Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation.

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.

A NiO-nanostructure-based electrochemical sensor functionalized with supramolecular structures for the ultra-sensitive detection of the endocrine disruptor bisphenol S in an aquatic environment.

Herein, NiO nanoparticles (NPs) functionalized with a para-hexanitrocalix[6]arene derivative (p-HNC6/NiO) were synthesized by using a facile method and applied as a selective electrochemical sensor for the determination of bisphenol S (BPS) in real samples. Moreover, the functional interactions, phase purities, surface morphologies and elemental compositions of the synthesized p-HNC6/NiO NPs were investigated via advanced analytical tools, such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). Additionally, the synthesized p-HNC6/NiO NPs were cast on the surface of a bare glassy carbon electrode (GCE) via a drop casting method, which resulted in uniform deposition of p-HNC6/NiO/GCE over the surface of the GCE. Additionally, the developed p-HNC6/NiO/GCE sensor demonstrated an outstanding electrochemical response to BPS under optimized conditions, including a supporting electrolyte, a Briton-Robinson buffer electrolyte at pH 4, a scan rate of 110 mV s-1 and a potential window of between -0.2 and 1.0 V. The wide linear dynamic range was optimized to 0.8-70 µM to obtain a brilliant linear calibration curve for BPS. The limit of detection (LOD) and limit of quantification (LOQ) of the developed sensor were estimated to be 0.0059 and 0.019 µM, respectively, which are lower than those of reported sensors for BPS. The feasibility of the developed method was successfully assessed by analyzing the content of BPS in waste water samples, and good recoveries were achieved.

Nanomedicine: Patuletin-conjugated with zinc oxide exhibit potent effects against Gram-negative and Gram-positive bacterial pathogens.

With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO' nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin's effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work.

Anti-Acanthamoebic effects of silver-conjugated tetrazole nanoparticle.

Tetrazoles are five-membered ring aromatic heterocyclic molecules that consist of one carbon and four nitrogen atoms. Several tetrazole-based drugs have shown promising activities against bacteria, fungi, asthma, cancer, hypertension etc. The overall aim of this study was to determine anti-Acanthamoebic properties of tetrazoles and tetrazole-conjugated silver nanoparticles. Tetrazole-conjugated silver nanoparticles were synthesized and confirmed using ultraviolet-visible spectrometry, Dynamic light scattering, and Fourier-transform infrared spectroscopy. Using amoebicidal, encystment, and excystment assays, the findings revealed that tetrazoles exhibited antiamoebic properties and these effects were enhanced when conjugated with silver nanoparticles. Importantly, conjugation with silver nanoparticles inhibited parasite-mediated human cell death in vitro, as measured by lactate dehydrogenase release, but it reduced toxic effects of drugs alone on human cells. Overall, these results showed clearly that tetrazoles exhibit potent antiamoebic properties which can be enhanced by conjugation with silver nanoparticles and these potential in the rational development of therapeutic interventions against parasitic infections such as keratitis and granulomatous amoebic encephalitis due to pathogenic Acanthamoeba.

The effect of educational animation compared to leaflets on patients' knowledge regarding root canal treatment: a randomized controlled trial.

