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MS-275, a histone deacetylase inhibitor, has proven anticancer activities against various malignancies. However, its clinical application has been constrained by dose-limiting toxicity, off-target effects, and variable clinical outcomes. Clinical data suggest that sustained low MS-275 doses could achieve a more selective and consistent effect. This study aimed at enhancing the anticancer activity of MS-275 by encapsulating it in D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles. The produced nanoformulations were characterized by their low polydispersity (0.201), negative zeta potential (−0.397 mV), and high entrapment efficiency (98.8%). Experimental evaluation of the formulation showed a significant reduction in HepG2, HCT116, and MCF7 cells’ viability, associated with enhanced apoptosis at a lower IC50 compared to MS-275 alone. The formulation was further examined on cancer cells xenografted on the chorioallantoic membrane (CAM) of chick embryos. The results showed a substantial reduction in tumor size. TPGS micelles alone induced an accumulation in G1 and slightly reduced the cellular viability of the examined cell lines. Our results suggest that encapsulating MS-275 in TPGS micelles represents a promising strategy to enhance MS-275 therapeutic impact while minimizing its pharmacological dosage.

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Perillyl alcohol (PA), a naturally existing monocyclic terpene related to limonene, is characterized by its poor aqueous solubility and very limited bioavailability. Its potential anti-cancer activity against malignant glioma has been reported. The aim was to develop PA-loaded lipid-based nanocarriers (LNCs), and to investigate their anti-cancer activity against two different brain cell lines. Non-medicated and PA-loaded LNCs were prepared and characterized. The mechanism of cytotoxic activity of PA was conducted using a molecular docking technique. The cell viabilities against A172 and ANGM-CSS cells were evaluated. The results revealed that the average particle size of the prepared LNCs ranged from 248.67 ± 12.42 to 1124.21 ± 12.77 nm, the polydispersity index was 0.418 ± 0.043–0.509 ± 0.064, while the zeta potential ranged from −36.91 ± 1.31 to −15.20 ± 0.96 mV. The molecular docking studies demonstrated that the drug had binding activity to human farnesyltransferase. Following exposure of the two glioblastoma cell lines to the PA-loaded nanoformulations, MTS assays were carried out, and the data showed a far lower half-maximal inhibitory concentration in both cell lines when compared to pure drug and non-medicated nanocarriers. These results indicate the potential in vitro antiproliferative activity of PA-loaded LNCs. Therefore, the prepared PA-loaded nanocarriers could be used to enhance drug delivery across the blood–brain barrier (BBB) in order to treat brain cancer, especially when formulated in a suitable dosage form. The size, surface charge, and lipid composition of the LNCs make them promising for drug delivery across the BBB. Detailed pharmacokinetic and pharmacodynamic assessments, including the evaluation of BBB penetration, are necessary to better understand the compound’s distribution and effects within the brain.

The synthetic allosteric effector of hemoglobin, TD-7 has been investigated as a potential therapeutic agent for the treatment of sickle cell disease. The pharmacologic activity of TD-7 is due to formation of a Schiff-base interaction between its aldehyde group and the two N-terminal αVal1 amines of hemoglobin, effectively inhibiting sickling of red blood cells. However, TD-7 faces a challenge in terms of poor oral bioavailability due to rapid in-vivo oxidative metabolism of its aldehyde functional group. To address this shortcoming, researches have explored the use of a L-cysteine ethyl ester group to cap the aldehyde group to form a thiazolidine aromatic aldehyde prodrug complex, resulting in the improvement of the metabolic stability of this class of compounds. This report details the synthesis of a thiazolidine prodrug of TD-7, referred to as Pro-7, along with a comprehensive investigation of Pro-7 functional and biological properties. In an in-vitro Hb modification and Hb oxygen affinity studies using normal whole blood, as well as erythrocyte sickling inhibition using sickle whole blood, Pro-7 exhibited a gradual onset but progressive increase in all activities. Additionally, in-vivo pharmacokinetic studies conducted with Sprague Dawley rats demonstrated that Pro-7 can undergo hydrolysis to release TD-7. However, the blood concentration of TD-7 did not reach the desired therapeutic level. These findings suggest that the incorporation of the L-cysteine ethyl ester group to TD-7 represents a promising strategy to enhance the metabolic stability of aromatic aldehydes that could lead to the development of a more effective drug for the treatment of sickle cell disease.

