Emergence of the novel infectious bursal disease virus variant in vaccinated poultry flocks in Egypt.

RESEARCH HIGHLIGHTS: New variant IBDV which emerged in Egypt clustered with Chinese nVarIBDV.nVarIBDV spread subclinically across a wide geographic area.Mutation at 321 represents capsid's most exposed part, a defining feature.Antigenically modified vvIBDV still circulating in Egypt with typical lesions.

Exosomal miR-122, miR-128, miR-200, miR-298, and miR-342 as novel diagnostic biomarkers in NAFL/NASH: Impact of LPS/TLR-4/FoxO3 pathway.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder affecting a quarter of the global residents. Progression of NAFL into nonalcoholic steatohepatitis (NASH) may cause cirrhosis, liver cancer, and failure. Gut microbiota imbalance causes microbial components translocation into the circulation, triggering liver inflammation and NASH-related fibrosis. MicroRNAs (miRNAs) regulate gene expression via repressing target genes. Exosomal miRNAs are diagnostic and prognostic biomarkers for NAFL and NASH liver damage. Our work investigated the role of the gut microbiota in NAFLD pathogenesis via the lipopolysaccharide/toll-like receptor 4/Forkhead box protein O3 (LPS/TLR-4/FoxO3) pathway and certain miRNAs as noninvasive biomarkers for NAFL or its development to NASH. miRNA expression levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 NAFL patients, 50 NASH patients, and 50 normal controls. Plasma LPS, TLR-4, adiponectin, peroxisome proliferator-activated receptor γ (PPAR-γ), and FoxO3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In NAFL and NASH patients, miR-122, miR-128, FoxO3, TLR-4, LPS, and PPAR-γ were upregulated while miR-200, miR-298, miR-342, and adiponectin were downregulated compared with the normal control. The examined miRNAs might distinguish NAFL and NASH patients from the normal control using receiver operating characteristic analysis. Our study is the first to examine these miRNAs in NAFLD. Our findings imply that these are potentially promising biomarkers for noninvasive early NAFL diagnosis and NASH progression. Understanding the LPS/TLR-4/FoxO3 pathway involvement in NAFL/NASH pathogenesis may aid disease management.

COVID-19 data reporting systems in Africa reveal insights for future pandemics.

Globally, countries have used diverse methods to report data during the COVID-19 pandemic. Using international guidelines and principles of emergency management, we compare national data reporting systems in African countries in order to determine lessons for future pandemics. We analyse COVID-19 reporting practices across 54 African countries through 2020. Reporting systems were diverse and included summaries, press releases, situation reports and online dashboards. These systems were communicated via social media accounts and websites belonging to ministries of health and public health. Data variables from the reports included event detection (cases/deaths/recoveries), risk assessment (demographics/co-morbidities) and response (total tests/hospitalisations). Of countries with reporting systems, 36/53 (67.9%) had recurrent situation reports and/or online dashboards which provided more extensive data. All of these systems reported cases, deaths and recoveries. However, few systems contained risk assessment and response data, with only 5/36 (13.9%) reporting patient co-morbidities and 9/36 (25%) including total hospitalisations. Further evaluation of reporting practices in Cameroon, Egypt, Kenya, Senegal and South Africa as examples from different sub-regions revealed differences in reporting healthcare capacity and preparedness data. Improving the standardisation and accessibility of national data reporting systems could augment research and decision-making, as well as increase public awareness and transparency for national governments.

The effect of surgical technique, age, and Trisomy 21 on early outcome of surgical management of complete atrioventricular canal defect.

