Search Results (96)

Infectious bronchitis virus (IBV) commonly produces a range of genetic sequences during replication, particularly in the spike 1 (S1)-coding portion of the S gene, leading to distinct subpopulations within the broader viral population. It has been shown that certain microenvironments exert selective pressure on the S1-coding sequences and their encoded proteins, influencing the selection of viral subpopulations in these environments. In this study, high-throughput next-generation sequencing (NGS) was used to analyze the S1-coding sequences from tissues of the respiratory, digestive, renal, and reproductive systems of specific pathogen-free (SPF) laying hens. These tissues were collected nine days after infection with the California 1737/04 (CA1737/04) IBV strain, which is known to cause varying degrees of pathology in these tissues. Using a specific bioinformatics pipeline, 27 single nucleotide variants (SNVs) were detected in the S1-coding sequences derived from different tissues. These SNVs shaped multiple subpopulations (SP1–SP15), with SP1 being the core subpopulation present in all tissues, while others were tissue-specific. The IBV RNA loads in the tissues were negatively correlated with the number of SNVs or the Shannon entropy values, and phylogenetic analysis revealed a genetic divergence in the S1-coding sequences from certain tissues with lower viral RNA loads, particularly those from the trachea and ovary. Furthermore, the SNVs were associated with nonsynonymous mutations, primarily located in hypervariable region 2 (HVR 2) within the N-terminal domain of S1 (S1-NTD), except for those in SP7, which was exclusive to the trachea and contained changes in HVR 3 in the C-terminal domain of S1 (S1-CTD). Overall, this study adds to the existing knowledge about IBV evolution by highlighting the role of tissue-specific environments in shaping viral genetic diversity. Full article

Outbreaks of the West Nile Virus (WNV) have increased significantly in recent years in the Mediterranean region, including Tunisia. To understand the risks for animal and human health and to mitigate the impact of future outbreaks, comprehensive viral surveillance in vertebrate hosts and vectors is needed. We conducted the first serosurvey for the WNV in ruminants in southern Tunisia using the ELISA test and confirmed it with the micro-virus neutralization test (VNT). Antibodies were detected by the ELISA test in camels (38/112), sheep (9/155), and goats (7/58), and six samples were doubtful (five camels and one sheep). The ELISA positive and doubtful sera (n = 60) were further analyzed to confirm the presence of specific anti-WNV and anti-Usutu virus (USUV) antibodies using the micro-virus neutralization test (VNT). Out of the 60 sera, 33 were confirmed for specific WNV antibodies, with an overall seroprevalence of 10.15% [95% CI: 7.09–13.96]. The high seroprevalence observed in camels (22.3%) suggests their potential use as sentinel animals for WNV surveillance in southern Tunisia. The viral genome, and consequently active circulation, could not be detected by real-time RT-qPCR in blood samples. Ongoing surveillance of the WNV in animals, including camels, sheep, and goats, may be used for the early detection of viral circulation and for a rapid response to mitigate potential outbreaks in horses and humans. Full article

This study investigates the influences of financial performance and economic determinants (inflation rate and economic growth) on financial distress (FD) in the MENA region in the context of the contagion effect theory and Minsky’s financial instability theory. This paper examines the determinants of financial distress in the MENA region from 2002 until 2020 using pooled OLS, fixed effect, and GMM panel estimation models; then the results are used to estimate the effect over the long run. The results show that the things that cause financial distress are changing a lot between countries in the MENA region. This shows how important it is to separate the effects of economic and financial factors. The results show the significance of economic growth, ROA, ROE, inflation, and stock market profitability using fixed effects. The results changed when we used GMM, concluding that economic growth, ROA, ROE, and stock market profitability were significant, while inflation was not significant. Therefore, there is a significant and negative relationship between financial distress and economic growth in GCC-MENA as well as other MENA countries. Our results can be of importance to investors and regulators. The introduction of a more stable political environment and engagement in international economic and financial markets will decrease the negative impacts of financial distress and boost economic growth and its sustainability in the MENA region. Full article

