularly. Furthermore, after 2 or 6 h of incubation, the intracellular DOX fluorescence was observed with different extents of DOX endocytosis in mouse osteosarcoma K7 cells. Specifically, the DOX fluorescence could be apparently detected in the cells treated with free DOX after 2 h, while the fluorescent signal was actually weaker in the cells cultured with CDDP3.3HANG/DOX5.4. However, when the culture time was prolonged to 6 h, the intracellular DOX fluorescence intensity remarkably enhanced in the CDDP3.3HANG/DOX5.4 group, but the increase of fluorescence intensity was negligible in the cells treated with free DOX. These phenomena might be attributed to their different cell internalization mechanisms and variant fluorescence characteristics.Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to investigate the cell internalization and intracellular DOX release. As shown in CDDP3.3HANG/DOX5.4 was taken up by the cells via endocytosis pathway, which had a temperate efficiency at the outset and then revealed the enhanced fluorescence signal after effective drug release.CDDP3.3HANG/DOX5.4 group in the early period. However, the superiority of diffusion pathway could not sustain for a long time, and the endocytosis approach demonstrated its long‐term advantage entirely at the later period. As depicted in Figure CDDP3.3HANG/DOX5.4 were further confirmed by FCM, and consistent results could be obtained. In summary, CDDP3.3HANG/DOX5.4 revealed excellent performance on K7 cell endocytosis and intracellular drug release.As a small‐molecule chemotherapeutic drug, DOX could pass through the cell membrane by fast diffusion. On the contrary, CDDPHANG/DOX in proliferation inhibition toward K7 cells in vitro was further confirmed by MTT assay. First, the cytotoxicity of HA toward K7 cells was measured . Only negligible cytotoxicity to the cells could be detected at all the tested concentrations of HA after 72 h of incubation, indicating its prominent biocompatibility. The in vitro cytotoxicities of free DOX plus CDDP and CDDPHANG/DOX were measured after 24 and 72 h of incubation. As shown in Figure CDDPHANG/DOX samples. However, the cytotoxicity of CDDPHANG/DOX was obviously higher than that of free DOX plus CDDP at 72 h.The feasibility of 50) directly estimated from Figure Table50 of CDDPHANG/DOX was lower than that of free DOX plus CDDP at either 24 or 72 h. To be specific, after 24 h of incubation, the IC50 values of CDDP3.3HANG/DOX5.4, CDDP1.0HANG/DOX5.8, and CDDP0.6HANG/DOX6.3 were 1.7, 1.5, and 1.8 times lower than that of free DOX plus CDDP, respectively. Similarly, at 72 h, the IC50 values of CDDP3.3HANG/DOX5.4, CDDP1.0HANG/DOX5.8, and CDDP0.6HANG/DOX6.3 was 2.8, 2.5, and 2.2 times lower than that of free DOX plus CDDP, respectively. These results were consistent with that demonstrated by CLSM and FCM. The enhanced cytotoxicity of CDDPHANG/DOX was possibly ascribed to its enhanced stability and deferred drug release process.The half maximal inhibitory concentrations  and an inductively coupled plasma mass spectrometer. As shown in FigureCDDP3.3HANG/DOX5.4 distinctly prolonged the blood circulation of the drugs and maintained much higher plasma concentrations after the injection, as compared with the free DOX and CDDP groups (P < 0.05 for DOX and P < 0.01 for CDDP). Specifically, for the CDDP3.3HANG/DOX5.4 group, the maximum concentrations (Cmax) of DOX and CDDP were 22.5 and 12.5 µg mL−1, respectively. However, those were 11.8 and 7.5 µg mL−1 in the free DOX and free CDDP groups, respectively. The area under the concentration versus time curve from 0 to final time (AUC0–t) of DOX and CDDP were 60.1 and 51.4 µg (mL h)−1 in the CDDP3.3HANG/DOX5.4 group, which were 5.2 and 10.1 times higher than those of the free DOX plus CDDP group, respectively. The significantly improved pharmacokinetics for CDDP3.3HANG/DOX5.4 was probably due to their high crosslinking density that resulted in not only superior stability but also inhibited drug leakage in vivo.In the present study, the pharmacokinetic profiles of free drugs and CDDP3.3HANG/DOX5.4 group, the increased accumulation of DOX in other organs was detected with a conspicuous attenuation compared to free DOX, especially to the kidney, which might owe to an enhanced biocompatibility of nanogel. Moreover, due to the EPR effect of nanosized, DOX‐loaded particles, significantly stronger intratumoral DOX fluorescence could be observed in the CDDP3.3HANG/DOX5.4 group, as compared with that of the free DOX group. The consistent results could also be obtained when the fluorescence images of the organs were compared at 12 h postinjection. Compared with the free DOX‐treated mice, an obviously enhanced DOX fluorescence intensity at tumor site was detected in the CDDP3.3HANG/DOX5.4 ones at 12 h postinjection.Tissue biodistribution of drugs was a crucial aspect of estimating the drug effectiveness and potential organ toxicity as well as systemic side effects. Here, the ex vivo fluorescence imaging of K7 osteosarcoma tumors and main organs isolated from BALB/c mice were carried out at 6 and 12 h postinjection. All animals received care in compliance with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals, and all procedures were approved by the Animal Care and Use Committee of Jilin University. As shown in Figure CDDP3.3HANG/DOX5.4 group were 1.6 and 1.7 times higher than that in the free drug group at 6 and 12 h postinjection, respectively. These results further verified the distinct enhanced DOX accumulation in tumor site by CDDP3.3HANG/DOX5.4 after intravenous injection, and this satisfactory biodistribution property was also helpful in reducing the systemic toxicity of the drugs.To be specific, as shown in Figure 2.5CDDP3.3HANG/DOX5.4 was examined in xenografted tumor mouse model of osteosarcoma. As shown in Figure3, free DOX plus CDDP and CDDP3.3HANG/DOX5.4 were administered by intravenous injection (DOX dosage: 5.0 mg kg−1) every 4 days. As shown in Figure 3 on average volume at a rapid speed within 25 days. In contrast, either of the other two groups treated with free DOX plus CDDP and CDDP3.3HANG/DOX5.4 had revealed expected tumor inhibition efficiency, compared to the control group. Furthermore, CDDP3.3HANG/DOX5.4 exhibited enhanced tumor inhibition efficiency than free DOX plus CDDP. Consistent results could be obtained through a quantitative analysis of tumor inhibition rate. After six treatments with free DOX plus CDDP and CDDP3.3HANG/DOX5.4, a dramatic different result on tumor inhibition rate was obtained (62.1% for free DOX plus CDDP and 89.1% for CDDP3.3HANG/DOX5.4). The tumor