BACKGROUND: Incorporating video as a tool for education offers a multitude of advantages. However, it is unknown what is the best educational tool to use for increasing public awareness, consequently reducing fear about root canal treatment. For this reason, this study aimed to compare the effectiveness of educational animation and leaflets as delivery methods for providing information on root canal treatment to patients and to assess their ability to retain the information. METHODS: One hundred fifty adult volunteers were recruited via social media and Umm Al-Qura University Dental Hospital to participate in this randomized control trial study. The volunteers were divided into the study group (SG) and the control group (CG). The SG was provided with information through animations created by the research team, while the CG received the same information through a leaflet. Pre-intervention (T1), immediate post-intervention (T2), and one-month post-intervention (T3) validated questionnaires were completed by the participants to assess the changes in their knowledge. To evaluate the impact of the information delivery method, the knowledge scores of T2 and T3 were compared to T1 within each group using Paired T-tests. Additionally, the study compared the knowledge scores of the two groups using unpaired T-tests. The significance level was set at a P-value of less than 0.05. RESULTS: A significant improvement in endodontic therapy knowledge among the participants in both groups (T1 compared to T2 in the same group) was noted (P < 0.050). However, when comparing T2 between groups, no significant difference was found in delivering the information and improving the knowledge (P = 0.080). Still, the mean differences between T1 and T2, as well as T1 and T3, were greater (P < 0.050) in the SG than in the CG. Furthermore, the total knowledge score in the SG at T3 was significantly higher than the CG. CONCLUSION: Both educational animation and leaflets are practical tools to increase patients' awareness about root canal treatment. However, educational videos are more effective than leaflets in delivering and retaining information about root canal treatment. TRIAL REGISTRATION: This study was retrospectively registered as a randomized control trial at the ISRCTN registry with the document number ISRCTN18413241, 15/05/2023.

Cell death of Acanthamoeba castellanii following exposure to antimicrobial agents commonly included in contact lens disinfecting solutions.

Several antimicrobial agents are commonly included in contact lens disinfectant solutions including chlorhexidine diacetate (CHX), polyhexamethylene biguanide (PHMB) or myristamidopropyl dimethylamine (MAPD); however, their mode of action, i.e. necrosis versus apoptosis is incompletely understood. Here, we determined whether a mechanism of cell death resembling that of apoptosis was present in Acanthamoeba castellanii of the T4 genotype (NEFF) following exposure to the aforementioned antimicrobials using the anticoagulant annexin V that undergoes rapid high affinity binding to phosphatidylserine in the presence of calcium, making it a sensitive probe for phosphatidylserine exposure. The results revealed that under the conditions employed in this study, an apoptotic pathway of cell death in this organism at the tested conditions does not occur. Our findings suggest that necrosis is the likely mode of action; however, future mechanistic studies should be accomplished in additional experimental conditions to further comprehend the molecular mechanisms of cell death in Acanthamoeba.

The anti-amoebic potential of carboxamide derivatives containing sulfonyl or sulfamoyl moieties against brain-eating Naegleria fowleri.

Naegleria fowleri is a free-living thermophilic flagellate amoeba that causes a rare but life-threatening infection called primary amoebic meningoencephalitis (PAM), with a very high fatality rate. Herein, the anti-amoebic potential of carboxamide derivatives possessing sulfonyl or sulfamoyl moiety was assessed against pathogenic N. fowleri using amoebicidal, cytotoxicity and cytopathogenicity assays. The results from amoebicidal experiments showed that derivatives dramatically reduced N. fowleri viability. Selected derivatives demonstrated IC50 values at lower concentrations; 1j showed IC50 at 24.65 µM, while 1k inhibited 50% amoebae growth at 23.31 µM. Compounds with significant amoebicidal effects demonstrated limited cytotoxicity against human cerebral microvascular endothelial cells. Finally, some derivatives mitigated N. fowleri-instigated host cell death. Ultimately, this study demonstrated that 1j and 1k exhibited potent anti-amoebic activity and ought to be looked at in future studies for the development of therapeutic anti-amoebic pharmaceuticals. Further investigation is required to determine the clinical relevance of our findings.

Expert opinion on the use of transvaginal sonography for presurgical staging and classification of endometriosis.