Self-emulsifying drug delivery systems (SEDDS) represent an innovative approach to improving the solubility and bioavailability of poorly water-soluble drugs, addressing significant challenges associated with oral drug delivery. This review highlights the advancements and applications of SEDDS, including their transition from liquid to solid forms, while addressing the formulation strategies, characterization techniques, and future prospects in pharmaceutical sciences. The review systematically analyzes existing studies on SEDDS, focusing on their classification into liquid and solid forms and their preparation methods, including spray drying, hot-melt extrusion, and adsorption onto carriers. Characterization techniques such as droplet size analysis, dissolution studies, and solid-state evaluations are detailed. Additionally, emerging trends, including 3D printing, hybrid systems, and supersaturable SEDDS (Su-SEDDS), are explored. Liquid SEDDS (L-SEDDS) enhance drug solubility and absorption by forming emulsions upon contact with gastrointestinal fluids. However, they suffer from stability and leakage issues. Transitioning to solid SEDDS (S-SEDDS) has resolved these limitations, offering enhanced stability, scalability, and patient compliance. Innovations such as personalized 3D-printed SEDDS, biologics delivery, and targeted systems demonstrate their potential for diverse therapeutic applications. Computational modeling and in silico approaches further accelerate formulation optimization. SEDDS have revolutionized drug delivery by improving bioavailability and enabling precise, patient-centric therapies. While challenges such as scalability and excipient toxicity persist, emerging technologies and multidisciplinary collaborations are paving the way for next-generation SEDDS. Their adaptability and potential for personalized medicine solidify their role as a cornerstone in modern pharmaceutical development. Full article

Background/Objectives: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repeated administration. The current inquiry intended to fabricate nose-to-brain chitosan-grafted cationic leciplexes of MRZ (CS-MRZ-LPX) to improve its pharmacokinetic weaknesses and boost the pharmacodynamics aspects. Methods: Primarily, MRZ-loaded leciplexes (MRZ-LPXs) were fabricated and tailored employing a central composite design (CCD). Vesicle diameter size (VS), entrapment efficiency (EE %), cumulative MRZ release percentage (CMRZR %), and total quantity penetrating after twenty-four hours (Q24) were the four parameters assessed. Then, the determined optimum formulation was coated with chitosan (CS-MRZ-LPX) and utilized in pharmacodynamics investigations and in vivo biologic distribution studies in Wistar male rats. Results: The customized MRZ-LPX formulation had a diameter size of 186.2 ± 3.5 nm and drug EE of 45.86 ± 0.76%. Also, the tailored MRZ-LPX formulation had a cumulative amount of MRZ released of 76.66 ± 3.06% and the total Q24 permeated was 383.23 ± 13.08 µg/cm². Intranasal delivery of the tailored CS-MRZ-LPX revealed notably superior pharmacokinetic attributes inside the brain and circulation compared to the orally administered MRZ suspension and the intranasal free drug suspension (p < 0.05); the relative bioavailability was 370.9% and 385.6% for plasma and brain, respectively. Pharmacodynamics’ and immunohistopathological evaluations proved that optimum intranasal CS-MRZ-LPX boosted antidepressant activity compared to the oral and free nasal drug administration. Conclusions: CS-MRZ-LPX tailored formulation can potentially be regarded as a prospective nano platform to boost bioavailability and enhance pharmacodynamics efficacy. Ultimately, intranasal CS-MRZ-LPX can be considered a promising avenue for MRZ targeted brain delivery as an antidepressant. Full article

Background: The study aimed to assess dental anxiety (self and proxy reported) using a Modified Dental Anxiety Scale (MDAS) and modified short State-Trait Anxiety Inventory scale (Emoji). Methods: 200 children visiting the pediatric dental clinic at the College of Dentistry at Prince Sattam bin Abdulaziz University were recruited to assess their anxiety levels. The anxiety score was measured before and after the treatment using a short STAI scale and MDAS of 200 children using a Modified Dental Anxiety Scale (MDAS) and a modified short STAI (Emoji) Scale. Results: The perception of children with MDAS was found to have the highest mean score of 14.54 ± 3.82 before the dental procedure compared to the mean score of 9.40 ± 2.90 after the dental procedure. This difference was statistically significant (p < 0.001). A statistically significant difference was observed in MDAS after the dental procedure and, in short, STAI before the dental procedure. Conclusion: All children improved their dental anxiety levels before and after the procedure. Therefore, procedural experience may improve the child’s response. Full article