BACKGROUND: The optimal timing, surgical technique, and the influence of Trisomy 21 on the outcome of surgical repair of Complete Atrioventricular Canal Defect remains uncertain. We reviewed our experience in the repair of CAVC to identify the influence of these factors on operative outcomes. METHODS: A prospective study included 70 patients, who underwent repair of CAVC at our institute between July, 2016 and October, 2019. Primary endpoint was mortality and the secondary endpoint was a degree of left atrioventricular valve regurgitation. RESULTS: No significant difference was noted between patients operated on, at the first 6 months of age versus later, regarding mortality or LAVV regurgitation. Surgical repair by modified single-patch technique showed a significant reduction in bypass time (71.13 ± 13.507 min versus 99.19 ± 27.092 min, p-value = 0.001). Compared to closure of cleft only, posterior annuloplasty used for repair of LAVV resulted in significant reduction in the occurrence of post-operative valve regurgitation during the early period (LAVV 2 + 43 versus 7 %, p-value = 0.03) and at 6 months of follow-up (LAVV 2 + 35.4 versus 0 %, p-value = 0.01), respectively. CONCLUSIONS: Early intervention, in the first 6 months in patients with CAVC by surgical repair gives comparable acceptable results to later repair; Trisomy 21 was not found to be a risk factor for early intervention. Repair of common AV valve by cleft closure with posterior LAVV annuloplasty showed better results with a significant decrease in post-operative LAVV regurgitation and early mortality in comparison to the closure of cleft only.

Treatment of tibial shaft nonunion with a retained nail in morbidly obese patients.

PURPOSE: Morbid obesity is a rising worldwide health problem. Tibial shaft nonunion with retained intramedullary nail (IMN) in the morbidly obese is a challenging orthopaedic problem. Prolonged immobilization carries a significant risk of complications. This study aimed to investigate whether decortication and cancellous bone grafting with the application of a circular external fixator (CEF) over the preexisting IMN can achieve fracture union and avoid serious complications. METHODS: We retrospectively reviewed 27 consecutive morbidly obese patients treated for tibial diaphysis aseptic nonunion after failed IMN. All cases were treated with osteoperiosteal decortication, cancellous bone grafting, and fixation with CEF over the IMN. Peri-operative multidisciplinary patient evaluation included internal medicine, cardiology, chest, vascular surgery, and anesthesia consultations. The union rate, bone results, functional results, and complications were recorded. RESULTS: The mean age of the patients was 37.9 years. The mean BMI was 45.8. Sixteen cases (59.3%) were treated for hypertrophic nonunion, while 11 cases (40.7%) were treated for atrophic nonunion. Seven cases (25.9%) had open initial injury, 14 cases (51.9%) had associated comorbidities, and seven cases (25.9%) were smokers. Twenty-six cases united. The mean time to union was 5.2 months. Bone results and functional results were good to excellent in 96.3% of the cases. We recorded 25 complications in 21 patients. However, most of the complications were minor. CONCLUSION: Decortication and cancellous bone grafting with the application of CEF over the preexisting nail is a safe and reliable treatment method for aseptic tibial shaft nonunion with retained IMN in morbidly obese patients.

Trans-calcaneal retrograde nailing for secondary-displaced traumatic ankle fractures in diabetics with insensate feet: a less-invasive salvage-arthrodesis technique.

