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Abstract Background The two main input indicators needed to assess the success of assisted reproductive technology (ART) strategies are cost-effectiveness and clinical outcome. Therefore, we focused in our study on the direct cost associated with the Progesterone Prime Ovulation Induction Protocol (P-P-OP protocol) compared to other protocols, and the clinical outcomes of this strategy were measured in their effect on implantation and pregnancy rates. Methods A pilot single-armed study was conducted on 47 infertile women coming for an ICSI cycle. Progesterone priming was started with 10 mg dydrogesterone along with HMG 150–300 IU from the second day of the menstrual cycle and was maintained until the day of ovulation trigger. The primary outcome was the cost per cycle, while the secondary outcome was the clinical pregnancy rate. The cost per cycle, including the cryopreservation cost, was calculated for economic evaluation. Results Per each cycle, the number of retrieved oocytes was 14.87 ± 8.09, the number of mature oocytes was 9.81 ± 4.67, the number of total embryos was 8.74 ± 4.28 (grade A = 67.40%, grade B = 11.92%, grade C = 20.68%), and the number of transferred embryos was 2.43 ± 0.68. The clinical pregnancy rate in our study was 42.5%. Economically, the cost of the P-P-OP protocol for each patient was only 56 USD. Conclusion The P-P-OP protocol is a simplified approach suitable for freeze-only strategies, offering the benefits of positive results, fewer injections, lower costs, and increased patient convenience.

Burn injuries, which significantly affect global public health, require effective treatment strategies tailored to varying severity. Fungi are considered a sustainable, easily propagated source for lead therapeutic discovery. In this study, we explored the burn wound healing potential of Aspergillus terreus through a combination of in vitro, in vivo, metabolite profiling, and in silico analysis. The in vitro scratch assays performed with human skin fibroblast cells showed promising wound healing activity. Furthermore, the burn-induced rats model showed a marked improvement in cutaneous wound healing, evidenced by an accelerated rate of wound closure and better skin regeneration after A. terreus extract treatment at 14 days. The results of this study demonstrated significant enhancements in wound closure and tissue regeneration in the treated rat model, surpassing the outcomes of standard treatments. This controlled healing process, evidenced by superior collagen synthesis and angiogenesis and confirmed by histopathological studies, suggests that A. terreus has potential beyond the traditionally studied fungal metabolites. The metabolite profiling of 27 bioactive compounds was further investigated by docking analysis for the potential inhibition of the NF-κB pathway, which has an important function in inflammation and wound repair. The compounds eurobenzophenone A (7), aspernolide D (16), asperphenalenone A (23), aspergilate D (15), kodaistatin A (18), and versicolactone A (14) showed the highest binding affinity to the target protein with a pose score of −16.86, −14.65, −12.65, −12.45, −12.19, and −12.08 kcal/mol, respectively. Drug-likeness properties were also conducted. The findings suggest the potential wound healing properties of A. terreus as a source for lead therapeutic candidate discovery.

ABSTRACT The primary challenge posed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19-related mortality, often exacerbated by additional medical complications, such as COVID-19-associated kidney injuries (CAKIs). Up to half of COVID-19 patients experience kidney complications, with those facing acute respiratory failure and kidney injury having the worst overall prognosis. Despite the significant impact of CAKI on COVID-19-related mortality and its enduring effects in long COVID, the underlying causes and molecular mechanisms of CAKI remain elusive. In this study, we identified a functional relationship between the expression of the SARS-CoV-2 ORF3a protein and inflammation-driven apoptotic death of renal tubular epithelial cells in patients with CAKI. We demonstrate in vitro that ORF3a independently induces renal cell-specific apoptotic cell death, as evidenced by the elevation of kidney injury molecule-1 (KIM-1) and the activation of NF-kB-mediated proinflammatory cytokine (TNFα and IL-6) production. By examining kidney tissues of SARS-CoV-2-infected K18-ACE2 transgenic mice, we observed a similar correlation between ORF3a-induced cytopathic changes and kidney injury. This correlation was further validated through reconstitution of the ORF3a effects via direct adenoviral injection into mouse kidneys. Through medicinal analysis, we identified a natural compound, glycyrrhizin (GL4419), which not only blocks viral replication in renal cells, but also mitigates ORF3a-induced renal cell death by inhibiting activation of a high mobility group box 1 (HMGB1) protein, leading to a reduction of KIM-1. Moreover, ORF3a interacts with HMGB1. Overproduction or downregulation of hmgb1 expression results in correlative changes in renal cellular KIM-1 response and respective cytokine production, implicating a crucial role of HMGB1 in ORF3a-inflicted kidney injuries. Our data suggest a direct functional link between ORF3a and kidney injury, highlighting ORF3a as a unique therapeutic target contributing to CAKI.IMPORTANCEThe major challenge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the pandemic is COVID-19-related mortality, which has tragically claimed millions of lives. COVID-19-associated morbidity and mortality are often exacerbated by pre-existing medical conditions, such as chronic kidney diseases (CKDs), or the development of acute kidney injury (AKI) due to COVID-19, collectively known as COVID-19-associated kidney injuries (CAKIs). Patients who experience acute respiratory failure with CAKI have the poorest clinical outcomes, including increased mortality. Despite these alarming clinical findings, there is a critical gap in our understanding of the underlying causes of CAKI. Our study establishes a direct correlation between the expression of the SARS-CoV-2 viral ORF3a protein and kidney injury induced by ORF3a linking to CAKI. This functional relationship was initially observed in our clinical studies of COVID-19 patients with AKI and was further validated through animal and in vitro cellular studies, either by expressing ORF3a alone or in the context of viral infection. By elucidating this functional relationship and its underlying mechanistic pathways, our research deepens the understanding of COVID-19-associated kidney diseases and presents potential therapeutic avenues to address the healthcare challenges faced by individuals with underlying conditions.