inhibition rate of CDDP3.3HANG/DOX5.4 was 1.4 times higher than that of the free drug combination (free DOX plus CDDP), which can be explained by the enhanced drug accumulation retention at the tumor site, synergistic nanoparticulate drug combination, as well as the accelerated drug release at the acidic tumor microenvironment.The therapeutic efficacy of CDDP3.3HANG/DOX5.4, the tumors were excised from mice and sectioned for histopathological analyses after treatment. As shown in the hematoxylin and eosin (H&E) stained images  than the PBS (1.6% ± 0.7%) and free DOX plus CDDP groups (54.08% ± 6.2%), indicating its enhanced antitumor activity.To further investigate the antitumor efficacy of CDDP3.3HANG/DOX5.4 groups, indicating the fastest and slowest cell proliferation rates of osteosarcoma, respectively. Notably, CDDP3.3HANG/DOX5.4 induced more extensive K7 cells apoptosis in contrast to DOX plus CDDP, and the PBS treatment did not possess any significant therapeutic effect. The antiproliferation effects were further confirmed by semiquantitative evaluation of the immunohistochemical images. The fluorescence intensity of control group was set as “1.” As shown in Figure CDDP3.3HANG/DOX5.4 group, respectively. All of the above results confirmed the strong therapeutic effect of CDDP3.3HANG/DOX5.4 in osteosarcoma.Ki‐67 was a nuclear marker for indicating cell proliferation, and also demonstrated as an optimal proliferation antigen for assessing the prognosis of cancer patients.2.6CDDP3.3HANG/DOX5.4 could be injected into bloodstream with negligible destruction on hemodynamics and exhibit its antitumor efficiency with reduced side effects is closely related to its further translation. In our study, we verified the safety of CDDP3.3HANG/DOX5.4 through the hemolytic test, body weight monitoring, survival rate, organ index, and histopathological examination of several susceptible organs.Safety is another indispensable evaluation of the drug delivery systems. Whether CDDP3.3HANG/DOX5.4. As depicted in Figure S2B (Supporting Information), no noticeable hemolysis could be explored in all the test concentrations of CDDP3.3HANG/DOX5.4. Such an excellent hemocompatibility makes CDDP3.3HANG/DOX5.4 hold potential for the systemic chemotherapy after intravenous injection.Blood compatibility was a crucial point of vesicular formulations based on whether it could be an appropriate option for intravenous injection into blood vessels.] Poor blood compatibility would result in disintegration and dissolution to the membranes of red blood cells (RBCs), and this was demonstrated as a primary obstacle that restricted some kinds of drug carriers administrated through intravenous injection. In this study, hemolysis assay was employed to estimate the hemocompatibility of our nanomedicine, FigureCDDP3.3HANG/DOX5.4 showed a reduced system toxicity effect, and resulted in an obviously mitigatory body weight loss.In our study, the body weight was monitored to estimate the potential adverse effect for all groups during the treatments. As shown in −1) were calculated. As depicted in Figure S3B (Supporting Information), a significant change was observed in the spleen. The spleen index of the free drug combination group was dramatically lower than the other two groups treated with PBS and CDDP3.3HANG/DOX5.4, respectively, which account of the murdering of tremendous spleen cells induced by DOX.After completion of the 25 days therapeutic efficacy study, two mice of each group were executed randomly, then the tumors and major organs were dissected and weighted. The pictures of excised organs were partially shown in Figure S3A (Supporting Information). To accurately appraise the diversity of these isolated organs, organ indices , which indicated excellent performances of CDDP3.3HANG/DOX5.4 in abating untargeted drug accumulation and reducing systematic toxicity once again.Simultaneously, the survival rate was clustered as an essential indicator to evaluate the overall therapeutic tolerance and efficacy. The residual five living mice in each treatment group were raised without any cure for this assay. Compared to PBS and free DOX plus CDDP, mice treated with CDDP3.3HANG/DOX5.4, as compared with that of the control group. However, varying degree of organ damages could be detected obviously in the heart, liver, and kidney. Especially to the heart tissue, critical texture deranging and fracture of the muscle fibers were found in the mice treated with free DOX plus CDDP. However, in the group treated with CDDP3.3HANG/DOX5.4, valid reduced pathological changes and necrosis of heart were detected assuredly. The analogous phenomenon could also be testified in the kidney. Compare to the mice treated with CDDP3.3HANG/DOX5.4, the mice treated with free DOX plus CDDP revealed a distinct disorder in the organizational structure of glomerulus and renal tubule. In liver, the structure of hepatocytes and hepatic lobule was necrosed and disturbed slightly for free DOX plus CDDP group, while the damage in the CDDP3.3HANG/DOX5.4 group was more moderate. The negligible organic injury of CDDP3.3HANG/DOX5.4 potently proved its reduced long‐term toxicity. These perfect performances showed the enormous potential of CDDP3.3HANG/DOX5.4 for clinical application.H&E staining of the major organs was also used to observe and estimate the long‐term toxicity of all the groups.3CDDPHANG/DOX prepared through a green and innocuous method possessed a stable structure and an outstanding ability on codelivery and subsequently controlled the release of DOX and CDDP. Accompanied with the pH‐responsive release of DOX, CDDP was also dissociative and then exhibited the synergistic antitumor effect. Moreover, after CDDP in situ crosslinking, a striking enhancement could be confirmed on its stability and tolerability. This also led to the optimized biodistribution, enhanced antitumor potency, and reduced multiorgan toxicity side effect of the drug in vivo. Based on these, CDDPHANG/DOX revealed an excellent performance in either delivering drugs into tumor cells in vitro or suppressing the growth of xenografted K7 osteosarcoma in vivo. The significant tumor growth inhibition can be resulted from the prolonged blood circulation, enhanced tumor accumulation, and bioresponsive intracellular release of the drugs, after CDDPHANG/DOX administrated via intravenous injection. Taken together, our CDDP crosslinked DOX‐loaded nanogel is a versatile platform for drug codelivery and holds great potential for synergistic tumor therapy.The authors declare no conflict of interest.SupplementaryClick here for additional data file.


