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Background This study aimed to compare the perceived masticatory ability (PrMA) in completely edentulous patients (EDPs) with thermoplastic conventional complete dentures (CDs) versus single implant-retained mandibular overdentures. Methods The current study was conducted in the outpatient Prosthodontic Clinic, Faculty of Dental Medicine, Al-Azhar University, Cairo, Egypt. PrMA was evaluated in 45 completely edentulous patients (46% males, mean age 50.4 ± 4.7 years). Each patient received a thermoplastic PMMA complete denture (Polyan IC TM Bredent GmbH & Co.KG, Germany). The PrMA was evaluated at one-month and six-month intervals of denture use. An immediate loading single implant was placed into the mid-symphyseal for each patient, and the denture was adjusted. Subsequently, the PrMA was reevaluated after one month and six months. The data were collected and statistically analyzed using the SPSS@V25 to assess the changes in PrMA. Results The PrMA demonstrated improvement after six months of thermoplastic conventional denture use. However, this improvement was not statistically significant (p = 0.405). In addition, the PrMA showed a substantial increase following a single implant placement at one and six months (p

The design of university buildings plays a critical role in users' productivity, health, and behavior. The design should incorporate end users' and architects' perceptions to prevent decreased satisfaction, productivity, and health issues. Meeting user needs and preferences is essential for creating functional buildings that cater to their requirements. However, user needs change over time, and research does not clearly define user-centered requirements in the design of university buildings. This study addresses the unclear definition of user-centered design requirements for university buildings, essential for ensuring spaces effectively meet evolving user needs. Aiming to identify these requirements and the challenges of integrating them into architectural design, two parts of the survey were conducted with 59 participants, including end-users from 11 academic institutions and architects in Egypt. The survey revealed a consensus on the importance of aesthetics, functionality, and indoor environmental quality. From the results, a satisfaction model for university buildings was developed, highlighting design attributes valued by users and architects alike. This model facilitates overcoming design challenges, thereby proposing a path towards creating functional, user-satisfying university spaces. This study's findings underscore the necessity of merging architectural practices with dynamic user expectations, contributing to the discourse on user-centered design in educational environments.

Universities are large institutions that consume significant amounts of energy and water, produce waste and greenhouse gases, and significantly impact the surrounding environment, making evaluating and improving universities' sustainability crucial. Egypt has its building sustainability rating tool called the Green Pyramid Rating System (GPRS), which is not specifically customized for university buildings. Hence, this study aims to develop a customized weighting system based on the green pyramid rating system to assess the sustainability of university buildings by involving stakeholders. A comprehensive questionnaire was developed and distributed to a targeted sample of experts and university building stakeholders, including architects, engineers, project managers, consultants, contractors, decision-makers, policymakers, operation managers, facility managers, and senior students majoring in architecture, construction, and sustainable engineering. The data collected was analyzed using statistical analysis and the Analytical Hierarchy Process (AHP) to assign weights to each category and criterion. The results highlighted that the respondents prioritize Energy Efficiency (EE) with a weight of 21%, followed by Water Efficiency (WE) at 19%. Indoor Environmental Quality (IEQ) and Sustainable Sites (SS) are given equal priority with a weight of 17% each. Materials and Resources (MR) receive a weight of 14%, and Management Protocols (MP) have the lowest weight of 12%. Hence, prioritizing these aspects can significantly enhance university buildings' energy efficiency and overall sustainability.

Abstract The debate about which surgical technique for tonsillectomy could be superior over another is continuous. Tonsillectomy techniques are classified into cold and hot procedures. In cold techniques, no heat is used; they include dissection, guillotine, microdebrider, harmonic scalpel, and cryosurgery. Hot techniques include electrocautery, coblation, radio frequency, and laser. In Egypt, the used methods are cold dissection, electrocautery, cold dissection with electrocautery hemostasis, coblation, and less commonly laser. In this study, we described the advantages and disadvantages of each technique. Hot techniques have shorter operative time and less intraoperative bleeding, while cold dissection technique has less postoperative pain and less postoperative complications especially secondary hemorrhage, with more rapid wound healing. However, coblation technique may have less pain in the first few hours postoperatively relative to cold technique. Electrocautery technique is the most painful method with delayed wound healing. Laser technique is nearly equivalent to electrocautery with slightly less pain. Cold dissection technique is less costly when compared to other techniques. Family satisfaction after tonsillectomy is dependent mainly on less postoperative pain and rapid recovery. Cold dissection is still considered the gold standard technique. Caution should be taken on using hot techniques especially when used for dissection, and the trainee surgeons should become familiar with cold dissection before shifting to other tonsillectomy techniques. From this study, we can say that hot techniques should not be used except after mastering the cold dissection tonsillectomy; also, the new advanced techniques can be reserved for high-risk patients such as having bleeding disorders.

Key Clinical Message Although ligating femoral pseudoaneurysm is a safe procedure, some cases require revascularization, and the appropriate treatment should be tailored to the patient. Abstract In this case report, we highlight the challenge in treating infected femoral artery pseudoaneurysm. The patient, a 37‐year‐old male intravenous drug abuser, presented to the emergency department with a 2‐month history of a progressively growing lump over his right groin. Two days before the presentation the swelling became hot and painful. After physical examination, it was revealed that the localized swelling is about 15 × 15 cm in size. It is pulsating, expanding in all directions, moving from side to side, and has been reduced in size due to proximal artery compression with the inflamed overlying skin causing slight flexion of the right hip joint and there was serosanguineous discharge as well. The affected leg was warm with intact motor and sensory function, palpable femoral, and popliteal arterial pulses, but non‐palpable left posterior tibial and anterior tibial arterial pulses, both of which had triphasic wave signals on a portable hand‐held Doppler (there was below knee marked edema). CT angiography (CTA) revealed a large well‐defined heterogeneous cystic structure at the right groin with an average diameter of 11 × 10 × 9 cm, with a connection with the common femoral artery. After proximal and distal control, excision of the infected femoral pseudoaneurysm, a swab was taken, and ligation of the common femoral artery superficial femoral artery, and profunda femoral artery. No signals were detected on the posterior or anterior tibial arteries by hand‐held Doppler and oxygen saturation on the big toe was markedly decreased, so we did an extra‐anatomic lateral ilio‐femoral anastomosis using silver‐impregnated vascular graft.

