From NAFLD to NASH: Understanding the spectrum of non-alcoholic liver diseases and their consequences.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent chronic liver diseases worldwide in recent decades. Metabolic diseases like excessive blood glucose, central obesity, dyslipidemia, hypertension, and liver function abnormalities cause NAFLD. NAFLD significantly increases the likelihood of liver cancer, heart disease, and mortality, making it a leading cause of liver transplants. Non-alcoholic steatohepatitis (NASH) is a more advanced form of the disease that causes scarring and inflammation of the liver over time and can ultimately result in cirrhosis and hepatocellular carcinoma. In this review, we briefly discuss NAFLD's pathogenic mechanisms, their progression into NASH and afterward to NASH-related cirrhosis. It also covers disease epidemiology, metabolic mechanisms, glucose and lipid metabolism in the liver, macrophage dysfunction, bile acid toxicity, and liver stellate cell stimulation. Additionally, we consider the contribution of intestinal microbiota, genetics, epigenetics, and ecological factors to fibrosis progression and hepatocellular carcinoma risk in NAFLD and NASH patients.

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.

The efficacy of green silica nanoparticles synthesized from rice straw in the management of Callosobruchus maculatus (Col., Bruchidae).

Rice straw, a byproduct of harvesting rice, must be disposed of by farmers in a variety of ways, including burning, which is hazardous for the environment. To address this issue, the straw needs to be utilized and turned into valuable products. One such product is nano-silica (SNPs), which will be synthesized and investigated in our study as a safe alternative to chemical insecticides. Rice straw-derived SNPs were synthesized using the Sol-Gel method. The contact toxicity of SNPs on Callosobruchus maculatus, a major pest of cowpea seeds, has been assessed. The size of synthesized SNPs was determined by transmission electron microscopy to be ~ 4 nm. The SNPs estimated LC50 on C. maculatus adults was 88.170 ppm after 48h exposure. By raising the tested concentration, SNPs treatment increased the mortality%, which reached 100% at 200 ppm exposures. Additionally, SNPs at LC50 treatment decreased adult longevity and the average number of emerged adults. The findings also verified that SNPs had no phytotoxic effects on the cowpea seeds germination. Rather, their application improved seed germination efficacy. This study proposed that rice straw can be utilized to manufacture highly efficient SNPs which can be efficiently employed to preserve stored grains from C. maculatus infestation.

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.

Efficacy of lidocaine local anesthesia on pain perception during amniocentesis: A meta-analysis of randomized controlled trials.

To evaluate the efficacy of lidocaine local analgesia on maternal pain reduction during amniocentesis. Web of Science, Scopus, PubMed, and CENTRAL databases were screened from inception and updated in July 2022. The included randomized controlled trials (RCTs) were evaluated for the risk of bias via the Cochrane tool. The primary outcome was pain perception using the 10 cm visual analog scale, and was summarized as mean difference (MD) with 95% confidence interval (CI) in a random-effects model. Subgroup analysis was performed according to the mode of administration. Meta-analysis was done via Review Manager software. We included five RCTs totaling 1004 women (lidocaine arm n=502 patients and control arm n=502 patients). Overall, there was no significant difference between both arms [MD=-0.21, 95% CI (-0.48, 0.07), p=0.80]. The pooled analysis showed homogeneity (p=0.13, I2=43%). Subgroup analysis according to the mode of administration showed that pain perception did not significantly differ between both arms when lidocaine was employed as injection [n=3 RCTs, MD=-0.26, 95% CI (-0.76, 0.23), p=0.29] or non-injection [n=2 RCTs, MD=-0.18, 95% CI (-0.55, 0.18), p=0.33]. The pooled analyses showed heterogeneity (p=0.05, I2=66%) and homogeneity (p=0.27, I2=19%), respectively. There was no noteworthy change concerning maternal pain perception between the lidocaine and control arms. Most women reported just minimal discomfort during amniocentesis. Counseling should educate patients that the pain they might experience during amniocentesis is comparable to venous blood sampling.

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.

Selenium nanoparticles enhance the efficacy of homologous vaccine against the highly pathogenic avian influenza H5N1 virus in chickens.