6-Mercaptopurine (6-MP) is a chemotherapeutic agent with inadequate efficacy due to its poor aqueous solubility and limited bioavailability. Turmeric oil is a naturally occurring bioactive substance obtained from the rhizomes of Curcuma longa Linn that has well-known antiproliferative activities. The aim of this study was to develop a 6-MP-loaded turmeric oil-based self-nanoemulsifying drug delivery system (SNEDDS) to improve the anticancer activity of 6-MP. Turmeric oil was extracted and used in a range of 15–25% to develop SNEDDS formulations utilizing tween 80 and dimethyl sulfoxide as the surfactant and cosurfactant, respectively. The size, charge, and effect of the formulations on the viability against HepG2 and MCF-7 cell models, as well as the apoptosis and cell cycle, were analyzed. The prepared SNEDDS formulations were in the size range of 425.7 ± 7.4–303.6 ± 19.3 nm, using a polydispersity index of 0.429–0.692 and electronegative surface charges. Moreover, 6-MP-loaded SNEDDS with 15% turmeric oil content (F1) showed smaller particle sizes and a noticeable antiproliferative activity against both cell line models. Also, F1 showed a higher rate of late apoptosis than the pure drug and the corresponding non-medicated formulation. A morphological study revealed significant changes in the HepG2 cells compared to untreated cells. More cells halted in the S phase, and a marked decrease in the proportions of cells in the G1/G0 phase was observed when using SNEDDS formulation compared to pure drug. Thus, SNEDDS formulation is a promising drug delivery system for improving the antiproliferative activity of 6-MP, especially when turmeric oil is incorporated.

Abstract Background Rosuvastatin (RSV) is a poorly water-soluble drug that has an absolute oral bioavailability of only 20%. The aim of this work was to prepare a positively charged chitosan coated flexible lipid-based vesicles (chitosomes) and compare their characteristics to the corresponding negatively charged flexible liposomal nanoparticles (NPs) in order to develop new RSV nanocarrier systems. Methods Three formulation factors affecting the development of chitosomes nano-formulation were optimized for their effects on the particles size, entrapment efficiency (EE) and zeta potential. The optimized flexible chitosomes and their corresponding liposomal NPs were characterized for morphology, in vitro release, flexibility and intestinal cell viability. The half maximum inhibitory concentrations (IC50) for both formulations were calculated. Results The drug to lipid molar ratio, edge activator percent and the chitosan concentration were significantly affecting the characteristics of NPs. The optimized chitosomes nano-formulation exhibited larger size, higher EE and greater zeta potential value when compared to the corresponding liposomal NPs. Both formulations showed a spherical shape nanostructure with a marked outer shell for the chitosomes nano-formulation. Chitosomes illustrated an extended drug release profile when compared with the corresponding liposomal NPs and the prepared drug suspension. Flexibility of both vesicles was confirmed with superiority of liposomal NPs over chitosomes. RSV loaded chitosomes nano-formulation exhibited lower IC50 values and higher therapeutic window while liposomal NPs were compatible with the intestinal cells. Conclusions RSV loaded chitosomes nano-formulation could be considered as a promising nanocarrier system with a marked cytotoxic activity while, RSV loaded liposomal NPs are suitable nanocarrier to improve RSV activity in treatment of cardiovascular disorders.