PURPOSE: Secondary displacement of traumatic ankle fractures with subsequent soft-tissue breakdown is a troublesome issue after inappropriate conservative treatment among non-compliant diabetic patients with severe peripheral neuropathy. This study was conducted to evaluate the results of a less-invasive arthrodesis procedure as an alternative to osteosynthesis in these complex scenarios. METHODS: A total of 46 diabetics, who underwent fluoroscopy-assisted trans-calcaneal retrograde nailing-based ankle arthrodesis between 2012 and 2018 for salvaging secondary-displaced diabetic ankle fractures in their insensate feet, were evaluated in this retrospective study. All fractures were associated with uninfected mechanical ulcers overlying malleoli, without Charcot changes, after failed conservative cast immobilization. The patients (mean age: 52.52 ± 3.70 years; 18 males; 46 feet) were evaluated radiologically for union and clinically for limb salvage, modified American Orthopedic Ankle and Foot Scale (AOAFS), and the overall subjective patients' satisfaction. RESULTS: The mean follow-up was 29.5 ± 3.1 months. All ulcers have healed with local care only with 100% limb salvage. Four patients experienced minor wound healing problems at posterior heel, and another one developed acute Charcot changes that was successfully managed by offloading and repeat surgery. Forty patients (86.96%) had fully consolidated fusions with a mean time to fusion 15.78 ± 2.58 weeks, while the other six cases had stable fibrous-union. At the final follow-up, the mean modified-AOFAS was 76.85 ± 6.0 from 86 total points. All, but four patients (91.30%) were completely satisfied while the other four patients were partially satisfied. CONCLUSIONS: The presented less-invasive arthrodesis technique is reproducible and effective alternative for salvaging unstable diabetic ankle fractures in the insensate feet when standard surgical procedures would be more risky. LEVEL OF EVIDENCE: IV, retrospective case series.

SPETS: Secure and Privacy-Preserving Energy Trading System in Microgrid.

Recently, the development of distributed renewable energy resources, smart devices, and smart grids empowers the emergence of peer-to-peer energy trading via local energy markets. However, due to security and privacy concerns in energy trading, sensitive information of energy traders could be leaked to an adversary. In addition, malicious users could perform attacks against the energy market, such as collusion, double spending, and repudiation attacks. Moreover, network attacks could be executed by external attackers against energy networks, such as eavesdropping, data spoofing, and tampering attacks. To tackle the abovementioned attacks, we propose a secure and privacy-preserving energy trading system (SPETS). First, a permissioned energy blockchain is presented to perform secure energy transactions between energy sellers and buyers. Second, a discrete-time double auction is proposed for energy allocation and pricing. Third, the concept of reputation scores is adopted to guarantee market reliability and trust. The proposed energy system is implemented using Hyperledger Fabric (HF) where the chaincode is utilized to control the energy market. Theoretical analysis proves that SPETS is resilient to several security attacks. Simulation results demonstrate the increase in sellers' and buyers' welfare by approximately 76.5% and 26%, respectively. The proposed system ensures trustfulness and guarantees efficient energy allocation. The benchmark analysis proves that SPETS consumes few resources in terms of memory and disk usage, CPU, and network utilization.

Chitosan caged liposomes for improving oral bioavailability of rivaroxaban: in vitro and in vivo evaluation.

In this study, chitosan (CS) caged classic liposomes (CLs) and flexible liposomes (FLs) were developed to enhance the oral bioavailability of rivaroxaban (RVX) in the fasted condition. The prepared formulations were subjected to physicochemical characterization included: FTIR, DSC, zeta potential, particle size, polydispersity index, entrapment efficiency, in vitro dissolution, and transmission electron microscope imaging. The selected formulation (RVX-TFL2) composed of PL S100/Tween 80 (85/15% w/w) and coated with CS solution in the strength of (0.2% w/v) had a particle size of 105.67 nm, a zeta potential of +5.67 mV and EE of 96.07%. Compared to RXV suspension, the pharmacokinetic parameters (C max, AUC0-24, and AUC0-∞) of RVX-TFL2 showed no statistically significant difference (P > 0.05) in the fasted and fed test animals. Besides, RVX bioavailability with RVX-TFL2 was improved by 59.66% and 26.97% in the fed and fasted states, respectively, compared to RVX suspension in the fed state. The result highlighted the efficacy of the prepared liquid formulation comprising CS coated liposomes in improving the oral bioavailability of RVX regardless of the fed state. Moreover, the studied liquid formulation could be utilized in developing a liquid dosage form that might be useful as a pediatric formulation of RVX.