A proper vaccination against avian influenza viruses in chicken can significantly reduce the risk of human infection. Egypt has the highest number of recorded humans highly pathogenic avian influenza (HPAI)-H5N1 infections worldwide despite the widespread use of homologous vaccines in poultry. Enhancing H5N1 vaccine efficacy is ultimately required to better control HPAI-H5N1. The aim of this study is to boost chicken immunity by combined with inactivated HPAI-H5N1 with selenium nanoparticles (SeNPs). The chickens groups 1-3 were fed diets supplemented with SeNPs concentrations (0.25, 0.5, and 1 mg/kg) for 3 weeks and then vaccinated (inactivated HPAI-H5N1). while groups 4,5 and 6 were fed with SeNPs free diets and administered with 0.5 ml of the vaccine combined with 0.02, 0.06, and 0.1 mg/dose of SeNPs and then all groups were challenged with homologous virus 3 weeks post-vaccination (WPV). Group 7, 8 were used as control positive and negative respectively. At 4, 5, and 6 WPV, antibody titer was considerably higher in the group fed a meal supplemented with 1 mg SeNPs/kg. In contrast, both methods of SeNPs supplementation significantly increased the Interleukin 2 (IL2), Interleukin 6 (IL6), and Interferon γ (IFNγ) expressions in the blood cells in a dose-dependent manner, with a higher expression observed in the group that was vaccinated with 0.1 mg/dose. After the challenge, all groups that received SeNPs via diet or vaccines dose showed significant reduction in viral shedding and milder inflammation in lung, trachea, spleen, and liver in addition to higher expression of IL2, IL6, and IFNγ, with the highest expression observed in the group that was vaccinated with 0.1 mg/dose compared the plain vaccinated group. The groups of 1 mg SeNPs/kg and combined vaccinated with 0.1 mg/dose showed the best vaccine efficacy. However, the group vaccinated with 0.1 mg/dose showed the earliest reduction in viral shedding. Overall, SeNPs supplementation in the diet and the administration of the vaccine formula with SeNPs could enhance vaccine efficacy and provide better protection against HPAI-H5N1 in chickens by enhancing cellular immunity and reducing inflammation. We recommend using SeNPs as a vaccine combination or feeding with diet to increase the immunity and vaccine efficacy against H5N1.

Intra-operative ultrasound: does it improve the results of percutaneous repair of acute Achilles tendon rupture?

PURPOSE: Percutaneous repair is a good option for acute Achilles tendon rupture. Although it overcomes the complications of open technique, it carries the risk of sural nerve injury and inadequate repair. In this study, we explore if the use of intra-operative ultrasound with percutaneous technique has any advantageous effect on final results of repair. METHODS: This is a prospective randomized study done between May 2014 and December 2020. It included 91 patients with complete acute Achilles tendon rupture distributed in 2 groups with homogenous clinical and demographic data. Group A (n = 47) included those managed by percutaneous repair with assistant of an intra-operative ultrasound. Group B (n = 44) included those done without the assistant of ultrasound. Post-operative evaluation was done clinically by the American Orthopedic Foot and Ankle Society score, calf muscle circumference and single heel rise test and radiologically by Magnetic Resonance Image. RESULTS: Patients of both groups reported continuous improvement of the American Orthopedic Foot and Ankle Society score with time. However, patient of group A recorded better functional outcome score at 3 months postoperatively. We recorded longer operative time in group A than those in group B. Continuous improvement of maximum calf circumference was observed in both groups. Satisfactory healing was noticed to happen faster in patients of group A than those of group B. We recorded two cases of re-rupture and two cases of sural nerve injury in group B with no reported complication in group A. CONCLUSION: The use of an intra-operative ultrasound with percutaneous repair of acute rupture of Achilles tendon can improve the quality of repair as evidenced by quicker satisfactory healing and earlier regain of activity. Also, it can help in proper localization of sural nerve in relation to lateral edge of Achilles tendon. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT04935281.

Efficacy of oxytocics on reducing intraoperative blood loss during abdominal myomectomy: A systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis on the efficacy of oxytocics administration (oxytocin and carbetocin) on reducing intraoperative bleeding during abdominal myomectomy. METHODS: PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar databases were searched from inception until March 2021. Only randomized placebo-controlled trials (RCTs) were considered. The included RCTs were evaluated for risk of bias. The main outcome measures were mean intraoperative blood loss (ml), mean duration of hospital stay (day), mean operation time (min), mean difference of postoperative hemoglobin (g/dl), mean difference of postoperative hematocrit (%), and rate of blood transfusion (%). Pooled outcomes were summarized as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI) in a random-effects model. RESULTS: Seven RCTs met the inclusion criteria (n=758 patients; 329 patients per group). Compared with control group, oxytocin and carbetocin resulted in a significantly lower intraoperative blood loss (MD=-281.08 ml, 95% CI [-400.63, -161.53], p<0.001), hospital stay (MD=-0.21 days, 95% CI [-0.31, -0.10], p<0.001), and need for blood transfusion (RR=0.32, 95% CI [0.22, 0.46], p<0.001). Subgroup analysis revealed that oxytocin, but not carbetocin, correlated with a reduced mean difference of postoperative hemoglobin (MD=0.60 g/dl, 95% CI [0.24 to 0.96], p=0.001), postoperative hematocrit (MD=2.29%, 95% CI [1.06, 3.52], p<0.001), and operation time (MD=-14.66 min, 95% CI [-21.04, -8.25], p<0.001) compared with control group. CONCLUSION: Among women undergoing abdominal myomectomy, administration of oxytocin and carbetocin correlated with several beneficial clinical outcomes, such as reduced intraoperative blood loss, hospital stay, and blood transfusion requirement.