The development of an oral anti-diabetic medication characterized by enhanced hypoglycemic activity is in high demand. The goal was to study the hypoglycemic activity and pancreatic histopathology after the black-seed-based self-nanoemulsifying drug delivery system (SNEDDS) loaded with glimepiride liquisolid tablets to diabetic rats. The solubility of glimepiride in various vehicles was investigated. An optimization SNEDDS formulation was developed using a mixture of the experimental design approach. Box–Behnken design (BBD) was used to develop glimepiride liquisolid tablets utilizing Avicel PH 101 and Neusilin as a carrier mixture and FujiSil as a coating material. The quality attributes of the prepared tablets were assessed. Following the administration of the optimized tablets to diabetic rats, the pharmacodynamics and histopathological changes were investigated and compared to a commercial drug product. Results revealed that the optimized SNEDDS formulation that contains 15.43% w/w black seed oil, 40% w/w Tween 80, and 44.57% w/w Polyethylene glycol 400 showed an average droplet size of 34.64 ± 2.01 nm and a drug load of 36.67 ± 3.13 mg/mL. The optimized tablet formulation contained 0.31% Avicel in the carrier mixture, a 14.99 excipient ratio, and 8% superdisintegrant. Pre- and post-compression properties were satisfactory, and the optimized glimepiride liquisolid tablet showed a two-fold increase in dissolution. The optimized tablet demonstrated superior pharmacodynamics. The pancreatic tissues of the group treated with the optimized tablet displayed normal histological structure. The obtained data offered a commercially viable alternative for manufacturing solid dosage forms containing water-insoluble drugs, but additional clinical research is required.

6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.

Vasodilators are an important class of antihypertensive agents. However, they have limited clinical use due to the reflex tachycardia associated with their use which masks most of its antihypertensive effect and raises cardiac risk. Chemical investigation of Psiadia punctulata afforded five major methoxylated flavonoids (1–5) three of which (1, 4, and 5) showed vasodilator activity. Linoleic acid-based self-nanoemulsifying drug delivery system (SNEDDS) was utilized to develop intravenous (IV) formulations that contain compounds 1, 4, or 5. The antihypertensive effect of the prepared SNEDDS formulations, loaded with each of the vasodilator compounds, was tested in the angiotensin-induced rat model of hypertension. Rats were subjected to real-time recording of blood hemodynamics and surface Electrocardiogram (ECG) while the pharmaceutical formulations were individually slowly injected in cumulative doses. Among the tested formulations, only that contains umuhengerin (1) and 5,3′-dihydroxy-6,7,4′,5′-tetramethoxyflavone (5) showed potent antihypertensive effects. Low IV doses, from the prepared SNEDDS, containing either compound 1 or 5 showed a marked reduction in the elevated systolic blood pressure by 10 mmHg at 12 μg/kg and by more than 20 mmHg at 36 μg/kg. The developed SNEDDS formulation containing either compound 1 or 5 significantly reduced the elevated diastolic, pulse pressure, dicrotic notch pressure, and the systolic–dicrotic notch pressure difference. Moreover, both formulations decreased the ejection duration and increased the non-ejection duration while they did not affect the time to peak. Both formulations did not affect the AV conduction as appear from the lack of effect on p duration and PR intervals. Similarly, they did not affect the ventricular repolarization as no effect on QTc or JT interval. Both formulations decreased the R wave amplitude but increased the T wave amplitude. In conclusion, the careful selection of linoleic acid for the development of SNEDDS formulation rescues the vasodilating effect of P. punctulata compounds from being masked by the reflex tachycardia that is commonly associated with the decrease in peripheral resistance by most vasodilators. The prepared SNEDDS formulation could be suggested as an effective medication in the treatment of hypertensive emergencies, after clinical evaluation.

Dapoxetine (DPX) is an orally administered drug for the treatment of premature ejaculation (PE). One of the challenges of administering DPX orally as a tablet is its poor bioavailability (ie, 42%) due to extensive first-pass metabolism. Thus, it is vital to develop a new formulation and mode of delivery to achieve the unmet needs of PE treatment. In this study, an optimized DPX polymeric nanoparticle (PNP) was developed and subsequently loaded into a transdermal film. The Box–Behnken design was utilized to optimize 3 formulation factors affecting the particle size and entrapment efficiency (EE) of chitosan (CS)-alginate (ALG) PNPs. A 3-level factorial design was used to study the effect of 2 variables affecting DPX cumulative percent released and percent elongation from transdermal films loaded with DPX-PNPs. Permeation parameters were calculated following ex vivo permeation study through rat skin. Transport of the PNPs across the skin layers was investigated using a fluorescence laser microscope. Results revealed that an optimized PNPs formulation was developed with a particle size 415.94 nm and EE 37.31%. Dapoxetine was successfully entrapped in the polymeric matrix. Chitosan and ALG interacted electrostatically with the studied cross-linking agents to form a polyelectrolyte complex. The ex vivo study illustrated a sustained release profile of DPX with enhanced skin permeation from the film loaded PNPs. Moreover, the PNPs was able to penetrate deeper into skin layers. Therefore, DPX transdermal film developed in this work could be considered as a successful drug delivery with better patient compliance for the treatment of PE.