The ever-evolving Omicron variant of the SARS-CoV-2 and its sub-lineages have prompted Saudi Arabia to continuously track circulating lineages. We focused on the presence of diverse SARS-CoV-2 circulation in Saudi Arabia and presented the whole genome sequencing study of 94 positive SARS-CoV-2 specimens procured between February and April 2022 in the city of Jeddah, Saudi Arabia. Following whole-genome sequencing, bioinformatics analysis was undertaken. The SARS-CoV-2 variant Omicron clades 21K and 21L constituted the entirety of sequenced specimens, belonging to BA.2 (n = 56) and BA.1.1 (n = 20), respectively, and low-frequency sub-lineages were BA.2.3 (n = 6), BA.1 (n = 4), BA.2.40.1 (n = 2), BA.1.14 (n = 1), BA.2.10 (n = 1), BA2.32 (n = 1), BA.2.57 (n = 1), BA2.64 (n = 1), and BA2.5 (n = 1). Mutational patterns were identified, as well as possible consequences for the spread of the virus. Comparative molecular docking of Omicron-specific Nucleocapsid protein harboring the mutations P13L, R203K, G204R, as well as S413R, and the deletions E31-, R32-, and S33- showed reduced interaction with human RIG-I protein with 8 interacting amino acid residues and 10 polar interactions, while the SARS-CoV-2 Nucleocapsid protein exhibited 15 interacting amino acid residues and 26 polar interactions. Ongoing monitoring is essential for assessing the genomic epidemiological consequences of tourist travel and pilgrimage in Jeddah and across Saudi Arabia, as well as the prompt identification of emerging variants for further investigation.

Abstract Background As systematically developed statements regarding possible courses of action, health system guidance (HSG) can assist with making decisions about addressing problems or achieving goals in health systems. However, there are conceptual and methodological challenges in HSG implementation due to the complexity of health-system policy-making, the diversity of available evidence and vast differences in contexts. To address these gaps, we aim to develop a theoretical framework for supporting HSG implementation as part of a broader effort to promote evidence-informed policy-making in health systems. Methods To develop a theoretical framework about facilitators, barriers and strategies for HSG implementation, we will apply a critical interpretive synthesis (CIS) approach to synthesize the findings from a range of relevant literature. We will search 11 electronic databases and seven organizational websites to identify relevant published and grey literature. We will check the references of included studies and contact experts to identify additional eligible papers. Finally, we will conduct purposively sampling of the literature to fill any identified conceptual gaps. We will use relevance and five quality criteria to assess included papers. A standardized form will be developed for extracting information. We will use an interpretive analytic approach to synthesize the findings, including a constant comparative method throughout the analysis. Two independent reviewers will conduct the literature screening and relevance assessment, and disagreements will be resolved through discussion. The principal investigator will conduct data extraction and synthesis, and a second reviewer will check the sample of extracted data for consistency and accuracy. Discussion A new theoretical framework about facilitators, barriers and strategies for HSG implementation will be developed using a CIS approach. The HSG implementation framework could be widely used for supporting the implementation of HSG covering varied topics and in different contexts (including low-, middle- and high-income countries). In later work, we will develop a tool for supporting HSG implementation based on the theoretical framework. Registration PROSPERO CRD42020214072. Date of Registration: 14 December 2020.

Users and buildings guarantee the sustainability of any built environment. Thus, monitoring user satisfaction is as important as monitoring energy consumption. The traditional method of user satisfaction assessment costs a lot of money, effort, and time, which are barriers to its frequent occurrence. The objective of this research is to take advantage of smart initiatives to develop a user satisfaction assessment model that evaluates user satisfaction simply and continuously. The model investigates the ability of the time parameter to monitor user satisfaction and building performance. The study examines the correlation between time and overall satisfaction in three government buildings, through a mixed quantitative and qualitative method using questionnaires and walkthrough. It was found that time spent in the building significantly contributes to user satisfaction (ρ = 0.473, and ρ = 0.521) for total and waiting time respectively. The proposed model overcomes the constrains of the previous methods and predicts user satisfaction with 60 % accuracy.

Abstract Mucormycosis is a life-threatening opportunistic angioinvasive fungal infection. We aimed to describe the frequency, presentations, predictors, and in-hospital outcome of mucormycosis patients in the scope of CoronaVirusDisease-19 (COVID-19) during the third viral pandemic wave. This cross-sectional retrospective study included all patients who fulfilled the criteria of mucormycosis with concurrent confirmed covid19 infection admitted to Assuit University Hospital between March 2021 and July 2021. Overall, 433 patients with definite covid-19 infection, of which 33 (7.63%) participants were infected with mucormycosis. Mucormycosis was predominantly seen in males (21 vs. 12; p = 0.01). Diabetes mellitus (35% vs. 63.6%; p

Abstract Background Scientific studies require a well-prepared cascade of steps starting from the idea and formulating a research question passing through collecting data and analysis of the results to proper writing a good article and publication. The methodology section is the core of any scientific article. Main body Study designs in otolaryngology can be classified as “observational studies,” “experimental (interventional) studies,” and “meta-analysis—systematic review.” There may be a huge range in quality between kinds of studies. To standardize the method of reporting the quality of studies and include all important aspects in the evaluation process, a team of scientists created the reporting guidelines checklists. Conclusions In this article, we give a comprehensive review that can help authors to understand study designs in otolaryngology along with the appropriate reporting guidelines used in each study.

Background & Aims: Elimination of chronic HBV/HDV infection remains a major global health challenge. Targeting excessive hepatitis B surface antigen (HBsAg) release may provide an interesting window of opportunity to break immune tolerance and to achieve a functional cure using additional antivirals. Methods: We evaluated a HBsAg-specific human monoclonal antibody, as part of either a prophylactic or therapeutic strategy, against HBV/HDV infection in cell culture models and in human-liver chimeric mice. To assess prophylactic efficacy, mice were passively immunized prior to infection with HBV or HBV/HDV (coinfection and superinfection setting). Therapeutic efficacy was assessed in HBV and HBV/HDV-coinfected mice receiving 4 weeks of treatment. Viral parameters (HBV DNA, HDV RNA and HBsAg) were assessed in mouse plasma. Results: The antibody could effectively prevent HBV/HDV infection in a dose-dependent manner with IC50 values of ∼3.5 ng/ml. Passive immunization showed complete protection of mice from both HBV and HBV/HDV coinfection. Moreover, HDV superinfection was either completely prevented or at least attenuated in HBV-infected mice. Finally, antibody treatment in mice with established HBV/HDV infection resulted in a significant decline in viremia and a concomitant drop in on-treatment HBsAg, with a moderate viral rebound following treatment cessation. Conclusion: We present data on a valuable antibody candidate that could complement other antivirals in strategies aimed at achieving functional cure of chronic HBV and HDV infection. Impact and implications: Patients chronically infected with HBV may eventually develop liver cancer and are at great risk of being superinfected with HDV, which worsens and accelerates disease progression. Unfortunately, current treatments can rarely eliminate both viruses from chronically infected patients. In this study, we present data on a novel antibody that is able to prevent chronic HBV/HDV infection in a mouse model with a humanized liver. Moreover, antibody treatment of HBV/HDV-infected mice strongly diminishes viral loads during therapy. This antibody is a valuable candidate for further clinical development.