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.

Proximal Femoral Plate, Intramedullary Nail Fixation Versus Hip Arthroplasty for Unstable Intertrochanteric Femoral Fracture in the Elderly: A Meta-analysis.

INTRODUCTION: Multiple operative modalities are available for management of unstable intertrochanteric femoral fractures. This meta-analysis was conducted to find out if there is superiority of surgical fixation by proximal femoral plate or surgical fixation by intramedullary nail over hip arthroplasty for management of unstable intertrochanteric femoral fractures in the elderly. METHODS: A search for relevant studies that published from January 2000 to November 2018 through the electronic literature database of Cochrane library, Medline, Trip Database and Wiley online library. RESULTS: A total of 19 studies including 14 prospective RCTs, and five retrospective studies. This meta-analysis showed that nail group had shorter operative time than plate group (P < 0.0001), and less blood loss than the plate and arthroplasty groups (P < 0.0001), cut-out was higher in nail group than the plate group (P < 0.0001), mortality rate was higher in hip arthroplasty compared to other groups (P < 0.0001), Harris hip score within 6 months of the operation was higher in the arthroplasty group compared with the nail and plate groups, while within 1 year of the operation, nail group had higher Harris hip score than arthroplasty group (P < 0.0001). CONCLUSIONS: This meta-analysis suggested that the intramedullary nail fixation method is a preferred method for management of unstable intertrochanteric femoral fractures in the elderly over hip arthroplasty and proximal femoral plate fixation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-021-00426-1.

Pathogenicity of three genetically distinct and highly pathogenic Egyptian H5N8 avian influenza viruses in chickens.

In late 2016, Egypt encountered multiple cases of the highly pathogenic avian influenza (HPAI) virus of the H5N8 subtype. In a previous study, three distinct genotypes, including A/common-coot/Egypt/CA285/2016 (H5N8) (CA285), A/duck/Egypt/SS19/2017 (H5N8) (SS19), and A/duck/Egypt/F446/2017 (H5N8) (F446), were isolated from wild birds, a backyard, and a commercial farm, respectively, during the first wave of infection. In this current study, we investigated the differences in the pathogenicity, replication and transmissibility of the three genotypes and A/chicken/Egypt/15S75/2015 (H5N1) (S75) was used as the control. The intravenous pathogenicity index was between 2.68 and 2.9. The chicken lethal dose 50 values of F446, SS19 and CA285 were 103.7, 103.7, an 104 with a natural route of infection, respectively. These strains took longer than S75 to cause death when infection was carried out through the natural route (HPAI H5N1). After inoculation with the original concentration of 105 and 106 egg infective dose 50 (EID50), F446 had a higher mortality rate with short mean death times of 4, and 7 days, respectively compared with the other H5N8 viruses. Chickens inoculated with F446 and contacted exposed chickens infected with F446 showed the highest viral titer with remarkable differences in all H5N8 tested swabs at 2-4 days postinfection (dpi) compared to S75 at 2 dpi. This indicates that F446 had a more efficient transmission and spread from contact exposed birds to other birds. All H5N8 viruses were able to replicate systematically in all organs (trachea, brain, lung, and spleen) of the chicken with high viral titer with significantly different and more pathological changes observed in F446 than in other H5N8 viruses at 2 and 4 dpi. Compared with H5N1, we recorded a significantly high viral titer in the samples obtained from the lung, brain and both cloacal and tracheal swabs at 2 and 4 dpi, respectively and in the samples obtained from the spleen at 2 and 4 dpi among the experimental chicken. The comparative pathogenesis study revealed that in comparison with the other HPAI H5N8 viruses, the genotype F446 was more pathogenic, and showed more efficient viral replication and transmissibility in chickens in Egypt. The genotype F446 also showed a high viral titer than HPAI H5N1 and short mean death time at the third day after inoculation with 106 and 105 EID50, which revealed a conservation of certain H5N8 genotypes and a decrease in the incidence of H5N1.

Tibial Tray with a Stem: Does It Have Any Role in Primary Cemented Total Knee Replacement?

Over many decades, total knee replacement (TKR) has become the ideal treatment option for advanced arthritis. Many designs were introduced to increase the stability of the tibial tray, hence the longevity of the prosthesis. This retrospective study was performed on 168 patients who received NexGen cemented primary total knee either with standard tibial tray (group A) or tibial tray with an intramedullary stem (group B) between May 2008 and May 2017. We reviewed all preoperative and postoperative clinical and radiological data retrospectively. In addition, a prospective clinical and radiological reassessment was done. Our aim was to answer the following questions: (1) Is there any difference between both groups in regard to clinical and radiological results? (2) Is there any difference in the revision rate? (3) Is there a role of using stemmed tibial tray in primary TKR? Better results were recorded in obese and severely obese patients having stemmed cemented tibial tray and so for patients with marked and severe preoperative varus angle. Our recommendations are to use cemented tibial tray with a stem in complicated primary surgery without fear of adverse effects on short and intermediate terms of follow-up.