Glimepiride is characterized by an inconsistent dissolution and absorption profile due to its limited aqueous solubility. The aim of this study was to develop glimepiride tablets using three different manufacturing techniques, as well as to study their quality attributes and pharmacokinetics behavior. Black seed oil based self-nanoemulsifying drug delivery system (SNEDDS) formulation was developed and characterized. Glimepiride liquisolid and directly compressed tablets were prepared and their pre-compression and post-compression characteristics were evaluated. Semi-solid pastes loaded with SNEDDS were prepared and used to develop three-dimensional printing tablets utilizing the extrusion technique. In vivo comparative pharmacokinetics study was conducted on Male Wistar rats using a single dose one-period parallel design. The developed SNEDDS formulation showed a particle size of 45.607 ± 4.404 nm, and a glimepiride solubility of 25.002 ± 0.273 mg/mL. All the studied tablet formulations showed acceptable pre-compression and post-compression characteristics and a difference in their in vitro drug release behavior. The surface of the liquisolid and directly compressed tablets was smooth and non-porous, while the three-dimensional printing tablets showed a few porous surfaces. The inner structure of the liquisolid tablets showed some cracks and voids between the incorporated tablet ingredients while that of the three-dimensional printing tablets displayed some tortuosity and a gel porous-like structure. Most of the computed pharmacokinetic parameters improved with the liquisolid and three-dimensional printed tablets. The relative bioavailabilities of the three-dimensional printed and liquisolid tablets compared to commercial product were 121.68% and 113.86%, respectively. Therefore, the liquisolid and three-dimensional printed tablets are promising techniques for modifying glimepiride release and improving in vivo performance but more clinical investigations are required.

Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5α-reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and male pattern baldness. The drug is of limited solubility that affect its dissolution and bioavailability. The aim was to study the effect of FSD particle size reduction on the pharmacokinetic, tissue distribution and cellular permeation. An optimized drug micro- and nano-particles were developed, characterized, administered to group of rats, and systemic pharmacokinetic and tissue distribution within target and not-target organs were determined using near-infrared (NIR) spectroscopy technique. Moreover, the cellular permeation of the prepared formulations through normal prostate epithelial cells was assessed and compared to pure FSD. The developed micro- and nano-particles were of 930 and 645 nm, respectively. Plasma maximum drug levels (Cmax) and overall exposure (AUC) of both formulations were not significantly higher than unformulated drug. However, micronized FSD achieved significant higher concentration within the target tissue (prostate) within the current study compared to pure drug and nano-sized formulation as well. Yet, this is explained by the higher sequestration ability of spleen tissue to the nano-sized formula compared to micro-sized FSD. At the cellular level, permeation of nano-sized FSD through prostate epithelial cells was superior to the unformulated FSD as well as the micro-sized drug formulation. FSD particle size reduction significantly influences its cellular permeation and to a lesser extend affect its systemic pharmacokinetics and tissue distribution after oral administration.

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6–11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety.

Background: Aromatic aldehydes, with their ability to increase the oxygen affinity of sickle hemoglobin, have become important therapeutic agents for sickle cell disease (SCD). One such compound, voxelotor, was recently approved for SCD treatment. Methyl 6-((2-formyl-3-hydroxyphenoxy)methyl) picolinate (PP10) is another promising aromatic aldehyde, recently reported by our group. Like voxelotor, PP10 exhibits O2-dependent antisickling activity, but, unlike voxelotor, PP10 shows unique O2-independent antisickling effect. PP10, however, has limited solubility. This study therefore aimed to develop oral and parenteral formulations to improve PP10 solubility and bioavailability. Methods: Oral drug tablets with 2-hydroxypropyl beta cyclodextrin (HP-β-CD), polyvinylpyrrolidone, or Eudragit L100-55 PP10-binary system, and an intravenous (IV) formulation with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or HP-β-CD, were developed. The pharmacokinetic behavior of the formulations was studied in Sprague-Dawley rats. PP10, a methylester, and its acid metabolite were also studied in vitro with sickle whole blood to determine their effect on Hb modification, Hb oxygen affinity, and sickle red blood cell inhibition. Results: Aqueous solubility of PP10 was enhanced ~5 times with the HP-β-CD binary system, while the TPGS aqueous micelle formulation was superior, with a drug concentration of 0.502 ± 0.01 mg/mL and a particle size of 26 ± 3 nm. The oral tablets showed relative and absolute bioavailabilities of 173.4% and 106.34%, respectively. The acid form of PP10 appeared to dominate in vivo, although both PP10 forms demonstrated pharmacologic effect. Conclusion: Oral and IV formulations of PP10 were successfully developed using HP-β-CD binary system and TPGS aqueous micelles, respectively, resulting in significantly improved solubility and bioavailability.