The energy sector is a main driver of African growth, particularly in regions with geopolitical conflicts like Sudan and South Sudan. The oil and gas industry notably influences these regions' economy, politics, humanitarian situation, and social stability. This study seeks to investigate how the Khartoum War affected the energy sector of both Sudan and South Sudan, particularly looking at the disruptions caused by recent conflicts and their impact on oil production, economic stability, and environmental conditions. The study employs a multi-disciplinary approach, utilising different sources such as regional legal agreements, government reports, academic articles, and press releases from international organisations. The key methodology includes qualitative analysis of several documents and quantitative assessment of production data and economic reports. The study's key findings show a significant decline in oil production and transportation due to the shutdown of key oilfields and pipelines, intensifying economic and humanitarian crises. Additionally, the damage to oil infrastructure has presented serious environmental risks, highlighting the delicate balance between resource management and regional stability. In conclusion, the study's findings underscore the intense impact of the Khartoum War on the energy sector of Sudan and South Sudan, and the urgent need for policy recommendations to mitigate these effects and foster sustainable development.

Abstract Background Pediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous. Methods After informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks. Results The study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042). Conclusion This study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA. Trial registration number Registry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered

Abstract Background Helicobacter pylori (H. pylori) is a well-known bacteria that is recognized as the most prevalent infection in humans and is present in the majority of people in the world. Aim To investigate the presence of an extragastric reservoir of Helicobacter pylori in tonsillectomy specimens to ascertain whether it is an etiologic factor in the development of chronic tonsillitis. Subjects and methods The study included 100 patients of both sexes with chronic tonsillitis who visited the ENT (ear, nose, and throat) outpatient department and tested positive for H. pylori antigen in stool and tonsillectomy materials. Giemsa stain was used. The population was patients with chronic tonsillitis who had been diagnosed based on physical examination and history-taking at the (Oto-Rhino-Laryngology) outpatient clinic. Results It is shown that patients with positive H. pylori had considerably more acute tonsillitis attacks per year than those with negative H. pylori. Examining the patients with Giemsa modification staining revealed 40% of them to be positive. Conclusion H. pylori was found in the tonsil tissue of 40% of the patients with chronic tonsillitis using the Giemsa modification staining method, suggesting that H. pylori may be contributing etiologic factors in the development of chronic tonsillitis.

This study is aimed to identify, analyze and evaluate strategies for transferring documents in the National Archives House in Cairo and a number of national archives in some Arab and foreign countries. The study used the descriptive and analytical method to describe the current situation and getting strategies that can be discussed by the National Archives. The study ended. Pointing out that these archives lack an integrated policy for transferring documents, with a proposal for a strategy for transferring them to the National Archives, in addition to a number of proposed recommendations that were reviewed in the research,

Abstract Background Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE). Results The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value

Background: Substance misuse among teenagers has increased dramatically in recent years, and drug abuse amongst younger people has also steadily increased, with more youngsters beginning to use substances at a young age.The Aim of the work: The purpose of this study is to provide insight into the prevalence of teenage substance misuse and its trends in the toxicology and psychiatry departments of Al-Azhar University Hospital [New Damietta] between December 2020 and December 2022.Methods: In order to determine the prevalence of substance usage, a total of 140 abused adolescents were involved, along with 30 healthy participants serving as a control group. Within sixty minutes after arriving at the hospital's emergency department, blood specimens were taken in tubes containing sodium fluoride [NaF]. After that, it was maintained at 4–8 °C for standard lab analyses. High-performance liquid chromatography [HPLC] was used as an additional confirmation, and radioimmunoassay strips were used as an initial test. Every health record was gathered for both the cases and the control subjects. This was conducted beside the clinical assessment, which focused on the Glasgow Coma Scale [GCS] and neurological evaluation.Results: Tramadol was the most often abused medication among adolescents, closely followed by cannabis. Tramadol and cannabis were the most often abused medications in the control group, then combined use and anti-psychotic medications, antihistamines, benzodiazepines and cough suppressants, amphetamine, and antidepressants. When comparing the study group to the controls, there was a notable variation in the way that tramadol, cannabis, cough suppressants, and pharmacological combinations were administered.Conclusion: The most commonly misused drug among teenagers is tramadol, which is followed by cannabis, combined use and anti-psychotic medications, benzodiazepines, antihistamines, amphetamine, cough suppressants, and anti-depressants, respectively.

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher’s exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann–Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM’s role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

Abstract Presently, Gulf Cooperation Council countries are lagging in the generation of real-world data and use of real-world evidence for patient-centered care compared with the global average. In a collaborative effort, experts from multiple domains of the healthcare environment from the Gulf Cooperation Council countries came together to present their views and recommended key action points for the generation of robust real-world data and leveraging real-world evidence in the countries. The opinions of the experts are presented, along with existing barriers to the effective generation of real-world evidence in the countries. The Gulf Cooperation Council countries are undergoing transformative changes paving the way for improved healthcare measures; however, the challenges in generating reliable, robust, accessible, and secure real-world evidence are persistent. Hence, ongoing public–private engagements, as well as collaborations between regulators, policymakers, healthcare professionals, insurance and pharmaceutical companies, and patients, are warranted. A few notable examples of real-world evidence studies highlighting the benefits of real-world evidence for gaining valuable insights into patient-centric decision making are also discussed. The actionable steps identified for successful real-world evidence generation would provide long-term, real-world evidence-based patient-centric benefits for the countries.

For meeting the demands of safety, traffic management, and high mobility, vehicular adhoc network (VANET) has become a promising component for smart transportation systems. However, the wireless environment of vehicular network leads to various challenges in the communication security. Hence, several authentication schemes have previously been proposed to address VANET security issues but their procedures disregard the balance between effectiveness and security. Thus, this paper presents a new decentralized authentication protocol that relies on lightweight functions such as the Chebyshev chaotic map and logical shift operator to achieve the high mobility requirement. In order to reduce the number of messages transferred over the network, this protocol attempts to eliminate any redundant authentication steps during its authentication stage. Additionally, the new protocol solves key management problems by applying a little modification to the public key infrastructure to ignore certificates transmission over the network. The proposed design incorporates the self-authentication concept to safeguard the vehicle trip route on the road. Moreover, the performance evaluation is conducted to verify that the proposed protocol outperforms the most related scheme in terms of security and efficiency aspects. Finally, the Scyther simulation validates the security robustness of the new protocol.