Antenatal perineal massage benefits in reducing perineal trauma and postpartum morbidities: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION AND HYPOTHESIS: Most vaginal births are associated with trauma to the perineum. The morbidity associated with perineal trauma can be significant, especially when it leads to third- and fourth-degree perineal tears. We hypothesized that antenatal perineal massage could decrease the incidence of perineal trauma, particularly severe perineal tears and other postpartum complications. METHODS: We searched four different databases from inception until August 2019 for the available trials. We included randomized controlled trials (RCTs) which assessed the effect of antenatal perineal massage (intervention group) versus control group (no antenatal perineal massage) in perineal trauma patients. Data were extracted from eligible studies and meta-analyzed using RevMan software. Primary outcomes were the risk of episiotomies and perineal tears. Secondary outcomes were perineal pain, second stage of labor duration, wound healing, anal incontinence, and Apgar scores at 1 and 5 min. RESULTS: Eleven RCTs with 3467 patients were analyzed. Women who received antenatal perineal massage had significantly lower incidence of episiotomies (RR = 0.79, 95% CI [0.72, 0.87], p < 0.001) and perineal tears (RR = 0.79, 95% CI [0.67, 0.94], p = 0.007), particularly the risk of third- and fourth-degree perineal tears (p = 0.03). Better wound healing and less perineal pain were evident in the antenatal perineal massage group. Antenatal perineal massage reduced the second stage of labor duration (p = 0.005) and anal incontinence (p = 0.003) with significant improvement in Apgar scores at 1 and 5 min (p = 0.01 and p = 0.02). CONCLUSIONS: Antenatal perineal massage is associated with a lower risk of severe perineal trauma and postpartum complications.

The role of levonorgestrel intra-uterine system in the management of adenomyosis: A systematic review and meta-analysis of prospective studies.

INTRODUCTION: The levonorgestrel intrauterine system (LNG-IUS) is a long-acting hormone-releasing uterine device that has many non-contraceptive benefits. The study aims to assess the safety and efficacy of LNG-IUS in the management of adenomyosis. MATERIAL AND METHODS: We searched the following bibliographic databases: MEDLINE via PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Google Scholar for the relevant studies which used LNG-IUS in management of patients with clinically or ultrasonographic diagnosed adenomyosis.The main outcome measures are pain score at the end of follow-up, bleeding, symptomatic relief, uterine volume (mL), endometrial thickness (mm) and/or hemoglobin level. RESULTS: Ten prospective studies (patients n = 551) were included. The overall effect estimates showed that the LNG-IUS led to significant reductions in pain score after 12 months (standardized mean difference [SMD[ -3.87, 95% confidence interval [CI] -5.51 to -2.23, P < .001), 24 months (SMD -5.56, 95% CI -9.80 to -1.32, P = .01) and 36 months of insertion (SMD -3.81, 95% CI -4.27 to -3.36, P < .001). Similarly, the Pictorial Blood Assessment Chart (PBAC) showed significant reduction up to 36 months after LNG-IUS insertion (SMD -2.32, 95% CI -2.91 to -1.73, P < .001). The LNG-IUS led to significant reductions in the uterine volume 12 months (SMD -.60, 95% CI -0.88 to -.31, P < .001) and 36 months after insertion (SMD -0.42, 95% CI -0.69 to -0.14, P = .003). CONCLUSIONS: LNG-IUS is a promising and effective option for the management of adenomyosis. Its use effectively reduced the severity of symptoms, uterine volume and endometrial thickness, and improved laboratory outcomes.