Ketoconazole (KET), a synthetic imidazole broad-spectrum antifungal agent, is characterized by its poor aqueous solubility and high molecular weight, which might hamper its corneal permeation. The aim was to develop an ophthalmic formulation loaded with optimized trans-ethosomal vesicles to enhance KET ocular permeation, antifungal activity, rapid drug drainage, and short elimination half-life. Four formulation factors affecting the vesicles’ size, zeta potential, entrapment efficiency, and flexibility of the trans-ethosomes formulations were optimized. The optimum formulation was characterized, and their morphological and antifungal activity were studied. Different ophthalmic formulations loaded with the optimized vesicles were prepared and characterized. The ocular irritation and in vivo corneal permeation were investigated. Results revealed that the drug-to-phospholipid-molar ratio, the percentage of edge activator, the percentage of ethanol, and the percentage of stearyl amine significantly affect the characteristics of the vesicles. The optimized vesicles were spherical and showed an average size of 151.34 ± 8.73 nm, a zeta potential value of +34.82 ± 2.64 mV, an entrapment efficiency of 94.97 ± 5.41%, and flexibility of 95.44 ± 4.33%. The antifungal activity of KET was significantly improved following treatment with the optimized vesicles. The developed in situ gel formulations were found to be nonirritating to the cornea. The trans-ethosomes vesicles were able to penetrate deeper into the posterior eye segment without any toxic effects. Accordingly, the in situ developed gel formulation loaded with KET trans-ethosomes vesicles represents a promising ocular delivery system for the treatment of deep fungal eye infections.

Objective(s): The aim of this work was to investigate the effect of the natural and the chemically modified form of cyclodextrins namely; β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) respectively on the solubility and dissolution rate of aripiprazole; an antipsychotic medication showing poor aqueous solubility. Materials and Methods: Phase solubility of aripiprazole with the studied CDs and the complexation efficiency values (CE) which reflect the solubilizing power of the CDs towards the drug was performed. Solid binary systems of aripiprazole with CDs were prepared by kneading, microwave irradiation and freeze-drying techniques at 1:1 and 1:2 (drug to CD) molar ratios. Drug-CD physical mixtures were also prepared in the same molar ratios for comparison. The dissolution of aripiprazole-binary systems was carried out to select the most appropriate CD type, molar ratio and preparation technique. Results: Phase solubility study indicated formation of higher order complexes and the complexation efficiency values was higher for HP-β-CD compared to β-CD. Drug dissolution study revealed that aripiprazole dissolution was increased upon increasing the CD molar ratio and, the freeze-drying technique was superior to the other studied methods especially when combined with the HP-β-CD. The cyclodextrin type, preparation technique and molar ratio exhibited statistically significant effect on the drug dissolution at P≤ 0.05. Conclusion: The freeze-dried system prepared at molar ratio 1:2 (drug: CD) can be considered as efficient tool for enhancing aripiprazole dissolution with the possibility of improving its bioavailability

Abstract Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptors and has a poor prognosis as it is resistant to chemotherapy. A new treatment option for this type of cancer may be by putting these malignant cells into dormancy. The oocyte’s embryonic milieu presents a unique tumor reversion microenvironment by inducing growth arrest and changing cells’ phenotypes. We conducted an in-silico study to determine the most likely oocyte extract (OE) proteins involved in inducing dormancy using HDock, CluPro, and molecular dynamic (MD) simulation. Results showed low energy scores for complexes between OE proteins and four surface markers: K1C14, CLD3, CLD4, and ITA6. Apolipoprotein A1 (APOA1) and Apolipoprotein C3 (APOC3) showed the highest stability and affinity with these four surface markers: K1C14, CLD3, CLD4, and ITA6. These proteins are involved in key tumor-related pathways such as angiogenesis, proliferation, apoptosis, and migration. This will pave the way for exploring novel therapeutic options to induce dormancy in TNBC cells.