Plasmodium falciparum malaria. A high number of treatment failures (14/40) was found, and piperaquine resistance in Vietnam was confirmed. A change in the malaria treatment policy for Vietnam is in process.We conducted a study in Binh Phuoc, Vietnam, in 2015 on the therapeutic efficacy of dihydroartemisinin/piperaquine for  Plasmodium falciparum malaria has been a growing concern in the Greater Mekong Subregion of Southeast Asia. High numbers of treatment failures were reported for dihydroartemisinin/piperaquine in Cambodia  copy number  years, and 93% (43/46) were male. Geometric mean parasitemia on day 0 was 17,759 /μL.Forty-six patients with uncomplicated On day 3, half (23/46) of patients were parasitemic. On day 42, a total of 65%  had an ACPR, and 35% (14/40) had recrudescence; 4 were withdrawn because they became reinfected.K13 propeller domain, the most prevalent being the C580Y mutation in the eastern Greater Mekong Subregion  from our study showed that 90.5% (38/42) were C580Y and 9.5% (4/42) were wild-type. This C580Y prevalence is higher than that reported in a previous study done in Binh Phuoc in 2014, in which 34.5% of samples had the C580Y mutation .Artemisinin resistance is defined as delayed parasite clearance and is associated with mutations in the PfPM2 showed that 25/46 (54.3%) samples had multiple copies of the gene. Of the 42 samples with known K13 types, 22 (52.4%) had both C580Y and PfPM2 amplifications. The remaining 3 had unknown K13 types. All 46 samples had a single copy of Pfmdr1, indicating that all parasites were sensitive to mefloquine  was 35.7 (range 11.1–71.0) ng/mL. In 57.1% (24/42) of patients, this concentration was at or above the cutoff value (30 ng/mL) associated with adequate piperaquine exposure  alone did not lead to dihydroartemisinin/piperaquine failures. The association between the presence of molecular markers and recrudescence is confounded by various factors, including parasite load, immunity, and drug levels. Of the 3 patients who had recrudescence and were infected with P. falciparum without PfPM2 amplifications, 2 had inadequate piperaquine levels. Of the 11 patients who had recrudescence and an infection with P. falciparum with PfPM2 amplifications, 7 had adequate piperaquine levels. Low piperaquine blood levels, irrespective of the presence of PfPM2 amplifications, might play a role in some treatment failures. Treatment failures in cases with PfPM2 amplification–positive parasites and adequate piperaquine exposure support the presence of piperaquine resistance in Vietnam. Of the 14 patients who experienced recrudescence, 10 had parasites with the C580Y mutation and K13 mutation has become dominant and that piperaquine resistance is present in Vietnam. A change in the malaria treatment policy to treat with artesunate/mefloquine in Binh Phuoc Province is underway.Our results show that 1


Access to laparoscopy is low in Cameroon where customers' satisfaction has not been reported so far. We assessed patients' satisfaction with the process of care during laparoscopic surgery in a new tertiary hospital.A questionnaire was addressed to consenting patients (guardians for patients under 18) with complete medical records who underwent laparoscopy at the Douala Gynaeco-Obstetric and Paediatric Hospital (Cameroon) from November 1, 2015 to July 31, 2016. The following modified Likert's scale was used to assess satisfaction: very weak: 0-2.5; weak 2.6-5; good: 5.1-7.5; very good: 7.6-10. Only descriptive statistics were used.Response rate was 90% (45/50). Of the 45 respondents, 39 (86.7%) were female, 14(31.1%) were referred and 39 (86.7%) paid by direct cash deposit. Mean age was 36.8±11.9 years. Laparoscopies were carried out in emergency for 3 (6.7%) patients. Digestive abnormalities indicated 13 (28.9%) laparoscopies while gynaecologic diseases accounted for 32 (71.1%) cases. Perception of the overall care process was good with a mean satisfaction score of 6.8 ± 1.4. Scores in categories were: 0% (Very weak); 13.3% (weak); 57.8% (good) and 28.9% (very good). Specifically mean satisfaction scores were: 7.8 ± 1.0 with doctors' care; 7.1 ± 1.3 with hospital administration; 7.0 ± 1.2 with nursing and 4.7 ± 1.4 with the costs. Main complaints were: long waiting time (73.3%), constraining geographical access (66.7%) and expensiveness (48.9%).Patients were globally satisfied with the process of care but financial and geographical barriers should be addressed. Over the past two decades, patients' satisfaction (PS) has emerged as an important indicator of health care quality ,2. PS caStudy design and site: We carried out a cross-sectional study at the Douala Gynaeco-Obstetric and Paediatric Hospital (DGOPH). This hospital was opened in September 2015. It is the largest health facility dedicated to mother and child's care in Cameroon .Sampling and procedure: Our sample was convenient. We consecutively included all consenting patients  who underwent laparoscopic surgery from November 1, 2015 to July 31, 2016. Patients with incomplete medical records were excluded. Data were collected through a self-administered questionnaire on the following items: doctors' care, nursing, administrative procedures and cost. Participants were also asked to list their main complaints. Following a modified Likert's scale, participants were asked to score their satisfaction from 0 to 10 . Then a technical form was used to retrieve the followings parameters: age, sex, gravidity and parity (for women), marital status, mode of payment, occupational status, referral status, previous abdominopelvic surgery (laparoscopy or laparotomy), pregnancy status during laparoscopic surgery and its indication. Data were managed with Microsoft Office Excel® (version 2010) software and descriptive statistics were computed.Ethics: Our study was conducted in accordance with the Declaration of Helsinki on biomedical research involving human subjects. A clearance was obtained from the institutional committee of ethics of the DGOPH. (N°001/AR/HGOPED/DG/DM/SRFESS/pt). Written informed consent was obtained prior to participation from adult participants and from either parents or legal guardians of non-adult participants. Confidentiality was observed.During the study period, 56 patients underwent laparoscopic surgery. For 6 of them, medical records were incomplete and 5 did not consent to participate (90% response rate).Baseline characteristics of patients and indications of laparoscopic surgeries:Patients' satisfaction and complaints after laparoscopic surgery:Women predominated in our study . This is due to the fact that the study took place in a hospital dedicated to women and child health. The majority of participants was employed ; this is understandable given that the study took place in the economic capital of the country. Infertility was the most frequent indication of laparoscopy . Similar findings are commonly reported in Cameroon for at least two reasons: laparoscopy was introduced in Cameroon three decades ago by gynaecologists; laparoscopic procedures indicated for infertility belong to the second levelof the European Society for Gynaecological Endoscopy classification for which local laparoscopic surgeons and gynaecologists are generally proficient . The levPatients were satisfied with the process of care during hospital stay for laparoscopic surgery. The costs, long waiting time and constraining geographic access were the main complaints.Patients' satisfaction with laparoscopic surgery is good in developed countries where it is regularly assessed to maintain good quality of care;Satisfaction of Cameroonians patients with surgery in general and with laparoscopy in particular has not been assessed (to the best of our knowledge).Our study gives a first appraisal of patients' satisfaction with laparoscopic surgery ;Expensiveness and poor geographical accessed are the main grievances reported by patients after laparoscopy.The authors declare no competing interests.