Vaginal Dinoprostone in Reducing Pain Perception During Diagnostic Office Hysteroscopy in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY OBJECTIVE: To evaluate the efficacy of vaginal dinoprostone in reducing pain perception during diagnostic office hysteroscopy (OH) in postmenopausal women. DESIGN: Randomized, double-blind controlled trial. SETTING: Tertiary university hospital. PARTICIPANTS: Postmenopausal patients scheduled for OH. INTERVENTIONS: Eligible participants were randomized in a 1:1 ratio to the dinoprostone and placebo groups. The severity of pain was assessed with a visual analog scale (VAS) ranging from 0, no pain to 10, worst pain during OH and 30 minutes after OH. MEASUREMENTS AND MAIN RESULTS: The difference in the intensity of pain using the VAS score during the procedure. One hundred women (50 in each arm) were included in the study. The mean VAS score during OH was significantly lower in the dinoprostone group compared with the placebo group (3.9 ± 0.8 vs 5.6 ± 0.7; p <.001). The passage of the hysteroscope through the cervical canal was easier in the dinoprostone group (62.4 ± 9.5 vs 42.8 ± 10.8; p <.001). The 2 groups were comparable in terms of the duration of the procedure (p = .91) and the rate of adverse effects. CONCLUSION: Vaginal dinoprostone is effective in relieving pain during diagnostic OH in postmenopausal women with few adverse effects.

Evaluation and ranking of different interventions for pain relief during outpatient hysteroscopy: A systematic review and network meta-analysis.

AIM: To identify the highest-ranked pharmacological and nonpharmacological interventions for pain relief during outpatient hysteroscopy. METHODS: We conducted an online bibliographic search in different databases from inception till July 2019. We included randomized controlled trials assessing effect of pharmacological and nonpharmacological interventions on pain relief during outpatient hysteroscopy. Our main outcomes were pain scores at different endpoints of the procedure. We applied this network meta-analysis based on the frequentist approach using statistical package 'netmeta' (version 1.0-1) in R. RESULTS: The review included 39 randomized controlled trials (Women n = 3964). Misoprostol plus intracervical block anesthesia (mean difference [MD] = -3.32, 95% confidence interval [CI] [-6.06, -0.59]), misoprostol (MD = -1.92, 95% CI [-3.04, -0.81]) and IV analgesia (MD = -2.01, 95% CI [-3.27, -0.25]) were effective in reducing pain during the procedure compared to placebo. Ranking probability showed that misoprostol plus intracervical block anesthesia was the highest ranked pharmacological treatment for pain relief during the procedure (P score = 0.92) followed by misoprostol alone (P score = 0.78), and IV analgesia (P score = 0.76). Regarding nonpharmacological treatments, transcutaneous electrical nerve stimulation (TENS) showed a significant pain reduction compared to placebo (MD = -1.80, 95% CI [-3.31, -0.29]). TENS ranked as the best nonpharmacological treatment (P score = 0.80) followed by CO2 distention (P score = 0.65) and bladder distention (P score = 0.60). CONCLUSION: Combination of misoprostol plus local anesthesia appears to be the most effective pharmacological approach for pain reduction during and after outpatient hysteroscopy. Nonpharmacological approaches as TENS and bladder distention showed considerable efficacy but should be further investigated.

Benefits of vaginal dinoprostone administration prior to levonorgestrel-releasing intrauterine system insertion in women delivered only by elective cesarean section: a randomized double-blinded clinical trial.

PURPOSE: This study aimed at investigating the efficacy and safety of dinoprostone 3 mg vaginally prior to levonorgestrel-releasing intrauterine system (LNG-IUS) insertion in women undergoing elective cesarean delivery (CD). METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled trial at family planning clinic of Cairo University hospitals from August 2019 to January 2020. We included 200 women aged ≥ 18 years who previously delivered by elective CD willing to receive LNG-IUS. Women were randomly assigned with a 1:1 allocation ratio to receive 3 mg vaginal dinoprostone or placebo tablets two hours before LNG-IUS insertion. Our main outcomes were patient-reported pain during insertion and 30 min post-procedure, ease of insertion, satisfaction, duration of insertion, and different side effects. RESULTS: Patient-perceived pain during LNG-IUS insertion was significantly reduced in dinoprostone compared to placebo (4.1 ± 1.7 vs 6.4 ± 1.3; p < 0.001). Dinoprostone reduced pain scores 30 min post-procedure compared to placebo, but the difference was not statistically significant (3.5 ± 1.1 vs 3.7 ± 1.6; p = 0.25). Satisfaction score was higher in dinoprostone compared to placebo (7.9 ± 1.0 vs 5.9 ± 0.8; p < 0.001). The insertion was significantly easier and shorter in dinoprostone than placebo (3.9 ± 1.1 vs 5.9 ± 1.1; p < 0.001) and (5.6 ± 0.9 vs 7.2 ± 0.8; p < 0.001), respectively. Adverse events were not significantly different between both groups. CONCLUSION: Dinoprostone administration 2 h before LNG-IUS insertion in women delivered by elective CD effectively reduced pain during insertion and 30 min post-procedure. Women received dinoprostone had easier and shorter insertion and were more satisfied with tolerable side effects.