Abstract Background The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

INTRODUCTION. Chronic kidney disease (CKD) is an important health well-being problem globally, with increasing incidence. That tends to create an “epidemic”. Generalized muscle weakness in hemodialysis patients typically affects the lower limbs and proximal muscles. Patients experience impaired endurance and quality of life. Exercise is prescribed for these individuals to improve their physical health and prevent disease consequences. AIM. To find out the effect of interval versus continuous intradialytic training on muscle quality index and functional capacity in Hemodialysis patients. MATERIALS AND METHODS. Sixty men with chronic renal insufficiency grade 5 on hemodialysis aged from 45 to 55 years were divided into two groups using computerized block randomization: Groups (A) and (B) each containing 30 patients. They underwent 8-week program of high intensity interval training (HIIT), moderate intensity continuous training (MICT) intradialytic pedaling exercise plus hemodialysis three times per week. Pre-test and post-test evaluations have been carried out for 6-minute walk test (6MWT) and muscle quality index (MQI) of all patients. RESULTS. Both groups had a significant positive improvement in MQI and 6MWT with different proportions, patients received high intensity interval intradialytic pedaling exercise had a slightly significant improvement in MQI compared to moderate intensity continuous training group. While, moderate intensity training group had a more significant improvement in 6MWT compared to high intensity training group. CONCLUSION. Both HIIT and MICT are realistic and good options for individuals with CKD and have parallel profits on functional capability and, skeletal muscle quality and overall quality of life.

We redefine a system of varieties definable by a schema of equations to include finite dimensions. Then we present a technique using ultraproducts enabling one to lift results proved for every finite dimension to the transfinite. Let \(\bf Ord\) denote the class of all ordinals. Let \(\langle \mathbf{K}_{\alpha}: \alpha\in \bf Ord\rangle\) be a system of varieties definable by a schema. Given any ordinal \(\alpha\), we define an operator \(\mathsf{Nr}_{\alpha}\) that acts on \(\mathbf{K}_{\beta}\) for any \(\beta>\alpha\) giving an algebra in \(\mathbf{K}_{\alpha}\), as an abstraction of taking \(\alpha\)-neat reducts for cylindric algebras. We show that for any positive \(k\), and any infinite ordinal \(\alpha\) that \(\mathbf{S}\mathsf{Nr}_{\alpha}\mathbf{K}_{\alpha+k+1}\) cannot be axiomatized by a finite schema over \(\mathbf{S}\mathsf{Nr}_{\alpha}\mathbf{K}_{\alpha+k}\) given that the result is valid for all finite dimensions greater than some fixed finite ordinal. We apply our results to cylindric algebras and Halmos quasipolyadic algebras with equality. As an application to our algebraic result we obtain a strong incompleteness theorem (in the sense that validitities are not captured by finitary Hilbert style axiomatizations) for an algebraizable extension of \(L_{\omega,\omega}\).

The research aimed to identify the degree of benefit and satisfaction of rural fishermen with the activities and services provided by cooperative societies for rural fishermen in Aswan Governorate. The research carried out on a random sample of rural fishermen which consisting of 302 respondents. Data were collected by personal interview questionnaire. Percentages, frequency distribution, graph and weighted average were used to show and describe the research data. Excel was used to prepare the graphs. Spearman’s correlation coefficient for ranks was used to determine the relationship between the search variables by SPSS. Results were showed that: The most beneficial activities were: lending to fishermen and their families, establishing and managing fish farms, establishing centers for collecting fish, which are arranged in descending order with a weighted average respectively (2.85, 2.82, 2.71). The degree of satisfaction of the respondents was high with one of the services provided by cooperative societies were: issuing official papers, with a weighted average of 2.69. The degree of benefit of the respondents was positively related to years of work in fishing, age, and the number of years of education. The degree of respondents' satisfaction was positively correlated with age, years of education, level of ambition, years of work in fishing at the significant level 0.01, 0.05. The most important suggestions for activating the role of fishermen's cooperative societies were: the necessity of insuring fishermen and their boats (99.7%), providing protection for fishermen's families (99.3%), and helping to solve problems (98%).