Abstract Background The Nasal Obstruction Symptom Evaluation (NOSE) scale has been developed and validated in English to overcome the controversies concerning other methods of evaluation of nasal obstruction. The scale is currently used worldwide and has been translated into several languages. The purpose of the present work was to translate the English (NOSE) scale into Arabic (A-NOSE) and to assess its validity and reliability in Arabic-speaking patients. Results The internal consistency and test-to-test reliability of the Arabic scale were statistically good. The differences between the scores of the patients and control subjects were statistically significant. Postoperative scores of the patients were significantly higher than preoperative scores. All participants completed the Arabic questionnaire easily and few of them required slight assistance. Conclusions The translated NOSE scale is easy to administer and can be a robust and usable outcome measure for patients with nasal obstruction. The translated scale is sensitive to changes in nasal airway patency and can be used in clinical practice and outcome research.

Abstract Background Randomized controlled trials (RCTs) are prospective comparative studies in which study groups are allocated randomly to intervention or serve as controls. RCT is the mainstay to achieve evidence in the literature in clinical research. A RCT is the main research design to study the effect of an intervention and the only way to confirm the value of a new treatment. Main body RCT also gives the way to generate meta-analyses and systematic reviews giving a stronger evidence for clinical practice. Evidence-based medicine (EBM) is crucial for safe, effective, and standardized patient care. Although there is an agreement on the importance of performing RCT, it can be challenging to do it efficiently including different aspects like study design, funding, randomization, blinding, follow-up, data analysis, statistics, generalization of results, and reporting of quality of the studies. Conclusion In this article, we gave a comprehensive review for RCT in otolaryngology discussing their importance, advantages, and drawbacks, types, steps, challenges, reporting their quality and their prevalence in the literature.

Abstract Background Allergic rhinitis is the most prevalent allergic disease, and the prevalence and sensitization patterns differ among countries. Identifying the most common inhalant allergen in each region plays a key role in the diagnosis and management of allergic rhinitis. There are no data available about the most prevalent aeroallergen among allergic rhinitis patients in Egypt. The aim of this study is to evaluate the prevalence of positive serum allergen-specific IGE to common inhalant allergens among allergic rhinitis patients in Egypt. A cross-sectional study was conducted on 354 allergic rhinitis patients, serum allergen-specific IGE was measured by using the Immuno CAP system to 16 common regional aeroallergens including (pollens, mite, molds, animal dander, and cockroach). Results The overall rate of sensitization to any allergen was 74.6%. Dermatophagoides pteronyssinus, birch pollens, and Dermatophagoides farina were the most prevalent allergens (29.7%, 23.7%, and 18.6%), respectively. Cladosporuim molds were the least prevalent individual allergens (1.7%). Conclusion Our data suggest that Dermatophagoides pteronyssinus and birch pollens were the predominant allergen sources among allergic rhinitis patient in Egypt.

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients’ age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.

Background: Jasmonic acid (JA) is a signal transducer molecule that plays an important role in plant development and stress response; it can also efficiently stimulate secondary metabolism in plant cells. Results: RNA-Seq technology was applied to identify differentially expressed genes and study the time course of gene expression in Rhazya stricta in response to JA. Of more than 288 million total reads, approximately 27% were mapped to genes in the reference genome. Genes involved during the secondary metabolite pathways were up- or downregulated when treated with JA in R. stricta. Functional annotation and pathway analysis of all up- and downregulated genes identified many biological processes and molecular functions. Jasmonic acid biosynthetic, cell wall organization, and chlorophyll metabolic processes were upregulated at days 2, 6, and 12, respectively. Similarly, the molecular functions of calcium-transporting ATPase activity, ADP binding, and protein kinase activity were also upregulated at days 2, 6, and 12, respectively. Time-dependent transcriptional gene expression analysis showed that JA can induce signaling in the phenylpropanoid and aromatic acid pathways. These pathways are responsible for the production of secondary metabolites, which are essential for the development and environmental defense mechanism of R. stricta during stress conditions. Conclusions: Our results suggested that genes involved in flavonoid biosynthesis and aromatic acid synthesis pathways were upregulated during JA stress. However, monoterpenoid indole alkaloid (MIA) was unaffected by JA treatment. Hence, we can postulate that JA plays an important role in R. stricta during plant development and environmental stress conditions.How to cite: Hajrah, NH, Rabah SO, Alghamdi MK, et al. Transcriptional analysis of Rhazya stricta in response to jasmonic acid. Electron J Biotechnol 2021;50. https://doi.org/10.1016/j.ejbt.2021.01.004

يتم في هذا البحث دراسة مفهوم التجمعات العمرانية المستدامة، ورکائزها الأساسية والترکيز على المبادئ الأساسية لاستدامة المياه في التجمعات العمرانية المستدامة حيث توصلت الدراسات السابقة الى المبادئ الرئيسية لاستدامة الموارد المائية في العمران وهي مرونة التعامل مع الموارد المائية، وجودة الموارد المائية، واخيرا مبدأ کفاءة استخدام الموارد المائية، والذي يرکز البحث عليه من خلال دراسة تجارب بعض الدول المختلفة في الظروف البيئية والمناخية وتوافر الموارد المائية في تحقيق کفاءة استخدام الموارد المائية في مناطق اسکان التجمعات العمرانية وهي الهند، والإمارات، واستراليا، فبالرغم من اختلاف خصائصها الا انها تتفق في الهدف، وهو تحقيق اقصى استغلال ممکن للموارد المائية من خلال العناصر العمرانية. وتم دراسة تأثير بعض العوامل العمرانية مثل الکثافة العمرانية، وتوزيع استعمالات الأراضي، والاشتراطات البنائية بالمناطق السکنية على کفاءة استخدام المياه في مناطق إسکان التجمعات العمرانية، ومن دراسة هذه التأثيرات توصل البحث الى تحديد العلاقة بين اهم هذه العوامل العمرانية، وکفاءة استخدام الموارد المائية، وبالتالي خلصت النتائج الى مجموعة من التوصيات التي يجب مراعاتها عند تخطيط المناطق السکنية، لتحقيق کفاءة استخدام المياه في العمران. Resiliency, Quality and Efficiency are the most important principles of water sustainability in urban Communities, and the research focuses on water use efficiency. The efficiency of using the water resources in the urban communities' housing areas is largely affected by some urban factors such as: distribution of land uses, urban density, construction conditions and infrastructure network. The research pinpoints the relationship between different urban factors of the housing areas in urban communities and the efficiency of using the water resources, through the analysis of the experiences in three different countries, namely India, UAE, and Australia. Consequently, the results concluded recommendations that must be considered when planning residential areas, to achieve water use efficiency in urban areas.