The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability to mutate, high mortality and morbidity, and enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue to emerge. Antiviral medications offer a viable alternative, but their success has been inconsistent. Therefore, there remains an ongoing need to identify innovative antiviral drugs for treating COVID-19 and its post-infection complications. The ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents a promising target for antiviral treatment due to its multifaceted role in viral pathogenesis, cytokine storms, disease severity, and mortality. ORF3a contributes significantly to viral pathogenesis by facilitating viral assembly and release, essential processes in the viral life cycle, while also suppressing the body’s antiviral responses, thus aiding viral replication. ORF3a also has been implicated in triggering excessive inflammation, characterized by NF-κB-mediated cytokine production, ultimately leading to apoptotic cell death and tissue damage in the lungs, kidneys, and the central nervous system. Additionally, ORF3a triggers the activation of the NLRP3 inflammasome, inciting a cytokine storm, which is a major contributor to the severity of the disease and subsequent mortality. As with the spike protein, ORF3a also undergoes mutations, and certain mutant variants correlate with heightened disease severity in COVID-19. These mutations may influence viral replication and host cellular inflammatory responses. While establishing a direct link between ORF3a and mortality is difficult, its involvement in promoting inflammation and exacerbating disease severity likely contributes to higher mortality rates in severe COVID-19 cases. This review offers a comprehensive and detailed exploration of ORF3a’s potential as an innovative antiviral drug target. Additionally, we outline potential strategies for discovering and developing ORF3a inhibitor drugs to counteract its harmful effects, alleviate tissue damage, and reduce the severity of COVID-19 and its lingering complications.

Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs). Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m (99mTc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice. Results: The prepared NCs improved ORL’s solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice. Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC.

Network traffic and overload are constantly increasing. This situation leads to congestion and packet losses at bottlenecks and across the different parts and devices of the network. Luckily, network technologies and techniques are developing rapidly. This paper is dedicated to applying and testing the impact of load balancing mechanisms on network performance. Two networking scenarios are considered: "server on-premise" and "server on cloud ."The research takes place in a vast scale network where two of the most popular technologies are spotted in an integrated multiprotocol scenario of Wireless Area networks (WLAN) with the Internet of Things (IoT) ZigBee. Previous studies were concerned by the challenges present due to the very different natures of IoT ZigBee and WLAN networks. This paper presents a better quality of service (QoS) by applying load balancing to these integrated scenarios. Not just that, it also introduces an even better Qos by deploying the rapidly growing popular technology of cloud computing to the same scenario of integrated networks with load balancing. By applying the same data rates with the same timers and networking parameters, network performance is measured and compared to show the difference between previous work without load balancing, and this papers work after deploying load balancing. The research shows whether load balancing has a positive or a negative effect on network performance or does not affect some cases. The network performance parameters under consideration are traffic dropped; traffic received, delay and throughput. Load balancing is tested regarding two different server positions.

Abstract Background Resistance to antibiotics and anticancer therapy is a serious global health threat particularly in immunosuppressed cancer patients. Current study aimed to estimate the antibacterial and anticancer potentials of short-term exposure to extremely low frequency electromagnetic field (ELF-EMF) and silver nanoparticles (AgNPs) either in sole or combined form. Methods Antibacterial activity was evaluated via determination of the bacterial viable count reduction percentage following exposure, whereas their ability to induce apoptosis in breast cancer (MCF-7) cell line was detected using annexin V-fluorescein isothiocyanate and cell cycle analysis. Also, oxidative stress potential and molecular profile were investigated. Results ELF-EMF and AgNPs significantly (p

There is a great need for novel approaches to treating bacterial infections, due to the vast dissemination of resistance among pathogenic bacteria. Staphylococcus aureus are ubiquitous Gram-positive pathogenic bacteria and are rapidly acquiring antibiotic resistance. Here, celecoxib was encapsulated into cubosomal nanoparticles, and the particle morphology, size distribution, zeta potential, entrapment efficiency, and celecoxib release were evaluated in vitro. Also, a systemic infection model in mice elucidated the in vivo antibacterial action of the celecoxib cubosomes. Cubosomes are a nanotechnology-based delivery system which can adhere to the external peptidoglycan layers of Gram-positive bacteria and penetrate them. The size distribution investigation revealed that the prepared celecoxib-loaded cubosomes had a mean particle size of 128.15 ± 3.04 nm with a low polydispersity index of 0.235 ± 0.023. The zeta potential measurement showed that the prepared cubosomes had a negative surface charge of −17.50 ± 0.45, indicating a highly stable nanodispersion formation with little susceptibility to particle aggregation. The cubosomal dispersion exhibited an entrapment efficiency of 88.57 ± 2.36%. The transmission electron micrograph for the prepared celecoxib-loaded cubosomes showed a narrow size distribution for the cubosomal nanoparticles, which had a spherical shape and were non-aggregated. The tested cubosomes diminished the inflammation in the treated mice’s liver and spleen tissues, as revealed by hematoxylin and eosin stain and Masson’s trichrome stain. The immunostained tissues with nuclear factor kappa B and caspase-3 monoclonal antibodies revealed a marked decrease in these markers in the celecoxib-treated group, as it resulted in negative or weak immunostaining in liver and spleen that ranged from 4.54% to 17.43%. This indicates their inhibitory effect on the inflammatory pathway and apoptosis, respectively. Furthermore, they reduced the bacterial burden in the studied tissues. This is alongside a decrease in the inflammatory markers (interleukin-1 beta, interleukin-6, cyclooxygenase-2, and tumor necrosis factor-alpha) determined by ELISA and qRT-PCR. The IL-1β levels were 16.66 ± 0.5 pg/mg and 17 ± 0.9 pg/mg in liver and spleen, respectively. Also, IL-6 levels were 85 ± 3.2 pg/mg and 84 ± 2.4 pg/mg in liver and spleen, respectively. In conclusion, the current study introduced cubosomes as an approach for the formulation of celecoxib to enhance its in vivo antibacterial action by improving its oral bioavailability.