Role of Oral Tramadol 50 mg in Reducing Pain During Colposcopy-Directed Cervical Biopsy: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to assess safety and efficacy of 50-mg tramadol in reducing patient-perceived pain during colposcopy. MATERIAL AND METHODS: We conducted a randomized double-blind placebo-controlled trial in the colposcopy unit of a tertiary referral hospital, Cairo, Egypt, from April 2018 to October 2018. Our primary outcome was pain during colposcopy-guided ectocervical punch biopsy. Our secondary outcomes were pain during speculum insertion, acetic acid application, Lugol iodine application, endocervical curettage (ECC), endocervical brushing, 10-minute postprocedure, and additional analgesia requirement. Pain was assessed using 10-cm visual analog scale. RESULTS: One hundred fifty women were randomized into 2 groups: tramadol group (n = 75) received oral 50-mg tramadol tablets, and control group (n = 75) received placebo tablets. Both groups showed no significant difference in anticipated pain score (p = .56), pain scores during speculum insertion (p = .70), application of acetic acid (p = .40), and Lugol iodine (p = .79). However, the mean pain scores were significantly lower in tramadol group compared with placebo at ectocervical biopsy (p = .001), ECC (p = .001), endocervical brushing (p = .001), and 10 minutes after colposcopy (p = .001). Need for additional analgesia was significantly lower in tramadol group (p = .03). CONCLUSIONS: Oral tramadol 50 mg significantly reduces pain perception during colposcopy-guided ectocervical biopsy, ECC, endocervical brushing, and 10 minutes after colposcopy with tolerable adverse effects.

Mucoadhesive thermoreversible formulation of metoclopramide for rectal administration: a promising strategy for potential management of chemotherapy-induced nausea and vomiting.

The study aimed to investigate the feasibility of incorporation of metoclopramide hydrochloride (MCP HCl) in mucoadhesive thermoreversible liquid suppository (MCP HCl-LS) to bypass the first-pass metabolism and maximize its efficacy to be a promising substitute for parenteral therapy. MCP HCl-LS was formulated using Pluronic (PF127/PF68) and hydroxypropylmethylcellulose (HPMC) and in vitro evaluated through their gelation temperature, gel strength (GS), mucoadhesive force, and in vitro release studies. Also, the MCP HCl-LS was evaluated for its rheological behavior and examined for rectal mucosal integrity after administration. The results revealed that the MCP HCl-LS; composed of PF127/PF68/HPMC (20/7/0.5% w/w) was in the liquid state at room temperature, experienced gelation at 30.23 °C, with suitable GS of 28.66 s and rectal retention force of 43.03 × 102 dyne/cm2. The pharmacokinetic data showed that the MCP HCl-LS exhibited a significant increase (p < 0.05) in AUC0-480 (219.688 vs 172.333 ng.h.mL-1 of the marketed) and 1.3-fold increase in relative bioavailability compared to Primperan® suppository, indicating that LS formula bypassed the first-pass metabolism. Moreover, MCP HCl-LS did not cause any morphological harm to the rectal tissues suggested that the developed formulation was safe and could be a potentially useful alternative drug carrier for rectal delivery of MCP HCl in patients experiencing chemotherapy-induced nausea and vomiting.