The supervised classification of the Landsat imageries revealed an increase in portion of the lake covered by bare ground and sandy soil within the reference years (13 490.8–17 503.10 km2) with 4.98% total range of increase. The lake portion intersected with vegetated ground and soil also reduced within the period (11 046.44–10 078.82 km2) with 5.40% (967.62 km2) total decrease. The shrunk part of the lake covered singly with vegetation increased by 2.74% from 1987 to 2005. The shrunk part of the lake reduced to sand and turbid water showed 5.62% total decrease from 1987 to 2005 and a total decrease of 1805.942 km2 in area. The study disclosed an appalling rate of shrinkage and damaging influences on the hydrologic potential, eco-sustainability and socio-economics of the drainage area as revealed using ILWIS 3.3.Lake Chad commonly serves as a major hub of fertile economic activities for the border communities and contributes immensely to the national growth of all the countries that form its boundaries. However, incessant and multi-decadal drying via climate change pose greater threats to this transnational water resource, and adverse effects on ecological sustainability and socio-economic status of the catchment area. Therefore, this study assessed the extent of shrinkage of Lake Chad using remote sensing. Landsat imageries of the lake and its surroundings between 1987 and 2005 were retrieved from Global Land Cover Facility website and analysed using Integrated Land and Water Information System version 3.3 (ILWIS 3.3). Supervised classification of area around the lake was performed into various land use/land cover classes, and the shrunk part of its environs was assessed based on the land cover changes. The shrinkage trend within the study period was also analysed. The lake water size reduced from 1339.018 to 130.686 km Retractions and extinctions of waterbodies are primarily connected to climate change, hydro-climatological pressures and anthropological workouts –6. Of coet al. [2 [2 and 3000–7000 km2, respectively [Lake Chad is one of the most important transnational and transboundary freshwater resources in the world. It occupies 8% of African continental land area. The lake expanse extends to eight African nations involving Cameroon, Algeria, Chad, Central African Republic, Niger, Libya, Sudan and Nigeria . The laket al.  recentlyt al. [2 , approxit al. [2 , approxit al. [2 . Adewuyit al. [2  also estt al. [2  found tht al. [2  recordedectively ,21.Previous studies on Lake Chad and vicinity employed instrumentation of direct site survey including interviews, questionnaires and photographs . Besideset al. [Nevertheless, the effective, efficient and accurate application of remote sensing in assessment of areal extent of lakes and other freshwater resources is largely not independent of the dataset, data source and instrumentation. For illustration, Adewuyi  employedet al.  used satet al. . Nigeriaet al. . However2.2.1.2 extent) constitutes freshwater source shared by eight African countries which are Niger, Cameroon, Nigeria, Chad Republic, Central African Republic, Sudan, Libya and Algeria. It is fed by Chari-Logone river systems from the south and Komadugu/Yobe-Ngadda river systems from the western part of the lake. The catchment area occupies approximately 2 434 000 km2 (approx. 8%) of African total continental land surface [The ‘standard’ Lake Chad is situated between latitudes 12°10′ N and 14°30′ N, and longitudes 13° E and 15°30′ E in the hot semi-arid region. The lake is located along the international boundary of four countries which are Nigeria, Niger, Chad and Cameroon, and it is the fourth largest lake in Africa. Its hydrological basin (2.4 million km surface . It is s surface  (figure 2.2.http://glcfapp.glcf.umd.edu/) and the National Space Research and Development Agency, Nigeria, respectively. The data attributes are presented in Landsat imageries and ILWIS 3.3 of the lake and its environs for years 1987–2005 were acquired from Global Land Cover Facility website . The band combination of satellite images was carried out in order of red, green and blue.2.3.2.The pictorial image or general overview (features) of the location obtained from band combination was further subjected to supervised classification using ILWIS 3.3. This was done to categorize physical (Earth) characteristics feature of the study location. Unlike unsupervised classification whereby the software picks the characteristics features (points) of the images and places them in categories without specific name, the supervised classification involves a human operator deciding the points or area of the combined image to be categorized with specific name tag. The land cover classes considered in the supervised classification include (i) current water in the lake, (ii) sandy soil and bare ground, (iii) the shrunk part of the lake covered with vegetation, (iv) the shrunk part of the lake covered with soil and vegetation, and (v) the shrunk part of the lake reduced to sand and turbid water. The knowledge of correct band combination helps in the interpretation of the already classified image. The classified image was then embellished by adding appropriate layout . Also, comparison plots of the years were performed.In all cases, the number of pixels corresponding to a specific land cover class was determined with raster calculator. Then, corresponding coverage area was estimated through cross-multiplication of its number of pixels in the attribute table and the image resolution.3.3.1.2. The portion covered by sandy soil and bare ground was 13 490.8 km2. While the shrunk part covered with soil and vegetation was 11 046.44 km2, the shrunk area vegetated only was 4610.831 km2. A 2306.929 km2 area of the shrunk part was reduced to sand and turbid water at 1987.The supervised classification of Lake Chad and its environs for year 1987 is presented in 3.2.2 (2.6%) for current water. Sandy soil and bare ground covered 11 486.33 km2 (34.14%). The shrunk part of the lake reduced to vegetation only covered 9362.569 km2 (27.83%). Approximately, 4.17% (1402.323 km2) of the shrunk portion of the lake was reduced to sand and turbid water at year 1999.3.3.The 2001 supervised classification image of Lake Chad basin is presented in 3.4.2 (3.39%) area coverage attributed to current water in the lake. While sandy soil and bare ground occupied 17 503.1 km2 (49.12%) land coverage area. The shrunk part of the lake covered with vegetated soil was 10 078.83 km2 (28.28%). The shrunk area of the lake covered solely with vegetation was 6342.145 km2 (17.8%). A 500.988 km2 (1.41%) area of the shrunk part of the lake was reduced to sand and turbid water at 2005.The physical characteristics of Lake