Gynecological ultrasonography plays a central role in the management of endometriosis. The rapid technical development as well as the currently increasing evidence for non-invasive diagnostic methods require an updated compilation of recommendations for the use of ultrasound in the management of endometriosis. The present work aims to highlight the accuracy of sonography for diagnosing and classifying endometriosis and will formulate the present list of key messages and recommendations. This paper aims to demonstrate the accuracy of TVS in the diagnosis and classification of endometriosis and to discuss the clinical applications and consequences of TVS findings for indication, surgical planning and assessment of associated risk factors. (1) Sophisticated ultrasound is the primary imaging modality recommended for suspected endometriosis. The examination procedure should be performed according to the IDEA Consensus. (2) Surgical intervention to confirm the diagnosis alone is not recommended. A preoperative imaging procedure with TVS and/or MRI is strongly recommended. (3) Ultrasound examination does not allow the definitive exclusion of endometriosis. (4) The examination is primarily transvaginal and should always be combined with a speculum and a bimanual examination. (5) Additional transabdominal ultrasonography may enhance the accuracy of the examination in case of extra pelvic disease, extensive findings or limited transvaginal access. (6) Sonographic assessment of both kidneys is mandatory when deep endometriosis (DE) and endometrioma are suspected. (7) Endometriomas are well defined by sonographic criteria. When evaluating the ovaries, the use of IOTA criteria is recommended. (8) The description of sonographic findings of deep endometriosis should be systematically recorded and performed using IDEA terminology. (9) Adenomyosis uteri has sonographically well-defined criteria (MUSA) that allow for detection with high sensitivity and specificity. MRI is not superior to differentiated skilled ultrasonography. (10) Classification of the extent of findings should be done according to the #Enzian classification. The current data situation proves the best possible prediction of the intraoperative situs of endometriosis (exclusive peritoneum) for the non-invasive application of the #Enzian classification. (11) Transvaginal sonographic examination by an experienced examiner is not inferior to MRI diagnostics regarding sensitivity and specificity in the prediction of the extent of deep endometriosis. (12) The major advantage of non-invasive imaging and classification of endometriosis is the differentiated planning or possible avoidance of surgical interventions. The recommendations represent the opinion of experts in the field of non-invasive and invasive diagnostics as well as therapy of endometriosis. They were developed with the participation of the following national and international societies: DEGUM, ÖGUM, SGUM, SEF, AGEM/DGGG, and EEL.

Density Functional Theory Calculations and Molecular Docking Analyses of Flavonoids for Their Possible Application against the Acetylcholinesterase and Triose-Phosphate Isomerase Proteins of Rhipicephalus microplus.

Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-ß-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases.

Review on carbon-based adsorbents from organic feedstocks for removal of organic contaminants from oil and gas industry process water: Production, adsorption performance and research gaps.

Large amounts of process water with considerable concentrations of recalcitrant organic contaminants, such as polycyclic aromatic hydrocarbon (PAHs), phenolic compounds (PCs), and benzene, toluene, ethylbenzene, and xylene (BTEX), are generated by several segments of oil and gas industries. These segments include refineries, hydraulic fracturing (HF), and produced waters from the extraction of shale gas (SGPW), coalbed methane (CBMPW) and oil sands (OSPW). In fact, the concentration of PCs and PAHs in process water from refinery can reach 855 and 742 mg L-1, respectively. SGPW can contain BTEX at concentrations as high as 778 mg L-1. Adsorption can effectively target those organic compounds for the remediation of the process water by applying carbon-based adsorbents generated from organic feedstocks. Such organic feedstocks usually come from organic waste materials that would otherwise be conventionally disposed of. The objective of this review paper is to cover the scientific progress in the studies of carbon-based adsorbents from organic feedstocks that were successfully applied for the removal of organic contaminants PAHs, PCs, and BTEX. The contributions of this review paper include the important aspects of (i) production and characterization of carbon-based adsorbents to enhance the efficiency of organic contaminant adsorption, (ii) adsorption properties and mechanisms associated with the engineered adsorbent and expected for certain pollutants, and (iii) research gaps in the field, which could be a guidance for future studies. In terms of production and characterization of materials, standalone pyrolysis or hybrid procedures (pyrolysis associated with chemical activation methods) are the most applied techniques, yielding high surface area and other surface properties that are crucial to the adsorption of organic contaminants. The adsorption of organic compounds on carbonaceous materials performed well at wide range of pH and temperatures and this is desirable considering the pH of process waters. The mechanisms are frequently pore filling, hydrogen bonding, π-π, hydrophobic and electrostatic interactions, and same precursor material can present more than one adsorption mechanism, which can be beneficial to target more than one organic contaminant. Research gaps include the evaluation of engineered adsorbents in terms of competitive adsorption, application of adsorbents in oil and gas industry process water, adsorbent regeneration and reuse studies, and pilot or full-scale applications.