In Vitro Release of 5-Fluorouracil and Methotrexate from Different Thermosensitive Chitosan Hydrogel Systems.

5-Fluorouracil is a member of cytotoxic drugs with poor selectivity to cancer cells. Currently, systemic administration of this anti-cancer drug (oral or injection) exposes normal tissues to the drug-induced toxicity. Nowadays, attention has been greatly directed towards in situ gel-forming systems that can be injected into the affected tissues in its sol form with a minimally invasive technique. More specifically, chitosan hydrogel systems were in focus due to their antibacterial effect as well as their biodegradable, biocompatible, and mucoadhesive properties. In the present work, 5-fluorouracil was loaded on various thermosensitive chitosan hydrogel systems cross linked with different linking agents like ß-glycerophosphate, pluronic F127, and hydroxyapatite. Also, methotrexate was added to 5-fluorouracil in order to gain its previously reported synergistic effects. Firstly, a compatibility study was performed using UV-spectrophotometric, infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) techniques to exclude the possibility of any physical or chemical interactions between the selected drugs and excipients. The prepared hydrogel systems were characterized for their physicochemical properties including organoleptic, pH, syringeability and injectability, viscosity, and gelation temperature (Tgel) by various analysis techniques. Moreover, the in vitro release behavior of 5-fluorouracil and methotrexate was determined with a modified analytical method. The results indicated that chitosan hydrogel system cross-linked with a combination of ß- glycerophosphate, and 10 % pluronicF127 (F4) showed the most suitable physicochemical properties and release profile. Accordingly, this formula can be considered as a missionary system for localized sustained delivery of cytotoxic drugs.

Developed simvastatin chitosan nanoparticles co-crosslinked with tripolyphosphate and chondroitin sulfate for ASGPR-mediated targeted HCC delivery with enhanced oral bioavailability.

Simvastatin (SV) repurposing has emerged as an alternative approach for the treatment of cancer. In this study, SV chitosan nanoparticles co-crosslinked with tripolyphosphate and chondroitin sulfate (SVCSChSNPs) were developed in order to maximize SV therapeutic efficiency. The hepatic targeting was realized using N-acetylgalactosamine (GalNAc) residues of ChS, which can be identified by the ASGPR receptors specifically expressed in hepatocytes. SV was repurposed as an anticancer agent against hepatocellular carcinoma (HCC). NPs were fabricated by the ionic gelation method, and the formulation variables (CS concentration, CS:ChS ratio, and CS solution pH) were optimized using a three-factor, three-level Box-Behnken design. The optimized NPs were investigated for particle size, size distribution, zeta potential, morphology, in vitro cytotoxicity, apoptotic effects against human hepatocellular carcinoma HepG2 cells, and detection of intracellular localization. The NPs were further evaluated for in vitro release behavior of SV and pharmacokinetics using Wister albino rats. Transmission electron microscopy (TEM) imaging showed a spherical shape with regular surface NPs of < 100 nm diameter. In vitro cytotoxicity testing showed that the SVCSChSNPs exhibited greater inhibition of proliferation in HepG2 cells and high cellular uptake through ASGPR-mediated endocytosis. The in vitro dissolution profile was 2.1-fold greater than that of pure SV suspension. Furthermore, in vivo oral pharmacokinetics revealed that the obtained NPs enhanced the bioavailability of SV by up to 2- and 1.6-fold for SV and SVA, respectively, compared to the pure SV suspension. These findings demonstrated that hepatic-targeted CSChSNPs delivering SV could potentially serve as a promising platform for HCC and other liver-related diseases.