Abstract Background Accurate staging and proper management of axillary lymph nodes (ALNs) in breast cancer patients are important for treatment. Surgical management of the axilla has evolved greatly in the last 20 years. Sentinel lymph node biopsy (SLNB), which was first investigated in the early 1990s, has replaced routine axillary lymph node dissection. This study evaluates the capability of using an ultrasound (US) as an alternative tool for the frozen section in the assessment of the ex vivo sentinel lymph node biopsy in countries with limited resources. Results The study is a prospective study that included 216 female patients with early breast cancer and negative axillary lymph nodes. All excised lymph nodes were examined by the intraoperative US and frozen section examinations. All the results were correlated with the final histopathological results. The number of negative nodes by US, frozen, and paraffin section examination was 58.30%, 69.40%, and 69.40%, respectively. The number of positive nodes by the US, frozen, and paraffin section examinations was 41.70%, 30.60%, and 30.60% respectively. The sensitivity, specificity, PPV, NPV, and accuracy of US in the detection of positive lymph nodes were 95.45%, 82%, 70%, 97.62%, and 86.11%, respectively, and the sensitivity, specificity, PPV, NPV, and accuracy of frozen examination in the detection of positive lymph nodes were 90.91%, 96%, 90.91%, 96%, and 94.44%, respectively. Conclusion Intraoperative US is a good negative test in the assessment of ex vivo SLNB, but it is not a good positive test, so it cannot replace the intraoperative frozen section in the assessment of SLNs.

Background: LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods: Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results: There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups (p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin (p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion: These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.

Abstract Background Sugammadex reverses rocuronium more effective than neostigmine during deeper neuromuscular blockade levels. Relying upon the high cost of sugammadex we hypothesized that combined neostigmine with half-dose sugammadex (1.2 mg/kg) would be as effective as the full dose (2.4 mg/kg IBW) in reversing rocuronium-induced deep neuromuscular block in obese patients. A multimodal approach would be an effective cost saving strategy, while preserving the advantages of this novel agent. Patient and methods A prospective randomized study done on 50 morbid obese patients undergoing elective laparoscopic sleeve gastrectomy operation. Patients were allocated into two groups each of 25. Group NS received sugammadex 1.2 mg/kg and neostigmine 50 μg/kg with atropine 20 μg/kg. Group S received sugammadex 2.4 mg/kg and 10 mL of normal saline. Primary outcome Interval between administration of reversal and reaching TOF of 90%. Secondary outcomes Total dose of rocuronium (mg), duration between last dose rocuronium and reverse, number of patients reached TOF of 90% within 5 min, duration between IV reversal and extubation, and the number of patients with residual neuromuscular blockade. Results Number of patients who reached TOF 90% within 5 min, the interval between reversal and 90% TOF, the interval between reversal and extubation were comparable between the study groups. Conclusion As regards neuromuscular blocker reversal in obese patients, the neostigmine 50 μg/kg plus sugammadex half dose (1.2 mg/kg) is as effective as full-dose sugammadex (2.4 mg/kg) alone. Trial registration Institutional Research Board: (IRB code number): MS/17.12.195 on 16 January 2018.

The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein’s structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.

BackgroundMajor depressive disorder (MDD) is a public health burden that creates a strain not only on individuals, but also on the economy. Treatment-resistant depression in the course of major depressive disorder represents a clinically challenging condition that is defined as insufficient response to two or more antidepressant trails with antidepressants of the same or different classes that were administered at adequate daily doses for at least 4 weeks.Objective/HypothesisTo develop a treatment guideline for Treatment Resistant Depression (TRD).MethodologyExperts in the field gathered and reviewed the available evidence about the subject. Then, a series of meetings were held to create recommendations that can be utilized by Egyptian psychiatrists.ResultsThe guidelines provide recommendations in various clinical settings. It evaluates different situations, such as patients at risk of resistance, those with resistance and recommends strategies to resolve the clinical case.ConclusionThe consensus guidelines will improve the outcomes of patients, as they provide recommendations across various domains that are of concern for the practicing psychiatrist.

The aim of this research was to investigate the self-healing potential of damaged Al joints when bonded using novel eco-epoxide adhesives derived from tannic acid (TA). Two eco-epoxy components based on TA, (A) glycidyl ether and (B) glycidyl phosphate ester of TA, were produced. The effect of the eco-epoxy components on the self-healing ability was assessed in terms of the energy dissipation recovery after partial failure in a double cantilever beam (DCB) test, which was compared to the reference epoxy (R). The self-healing process required 2 h and 2 bars in an autoclave at 180 °C. Techniques such as DSC, FTIR and DMA showed residual activity and potential self-healing capability of the used adhesives. A combination of two monitoring techniques, Digital Image Correlation (DIC) and Acoustic Emission (AE), was used to monitor the strain distribution and damage propagation in the DCB specimens. The healing index for adhesives R, B and A was found to be 8.9%, 3.0%, and 82.5% respectively. The findings of this work highlighted the potential of using bio-based epoxy adhesives in structural adhesive bonding, as well as the prospect of utilizing their self-healing ability to restore the strength of such bonded parts.