Potential Antiviral Action of Alkaloids.

Viral infections and outbreaks have become a major concern and are one of the main causes of morbidity and mortality worldwide. The development of successful antiviral therapeutics and vaccines remains a daunting challenge. The discovery of novel antiviral agents is a public health emergency, and extraordinary efforts are underway globally to identify safe and effective treatments for different viral diseases. Alkaloids are natural phytochemicals known for their biological activities, many of which have been intensively studied for their broad-spectrum of antiviral activities against different DNA and RNA viruses. The purpose of this review was to summarize the evidence supporting the efficacy of the antiviral activity of plant alkaloids at half-maximum effective concentration (EC50) or half-maximum inhibitory concentration (IC50) below 10 µM and describe the molecular sites most often targeted by natural alkaloids acting against different virus families. This review highlights that considering the devastating effects of virus pandemics on humans, plants, and animals, the development of high efficiency and low-toxicity antiviral drugs targeting these viruses need to be developed. Furthermore, it summarizes the current research status of alkaloids as the source of antiviral drug development, their structural characteristics, and antiviral targets. Overall, the influence of alkaloids at the molecular level suggests a high degree of specificity which means they could serve as potent and safe antiviral agents waiting for evaluation and exploitation.

Defect Engineering in Metal-Organic Frameworks Towards Advanced Mixed Matrix Membranes for Efficient Propylene/Propane Separation.

Highly permselective and durable membrane materials have been sought for energy-efficient C3 H6 /C3 H8 separation. Mixed-matrix membranes (MMMs) comprising a polymer matrix and metal-organic frameworks (MOFs) are promising candidates for this application; however, rational matching of filler-matrix is challenging and their separation performances need to be further improved. Here, we propose a novel strategy of "defect engineering" in MOFs as an additional degree of freedom to design advanced MMMs. MMMs incorporated with defect-engineered MOFs exhibit exceptionally high C3 H6 permeability and maintained C3 H6 /C3 H8 selectivity, especially with enhanced stability under industrial mixed-gas conditions. The gas transport, sorption, and material characterizations reveal that the defect sites in MOFs provide the resulting MMMs with not only ultrafast diffusion pathways but also favorable C3 H6 sorption by forming complexation with unsaturated open metal sites, confirmed by in situ FT-IR studies. Most importantly, the concept is also valid for different polymer matrices and gas pairs, demonstrating its versatile potential in other fields.

Gestational weight gain and preterm birth in obese women: a systematic review and meta-analysis.

BACKGROUND: Prepregnant obesity is a global concern and gestational weight gain has been found to influence the risks of preterm birth. OBJECTIVE: To assess the relationship between gestational weight gain and risk for preterm birth in obese women. SEARCH STRATEGY: Four electronic databases were searched from 18 February through to 28 April 2015. SELECTION CRITERIA: Primary research reporting preterm birth as an outcome in obese women and gestational weight gain as a variable that could be compared to the 2009 Institute of Medicine's recommendations. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion. The Newcastle Ottawa Scale was used to assess study bias. MAIN RESULTS: Our search identified six studies meeting the inclusion criteria; five were conducted in the USA and one in Peru. Four studies with a total of 10 171 obese women were meta-analysed. Significant heterogeneity was found between studies in the pooled analysis. Results for indicated preterm birth in obese women with gestational weight gain above the Institute of Medicine's recommendations showed increased risk (adjusted odds ratio 1.54; 95% CI 1.09-2.16). CONCLUSIONS: Available science on this topic is limited to special populations of obese pregnant women. Generalisable research is needed to assess the variation in risk for preterm birth in obese women by differences in gestational weight gain and class of obesity controlling for significant variables in the pathway to preterm birth. This research has the potential to illuminate new science impacting preterm birth and interventions for prevention.

In silico identification of phytochemical inhibitors for multidrug-resistant tuberculosis based on novel pharmacophore generation and molecular dynamics simulation studies.