Background and Aim: As means for enhancing gastrointestinal (GI) motility, prokinetics have previously been evaluated in different breeds of horses with varying success. No previous studies were conducted to evaluate the effect of prokinetics on the intestinal tract of Arabian horses breed. Using B-mode ultrasound in the quantification of intestinal contractility, this study aimed to compare the impact of neostigmine and metoclopramide on the intestinal motility of healthy Arabian horses. Materials and Methods: Twenty-one clinically healthy Arabian horses were equally distributed into three groups. The control group was administered with 5 mL normal saline intramuscularly (IM). The second group was administered with neostigmine (0.044 mg/kg body weight [BW], IM), and the third group was administered with metoclopramide (0.25 mg/kg BW, IM). Duodenal, cecal, and colonic contractions were counted through ultrasonography for 3 min (pre-administration and 15, 30, 60, 120, and 180 min post-administration). Results: In the neostigmine group, a significant (p

Abstract Background Zinner’s syndrome is a rare congenital malformation involving the seminal vesicle that mostly shows cystic transformation. Embryogenesis of the kidney, ureter, seminal vesicle, and vas deferens can be altered if an insult occurs during the first trimester mainly between the 4th and the 13th gestational week. Cystic lesions of the seminal vesicle may present with a mass effect. Associated ipsilateral renal agenesis is a characteristic feature in more than 50% of patients as the seminal vesicles and ureteral buds originate from the mesonephric (Wolffian) duct. For management, the transrectal ultrasound provides good visualization of the seminal vesicles and the rest of the pelvic structures providing a good guidance for aspiration of the cysts. Case presentation We present a case of a seminal vesicle fluid-filled tubular lesion. The patient first complained of vague abdominal pain with lower abdominal fullness. He was clinically evaluated, and radiological evaluation was performed using different modalities, and finally, the patient took his decision to live with it without any intervention at present. Conclusions The combination of seminal vesicle cysts and ipsilateral renal agenesis, is a rare urological anomaly with an insult during the 1st trimester is to be considered as the first suspicion. Usual manifestations are caused by the seminal vesicle cysts that cause mass effect and irritation to the surroundings in the form of urinary bladder irritation and in sometimes obstruction as well as pain/discomfort in the perineum and scrotum. Epididymitis is frequently occurring as a complication. Treatment mainly consists of removing the seminal vesicle cyst/tubular lesion.

Melatonin, an antioxidant hormone secreted by the pineal gland, has been recognized as a regulator for numerous biological events. The deleterious effects of juglone, a polyphenolic extract of walnut trees, on embryo development has been previously reported. In the current study, we aimed to display the impact of melatonin administrated during in vitro oocyte maturation (IVM) on juglone-treated oocytes. Thus, in vitro matured oocytes were collected after 24 h post incubation with juglone in the presence or absence of melatonin. Reactive oxygen species (ROS), glutathione (GSH) content, mitochondrial distribution, and the relative abundance of mRNA transcription levels were assessed in oocytes, in addition, oocytes were in vitro fertilized to check the competency levels of oocytes to generate embryos. We found that administration of melatonin during the maturation of oocytes under juglone stress significantly improved the cleavage rate, 8-16 cell-stage embryos and day-8 blastocysts when compared to the sole juglone treatment. In addition, the fluorescence intensity of ROS increased, whereas the GSH decreased in juglone-treated oocytes compared to melatonin–juglone co-treated and untreated ones. Additionally, a significant increase in the mitochondrial aberrant pattern, the pattern that was normalized following melatonin supplementation, was observed following juglone administration. The mRNA analysis using RT-qPCR revealed a significant upregulation of autophagy and oxidative-stress-specific markers in the juglone-treated group compared to the co-treatment and control. In conclusion, the study reveals, for the first time, a protective effect of melatonin against the oxidative stress initiated following juglone treatment during the in vitro maturation of oocytes.

We have previously reported that juglone, a natural compound found in Juglandaceae with a wide range of biological activities, can reduces the developmental competence of bovine oocytes. In the current study, we investigated the possible mechanisms behind the toxicity of juglone and the relationship with PI3K/AKT/mTOR signaling during the in vitro maturation (IVM) of oocytes. Results show that oocyte exposure to juglone was associated with a significant decrease in filamentous actin (F-actin) accumulation. The RT-qPCR showed downregulation of the meiosis progression indicator GSK-3A, oocyte development marker BMP15, mitochondria fusion controlling MFN1, oxidative stress-related OGG1, and histone methylation-related EZH1, EZH2, SUZ12, G9a, and SUV39H2 genes in juglone-treated oocytes. In addition, glycolysis- (PFK1 and GLUT1), ATP synthesis- (ATPase8 and ATP5F1B), and OXPHOS-specific markers (SDHA and SDHD), as well as the oocyte survival regulators (SOD2, VEGF, and MAPK1) significantly decreased upon juglone treatment. Moreover, lower expression of PI3K, AKT, and mTOR was observed at the transcriptional and/or translational level(s). The autophagy markers LC3B and beclin-1 as well as the DNA damage-specific marker 8-OxoG displayed overexpression in juglone-exposed oocytes. Taken together, our results show that administration of juglone during the IVM can reduce the quality and developmental health of bovine oocytes through downregulation of the PI3K/AKT/mTOR pathway and its downstream signaling cascades.