Chad and its environs in the year 2005 are shown in the supervised classification in 3.5.2 (4.08%), 876.2975 km2 (2.6%) and 1208.332 km2 (3.39%), respectively. Similarly, the respective coverage area of sandy soil and bare ground was 13 490.8 km2 (41.14%), 11 486.33 km2 (34.14%) and 17 503.104 km2 (49.12%) for the years 1987, 1999 and 2005. The shrunk portion of the lake associated with soil and vegetation has area coverage of 11 046.44 km2 (33.68%), 10 519.73 km2 (31.26%) and 10 078.827 km2 (28.28%) in the years 1987, 1999 and 2005, respectively. Area coverage of 4610.831 km2 (14.06%), 9362.569 km2 (27.83%) and 6342.145 km2 (17.8%) accounted for shrunk part of the lake covered with vegetation only in the years 1987, 1999 and 2005, respectively. The shrunk area of the lake reduced to sand and turbid water was 2306.929 km2 (7.03%) in 1987, 1402.323 km2 (4.17%) in 1999 and 500.988 km2 (1.41%) in 2005.The compared land cover classes for the reference years 1987, 1999 and 2005 are shown in 4.The application of remote sensing via ILWIS 3.3 instrumentation to hydro-climatic phenomena associated with Lake Chad catchment area was carried out in this study. Owing to the merits that remote sensing allows vivid assessment of the extent of changes and estimate of accompanying earth physical characteristics, hydro-ecologic to socio-economic manifestations, the various changes in the lake extent and land cover classes of its environs were assessed. Remote sensing provides synoptically repeated observations, frequent wetland maps, surrounding land uses attributes and time-serial changes, which overcome limitations posed by spatial and temporal coverage in conventional measurements (field surveys/gauge stations) in wetland monitoring –34.4.1.2 in 1987 to 876.297 km2 in 1999, and a total size decrease of 130.686 km2 from 1987 to 2005 . In other words, it is the Earth surface that the lake presently covers due to its shrinkage in each reference year. The reduction in the lake water coverage area and extent from 1339.018 km to 2005 , could bet al. [K-means unsupervised classification in contrast with the supervised classification employed in this study. Thus, the supervised classification used in this study overcame possible classification of homogeneous spectra classes within the dataset which necessarily do not equal the same information family, unlike misclassification that commonly accompanies unsupervised classification [The lake extent or current water size obtained in this study showed discordant values to estimates in other studies ,23,25. Het al.  and GIS et al. . Ebenki et al.  in additfication ,41.2 [2 from 1963 to 1997, an approximately 88% areal size [2, an approximately 95% extent loss in 1963–2000 [2 (a 15% extent increase) and a decline in 2000–2007 from 10 011 to approximately 8251 km2 (11% extent reduction). Generally, Ebenki [Certain estimated shrinkage in Lake Chad reported in the literature includes 13 000–26 000 km2 , 40 000–eal size  and 20 9963–2000 . This pr963–2000 , who est963–2000  estimate, Ebenki  noted 154.2.2 in 1987 to 17 503.10 km2 in 2005, and with a range of 6016.774 km2, could be due to incessant abstraction of the lake for various purposes, desertification and frequent drought experienced in the basin. Drought conditions have been linked to increase in bare ground around lakes and diminished surface extent [This is the portion of the supervised classified Landsat images of Lake Chad for individual year  that depicts its surrounding covered by sandy soil and the ground surface only . The ince extent ,26,42. Ce extent . Oftentie extent . Fluctuae extent . A totale extent ,43.4.3.2 (33.68%) in 1987 to 10 078.82 km2 (28.28%) in 2005, totalling a 967.62 km2 (5.40%) decrease in the area, could generally be adduced to over-exploitation of wood and hydro-climatic forces. Eco-pastoral behaviours and grazing activities are potential linkages connected to the areal extent reduction in vegetated soil and ground coverage around the lake. Extensive bush burning, and deforestation, are other contributors to reduction in vegetated soil around the lake basin [This is the portion of the supervised classification of the Landsat images of Lake Chad intersected with a combination of vegetated ground and soil for individual year  . This lake basin . The diske basin . This ha4.4.2 (14.06%) in 1987 to 9362.57 km2 (27.83%) in 1999, and then a decline to 6342.15 km2 (17.8%), could depict possible precipitation pattern and interaction of various influences. Generally, a total of 2.74% areal extent increase in the shrunk part of the lake covered by vegetation from 1987 to 2005 could be attributed to hydro-climatological variables including water level and precipitation that might modulate the lake biomass and areal vegetation. Ecological succession, natural disturbances, impoundment and damming of inflow tributaries are other factors that could contribute to areal variability of lake vegetation [This is the portion of the supervised classification of the Lake vicinity covered by vegetation in the years 1987, 1999 and 2005 . This ar4.5.2) total decrease in the areal extent of the shrunk lake reduced to sand dune and turbid water from 1987 to 2005 could be ascribed to increasing successional colonization of the area by wetland plant species. Exposure of the zone due to contraction in lake water could lead to active germination of dormant lakeshore plant seeds and consequent regeneration of the region [This is area extent of the supervised classification of Lake Chad neighbourhood in 1987, 1999 and 2005 reduced to combination of eroded sand dunes, unclean or unclear pools of water. This part is in no way regarded as part of the present water in Lake Chad . The 5.6e region . Increase region –48.Other contributors to Lake Chad shrinkage include lake water discharge to groundwater, and dam construction on the tributaries. For instance, 45% water inflow reduction to the lake has been attributed to Tiga and Challawa dams constructed on Komadugu Yobe river in 1974 and 1992, respectively . Also, 45.The study revealed an alarming rate of Lake Chad contraction and damaging effects on the hydrologic potential, eco-sustainability and socio-economics of the drainage area. Also, ILWIS 3.3 showed a comparable utility in assessing hydro-meteorological events associated with freshwaters and wetlands. Its outputs concordantly fall within the same range and display similar patterns to other remote sensing instrumentations.Therefore, the present study appraised Lake Chad shrinkage using remote sensing and instrumentation of ILWIS 3.3. This was the first investigation that analysed remote sensed dataset (Landsat imageries) of the lake and its surroundings using ILWIS 3.3.


Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus-SFTSV. The seroprevalence of anti-SFTSV antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM), specific to SFTSV in the general population has been investigated in various epidemiological studies with inconsistent results. Here, we clarify this discrepancy and reach a more comprehensive result by mean of a meta-analysis.All relevant articles were searched in the electronic databases  up to November 2016. The pooled seroprevalence and 95% confidence intervals (95% CIs) were calculated by random- or fixed- model on the basis of heterogeneity.In total, 21 studies containing 23,848 blood samples from 7 provinces were included in this meta-analysis. The minimum and maximum reported seroprevalences of SFTSV among humans in China were 0.23% and 9.17%, respectively. The overall pooled seroprevalence of SFTSV antibodies was 4.3% (95%CI: 3.2%-5.5%). The pooled prevalence was 5.9% (95%CI: 4.7%-7.0%) in Zhejiang province, 4.9% (95%CI: 4.1–5.8%) in Anhui province, 3.9% (95%CI: 1.3%-6.4%) in Shandong province, and 0.7% (95%CI: 0.2%-1.1%) in Jiangsu province. Stratified by occupation, the pooled prevalence of farmer was 6.1% (95%CI: 3.4%-8.9%) and others (mainly are students) was 3.3% (95%CI: 2.4%-4.2%). Additionally, seroprevalence of SFTSV in people who lived in the same village with the patient were higher than that of people who lived in a different village. Seropositive rates in sampling years after 2012 were higher than that before 2012. The prevalence of SFTSV did not differ by age or gender. Sensitive analysis by omitting one study at a time indicated the results of the pooled seroprevalence were robust.Seroprevalence of SFTSV among healthy population in central and eastern China is high. Surveillance efforts on mild or asymptomatic infections among endemic persons are needed. Severe fever with thrombocytopenia syndrome (SFTS) is a notifiable infectious disease characterized by fever, weakness, leukopenia, thrombocytopenia, gastrointestinal symptoms, and central nervous system manifestations –3. The cTime range from March to November is the epidemic season of SFTS, May-July is the peak time of SFTSV infection. SFTSV is most likely to be transmitted by tick bite according to evidence from tick exposure history and SFTSV detection in ticks such as Haemaphysalis longicornis ticks, and virus gene sequence analysis showed the virus in ticks closely related to those circulating in humans –10. HighInfluenza A (H9N2), Ebola and Marburg viruses, and Enterovirus 71, etc [In past years, seroprevalence of SFTSV among healthy population has been widely investigated in various epidemiologic studies. Current estimates of the seroprevalence of SFTSV among general humans in China are almost based on one or several villages with relatively small sample size in one province rather than nationally representative sample of this population. In addition, seroprevalence of SFTSV among healthy humans in different gender, age groups, and endemic regions has yet to be illuminated. Meta-analysis is an effective method of pooling data of individual study together, thus enhancing the statistical power of the analysis for the estimates, to reach a more comprehensive result. It has been widely utilized in sero-epidemiological studies of infectious diseases, such as  71, etc –18. In pAll relevant articles about the seroprevalence of SFTSV in general population were searched via the following electronic databases: Pubmed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese WanFang Database. Date searches were carried out up to November 2016, without restrictions regarding language, publication year and district. The following search words and terms in English and Chinese were used in the final search:  and (“SFTS” or “SFTSV” or “Severe fever with thrombocytopenia syndrome” or “Severe fever with thrombocytopenia syndrome virus”). Moreover, all relevant references cited in original articles and reviews were also manually searched to identify additional articles not indexed by these databases.To obtain the valid articles we needed, the following criteria were established: 1) the study either reported the seroprevalence of SFTSV or had sufficient data for calculating the seroprevalence; 2) individuals neither had SFTS infection in the past, being hospitalized for any clinically similar disease, or contact with a person who had SFTS as defined previously [After initial evaluation, two authors independently and carefully screened the articles on title and abstract according to the eligibility criteria. Authors also filled out a standard quality assessment checklist with 11 items concerning the methodological aspects of cross-sectional studies for each study . If the The quality of the included studies was assessed by Agency for Healthcare Research and Quality (AHRQ), which is consisted of 11-item with a yes/no/unclear response option: “No” or “unclear” was scored “0” and the “Yes” would be scored “1”. ArticleAccording to the results of heterogeneity test in different groups, the proper model was adopted to assess a pooled value and 95%CI of seroprevalence of SFTSV antibodies in healthy population.2 statistics [P-values of the Cochran Q test less than 0.1 is considered to be statistically significant, and I2 value more than 75% indicates high heterogeneity. A significant Q statistic  indicate heterogeneity across studies, and then the DerSimonian and Laird method in random effect model result is used for meta-analysis. When the P-value of heterogeneity test is more than 0.1 , the results of Mante-Haenszel method in a fixed-effect model will be adopt. In order to explore the potential source of heterogeneity between studies and the seroprevalences of SFTSV antibodies with different characters such as gender, age, occupation and province, subgroups analysis were also conducted. Additionally, a leave-one-out sensitivity analysis was carried out to assess the impact of each study on the overall pooled estimate.Statistical heterogeneity across different studies was assessed by using the Cochran Q and Iatistics . P-valueP-value of Egger’s test was less than 0.05, statistically significant publication bias might exist.The potential publication bias was assessed by using Begg’s funnel plot . Funnel All statistical analysis were performed using STATA 11.0 .Table 1.The detailed study retrieval steps according to the PRISMA statement was shown in Table 1). Generally, the most prevalence studies were conducted in the center and east of China , the, theTablFig 3. The heterogeneity across the studies was high . The overall pooled seroprevalence estimate for SFTSV in random effect model was 4.3% (95%CI: 3.2%-5.5%).Seroprevalence of SFTSV antibodies varied from 0.23% to 9.17% and were displayed as forest plots in Table 2. Stratification by gender, the pooled prevalence of male was 5.3% (95%CI: 3.3%-7.2%), and female was 5.2% (95%CI: 3.4%-7.0%). Stratification by age, the pooled seroprevalence of less than age of 40 years was 4.1% (95%CI: 2.4%-5.7%), and more than age of 40 years was 4.9% (95%CI: 2.9%-7.0%). Stratification by occupation, the pooled seroprevalence of farmer was 6.1% (95%CI: 3.4%-8.9%) and others (mainly are students) was 3.3% (95%CI: 2.4%-4.2%). Seropositive rates were comparable among sampling years, seroprevalence in the years before 2012 and after 2012 was 3.1% (1.9%-4.4%) and 5.2% (4.6%-5.9%), respectively. Stratification by testing method, seroprevalence in the method of I-ELISA and D-ELISA was 6.2% (5.4%~7.1%) and 1.8% (1.1%~2.5%), respectively. Seroprevalence of SFTSV in people who lived in the same village with the patient and lived in a different village was 6.5% (4.7~8.3) and 4.1% (3.1%~5.1%), respectively. We also found seroprevalence in endemic area was 4.3% (3.1%~5.6%) and in rural village was 4.3% (3.2%~5.4%). Additionally, the pooled seroprevalence was 5.9% (95%CI: 4.7%-7.0%) in Zhejiang province, 3.9% (95%CI: 1.3%-6.4%) in Shandong province, 4.9% (95%CI: 4.1–5.8%) in Anhui province, 6.9% (5.5%~8.2%) in