Introduction: Although widespread, BCC is still relatively poorly understood in regards to pathogenesis and prognosis, particularly the lesions formed on anatomical sites away from sun exposure. With the aim of deepening our understanding of the pathogenesis and clinico-pathological correlations of BCCs, we conducted this study. Methods: Tissue blocks and data of 52 Egyptian patients diagnosed with BCC were retrieved for clinical information and inclusion criteria, then re-examined histologically; p16 immunostaining was carried out and evaluated for analysis and comparison between the two groups, i.e., sun-exposed and sun-protected. Results: Sex, age, clinical suspicion, tumor size, recurrence status, and histologic variants did not show a significant difference between the sun-protected and sun-exposed groups; however, the mean ages recorded were 67.2 vs. 62.7 for the sun-protected and sun-exposed groups, respectively. A total of 52% of BCCs were positive for p16. The sun-protected lesions showed p16 positivity in 61% of cases, whereas 49% of the sun-exposed lesions were positive with no significant difference. There was a significant difference in p16 expression between the recurrent and non-recurrent lesions. Conclusions: A significant difference was seen in the case of cancer recurrence, where all the recurrent BCCs in this study demonstrated negative p16 immunostaining of the primary lesions; however, the positively stained cases in total were 52% of BCCs. The mean patient age of the sun-protected group was much higher than in previous peer studies. We assume that the biological, prognostic, and clinical aspects of p16 protein expression in BCCs are still far from being clearly understood. Further studies are highly recommended, with more focus on its role in the pathogenesis and the prognostic factors.

Abstract The potato virus Y (PVY) is considered one of the most important viruses in terms of both economical and biological impact. Potential of using three different Streptomyces spp. crude filtrates (SCF) to induce of resistance against tuber necrotic strain of potato virus Y (PVYNTN) in four potato cultivars namely, Spunta, Nicola, Selatar, and Diamant, were evaluated. Foliar spraying of Streptomyces netropsis DSM 40093 (SCF7), S. ambofaciens (SCF11) and S. actuosus (SCF20), applied separately on potato cultivated in pots, showed various inhibitory activities against PVYNTN infection in all the potato cultivars. SCF20 was the most effective one, as expressed by (100%) reduction of apical necrosis symptoms on potato cv. Spunta, Nicola, and Diamant leaves under greenhouse conditions. Application was done 7 days before virus inoculation with PVYNTN (DBVI) and 7 days after inoculation (DAVI). The concentration of PVYNTN in treatments was significantly reduced than in the untreated PVYNTN infected plants as detected by DAS-ELISA (expressed by decreasing in OD value). Expression of PR-1b gene was detected 21 (DAVI) in all SCF11-treated cultivars but was not expressed in healthy and infected control plants. Gas chromatography-mass spectrometry (GC-MS) analysis of S. actuosus (SCF20) ethyl acetate extract revealed the majority of fatty acids (FAs) and their derivatives, Citroflex A, Hexanoic acid, anhydride, Hexadecanoic acid, Hexadecanoic acid, ethyl ester, and Diisooctyl phthalate which suggested to act as elicitor molecules for induction of systemic acquired resistance (SAR). Overall, the application of culture filtrates of Streptomyces has the potentiality to be used as inducer against PVYNTN infection.

Background and Objectives: Migraine is caused by genetic susceptibility that is triggered by environmental as well as biological factors, and it is also linked to many somatic comorbidities, including clinical and subclinical hypothyroidism. We aimed to estimate the potential association between subclinical hypothyroidism (ScH) and migraine in children at our tertiary hospital. Materials and Methods: Using a case–control strategy, 200 children and adolescents were assigned to two equal groups: a case group (patients with migraine) of 100 patients and a control group of 100 patients without migraine. Clinical and biochemical parameters (TSH, FT4) were compared between the groups using statistical analysis. Results: Thyroid function comparison between the groups showed higher TSH but normal FT4 among children with migraine headache compared to the control group, which means more frequent ScH cases among the migraine group relative to the control (17% vs. 2%, p < 0.001). Obesity and overweight were more frequent among patients with migraine than the control group (8 and 5% vs. 2 and 1%, respectively). The (overweight/obese) patients with migraine had about 77% ScH and 15.4% overt hypothyroidism compared to 8% ScH and no overt hypothyroidism among normal body weight migraine patients (p < 0.001). No significant difference in the prevalence of nodular goiter between patients with migraine and controls was found. Conclusions: Based on our results, subclinical hypothyroidism is significantly linked to childhood migraine. Obesity and being overweight are more frequent among patients with migraine. Therefore, it may be logical to test the thyroid function in migraineur children, especially those with high BMI. Further studies are recommended to discover the mechanism of this association in children.

Two synthesized eco-epoxy components based on TA: (A) glycidyl ether and (B) glycidyl phosphate ester, are used, as a replacement for the Bisphenol A (BPA) based epoxy component, for bonding aluminum (Al) and carbon fiber reinforced polymer (CFRP). Their effect on the mode I fracture toughness (GI) is evaluated by Double Cantilever Beam (DCB) testing while using Digital Image Correlation (DIC) for in-situ crack tip monitoring. Compared to the reference adhesive, an improvement of (GI) of Al (43%) and CFRP (100%) is obtained when using adhesive B. Moreover, regardless of the adherend material, a stick-slip pattern of crack growth is observed. Weak adhesion of the reference adhesive leads to an adhesive failure vs. a cohesive-adhesive failure in the case of adhesive B. On the contrary, the modification of adhesive A has an adverse effect on the GI of Al (−33%) and CFRP (−78%) as opposed to their reference counterparts.

Fission yeast can be used as a cell-based system for high-throughput drug screening. However, higher drug concentrations are often needed to achieve the same effect as in mammalian cells. Our goal here was to improve drug sensitivity so reduced drugs could be used. Three different methods affecting drug uptakes were tested using an FDA-approved HIV-1 protease inhibitor (PI) drug Darunavir (DRV). First, we tested whether spheroplasts without cell walls increase the drug sensitivity. Second, we examined whether electroporation could be used. Although small improvements were observed, neither of these two methods showed significant increase in the EC50 values of DRV compared with the traditional method. In contrast, when DRV was tested in a mutant strain PR836 that lacks key proteins regulating cellular efflux, a significant increase in the EC50 was observed. A comparison of nine FDA-approved HIV-1 PI drugs between the wild-type RE294 strain and the mutant PR836 strain showed marked enhancement of the drug sensitivities ranging from an increase of 0.56 log to 2.48 logs. Therefore, restricting cellular efflux through the adaption of the described fission yeast mutant strain enhances the drug sensitivity, reduces the amount of drug used, and increases the chance of success in future drug discovery.