A series of 3-substituted-4-chloro-thioxanthones and their corresponding S,S-dioxidethioxanthone derivatives were designed and synthesized. The effects of our synthesized compounds on cell viability toward the MCF-7 and MDA-MB-468 breast cancer cell lines were evaluated. The most active compound was 4f, which was active against the MCF-7 and MDA-MB-468 cell lines with respective IC50 values of 7.2 and 3.9 μM. Interestingly, compound 4f did not impair cell viability of the cardiac myoblast H9C2 cell line (IC50 > 25 μM), indicating that this compound might not exhibit cytotoxic effects on the normal cardiac cells. Further, compounds 4b, 4f, 4j, 4s, 5b, 5f, 5j, and 5s were characterized by the NCI screening system. Results revealed that compounds 4f and 4s had effective anticancer activities against various cancer cell lines. Finally, our results indicated that the 3-substituted-4-chloro-thioxanthone derivatives have the potential to be further developed as promising small molecules for anticancer applications. Keywords: Thioxanthone, Thioxanthen-9-one-10,10-dioxide, MCF-7, MDA-MB-468, NCI 60-cell panel assay

Abstract Background Desmoplastic small-round-cell tumor (DSRCT) is an extremely rare and highly aggressive malignancy. It is of yet unclear origin, but it is assumed to be of a mesothelial origin based on its tendency for widespread metastasis in serosal linings. Case presentation In this report, we describe a young female who presented with bilateral ovarian masses that mimicked the classic clinical picture of ovarian cancer. The patient had a cytoreductive surgery done in the form of total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic peritonectomy, low para-aortic and bilateral iliac lymphadenectomy. Postoperative course was smooth with no adverse events. The final pathology report revealed desmoplastic small-round-cell tumor. Afterwards, the patient was referred to medical oncologist to receive her adjuvant therapy. Conclusions DSRCT is still an unknown disease to us given the limited number of cases and poor survival. Given the lack of clear guidelines, treatment is offered based on the best available evidence and the collaborative effort of a multi-disciplinary team.

Enhancing Quality of life (QoL) in cities through achieving a livable and sustainable environment has become one of the imperatives of modern planning and of increasing concern to the public; this term nowadays is linked to the rapid urbanization process in cities especially among the less developing nations. Livability is a concept related to human well-being. Therefore, creating livable streets that enhance safety, comfort, and social relations is one of the main goals among all planners and policy makers. A major threat to quality of life is the high volume of vehicle traffic which is associated with different physical, health, social and environmental consequences. Keywords: Livability, Residential streets, Planning regulations, Livable streets, Statistical analysis

The World Health Organization (WHO) recently alerted the emergence of new pathogens causing acute hepatitis in children across several countries. This new situation directs us to the screening of neglected pathogens that cause acute hepatitis. Q-fever is a zoonotic disease, caused by Coxiella burnetii. Although a high seroprevalence of Coxiella burnetii was recorded in animals present in Egypt, Q-fever is still a neglected disease, and the diagnosis of Q-fever is not routinely performed in Egyptian hospitals. In this study, we performed a retrospective assessment for Coxiella burnetii in cases of hepatitis of unknown causes (HUC) enrolled in Assiut University hospitals, in Egypt. Out of 64 samples of HUC, 54 samples were negative for all hepatitis markers, labeled as acute hepatitis of unknown etiology (AHUE), and 10 samples tested positive for adenovirus and Hepatitis E virus (HEV). Q-fever was detected in 3 out of 54 (5.6%) of AHUE, and one sample was confirmed as coinfection of HEV/Q-fever. Jaundice was the most common clinical symptom developed in the patients. In conclusion, Coxiella burnetii was found to be a potential cause of acute hepatitis in HUC. The diagnosis of Q-fever should be considered in acute hepatitis cases in Egyptian hospitals.

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils’ anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 μg/mL, respectively. In contrast, at 20 MPa, the IC50 values were about 2.33, 6.59, and 19.0 μg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 μg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC50 14.4 μg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens.

Background: This study was designed to investigate Saudis' attitudes toward mental distress and psychotropic medication, attribution of causes, expected side effects, and to analyze participants' expectations toward alternative or complementary medicine using aromatic and medicinal plants, through a survey.Method: The study included 674 participants (citizens and residents in Saudi Arabia) who were randomly contacted via email and social media and gave their consent to complete a questionnaire dealing with 39 items that can be clustered in six parts. Descriptive statistics and Chi-square for cross-tabulation were generated using SPSS.Results: Among the 664 participants, 73.4% believed that there are some positive and negative outcomes of psychotropic medication. Participants (72.0%) think that the most important reason leading to psychological disorders is mainly due to the loss of a relative or beloved person, and 73.9% considered psychic session as one of the possible treatments of psychological disorders. Surprisingly, only 18.8% of the participants agreed that medicinal and aromatic plants could be a possible treatment of the psychological disorder. Participants (82%) consider that physicians are the most trustful and preferred source of information about alternative and complementary medicine.

As part of our research on developing multi-target small molecule anticancer agents, we designed, synthesized, and biologically evaluated a series of novel diversified analogues based on our thiadiazole-fused anthraquinone lead compound NSC745885. We initially screened our compounds based on their cytotoxicities against two prostate cancer cell lines (PC-3 and DU-145). Cytotoxicities of the selected compounds (3, 5, 6, 10, 11, 14, 15, 17, 18) were then evaluated using the single-dose testing against a panel of 60 cancer cell lines. Compounds which exceeded the threshold inhibition criteria (3, 6, 10, 11, 14, 17) were further evaluated using the five-dose cytotoxicity experiments against the panel of 60 cancer cell lines. Our compounds exhibited potent antiproliferative effects against the tested cancer cell lines with 50% growth inhibition (GI50) values in the sub-micro molar range. Furthermore, 3 and 6 showed high selectivity towards the leukemia subpanel, whereas 6 showed high selectivity towards the prostate subpanel. Our potent compound 11 (RV59, NSC763967) showed broad-spectrum cytotoxicity against different types of cancer cells, while being less cytotoxic than doxorubicin towards different normal cells (SV-HUC-1, WMPY-1, and RWPE-1). COMPARE analysis of the cytotoxicity data indicated that 11 is similar to the apoptosis-based anticancer drugs. We confirmed the apoptotic effects of 11 by microscopy, Western blotting, and flow cytometry of treated cancer cells, and found that it caused cells to exhibit apoptotic morphology, inhibited cyclin D1 and COX-2 in a dose-dependent manner, and accumulated cells at the G0/G1 phase with reduction of cells in the S and G2/M phases of cell cycle. Moreover, we tested the inhibition capabilities of our compounds towards Topoisomerases (TOP) using computational modeling and found that they are specific inhibitors to TOP1. Our data presented here presents our compounds as potential multi-target anticancer drugs.