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.

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.

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.

Antioxidant and anti-apoptotic prophylactic effect of silymarin against lead-induced hepatorenal toxicity in rats.

This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues' malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues' architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.

Migratory Wild Birds as a Potential Disseminator of Antimicrobial-Resistant Bacteria around Al-Asfar Lake, Eastern Saudi Arabia.

Migratory wild birds acquire antimicrobial-resistant (AMR) bacteria from contaminated habitats and then act as reservoirs and potential spreaders of resistant elements through migration. However, the role of migratory wild birds as antimicrobial disseminators in the Arabian Peninsula desert, which represents a transit point for birds migrating all over Asia, Africa, and Europe not yet clear. Therefore, the present study objective was to determine antimicrobial-resistant bacteria in samples collected from migratory wild birds around Al-Asfar Lake, located in Al-Ahsa Oasis, Eastern Saudi Arabia, with a particular focus on Escherichia coli virulence and resistance genes. Cloacal swabs were collected from 210 migratory wild birds represent four species around Al-Asfar. E. coli, Staphylococcus, and Salmonella spp. have been recovered from 90 (42.9%), 37 (17.6%), and 5 (2.4%) birds, respectively. Out of them, 19 (14.4%) were a mixed infection. All samples were subjected to AMR phenotypic characterization, and results revealed (14-41%) and (16-54%) of E. coli and Staphylococcus spp. isolates were resistant to penicillins, sulfonamides, aminoglycoside, and tetracycline antibiotics. Multidrug-resistant (MDR) E. coli and Staphylococcus spp. were identified in 13 (14.4%) and 7 (18.9%) isolates, respectively. However, none of the Salmonella isolates were MDR. Of the 90 E. coli isolates, only 9 (10%) and 5 (5.6%) isolates showed the presence of eaeA and stx2 virulence-associated genes, respectively. However, both eaeA and stx2 genes were identified in four (4.4%) isolates. None of the E. coli isolates carried the hlyA and stx1 virulence-associated genes. The E. coli AMR associated genes blaCTX-M, blaTEM, blaSHV, aac(3)-IV, qnrA, and tet(A) were identified in 7 (7.8%), 5 (5.6%), 1 (1.1%), 8 (8.9%), 4 (4.4%), and 6 (6.7%) isolates, respectively. While the mecA gene was not detected in any of the Staphylococcus spp. isolates. Regarding migratory wild bird species, bacterial recovery, mixed infection, MDR, and AMR index were relatively higher in aquatic-associated species. Overall, the results showed that migratory wild birds around Al-Asfar Lake could act as a reservoir for AMR bacteria enabling them to have a potential role in maintaining, developing, and disseminating AMR bacteria. Furthermore, results highlight the importance of considering migratory wild birds when studying the ecology of AMR.

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.

Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials.

Our objective was to assess and rank different pharmacological interventions for relieving endometriosis-related pain. We conducted an online bibliographic search in different databases from their inception until March 2019. We included randomized controlled trials (RCTs) that assessed different medical therapies in the management of endometriosis-related pain. We applied this network meta-analysis (NMA) based on the frequentist approach using statistical package "netmeta" (version 1.0-1) in R software. Our main outcomes were the change in severity of pelvic pain, dysmenorrhea score, non-menstrual pelvic pain score, and dyspareunia score. Overall, 36 RCTs were included in this study (patients no. = 7942). Dienogest (0.94), combined hormonal contraceptives (CHCs) (0.782), and elagolix (0.38) were the highest-ranked interventions for reducing the severity of pelvic pain at three months, while at six months, gonadotropin-releasing hormone (GnRH) analogues (0.75), levonorgestrel-releasing intrauterine system (LNG-IUS) (0.73), and dienogest (0.65) were linked to more reduction in pelvic pain. The ranking p-score showed that GnRH analogues was the highest-ranked treatment for reducing dysmenorrhea at 3 months (1.00), while CHCs were the highest-ranked treatment at 6 months (0.97), followed by GnRH analogues (0.89). GnRH analogues (0.63) and elagolix (0.54) at three months while desogestrel (0.94) and CHCs (0.91) at six months were the highest-ranked treatment to reduce non-menstrual pelvic pain. GnRH analogues and elagolix were the highest-ranked pharmacologic therapies for reducing dyspareunia. In conclusion, CHCs, GnRH analogues, progesterone, and elagolix were the best approaches in reducing the pain of endometriosis.