Compounds with novel modes of action are urgently needed to develop effective combination therapies for the treatment of tuberculosis. In this study, a series of compounds was evaluated for activity against replicating Mycobacterium tuberculosis and Vero cell line toxicity. Fourteen of the compounds with in vitro activities in the low micrometer range and a favorable selectivity index were classified using reporter strains of M. tuberculosis which showed that six interfered with cell wall metabolism and one disrupted DNA metabolism. Counter-screening against strains carrying mutations in promiscuous drug targets argued against DprE1 and MmpL3 as hits of any of the cell wall actives and eliminated the cytochrome bc1 complex as a target of any of the compounds. Instead, whole-genome sequencing of spontaneous resistant mutants and/or counter-screening against common isoniazid-resistant mutants of M. tuberculosis revealed that four of the six cell wall-active compounds, all pyridine carboxamide analogues, were metabolized by KatG to form InhA inhibitors. Resistance to two of these compounds was associated with mutations in katG that did not confer cross-resistance to isoniazid. Of the remaining seven compounds, low-level resistance to one was associated with an inactivating mutation in Rv0678, the regulator of the MmpS5-MmpL5 system, which has been implicated in non-specific efflux of multiple chemotypes. Another mapped to the mycothiol-dependent reductase, Rv2466c, suggesting a prodrug mechanism of action in that case. The inability to isolate spontaneous resistant mutants to the seven remaining compounds suggests that they act via mechanisms which have yet to be elucidated.

Background: Research is one of the crucial factors in the advancement of health. Undergraduate medical research training is a cornerstone in medical students' education. This study aimed to evaluate the knowledge and attitude of medical students toward medical research. Methods: This cross-sectional analytical study included 200 medical students in their fifth and sixth years at the Faculty of Medicine, University of Khartoum. Data was collected using a self-administered questionnaire, assessing students' knowledge and attitudes toward medical research, which were scored out of 100. Data were analyzed using the SPSS software. Results: Of the 200 students, 69% were females and 31% males; 81% of them held a Sudanese secondary school diploma and reported future clinical career choice. Their mean academic score was 16 out of 32 ± 6.6 points. Students' mean knowledge score was 36 out of 100, which was considered low. Their mean attitude score toward medical research was 48.2 out of 100, which was considered moderate. Conclusions: This study concluded that the knowledge of fifth- and sixth-year medical students about medical research was low. However, moderately positive attitude was reported among them. It is recommended that students' engagement in active research ought to be started early in their medical school. Additionally, more engaging and interactive methods of teaching research are endorsed to be implemented.

Mobile phone usage has been increased in the last few years emitting electromagnetic radiation (EMR), which disturbs normal cellular processes via oxidative stress. L-cysteine, a glutathione precursor, prevents oxidative damage. Transdermal patches (TDPs) loaded with L-cysteine hydrochloride (L-CyS-HCL) were fabricated by dispersion of L-CyS-HCL 5% w/w and different concentrations of sorbitol as a plasticizer in room-temperature vulcanizable synthetic silicone matrices (RTV-Si). The effect of sorbitol on patch physicochemical parameters was assessed; in-vitro L-CyS-HCL release profiles and ex-vivo permeation were studied. Pharmacokinetic parameters of endogenous synthetized in-vivo glutathione, after receiving IV bolus dose of L-CyS-HCl and L-CyS-HCl-RTV-Si-TDPs were studied in rat model. The influence of L-CyS-HCL-RTV-Si-TDPs against damaging effects of mobile phone EMR on rats' blood and brain tissues was studied. The results revealed that patch plasticity, intensity reflections, surface porosity, L-CyS-HCL release rate and skin permeation increased with increasing sorbitol concentration. Pharmacokinetic profile for IV dose and L-CyS-HCl-RTV-Si-TDPs revealed that the L-CyS-HCl-RTV-Si-TDPs provided a sustained glutathione plasma concentration–time profile over entire patch application. High significant differences in biological parameters (blood and brain samples) were observed for radiated rats using the patch in study compared with positive control rats. Promising long-term strategy for protection against mobile phone hazards was obtained. Keywords: Electromagnetic radiation, Mobile phone hazards, L-cysteine, Transdermal patches, Silicone transdermal patches, Glutathione

High selectivity design of an improved on-chip band pass filter for 60 GHz millimeter-wave applications using0.18 μm CMOS technology is presented. A new type of miniaturized microstrip bandpass filters with pseudo- interdigital structure without via holes grounded resonators is described. A very compact filter of this type, having a size less than quarter-wavelength by quarter-wavelength at a mid-band frequency of 60 GHz was designed. The adoption of a pseudo- interdigital BPF and utilization of two transmissions zero permits a compact size and high selectivity for the BPF. Besides, two defected ground structure cells are etched under the coupled lines to improve the filter insertion loss. The proposed BPF has the center frequency of 60 GHz, insertion loss of -3.6. dB, a 3dB band width of 8 GHz, and core size 200×500 μm2 with total chip size 500×300 μm2 (including bonding pads