Major depression disorder (MDD) has become a common life-threatening disorder. Despite the number of studies and the introduced antidepressants, MDD remains a major global health issue. Carthamus tinctorius (safflower) is traditionally used for food and medical purposes. This study investigated the chemical profile and the antidepressant-like effect of the Carthamus tincto-rius hot water extract in male mice and its mechanism using a transcriptomic analysis. The antidepressant effect of hot water extract (50 mg/kg and 150 mg/kg) was investigated in mice versus the untreated group (saline) and positive control group (fluoxetine 10 mg/kg). Hippocampus transcriptome changes were investigated to understand the Carthamus tinctorius mechanism of action. The GC-MS analysis of Carthamus tinctorius showed that hot water extract yielded the highest amount of oleamide as the most active ingredient. Neuro-behavioral tests demonstrated that the safflower treatment significantly reduced immobility time in TST and FST and improved performance in the YMSAT compared to the control group. RNA-seq analysis revealed a significant differential gene expression pattern in several genes such as Ube2j2, Ncor1, Tuba1c, Grik1, Msmo1, and Casp9 related to MDD regulation in 50 mg/kg safflower treatment as compared to untreated and fluoxetine-treated groups. Our findings demonstrated the antidepressant-like effect of safflower hot water extract and its bioactive ingredient oleamide on mice, validated by a significantly shortened immobility time in TST and FST and an increase in the percentage of spontaneous alternation.

Hydroxyapatite nanoparticles (HAn) have been produced as biomaterial from biowaste, especially snail shells (Atactodea glabrata). It is critical to recycle the waste product in a biomedical application to overcome antibiotic resistance as well as biocompatibility with normal tissues. Moreover, EDX, TEM, and FT-IR analyses have been used to characterize snail shells and HAn. The particle size of HAn is about 15.22 nm. Furthermore, higher inhibitory activity was observed from HAn than the reference compounds against all tested organisms. The synthesized HAn has shown the lowest MIC values of about 7.8, 0.97, 3.9, 0.97, and 25 µg/mL for S. aureus, B. subtilis, K. pneumonia, C. albicans, and E. coli, respectively. In addition, the HAn displayed potent antibiofilm against S. aureus and B. subtilis. According to the MTT, snail shell and HAn had a minor influence on the viability of HFS-4 cells. Consequently, it could be concluded that some components of waste, such as snail shells, have economic value and can be recycled as a source of CaO to produce HAn, which is a promising candidate material for biomedical applications.

Salmonella enterica is one of the most common causes of foodborne illness worldwide. Contaminated poultry products, especially meat and eggs are the main sources of human salmonellosis. Thus, the aim of the present study was to determine prevalence, antimicrobial resistance profiles, virulence, and resistance genes of Salmonella Enteritidis (S. enteritidis) and Salmonella Typhimurium (S. Typhimurium) isolated from laying hens, table eggs, and humans, in Sharkia Governorate, Egypt. The antimicrobial activity of Biosynthesized Silver Nanoparticles (AgNPs) was also evaluated. Salmonella spp. were found in 19.3% of tested samples with laying hens having the highest isolation rate (33.1%). S. Enteritidis) (5.8%), and S. Typhimurium (2.8%) were the dominant serotypes. All isolates were ampicillin resistant (100%); however, none of the isolates were meropenem resistant. Multidrug-resistant (MDR) was detected in 83.8% of the isolates with a multiple antibiotic resistance index of 0.21 to 0.57. Most isolates (81.1%) had at least three virulence genes (sopB, stn, and hilA) and none of the isolates harbored the pefA gene; four resistance genes (blaTEM, tetA, nfsA, and nfsB) were detected in 56.8% of the examined isolates. The AgNPs biosynthesized by Aspergillus niveus exhibit an absorption peak at 420 nm with an average size of 27 nm. AgNPs had a minimum inhibitory concentration of 5 µg/mL against S. enteritidis and S. typhimurium isolates and a minimum bactericidal concentration of 6 and 8 µg/mL against S. enteritidis and S. typhimurium isolates, respectively. The bacterial growth and gene expression of S. enteritidis and S. typhimurium isolates treated with AgNPs were gradually decreased as storage time was increased. In conclusion, this study indicates that S. enteritidis and S. typhimurium isolated from laying hens, table eggs, and humans exhibits resistance to multiple antimicrobial classes. The biosynthesized AgNPs showed potential antimicrobial activity against MDR S. enteritidis and S. typhimurium isolates. However, studies to assess the antimicrobial effectiveness of the biosynthesized AgNPs in laying hen farms are warranted.

Abstract Background Calotropis procera is a wild plant species in the family Apocynaceae that is able to grow in harsh, arid and heat stressed conditions. Understanding how this highly adapted plant persists in harsh environments should inform future efforts to improve the hardiness of crop and forage plant species. To study the plant response to droμght and osmotic stress, we treated plants with polyethylene glycol and NaCl and carried out transcriptomic and metabolomics measurements across a time-course of five days. Results We identified a highly dynamic transcriptional response across the time-course including dramatic changes in inositol signaling, stress response genes and cytokinins. The resulting metabolome changes also involved sharp increases of myo-inositol, a key signaling molecule and elevated amino acid metabolites at later times. Conclusions The data generated here provide a first glimpse at the expressed genome of C. procera, a plant that is exceptionally well adapted to arid environments. We demonstrate, through transcriptome and metabolome analysis that myo-inositol signaling is strongly induced in response to drought and salt stress and that there is elevation of amino acid concentrations after prolonged osmotic stress. This work should lay the foundations of future studies in adaptation to arid environments.

Abstract Background Targeted superparamagnetic iron oxide (SPIO) nanoparticles have emerged as a promising biomarker detection tool for molecular magnetic resonance (MR) image diagnosis. To identify patients who could benefit from Epidermal growth factor receptor (EGFR)-targeted therapies, we introduce lipid-encapsulated SPIO nanoparticles and hypothesized that anti-EGFR antibody cetuximab conjugated of such nanoparticles can be used to identify EGFR-positive glioblastomas in non-invasive T2 MR image assays. The newly introduced lipid-coated SPIOs, which imitate biological cell surface and thus inherited innate nonfouling property, were utilized to reduce nonspecific binding to off-targeted cells and prevent agglomeration that commonly occurs in nanoparticles. Results The synthesized targeted EGFR-antibody-conjugated SPIO (EGFR-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, gel electrophoresis mobility shift assays, transmission electron microscopy (TEM) images, and cell line affinity assays, and the results showed that the conjugation was successful. The targeting efficiency of the synthesized EGFR-SPIO nanoparticles was confirmed through Prussian blue staining and TEM images by using glioblastoma cell lines with high or low EGFR expression levels. The EGFR-SPIO nanoparticles preferentially targeted U-251 cells, which have high EGFR expression, and were internalized by cells in a prolonged incubation condition. Moreover, the T2 MR relaxation time of EGFR-SPIO nanoparticles could be used for successfully identifying glioblastoma cells with elevated EGFR expression in vitro and distinguishing U-251 cells from U-87MG cells, which have low EFGR expression. Conclusion These findings reveal that the lipid-encapsulated EGFR-SPIO nanoparticles can specifically target cells with elevated EGFR expression in the three tested human glioblastoma cell lines. The results of this study can be used for noninvasive molecular MR image diagnosis in the future.