BACKGROUND: Multidrug-resistant tuberculosis (particularly resistant to pyrazinoic acid) is a life-threatening chronic pulmonary disease. Running a marketed regime specifically targets the ribosomal protein subunit-1 (RpsA) and stops trans-translation in the non-mutant bacterium, responsible for the lysis of bacterial cells. However, in the strains of mutant bacteria, this regime has failed in curing TB and killing pathogens, which may only because of the ala438 deletion, which inhibit the binding of pyrazinoic acid to the RpsA active site. Therefore, such cases of tuberculosis need an immediate and effective regime. OBJECTIVE: This study has tried to determine and design such chemotypes that are able to bind to the mutant RpsA protein. METHODS: For these purposes, two phytochemical databases, i.e., NPASS and SANCDB, were virtually screened by a pharmacophore model using an online virtual screening server Pharmit. RESULTS: The model of pharmacophore was developed using the potential inhibitor (zr115) for the mutant of RpsA. Pharmacophore-based virtual screening results into 154 hits from the NPASS database, and 22 hits from the SANCDB database. All the predicted hits were docked in the binding pocket of the mutant RpsA protein. Top-ranked five and two compounds were selected from the NPASS and SANCDB databases respectively. On the basis of binding energies and binding affinities of the compounds, three compounds were selected from the NPASS database and one from the SANCDB database. All compounds were found to be non-toxic and highly active against the mutant pathogen. To further validate the docking results and check the stability of hits, molecular dynamic simulation of three compounds were performed. The MD simulation results showed that all these finally selected compounds have stronger binding interactions, lesser deviation or fluctuations, with greater compactness compared to the reference compound. CONCLUSION: These findings indicate that these compounds could be effective inhibitors for mutant RpsA.

Successful treatment of gastric bleeding caused by left phrenic artery pseudoaneurysm post-surgery with endovascular embolization: A case report.

Pseudoaneurysms are rare but potentially life-threatening complications that may occur after surgical procedures. This report presents the case of a 28-year-old woman who developed a pseudoaneurysm in the Left Inferior Phrenic Artery (LIPA) following a Laparoscopic Sleeve Gastrectomy (LSG). The complication manifested as severe gastrointestinal bleeding. Upper GI Endoscopy and multislice CT scan, repeated twice, failed to localize the bleeding source to treat it. Successful endovascular embolization using a Glue/Lipidol mixture was achieved despite difficulties in localizing the pseudoaneurysm, resulting in immediate symptomatic relief and avoiding surgical intervention. This case shows the importance of prompt identification and management of LIPA pseudoaneurysms following LSG, highlighting the importance of early diagnosis to prevent further hemodynamic deterioration and other adverse outcomes.

Low-Resistance Membrane vs. High-Resistance Membrane Performance Utilizing Electrodialysis-Evaporator Hybrid System in Treating Reject Brine from Kuwait Desalination Plants.

This work is an effort to mitigate the existing environmental issues caused by brine discharge from Kuwait's desalination plants and to find an economical and efficient way of managing reject brine from local desalination plants. Low- and high-resistance membranes (LRMs and HRMs, respectively) were used to produce salt and low-salinity water from brine effluent utilizing an electrodialysis (ED)-evaporator hybrid system. The effect of high current densities of 300, 400, and 500 A/m2 and brine flowrates of 450 and 500 L/h on the quality of produced salt and diluate were investigated for LRM and HRM. The recovered salt purity for LRM is up to 90.58%. Results show that the low-resistance membrane (LRM) achieved higher water recovery, energy consumption, desalination rate, operation time and ion removal rate than those of the high-resistance membrane (HRM) under the same operating conditions. The difference in concentration for 300 A/m2 between LRM and HRM increased from 0.93% at 10 min to 8.28% at 140 min. The difference in diluate concentration effluent is negligible for both membranes, whereas LRM produced higher concentrate effluent than HRM for all current densities and low flowrate (400 L/h). The maximum difference between LRM and HRM (with LRM achieving higher concentrations) is 10.7% for 400 A/m2. The permselectivity of LRM for monovalent cations decreased with current density, whereas the effect on permselectivity for HRM was insignificant for the current density values. The addition of a neutral cell was effective in reducing the buildup of divalent ions on the inner membrane of the cathode side.