Background: Students' academic performance is largely affected by their motivation. Moreover, health professions' education needs motivated students who are keen to tolerate the burden of clinical work along with the academic excellence to graduate competently. This study assessed the effect of tutors on students' motivation. Method: A cross-sectional, institution-based study of the first-year medical students at University of Khartoum, Sudan was conducted. A self-administered questionnaire was used comprising a modified Motivated Strategies for Learning Questionnaire (MSLQ) with students' evaluation of their tutors after semester one community medicine course. A total of 237 out of 324 students responded. Pearson product-moment correlation coefficient was used to test the relationship between motivation and evaluation. Hierarchical multiple regression model tested the ability of evaluation factors to predict motivation score. Results: There was a significant association between tutor's characteristics regarding creativity in conducting the sessions, igniting discussion, and adequacy of knowledge about the course contents and the motivation score (p-value = 0.001). There was a strong, positive correlation between the perceived evaluation score and perceived motivation score (r = 0.505, n = 206, p< 0.0005). After controlling age, gender, paternal educational levels, and scores of Sudanese certificate upon entry, R squared change = 0.28, F change (9.181) = 8.416, p< 0.001. In the final model, the content of the course was statistically significant, standardized Beta = 0.285, indicating that content uniquely explains 5.7% of the variance in total perceived motivation score. Conclusion: The evaluation score explained 28% of the variance in student motivation. Students' motivation is significantly associated with tutor's teaching skills concerning knowledge, creativity, students' involvement, and attractiveness in conducting the tutorials. Improving course content can enhance students' motivation toward community medicine.

BACKGROUND: Pan-scan (whole-body) computed tomography (CT) has a paramount role in the diagnosis of injuries in road traffic accidents (RTA). OBJECTIVE: Identify patterns of injuries on pan-CT scans. DESIGN: Retrospective medical record review. SETTING: Tertiary care center. PATIENTS AND METHODS: The records of all RTA patients who presented to the radiology department at King Fahad Military Medical Complex (KFMMC) in Dhahran for the 3-year period from July 2014 to July 2017 and underwent pan-CT were retrospectively reviewed. Drivers and front-seat passengers with complete clinical information on seating, safety and mechanism of injury were selected. Children under 5 years of age, pregnant women and back-seat passengers were excluded. Patterns of injuries were categorized as ‘no abnormality detected’ (NAD), isolated or combined head, face and neck (H), isolated or combined chest, abdomen and pelvis (C) or both regions of the body (B). MAIN OUTCOME MEASURES: Injury patterns on pan-CT scans. SAMPLE SIZE: 305 RESULTS: Most patients were males (n=287, 94.1%). The median age was 26 years for males (IQR, 22-33 years) and 30 years for females (IQR, 28-39). More than two-thirds were drivers (all males); the remainder were front-seat passengers. Young males were most often involved. The most common type of accident was a roll-over. Of those who sustained injuries, 273 (89.5%) were not wearing a seat belt (unrestrained). The patterns of injuries were NAD (87, 28%), H (27, 9%), C (93, 30.5%), B (98, 32%). CONCLUSION: When abnormalities were detected, most high-speed vehicular injuries affected the torso. Unrestrained young male drivers are most often involved in RTAs in Saudi Arabia. LIMITATIONS: Retrospective study with a small sample size. Types and severity of injuries on pan-CT were not documented. CONFLICT OF INTEREST: None.

Background : Hepatitis B is a serious chronic infection of the liver and caused by hepatitis B virus. It is an endemic disease in Sudan. Healthcare workers are occupationally more prone to acquire the disease. Evaluation of their knowledge, attitude and practice and their vaccination status, are very important in the control of the disease. The aim of this study was to assess the knowledge, attitude, and practice of healthcare workers towards hepatitis B and their vaccination status. Materials and Methods : In total, 372 healthcare workers were enrolled in the study, which was conducted at 10 public hospitals in Khartoum state during July-August 2015. After taking written informed consent from the Khartoum State Research Department, self-administrated questionnaires were distributed to the healthcare workers. The KAP score was the sum of the three categories, which is 32 points, and the mean was then obtained. Results : The study revealed that the respondents’ mean scores of knowledge, attitude, and practice (KAP) were 18.4, 2.14 and 2.49, respectively. The study also showed that doctors have the highest KAP score in comparison with other occupations. Doctors are the least occupational category that uses gloves when dealing with patient’s blood. The KAP score was found higher among vaccinated healthcare workers 27.4% in comparison to unvaccinated ones, That yield to a significant the association between KAP score and vac-cination status (p-value 0.007). Conclusions : This study concluded that, there is a positive association between the level of vaccination among Health care workers and their Knowledge, attitude and practice of hepatitis B virus. Further studies would be recommended on larger population.

In this study, gliclazide-loaded cubosomal particles were prepared for improving the oral bioavailability and antidiabetic activity of gliclazide. Four formulations of gliclazide-loaded cubosomal nanoparticles dispersions were prepared by the emulsification method using four different concentrations of glyceryl monooleate (GMO) and poloxamer 407 (P407) as the stabilizer. The prepared formulations were in vitro and in vivo evaluated. In vitro, the prepared gliclazide-loaded cubosomal dispersions exhibited disaggregated regular poly-angular particles with a nanometer-sized particle range from 220.60 ± 1.39 to 234.00 ± 2.90 nm and entrapped 73.84 ± 3.03 to 88.81 ± 0.94 of gliclazide. In vitro gliclazide release from cubosomal nanoparticles revealed an initially higher drug release during the first 2 h in acidic pH medium; subsequently, a comparatively higher drug release in alkaline medium relative to gliclazide suspension was observed. An in vivo absorption study in rats revealed a two-fold increase in the bioavailability of gliclazide cubosomal formulation relative to plain gliclazide suspension. Moreover, the study of in vivo hypoglycemic activity indicated that a higher percentage reduction in glucose level was observed after the administration of gliclazide cubosomal nanoparticles to rats. In conclusion, gliclazide-loaded cubosomal nanoparticles could be a promising delivery system for improving the oral absorption and antidiabetic activity of gliclazide.