Abstract Objective The objective of the study was to translate the Sino-Nasal Outcome Test 22 (SNOT-22) into Arabic and to check its reliability and validity in Arabic-speaking patients. Patients and methods The study included 178 patients with confirmed chronic rhinosinusitis (CRS) and 95 asymptomatic individuals as a control group. All participants completed the Arabic SNOT-22 (A-SNOT-22) questionnaire. The scores of the two groups were compared for validity analysis. Eighty-two patients completed the questionnaire twice, 1 week apart, for test-to-test reliability analysis. The A-SNOT-22 scores of 60 CRS patients were correlated with Lund–Mackay scores for criterion validity analysis. The preoperative and postoperative scores of 73 patients were compared for responsiveness analysis. Results All participants completed the questionnaire with no or minimal assistance. Internal consistency (α=0.90) and test-to-test reliability (intraclass correlation=0.78) were good. The differences between the scores of CRS patients and asymptomatic individuals were significant (P

Abstract Background Tonsillectomy is one of the commonest otolaryngological procedures performed. Multiple reports have demonstrated the safety of ambulatory (outpatient) pediatric Tonsillectomy, however Post-tonsillectomy hemorrhage remains the most serious complication of tonsillectomy. Patients and methods In this work, we analyzed different parameters including patient’s age, gender, type of surgery “Tonsillectomy or Adenotonsillectomy”, technique “Cold dissection or Bipolar”, evidence of tonsillar bed infection and pre-operative hemoglobin level in two groups of patients indicated for tonsillectomy. One group of 80 patients didn’t suffer from posttonsillectomy bleeding as a control group; the other of 20 patients having secondary post-tonsillectomy bleeding. Results According to our statistical analysis and data, no significant difference between the two groups regarding the occurrence of secondary post-tonsillectomy in the following parameters: patient’s age, gender, type of surgery “Tonsillectomy or Adenotonsillectomy” and preoperative hemoglobin level. Conclusion However there was higher incidence of secondary post tonsillectomy bleeding in patients operated by bipolar scissors. Also evidence of tonsillar bed infection raises the possibility of secondary post-tonsillectomy bleeding occurrenc.

Abstract Objectives To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. Trial design This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. Participants All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. Inclusion criteria: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. Exclusion criteria: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. Intervention and comparator The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. Main outcomes As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. Randomisation After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. Blinding (masking) Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. Numbers to be randomised (sample size) We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). Trial Status The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. Trial registration The protocol is registered before starting subject recruitment under the title: “Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial” in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Considerable health and climate benefits arising from the use of low-sulfur fuels has propelled the research on desulfurization of fossil fuels. Ideal fuels are urgently needed and are expected to be ultra-low in sulfur (10–15 ppm), with no greater than 50 ppm sulfur content. Although several sulfur removal techniques are available in refineries and petrochemical units, their high operational costs, complex operational needs, low efficiencies, and higher environmental risks render them unviable and challenging to implement. In recent years, mesoporous silica-based materials have emerged as promising desulfurizing agents, owing to their high porosity, high surface area, and easier functionalization compared to conventional materials. In this review, we report on recent progress in the synthesis and chemistry of new functionalized mesoporous silica materials aiming to lower the sulfur content of fuels. Additionally, we discuss the role of special active sites in these sorbent materials and investigate the formulations capable of encapsulating and trapping the sulfur-based molecules, which are challenging to remove due to their complexity, for example the species present in JP-8 jet fuels.

Nicotinamide (NAM), the amide form of vitamin B3, plays pivotal roles in regulating various cellular processes including energy production and maintenance of genomic stability. The current study aimed at deciphering the effect of NAM, when administered during in vitro maturation (IVM), on the developmental competence of bovine preimplantation embryos. Our results showed that low NAM concentrations reduced the oxidative stress and improved mitochondrial profile, total cleavage and 8–16 cell stage embryo development whereas the opposite profile was observed upon exposure to high NAM concentrations (10 mM onward). Remarkably, the hatching rates of day-7 and day-8 blastocysts were significantly improved under 0.1 mM NAM treatment. Using RT-qPCR and immunofluorescence, the autophagy-related (Beclin-1 (BECN1), LC3B, and ATG5) and the apoptotic (Caspases; CASP3 and 9) markers were upregulated in oocytes exposed to high NAM concentration (40 mM), whereas only CASP3 was affected, downregulated, following 0.1 mM treatment. Additionally, the number of cells per blastocyst and the levels of SIRT1, PI3K, AKT, and mTOR were higher, while the inner cell mass-specific transcription factors GATA6, SOX2, and OCT4 were more abundant, in day-8 embryos of NAM-treated group. Taken together, to our knowledge, this is the first study reporting that administration of low NAM concentrations during IVM can ameliorate the developmental competence of embryos through the potential regulation of oxidative stress, apoptosis, and SIRT1/AKT signaling.

The study underpins barcode characterization of insect species collected from Saudi Arabia and explored functional constraints during evolution at the DNA and protein levels to expect the possible mechanisms of protein evolution in insects. Codon structure designated AT-biased insect barcode of the cytochrome C oxidase I (COI). In addition, the predicted 3D structure of COI protein indicated tyrosine in close proximity with the heme ligand, depicted substitution to phenylalanine in two Hymenopteran species. This change resulted in the loss of chemical bonding with the heme ligand. The estimated nucleotide substitution matrices in insect COI barcode generally showed a higher probability of transversion compared with the transition. Computations of codon-by-codon nonsynonymous substitutions in Hymenopteran and Hemipteran species indicated that almost half of the codons are under positive evolution. Nevertheless, codons of COI barcode of Coleoptera, Lepidoptera and Diptera are mostly under purifying selection. The results reinforce that codons in helices 2, 5 and 6 and those in loops 2-3 and 5-6 are mostly conserved and approach strong purifying selection. The overall results argue the possible evolutionary position of Hymenopteran species among those of other insects.

With more than 71 million chronically infected people, the hepatitis C virus (HCV) is a major global health concern. Although new direct acting antivirals have significantly improved the rate of HCV cure, high therapy cost, potential emergence of drug-resistant viral variants, and unavailability of a protective vaccine represent challenges for complete HCV eradication. Relevant animal models are required, and additional development remains necessary, to effectively study HCV biology, virus–host interactions and for the evaluation of new antiviral approaches and prophylactic vaccines. The chimpanzee, the only non-human primate susceptible to experimental HCV infection, has been used extensively to study HCV infection, particularly to analyze the innate and adaptive immune response upon infection. However, financial, practical, and especially ethical constraints have urged the exploration of alternative small animal models. These include different types of transgenic mice, immunodeficient mice of which the liver is engrafted with human hepatocytes (humanized mice) and, more recently, immunocompetent rodents that are susceptible to infection with viruses that are closely related to HCV. In this review, we provide an overview of the currently available animal models that have proven valuable for the study of HCV, and discuss their main benefits and weaknesses.