Structure-based investigation of pyruvate dehydrogenase kinase-3 inhibitory potential of thymoquinone, targeting lung cancer therapy.

Protein kinases are an attractive therapeutic target for cardiovascular, cancer and neurodegenerative diseases. Cancer cells demand energy generation through aerobic glycolysis, surpassing "oxidative phosphorylation" (OXPHOS) in mitochondria. The pyruvate dehydrogenase kinases (PDKs) have many regulatory roles in energy generation balance by controlling the pyruvate dehydrogenase complex. Overexpression of PDKs is associated with the overall survival of cancer. PDK3, an isoform of PDK is highly expressed in various cancer types, is targeted for inhibition in this study. PDK3 has been shown to binds strongly with a natural compound, thymoquinone (TQ), which is known to exhibit anti-cancer potential. Detailed interaction between the PDK3 and TQ was carried out using spectroscopic and docking methods. The overall changes in the protein's structures after TQ binding were estimated by UV-Vis spectroscopy, circular dichroism and fluorescence binding studies. The kinase activity assay was also carried out to see the kinase inhibitory potential of TQ. The enzyme inhibition assay suggested an excellent inhibitory potential of TQ towards PDK3 (IC50 = 5.49 µM). We observed that TQ forms a stable complex with PDK3 without altering its structure and can be a potent PDK3 inhibitor which may be implicated in cancer therapy after desired clinical validation.

Investigating mechanistic insights of curcumin in blocking the Interleukin-8 signaling pathway associated with Breast Cancer: An in-silico approach.

Interleukin-8 (IL-8) is a chemokine, a type of signaling molecule that has a role in immunological responses and inflammation. In recent years, IL-8 is additionally related to cancer growth and recurrence. Breast cancer growth, progression, and metastatic development are all linked to IL-8. Breast cancer cells are known to develop faster when IL-8 stimulates their proliferation and survival. It can also cause angiogenesis, or the creation of new blood vessels, which is necessary for tumor nutrition and growth. IL-8 and curcumin have been subjects of interest in drug design, particularly in the context of inflammation-related disorders and cancer. This study aims to give an overview of the role of IL-8. Inhibitor-based treatment approaches were being used to target IL-8 with curcumin. Molecular docking method was employed to find a potential interaction to supress competitive inhibition of IL-8 with curcumin. PASS analysis and ADMET characteristics were also being carried out. In the end, IL-8 complexed with curcumin is chosen for MD simulations. Overall, our results showed that during the simulation, the complex stayed comparatively stable. It is also possible to investigate curcumin further as a possible treatment option. The combined results imply that IL-8 and their genetic alterations can be studied in precision cancer therapeutic treatments, utilizing target-driven therapy and early diagnosis.

African swine fever; insights into genomic aspects, reservoirs and transmission patterns of virus.

African swine fever is a hemorrhagic disease of pigs with high mortality rates. Since its first characterization in 1921, there has been sufficient information about African swine fever virus (ASFV) and related diseases. The virus has been found and maintained in the sylvatic cycle involving ticks and domestic and wild boars in affected regions. The ASFV is spread through direct and indirect contact with infected pigs, their products and carrier vectors especially Ornithodoros ticks. Severe economic losses and a decline in pig production have been observed in ASFV affected countries, particularly in sub-Saharan Africa and Europe. At the end of 2018, the ASFV adversely affected China, the world's leading pork-producer. Control strategies for the disease remained challenging due to the unavailability of effective vaccines and the lack of successful therapeutic measures. However, considerable efforts have been made in recent years to understand the biology of the virus, surveillance and effective control measures. This review emphasizes and summarizes the current state of information regarding the knowledge of etiology, epidemiology, transmission, and vaccine-based control measures against ASFV.