Polyester fibers (PEF) were successfully coated with Polyaniline (PANI) via in situ polymerization to make electrically conductive fibers (ECF). X-ray diffraction (XRD) analysis confirms the synthesis and scanning electron microscopy (SEM) confirms the coating of PANI on the surface of PEF. Both coated and uncoated fibers were tested for their DC conductivity, and the results showed a clear difference between the two. From a highly insulating state, it transitions to about 0.1 S/cm. Both the tensile strength and modulus seemed to rise, going from 0.5 MPa to 2.5 MPa and from 0.04 MPa to 0.4 MPa, respectively. Blocking electromagnetic (EM) waves primarily requires a material with good electrical conductivity. The fabric proved effective in blocking about 99.9% of the ultraviolet (UV) and near-infrared rays. Fabrics that effectively block electromagnetic waves are able to conceal the high-temperature human body from a thermal imaging camera, which detects heat signatures by observing the infrared (IR) radiation generated by objects. We also measured the dielectric characteristics using impedance analysis and found that the values for the dielectric constant, dielectric loss, and AC conductivity dramatically increased from the frequency range of 100 Hz to 5 MHz. Further, electromagnetic interference (EMI) and shielding efficiency were determined with the aid of the dielectric constant and dielectric loss (SE). The overall SE in the same 100 Hz to 5 MHz range was similarly more than 80 dB. Improved EMI shielding was feasible due to the non-woven fabric's strong electrical conductivity, homogenous PANI coating on the surface, and great compactness. These findings are enough to predict that these fibers will provide good EMI shielding and thermal imaging when used in any application.

Abstract Background Several researches have examined the impact of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but many did not evaluate the extent of neuromuscular block. Besides, they did not inspect the impact of distinct degrees of neuromuscular blockade on spectral entropy under dissimilar saturations of isoflurane inhalation. Hence, this study has evaluated variant degrees of minimum alveolar concentration (MAC) to estimate the isoflurane concentration, along with various levels of neuromuscular blockade. This study aims to evaluate the effect of muscle relaxants (atracurium and rocuronium) on entropy readings (state, response entropy, and response-state difference) during isoflurane anesthesia. This is a prospective randomized study, as forty patients have been included and divided into two study groups: patients in group A received atracurium, while patients in group R received rocuronium. Under 50% and 100% neuromuscular blockage, state and response entropy were observed at MACs of 0.8% and 1%, respectively. Results There was a positive correlation between state (SE) and response entropy (RE) at baseline, different MACs, and different trains of four (TOF) for both atracurium and rocuronium. State and response entropy decreased with increasing MAC of isoflurane (P < 0.001), while atracurium and rocuronium at TOF 50% and 100% showed no effect on SE, RE, or RE-SE (P > 0.05). Conclusions State and response entropy can be used effectively to evaluate the depth of anesthesia at different isoflurane MAC and atracurium or rocuronium doses. Registration number ClinicalTrials.gov identifier: NCT 05097508, Registered October 5, 2021 (prospectively registered), http://www.ClinicalTrial.gov

Background The addition of dexmedetomidine or nalbuphine to epidural bupivacaine was tested to decrease labor pain in women undergoing normal delivery.Patients and Methods Sixty-four patients were randomly allocated into 2 groups of 32 parturients, each with consent from the parturient. Groups A and B received a bolus of 12 ml volume consisting of 11 ml of 0.25% bupivacaine and 0.5 μg/ml dexmedetomidine (1 ml volume) through the epidural catheter, then a top-up dose of 6 ml volume consisting of 5 ml of 0.25% bupivacaine and 0.5 μg/ml dexmedetomidine (1 ml volume) was given when the VAS score becomes 4 or more, and a bolus of 12 ml volume consisting of 11 ml of 0.25% bupivacaine and 10 mg nalbuphine (1 ml volume) through the epidural and a top-up dose of 5 ml of 0.25% bupivacaine and 2 mg nalbuphine (1 ml volume) were given, respectively. Assessments included the VAS score, vital data monitoring, duration of stages of labor, APGAR score, and adverse effects.Results Both groups had satisfactory labor analgesia, but those in the dexmedetomidine group had lower pain scores than those in the nalbuphine group, because dexmedetomidine had a faster onset than nalbuphine.Conclusion Epidural dexmedetomidine seems to offer some advantages over epidural nalbuphine. Thus, it can be used safely as an adjuvant to epidural bupivacaine in labor analgesia.