Rhazya stricta is an evergreen shrub that is widely distributed across Western and South Asia, and like many other members of the Apocynaceae produces monoterpene indole alkaloids that have anti-cancer properties. This species is adapted to very harsh desert conditions making it an excellent system for studying tolerance to high temperatures and salinity. RNA-Seq analysis was performed on R. stricta exposed to severe salt stress (500 mM NaCl) across four time intervals (0, 2, 12 and 24 h) to examine mechanisms of salt tolerance. A large number of transcripts including genes encoding tetrapyrroles and pentatricopeptide repeat (PPR) proteins were regulated only after 12 h of stress of seedlings grown in controlled greenhouse conditions. Mechanisms of salt tolerance in R. stricta may involve the upregulation of genes encoding chaperone protein Dnaj6, UDP-glucosyl transferase 85a2, protein transparent testa 12 and respiratory burst oxidase homolog protein b. Many of the highly-expressed genes act on protecting protein folding during salt stress and the production of flavonoids, key secondary metabolites in stress tolerance. Other regulated genes encode enzymes in the porphyrin and chlorophyll metabolic pathway with important roles during plant growth, photosynthesis, hormone signaling and abiotic responses. Heme biosynthesis in R. stricta leaves might add to the level of salt stress tolerance by maintaining appropriate levels of photosynthesis and normal plant growth as well as by the participation in reactive oxygen species (ROS) production under stress. We speculate that the high expression levels of PPR genes may be dependent on expression levels of their targeted editing genes. Although the results of PPR gene family indicated regulation of a large number of transcripts under salt stress, PPR actions were independent of the salt stress because their RNA editing patterns were unchanged.

The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 values in the sub-micro molar range against cancer cells rather than normal cardiac cells. NSC757963 showed high selectivity towards the leukemia subpanel. Activities of both compounds strongly correlated to expression of NFKB1 and CSNK2B genes, implying that they may inhibit the NF-κB pathway. Immunocytochemical microscopy of OVCAR-3 cells showed clear cytosolic accumulation of the NF-κB p65 subunit following treatment. Western blotting showed dose dependent inhibition of the nuclear expression of the NF-κB p65 subunit with subsequent accumulation in the cytosol following treatment. Docking experiments showed binding of both compounds to the NF-κB activator IKKβ subunit preventing its translocation to the nucleus. Collectively, these results confirm the ability of our compounds to inhibit the constitutively active NF-κB pathway of OVCAR-3 cells. Furthermore, COMPARE analysis indicated that the activity of NSC757963 is similar to the antituberculosis agent rifamycin SV, this was confirmed by testing the antimycobacterial activity of NSC757963 against Mycobacterium tuberculosis, results revealed potent activity suitable for use in clinical practice. Molecular properties and Lipinski's parameters predicted acceptable bioavailability properties with no indication of mutagenicity, tumorigenicity, irritability and reproductive effects. Oral absorption experiments using the human Caco-2 model showed high intestinal absorption of NSC745885 by passive transport mechanism with no intestinal efflux or active transport mechanisms. The unique molecular characterization as well as the illustrated anticancer spectra of activity and bioavailability properties warrant further development of our compounds and present a foundation brick in the pre-clinical investigations to implement such compounds in clinical practice.

The Cas9 endonuclease is used for genome editing applications in diverse eukaryotic species. A high frequency of off-target activity has been reported in many cell types, limiting its applications to genome engineering, especially in genomic medicine. Here, we generated a synthetic chimeric protein between the catalytic domain of the FokI endonuclease and the catalytically inactive Cas9 protein (fdCas9). A pair of guide RNAs (gRNAs) that bind to sense and antisense strands with a defined spacer sequence range can be used to form a catalytically active dimeric fdCas9 protein and generate double-strand breaks (DSBs) within the spacer sequence. Our data demonstrate an improved catalytic activity of the fdCas9 endonuclease, with a spacer range of 15-39 nucleotides, on surrogate reporters and genomic targets. Furthermore, we observed no detectable fdCas9 activity at known Cas9 off-target sites. Taken together, our data suggest that the fdCas9 endonuclease variant is a superior platform for genome editing applications in eukaryotic systems including mammalian cells.

Thirty-six three-day old Saanen goat kids were divided into four groups (GM, WGM, MR and WMR). GM kids received goat milk to age 48 days. WGM group was initially fed goat milk, but started weaning at 25 days and was completely weaned by 40 days. MR kids were fed a milk replacer to age 48 days. WMR kids were initially fed the milk replacer and then subjected to the same weaning protocol used for WGM kids. During the experimental period, total consumption per group was recorded daily. Weekly, body weights were recorded and plasma samples were taken and analyzed for glucose, free aminoacids and insulin. Weaning significantly decreased dry matter intake in WGM and WMR. Nonetheless, no difference was observed in body weight between the four groups, throughout the study period. Weaning decreased plasma glucose, aminoacids and insulin in WGM and WMR groups. Soon after the first week of treatment, plasma glucose and free aminoacids began to be lower in milk replacer-fed kids (MR and WMR), in comparison to goat milk-fed ones (GM and WGM). Results suggest that weaning affects glucose and aminoacid metabolism and insulin secretion, while milk replacer feeding reduces plasma glucose and free aminoacids, without affecting insulin.

Eighteen three-day old Saanen goat kids were divided into MILK and WEAN groups. MILK kids received goat milk to age 48 days; WEAN kids were initially fed milk but started weaning at 25 days and were completely weaned by 40 days. Total intake per group was recorded daily. On day 25, 40 and 48, body weights were recorded, and plasma samples were taken and analyzed for glucose, free amino-acids and insulin. On day 48, all animals were slaughtered and pancreas samples were analyzed for total DNA and RNA content. Histological sections of pancreas were examined by light microscope and images analyzed by dedicated software. Seven days after the beginning of the weaning program, dry matter intake in the WEAN group began to decrease compared to the MILK one. Nonetheless, body weight did not differ throughout the study period. Weaning significantly decreased plasma levels of glucose, amino-acids and insulin. No difference was observed in pancreatic DNA and RNA content. Histological analysis of pancreas showed that the size of pancreatic islets was not different, but islet number per section was lower in the pancreas of WEAN animals. In conclusion, weaning affects glucose and amino-acid metabolism and influences endocrine pancreas activity and morphology.