Background/objectives: Idiopathic pulmonary fibrosis (IPF) is a prevalent interstitial lung disease that typically progresses gradually, leading to respiratory failure and ultimately death. IPF can be treated with the tyrosine kinase inhibitor, nintedanib (NTD), owing to its anti-fibrotic properties, which ameliorate the impairment of lung function. This study aimed to formulate, optimize, and assess NTD-loaded ufasomes (NTD-UFSs) as a nanosystem for its pulmonary targeting to snowball the bioavailability and therapeutic efficacy of the drug. Methods: To investigate the influence of numerous factors on NTD-UFSs assembly and to determine the optimal formulation, Box–Behnken statistical design was implemented with the assistance of Design-Expert^® software. The thin-film hydration strategy was employed to fabricate NTD-UFSs. The optimum NTD-UFSs formulation was subsequently selected and subjected to additional evaluations. Also, using a rat model, a comparative pharmacokinetic analysis was scrutinized. Results: The optimal NTD-UFSs elicited an accumulative release of 65.57% after 24 h, an encapsulation efficiency of 62.51%, a zeta potential of −36.07 mV, and a vesicular size of 364.62 nm. In addition, it disclosed remarkable stability and a continuous cumulative release pattern. In vivo histopathological studies ascertained the tolerability of NTD-UFSs administered intratracheally. According to the pharmacokinetic studies, intratracheal NTD-UFSs administration manifested a significantly higher AUC_0–∞ value than oral and intratracheal NTD suspensions, by approximately 5.66- and 3.53-fold, respectively. Conclusions: The findings of this study proposed that UFSs might be a promising nanoparadigm for the non-invasive pulmonary delivery of NTD. Full article

The present research emphasizes fabrication alongside the assessment of an innovative nano-vesicular membranous system known as invasomes (NVMs) laden with Mirtazapine for rectal administration. This system could circumvent the confines of orally administered counterparts regarding dose schedules and bioavailability. Mirtazapine invasomes were tailored by amalgamating phospholipid, cineole, and ethanol through a thin-film hydration approach rooted in the Box–Behnken layout. Optimization of composition parameters used to fabricate desired NVMs’ physicochemical attributes was undertaken using the Design-Expert^® program. The optimal MRZ-NVMs were subsequently transformed to a pH-triggered in situ rectal gel followed by animal pharmacodynamic and pharmacokinetic investigations relative to rectal plain gel and oral suspension. The optimized NVMs revealed a diameter size of 201.3 nm, a z potential of −28.8 mV, an entrapment efficiency of 81.45%, a cumulative release within 12 h of 67.29%, and a cumulative daily permeated quantity of 468.68 µg/cm². Compared to the oral suspension, pharmacokinetic studies revealed a 2.85- and 4.45-fold increase in calculated rectal bioavailability in circulation and brain, respectively. Pharmacodynamic and immunohistopathology evaluations exposed superior MRZ-NVMs attributed to the orally administered drug. Consequently, rectal MRZ-NVMs can potentially be regarded as a prospective nanoplatform with valuable pharmacokinetics and tolerability assets. Full article

In response to the high performance requirements of pulse width modulation (PWM) converters in grid-connected power systems, H-Infinity (H∞) control has attracted significant research interest due to its robustness against parameter variations and external disturbances. In this work, an advanced robust H∞ control is proposed for a grid-connected three-phase PWM rectifier. A two-level control strategy is adopted, where cascaded H∞ controllers are designed to simultaneously regulate the DC bus voltage and input currents even under load disturbances and non-ideal grid conditions. As a result, unit power factor, stable DC bus voltage, and sinusoidal input currents with lower harmonics can be accurately achieved. The design methodology and stability of the proposed controller are verified through a comprehensive analysis. Simulation tests and experimental implementation on a dSPACE 1103 board demonstrate that the proposed control scheme can effectively enhance disturbance rejection performance under various operating conditions. Full article