Hubei province and 0.7% (95%CI: 0.2%-1.1%) in Jiangsu province. Forest plots for the meta-analysis in different provinces were shown in Fig 4.To explore the potential source of the high heterogeneity, we did some subgroup analysis by gender, age, occupation and province. The detail results of subgroup analysis were shown in Fig 5). The Egger’s test results demonstrated evidence of publication bias, however, the Begg’s bias test was not significant for studies reporting seroprevalence of SFTSV (data not shown). A leave-one-out analysis which was performed to assess the impact of the individual study on the pooled estimates. Sensitive analysis showed that no single study qualitatively altered the pooled seroprevalence estimates, providing evidence of the stability of the meta-analysis .Potential publication bias of the included articles were evaluated by Begg’s funnel plots and Egger’s test. The shapes of the funnel plot was asymmetry evidently which gives rise to suspected publication bias . It was higher than a recent investigation in Korean population with a seroprevalence of 2.1% based on 1069 serum samples . SensitiPrevious study reported gender ratio of SFTS patients in China was about 1:1.15 , but it varied among different provinces . In thisAge composition of SFTS patients was widely, previous studies had demonstrated that SFTS patients ranged from 1 to 93 years old, but most of patients were aggregated in 40–79 years . GeneralThe infections rates of healthy population varied in different provinces. It reflects that incidences of the latent infection of SFTS are different in endemic regions. In this study, we found SFTSV seroprevalence was high in Henan, Hubei, Zhejiang, Shanxi, Anhui and Shandong provinces, and was relatively low in Jiangsu provinces with seroprevalence of 0.7% (95%CI: 0.2~1.1). However, this result should be interpreted with cautious because of limiting number of study and sample size in some provinces, which may lead to lack of representativeness.Additionally, different ELISA assay such as indirect ELISA (I-ELISA) and double-antigen sandwich ELISA system (D-ELISA) used to detect SFTSV-specific antibodies might also contribute to heterogeneity. Compared to the traditional I-ELISA, D-ELISA was considered having more higher sensitivity to detect total antibodies . HoweverSeroprevalence was also observed between different years, seroprevalence in the year after 2012 was higher than that before 2012, indicating ongoing and intensified circulation of SFTSV in endemic areas of China. Another discrepancy may be attributed to the sampling season, sampling method, previous contacting with animals , or antibody types  detection in different studies.The advantage of this systematic review and meta-analysis is that good quality studies from many centers were pooled for a relatively large sample size, but there are several limitations also should be addressed. Firstly, significant heterogeneity was detected across studies. Although we did some subgroup analysis to identify sources of heterogeneity, many unmeasured factors may have influenced the results. Secondly, funnel plots and Begg’s tests indicated that publication bias might be exist in the present study, which may distort the estimates of seroprevalence, so that the results should be interpreted with cautions.In summary, data from 21 published studies suggested that SFTS is circulated widely in China and could be a cause of considerable health problems in the country. Surveillance efforts on mild or asymptomatic infections among endemic persons are needed. Further subtle-designed studies are still needed to describe the exact epidemiology of the disease at a national level in other parts of China.S1 Dataset(XLS)Click here for additional data file.S1 Table(DOC)Click here for additional data file.S1 Text(DOC)Click here for additional data file.


Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life-long disorder. The best way to tackle IBD is to develop a site targeted drug delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. The aim of the present research was to develop a colon targeted drug delivery for treatment of IBD.Methods: Compression coated drug delivery system was designed and optimised. Core tablet contained drug, croscarmellose sodium (CCS-superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of experiment with 32 factorial design was applied for optimization of compression coated delivery. Chitosan and cellulose acetate phthalate were chosen as independent variables. Swelling index, hardness and % drug release were dependant variables.Results: Core tablet (C5 batch) containing 2.15% CCS showed disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of any significant physical and chemical interaction between drug and polymers. F8 was found to be optimised formulation. F8 contained 35% chitosan and 17.5% cellulose acetate phthalate. It showed drug release of 86.3% ± 6.1%, hardness 6.5 ± 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 ± 8.6% with 7.5 hrs lag time. The results confirmed that the lag time was highly affected by the coating of the polymers as well as the concentration of the superdisintegrant used in core tablet.Conclusion: In-vitro and in-vivo results confirmed a potential colon targeted drug therapy for treatment of IBD. Programmed release depends largely on the build-in program to release the drug rather than depending on interaction with the environment in a certain gastrointestinal segment (site specific target) or with a disease specific target. Examples of release profiles in this category are prolonged or delayed release. Triggered release technologies are the one where release is initiated upon interaction of the delivery system with a site specific target as pH, pressure or microbial flora. Since there is no influence of disease specific factors, this profile is often called site specific release.2 In last few years the development of colon targeted drug delivery has received an increasing interest not only for a better treatment of specific local pathologies but also for the systemic therapy of both conventional and labile molecules. Colon targeted drug delivery system can be used to treat a number of diseases like colitis, Crohn’s disease and colorectal cancer.3 Especially those drugs that degrade in the hostile environment of the stomach and intestine can be protected from degradation and delivered directly to the colon. A large number of anti-asthmatics are delivered through this route.Oral drug delivery is always the preferred form of delivery. The main problem with oral drug delivery is first pass metabolism. This becomes a major problem when drug needs to reach to the lower part of the gastrointestinal tract (GIT). To overcome this problem, targeted drug delivery systems are being developed. These formulations are designed to reach to the specific site to deliver drug.™and osmotic controlled drug delivery system.5 Pulsatile drug delivery systems are gaining a lot of interest now days. These systems are designed according to the circadian rhythm of the body. They deliver the drug at the specific time as per the pathophysiological need of the disease, resulting in improved patient compliance and therapeutic efficacy.7Various approaches have been used in colon targeted drug delivery. Few include pH dependent system, time dependent system, pH and time dependent system and microbiologically triggered system. Newly developed techniques include pressure controlled drug delivery system, CODES 8 pulsatile delivery of theophylline,9 flurbiprofen11 and simvastatin,12 piroxicam,13 compression coating of 5-aminosalicylic acid matrix tablets,14 fenoprofen calcium compressed coated tablets,15 pH dependent delivery system of lercanidipine hydrochloride16 etc.Literature survey has indicated that work has been carried out to target colon with delivery systems as time delayed capsule for diltiazem hydrochloride,20 Literature study showed that dosage forms designed for methylprednisolone include freeze-dried product, immediate release (IR) tablet, immediate release capsule, microparticles in treatment of arthritis and pH sensitive hydrogels.22 Commercially it is available as immediate release (IR) tablet. IR tablet has drawback of fluctuation to attain peak plasma concentration, variability in gastric emptying time, dose dumping, extensive first pass effect and low bioavailability. For colon diseases development of targeted drug delivery will release the drug at the site. This will minimize the side effects of the conventional dosage form and hence will improve the bioavailability and patient compliance. In the present research work methylprednisolone was chosen as a drug to target colon for treatment of IBD and colitis. The aim of the research was to give a site and time controlled drug delivery to colon. To achieve this aim, a compression coated drug delivery system containing chitosan and cellulose acetate phthalate was designed and optimized.Methylprednisolone is a potent anti-inflammatory steroid. It has greater anti-inflammatory potency than prednisolone. Even have fewer tendencies than prednisolone to induce sodium and water retention. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. It belongs to BCS class II drug. Absolute bioavailability of methylprednisolone in normal healthy subjects is high i.e 82% to 89% after oral administration. The mean elimination half-life for methylprednisolone is in range of 1.8 to 5.2 hrs. Drug undergo high hepatic metabolism.Methylprednisolone, chitosan, cellulose acetate phthalate (CAP), avicel, croscarmellose sodium (CCS), dicalcium phosphate (DCP), crospovidone, talc and magnesium stearate were purchased from Analab Fine chemicals, Mumbai.-1 with diffusion reflectance principle and differential scanning calorimeter (DSC-60) at a temperature range of 50-300 °C with rate of 10 °C per minute in nitrogen atmosphere.Drug was characterized for melting point (melting point apparatus - LABIN), FTIR spectra (Varian 640 IR) in the wavelength region of 4000-400 cmmax was reported. Calibration curve in three media were recorded. The analytical method was validated for accuracy, inter-day and intra-day precision, linearity, limit of detection and limit of quantification. Stability of the drug was checked in all three dissolution media for duration of 24 hrs.Solution of the drug in three different media  was scanned by UV-Visible spectrophotometer (UB Varian Carry 100) and λ Drug alone, drug with polymers (chitosan and CAP) were mixed in 1:1 ratio. They were kept in stability chamber  for one month at accelerated stability conditions at 40 ± 2°C / 75 ± 5% RH. At the end of month, samples were analysed for FTIR, DSC and UV spectra.Core tablet were prepared using crospovidone as superdisintegrant in concentration of 1-5%. But those tablets lacked in hardness and had broken easily. Hence, crospovidone was replaced by croscarmellose sodium (CCS). Dicalcium phosphate (DCP) was used as diluent and avicel as binder. Tablets were compressed on Cadmac, Rimeck Minipress (8 station) machine using 6 mm round concave punch. Formulations were prepared with different concentration of CCS (1.5-8.5%) as shown in 2.23 Preliminary trials had shown that 40% chitosan and 20% CAP crossed first two media and enter intact in third media in the dissolution study.Chitosan and CAP were chosen as polymer for outer coating of core tablet. Talc and magnesium stearate were added along with polymers as lubricant. DCP was dded as a diluent in the outer coat. At initial stage individual polymers were tried in different concentration. Individual polymer failed to maintain its integrity till it reaches to third media. Therefore for further study combination of polymer were tried. Chitosan was used in concentration range of 50-10 % and CAP in 10-50 %. To manufacture compression coated tablet direct compression method was used. 50% of coating mixture was first placed in the die cavity. Core tablet was then placed above this mixture. Then remaining quantity of coating mixture was added in die cavity to cover the core tablet. It was compressed on Cadmac, Rimeck Minipress compression machine (9 mm flat and plain punch) to obtain final weight of the tablet 200 mg with hardness 4-7 kg/cm2 factorial design was used as a tool to optimize the formula for coating polymer. In this design 3 levels and 2 factors were used. The factors were concentration of chitosan and concentration of CAP. The coded levels were +1, 0 and -1.25 Factorial batch formulations were prepared as shown in 253Core tablet was evaluated for thickness , hardness (Monsanto hardness tester), friability (Roche friabilator -Veego), uniformity of content (UV- Visible spectrophotometer), weight variation  and disintegration time  at 37 ± 2°C in 900 ml phosphate buffer pH 6.8.In- vitro dissolution study was carried out in 900 ml pH 6.8 phosphate buffer (PBS) at 37 ± 0.5°C in USP dissolution apparatus type II . Rotation speed was maintained at 50 rpm. Samples from this solution were withdrawn at time interval and analysed at λ max.Evaluation of powder flow properties was carried out by measuring angle of repose (fixed funnel method), bulk density and tapped density .Compressibility index and Hausner’s ratio was calculated.Evaluation of coated tablet for tablet thickness, friability, drug content, weight variation and hardness were carried out in similar manner as mention in evaluation of the core tablet.To determine swelling index for tablet, it was immersed in a flask of USP dissolution test apparatus containing 250 ml of medium at 37°C . At specific time interval, the swollen tablets were withdrawn from the medium and weighed. Light blotting with a filter paper was used for removal of excess surface water. Study was performed in three replicates. The swelling behavior of the coated tablet was calculated using Eq.1t -W0] / W0 ×100 Equation 1SI= .This proved purity of drug. FTIR spectra A showed The DSC graph for methylprednisolone A showed UV spectroscopic study showed λ max at 246.13 nm. It was found that the drug follows Beer-Lambert’s law. For accuracy study, percent recovery for 80% was 98.92%, for 100% it was 99.36% and for 120% it was 99.19%. From the data obtained from interday as well as intraday study, the method was found to be precise. The drug solution was found to be linear in the range on 5-25µg/mL. LOD and LOQ were found to be 0.157µg/mL and 0.549µg/mL respectively.-1and 1375 cm-1, 1680-1600 cm-1, 1300-1000 cm-1, 1725-1705 cm-1and broad absorption near 3400-3300 cm-1. Chitosan  in 7-8 hrs.31From be seen a that F6Batches F7 and F8 were studied in simulated media. Batch F8 (35% chitosan and 17.5% CAP) showed maximum drug release of around 97.51 ± 5.6% b.2), weight variation (199.54 ± 1.6 mg), friability (0.34 ± 1.1%), percent drug release (85.43 ± 5.9%) and percent drug content (98.16 ± 1.9%). There was no significant change in the values before and after indicating the stability of the formulation.After 3 months for batch F8, evaluation parameters were as thickness (0.2 ± 0.04 mm), diameter (9 ± 0.5 mm), hardness  obtained was 14. The value indicated that marketed formulation (immediate release) and the designed formulation were not similar in their release pattern. As the design dosage form was to be targeted to colon, this gave indication that the designed can reach to the colon.34The similarity factor  Project Grant for the present research work. The authors are thankful to SKN General Hospital and Medical College, Narhe, Pune, for providing facility to carry In-vivo x-ray imaging (placebo) study. Authors are also thankful to Dr. B. S. Kuchekar, Principal and management of MAEER’s Maharashtra Institute of Pharmacy, Pune for providing all the facilities to carry out the research work.The authors are thankful to Savitribai Phule Pune University, Maharashtra, India for providing financial assistance under Board of College and University Development The study was carried out as per World Medical Association guidelines and Helsinki ethical principle.The authors declare no conflict of interests.