Famotidine HCl has low bioavailability (40-45%) due to its narrow absorption window and low solubility in intestinal pH. Lipids were utilized in the formulation of novel gastroretentive dosage forms to increase the availability of famotidine HCl at its absorption site. Novel non-swellable gastroretentive lipid disks (D) and swellable compression coated tablets with a lipid core (T) were prepared. Formulae were characterized by friability testing, in-vitro buoyancy, in-vitro drug release and scanning electron microscopy (SEM). Factorial designs of 22× 31 and 32 were planned for the optimization of disks and tablets, respectively, using Design-Expert® software. X-ray imaging was used for the in-vivo visualization of the selected formula in human gastrointestinal tract (GIT). Moreover, a bioavailability study was performed in healthy human volunteers using the optimized disk formula (D10). Results showed that formulae D10 (containing stearyl alcohol and polyethylene glycol in a ratio of 9:1 w/w) and T7 (containing polyethylene oxide only) had highest desirability values (0.684 and 0.842, respectively). Lipids achieved instantaneous floating and sustained the release of famotidine HCl over a prolonged period of time with significant bioavailability enhancement.

Among the most challenging problems in the field of damage detection and condition assessment in large structures is the ability to reliably detect, locate, and quantify relatively small changes in their dynamic response, based on vibration signal analysis. In this study, a substructuring approach, which uses a nonparametric identification method, was applied to simulated damage data from a high-fidelity and validated three-dimensional (3D) finite element model of a 52-story high-rise office building, located in downtown Los Angeles. Results of this study indicate that the approach not only yields identification results that match well-known global (linear) system identification methods, such as NExT/ERA, but it also provides additional benefits that global identification approaches suffer from. These benefits include: (1) enhanced sensitivity to small structural parameter changes, (2) ability to provide location information about the region in the large structure in which damage has occurred, and (3) not assuming that the underlying structure is linear. Thus, the approach is capable of detecting, quantifying, and classifying changes, when they do occur, if the actual building is subjected to strong earthquake ground motion.

INTRODUCTION: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC.

METHODS: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment.

RESULTS: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03).

CONCLUSIONS: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

INTRODUCTION: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC.

METHODS: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment.

RESULTS: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03).

CONCLUSIONS: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

INTRODUCTION: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC.

METHODS: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment.

RESULTS: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03).

CONCLUSIONS: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn's disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn't change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.

The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile. Two novel series of 4,5-diarylthiazole and diarylimidazole were designed, synthesized in analogy to selective COX-1 inhibitors (mofezolac and FR122047) which lack gastric damaging effects. The new compounds were evaluated in vitro for their COXs inhibitory activity and in vivo for their anti-inflammatory and analgesic potentials. Four compounds; diphenylthiazole glycine derivatives (15a, 15b) and diphenylimidazolo acetic acid derivatives (19a, 19b), which possess carboxylic acid group exhibited significant activity and selectivity against COX-1 over COX-2. Of these compounds, (4,5-bis(4-methoxyphenyl)thiazol-2-yl)glycine 15b was the most potent compound against COX-1 with an inhibitory half maximal concentration (IC50) of 0.32μM and a selectivity index (COX-2 IC50/COX-1 IC50) of 28.84. Furthermore, an ulcerogenicity study was performed where the tested compounds demonstrated a significant gastric tolerance. Interestingly, the most selective COX-1 inhibitor showed higher analgesic activity in vivo as expected compared to their moderate anti-inflammatory activity. This study underscores the need for further design and development of novel analgesic agents with low tendency to cause gastric damage based on improving their COX-1 affinity and selectivity profile.