Effect of embryo selection based morphokinetics on IVF/ICSI outcomes: evidence from a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Debate exists for the optimal tool to select embryos for transfer in assisted reproductive technology (ART). Time-lapse monitoring (TLM) is a noninvasive tool suggested where each embryo can be captured every 5-20 min. Given the inconsistency in the existing studies, we conducted this meta-analysis of RCTs to summarize the evidence available concerning the predictive ability of morphokinetics compared with the routine assessment of embryo development in ART. METHODS: The primary databases MEDLINE, EMBASE, Cochrane, NHS, WHO, and Other Non-Indexed Citations were consulted for RCTs that have been published until November 2018, with no language restriction. RESULTS AND CONCLUSION: Our review includes 6 RCTs (n = 2057 patients). The data showed an improvement (~ 9%) in live birth TLM (OR 1.43; 95% CI 1.10-1.85; P = 0.007), with low-quality evidence. There was no evidence of a significant difference between both groups concerning ongoing pregnancy, clinical pregnancy and implantation rates. The data further showed that morphokinetics is associated with decreased early pregnancy loss rate. These estimates must be interpreted with caution owing to the statistical and clinical heterogeneities and the consequent difficulty in drawing any meaningful conclusion.

In vitro and in vivo characterization of fast dissolving tablets containing gliquidone-pluronic solid dispersion.

The main objective of this study is to increase the dissolution rate of gliquidone using its solid dispersions with pluronic F-68 by solvent evaporation method. The solid dispersion of the drug with pluronic at ratio 1:3 showed the highest dissolution efficiency (50.7%) after 10 min, so it was incorporated in fast dissolving tablets. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to study the interaction between gliquidone and pluronic in the solid state. The FTIR spectroscopic studies revealed no chemical interaction between the drug and pluronic, while the DSC results indicated the amorphous state of gliquidone in the solid dispersion. A 32 full factorial design was used to study the effect of varying concentrations of croscarmellose and sodium starch glycolate as superdisintegrants on the disintegration time and the percentage released after 10 min. The optimized formula showed a disintegration time of 39.1 ± 1.2 s and 85.43% ± 5.16% released after 10 min and was selected for the in-vivo studies in rabbits. The selected formula showed significant enhancement of gliquidone bioavailability, about 1.8 times compared with the commercial Glurenor tablets.

Tolmetin sodium-loaded thermosensitive mucoadhesive liquid suppositories for rectal delivery; strategy to overcome oral delivery drawbacks.

Tolmetin sodium (TS) is a nonsteroidal anti-inflammatory drug (NSAID) indicated for treatment of musculoskeletal issues. As other NSAID, TS displays a marked side effects on the gastro-intestinal (GI) tract after oral administration. Traditional solid suppositories can cause pain and discomfort for patients, may reach the end of the colon; consequently, the drug can undergo the first-pass effect. TS liquid suppository (TS-LS) was developed to enhance patient compliance and rectal mucosal safety in high-risk patients receiving highly NSAID therapy. This work was conducted to optimize and evaluate Poloxamer P407/P188-based thermoresponsive TS-LS by using mucoadhesive polymers such as methylcellulose (MC). TS-LS was prepared by cold method and characterized their in vitro physicochemical properties as gelation temperature (GT), gel strength, bioadhesive properties, and in vitro release. The safety of the prepared suppository on rectum, stomach, and liver was evaluated histologically. Pharmacokinetic analyses were performed to compare rectal TS-LS to orally Rhumtol® capsules. The results showed that the optimized TS-LS; composed of P407/P188/MC (21/9/0.5% w/w) displayed gelation at rectum temperature ∼32.90 °C, gel strength of 21.35 s and rectal retention force at the administration site of 24.25 × 102 dyne/cm2. Moreover, TS-LS did not cause any morphological damage to the rectal tissues. Pharmacokinetic parameters of optimized TS-LS formulation revealed 4.6 fold increase in bioavailability as compared to Rhumtol® capsules. Taken together, the results demonstrated that liquid suppository is a potential and physically safe rectal delivery carrier for improvement rectal bioavailability and in vivo safety of TS.