Despite the prevalent application of 18% Ni maraging steel in critical sectors such as aerospace and automotive due to its unique characteristics, including high ductility, yield strength, and hardenability, its machining presents enormous challenges, categorizing it as a difficult-to-machine material. The cutting tool’s geometry is crucial in machining, significantly affecting chip formation, cutting forces, power consumption, and obtainable surface quality. In particular, wiper insert technology, characterized by its multi-radius design, offers an increased contact area compared to conventional inserts, potentially enhancing the quality of the machined surface. This study explores the effectiveness of wiper inserts in the face-milling of maraging steel 350, conducting a comparative analysis across three distinct machining setups. These setups vary by alternating the number of wiper and conventional inserts within the same cutter, thereby examining the influence of insert configuration on machining outcomes. The research employs a reliable and well-established statistical approach to evaluate how different variables, such as cutting speed and feed rate, affect surface quality, power consumption, and material removal rate (MRR). It also sheds light on the material removal mechanisms facilitated by each type of insert. The findings reveal that incorporating a higher number of wiper inserts significantly enhances the surface finish but concurrently increases power consumption. Thus, the study successfully identifies an optimal set of process parameters that attain a balance between achieving superior surface quality and maintaining energy efficiency in the machining of maraging steel 350. This balance is crucial for optimizing manufacturing processes while adhering to the stringent quality and sustainability standards required in aerospace and automotive manufacturing. Full article

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul^® MCM, Gelucire^® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus^® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes. Full article

Chronic myeloid leukemia (CML), while traditionally a disease of the elderly, has recently risen in incidence among younger patients. Hence, fertility concerns have emerged considering the disease process and treatments, especially with the current scarce and conflicting recommendations. This review explores the impact of CML treatments including the first-line tyrosine kinase inhibitors (TKIs) and other treatments on male fertility in chronic myeloid leukemia (CML) patients. The aim of this review was to compile the available evidence on male fertility to ultimately tailor treatment plans for male CML patients for whom fertility and future chances for conception pose a concern. The data available on the conventional and newer TKIs to address fertility concerns were reviewed, particularly the potential long- and short-term effects. Also, the possible side effects on subsequent generations were a crucial focus point of this review to reach a more comprehensive CML management approach. We found and compared the evidence on TKIs approved to treat CML. We also reported the effects of hydroxyurea, interferon, and transplantation, which are considered second-line treatments. Our findings suggest that these drugs might have an undiscovered effect on fertility. More research with larger sample sizes and longer follow-up periods is essential to solidify our understanding of these effects. Full article

Hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) patients has transitioned from the standard of care to a treatment option limited to those with unsatisfactory tyrosine kinase inhibitor (TKI) responses and advanced disease stages. In recent years, the threshold for undergoing HSCT has increased. Most CML patients now have life expectancies comparable to the general population, and therefore, the goal of therapy is shifting toward achieving treatment-free remission (TFR). While TKI discontinuation trials in CML show potential for achieving TFR, relapse risk is high, affirming allogeneic HSCT as the sole curative treatment. HSCT should be incorporated into treatment algorithms from the time of diagnosis and, in some patients, evaluated as soon as possible. In this review, we will look at some of the recent advances in HSCT, as well as its indication in the era of aiming for TFR in the presence of TKIs in CML. Full article

A DC microgrid is an efficient way to combine diverse sources; conventional droop control is unable to achieve both accurate current sharing and required voltage regulation. This paper provides a new adaptive control approach for DC microgrid applications that satisfies both accurate current sharing and appropriate voltage regulation depending on the loading state. As the load increases in parallel, so do the output currents of the distributed generating units, and correct current sharing is necessary under severe load conditions. The suggested control approach raises the equivalent droop gains as the load level increases in parallel and provides accurate current sharing. The droop parameters were checked online and changed using the principal current sharing loops to reduce the variation in load current sharing, and the second loop also transferred the droop lines to eliminate DC microgrid bus voltage fluctuation in the adaptive droop controller, which is different and inventive. The proposed algorithm is tested using a variety of input voltages and load resistances. This work assesses the performance and stability of the suggested method using a linearized model and verifies the results using an acceptable model created in MATLAB/SIMULINK Software Version 9.3 and using Real-Time Simulation Fundamentals and hardware-based experimentation. Full article