Successful combination antiretroviral therapies (cART) eliminate active replicating HIV-1, slow down disease progression, and prolong lives. However, cART effectiveness could be compromised by the emergence of viral multidrug resistance, suggesting the need for new drug discoveries. The objective of this study was to further demonstrate the utility of the fission yeast cell-based systems that we developed previously for the discovery and testing of HIV protease (PR) inhibitors (PIs) against wild-type or multi-PI drug resistant M11PR that we isolated from an infected individual. All thirteen FDA-approved single-agent and fixed-dose combination HIV PI drugs were tested. The effect of these drugs on HIV PR activities was tested in pure compounds or formulation drugs. All FDA-approved PI drugs, except for a prodrug FPV, were able to suppress the wild-type PR-induced cellular and enzymatic activities. Relative drug potencies measured by EC50 in fission yeast were discussed in comparison with those measured in human cells. In contrast, none of the FDA-approved drugs suppressed the multi-PI drug resistant M11PR activities. Results of this study show that fission yeast is a reliable cell-based system for the discovery and testing of HIV PIs and further demonstrate the need for new PI drugs against viral multi-PI resistance.

The effect of the weaving architecture and the z-binding yarns, for 2D and 3D woven composites on the low-velocity impact resistance of carbon fibre reinforced composites, is investigated and benchmarked against noncrimp fabric (NCF). Four architectures, namely: NCF, 2D plain weave (2D-PW), 3D orthogonal: plain (ORT-PW) and twill (ORT-TW), were subjected to 15 J impact using a 16 mm-diameter, 6.7 kg hemispherical impactor. Nondestructive techniques, including ultrasonic C-scanning, Digital Image Correlation (DIC) and X-ray computed tomography (CT) were used to map and quantify the size of the induced barely visible impact damage (BVID). The energy absorption of each architecture was correlated to the damage size: both in-plane and in-depth directions. The 3D architectures, regardless of their unit-cell size, demonstrated the highest impact resistance as opposed to 2D-PW and the NCF. X-ray CT segmentation showed the effect of the higher frequency of the z-binding yarns, in the ORT-PW case, in delamination and crack arresting even when compared to the other 3D architecture (ORT-TW). Among all the architectures, ORT-PW exhibited the highest damage resistance with the least damage size. This suggests that accurate design of the z-binding yarns’ path and more importantly its frequency in 3D woven architectures is essential for impact-resistant composite structures.

Background: Urinary tract injuries occur in 3–10% of abdominal trauma, kidneys being the most commonly injured. Contrast-enhanced CT is the imaging technique of choice for renal trauma, since it can quickly and accurately demonstrate not only renal injuries, and also associated damage to other organs. CT can help detect active hemorrhage and urine leakage and is the most accurate screening test for high-grade injuries and is of great help in guiding transcatheter embolization and delineating preexisting disease entities. Aim of the work: To demonstrate different traumatic lesions of the kidneys using multi-detector CT, and its use in staging and management of lesions. Methods: Study was carried out on 41 patients with abdominal trauma and suspected renal injury. All patients were subjected to contrast-enhanced multiphasic renal CT study in correlation with surgical and conventional angiography data when available. Results: All patients were classified after the American Association for the Surgery of Trauma grading system. Grade I injury was diagnosed in 2.4% of patients, grade II in 7.3%, grade III in 29.3%, grade IV in 53.7% and grade V in 7.3%. 80.5% of patients were managed conservatively, 12.2% of patients underwent total nephrectomy and 7.3% of patients died before management. Conclusion: Multiphasic CT well demonstrated various traumatic renal lesions with proper diagnosis and staging of renal trauma and guiding management.

Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles.

The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P

Introduction: Primary CNS lymphoma is difficult to diagnose with conventional imaging modalities. Magnetic resonance proton spectroscopy, dynamic susceptibility contrast DSC perfusion and diffusion weighted images have been recently investigated as a problem-solving tool for evaluation of primary CNS lymphoma with favorable results. Aim of the work: To assess the value of advanced neuro-imaging (MR diffusion, perfusion and proton spectroscopy) in diagnosis of primary CNS lymphoma. Patients and methods: Five adult patients with suspected primary CNS lymphoma (as suggested by clinical or conventional imaging techniques) were prospectively studied by magnetic resonance proton spectroscopy, dynamic susceptibility contrast DSC perfusion and diffusion weighted images aiming to confirm the suspected diagnosis. The examinations were done on 1.5T machines using diffusion weighted, dynamic susceptibility contrast perfusion and chemical shift CSI imaging sequences. Results: Regarding DWI, all patients show low ADC values ranging from 0.61 to 0.67 × 10−3 mm2/s with a mean ADC value of 0.63 ± 0.025(SD) × 10−3 mm2/s, regarding the DSC perfusion. The max rCBV ratios are ranging from 0.23 to 1.52 with a mean ratio of 1.14 ± 0.54(SD). Regarding the MRI spectroscopy Cho/Cr ratios are ranging from 1.9 to 63 with a mean ratio of 19.16 ± 26 (SD), Cho/NAA ratios are ranging from 3.7 to 50 with a mean ratio of 14.8 ± 19.8, NAA/Cr ratios are ranging from 0.09 to 1.6 with a mean ratio of 0.72 ± 0.59, NAA/Cho ratios are ranging from 0.02 to 0.3 with a mean ratio of 0.19 ± 0.1 Lactate peak was found in three cases. Lipid peak was found in two cases. Myo inositol peak was found in one case. Conclusions: Restricted diffusion, relative hypo perfusion, increased Cho/Cr, Cho/NAA, decreased NAA/Cho, NAA/Cr and presence of lactate or lipid peaks are consistent imaging finding in CNS lymphoma.

On the basis of the translation from Arabic of the novel “Azazel” of the Egyptian writer Yusef Zeidan, the analysis of similarity of its substantial elements with the same-name work of famous Russian writer Boris Akunin is carried out by the authors in the article. Besides, the deep analysis and estimation of reflected in the novels reasons of appearance of both local social problems within the Russian and Egyptian societies, and global ones connected with religious fanaticism and political extremism, is held.