Background The physiological alterations that occur during the females’ reproductive age due to hormonal fluctuations throughout the menstrual cycle may affect the perioperative period and impact the postoperative outcome. This study evaluated the impact of menstrual cycle phases on pain perception, haemodynamic response to laryngoscopy, postoperative agitation, nausea, and vomiting in women undergoing laparoscopic gynaecological procedures.Methods This prospective observational study included 60 women who were randomly assigned to have diagnostic gynaecological laparoscopy during their menstrual cycle’s luteal or follicular phases. Patients were divided into two groups: follicular and luteal group. Preoperatively a blood sample was withdrawn for measurement of norepinephrine, estradiol, and progesterone levels. Anaesthetic techniques were standardized in both groups. In the postoperative period, another blood sample was withdrawn from all patients and sent for norepinephrine measurement.Before induction of anaesthesia, baseline HR, SBP, DBP, and MAP were measured. Then, following endotracheal intubation at 1, 3 and 5 minutes. Pain perception was assessed using Numerical Rating Scale (NRS); in response to IV cannulation, then postoperative abdominal pain and shoulder referred pain were assessed every 15 minutes till the end of 1st hour, then every 6 hours till discharge. The incidence of postoperative nausea and vomiting was recorded at the same time points of pain assessment. Postoperative agitation was assessed using Richmond Agitation-Sedation Scale (RASS).Results Women in the follicular phase showed higher postoperative pain, higher incidence of postoperative nausea, and more increase in HR and delayed return to baseline value post tracheal intubation as compared to luteal phase.

Let \(2

Fix a finite ordinal \(n\geq 3\) and let \(\alpha\) be an arbitrary ordinal. Let \(\mathsf{CA}_n\) denote the class of cylindric algebras of dimension \(n\) and \(\sf RA\) denote the class of relation algebras. Let \(\mathbf{PA}_{\alpha}(\mathsf{PEA}_{\alpha})\) stand for the class of polyadic (equality) algebras of dimension \(\alpha\). We reprove that the class \(\mathsf{CRCA}_n\) of completely representable \(\mathsf{CA}_n\)s, and the class \(\sf CRRA\) of completely representable \(\mathsf{RA}\)s are not elementary, a result of Hirsch and Hodkinson. We extend this result to any variety \(\sf V\) between polyadic algebras of dimension \(n\) and diagonal free \(\mathsf{CA}_n\)s. We show that that the class of completely and strongly representable algebras in \(\sf V\) is not elementary either, reproving a result of Bulian and Hodkinson. For relation algebras, we can and will, go further. We show the class \(\sf CRRA\) is not closed under \(\equiv_{\infty,\omega}\). In contrast, we show that given \(\alpha\geq \omega\), and an atomic \(\mathfrak{A}\in \mathsf{PEA}_{\alpha}\), then for any \(n

The aim of this study is to examine the determinants of Egyptian trade in general and Egyptian rice trade in particular with 11 rice-importing partner countries (Libya, Lebanon, Syria, Saudi Arabia, Sudan, Jordan, Turkey, the United Kingdom, Ukraine, Belgium, and Romania). To reach the main goals of the study, the gravity model was used to figure out which factors had the most impact on Egypt’s exports and imports. Using annual data on Egypt’s foreign and agricultural trade during the period 2001–2020 and data on the period 2001–2016 of rice crops with the 11 trading partners, the study reached several important conclusions. Among these conclusions, the Egyptian GDP variable had a negative effect on the total value of Egyptian imports and agriculture by increasing the value of total exports, agricultural exports, and rice exports to Egypt. Egyptian imports, exports, and population growth were all hurt by the Egyptian population variable. The study also shows that a 1% increase in export prices leads to a 3.97% increase in shipments of Egyptian rice to partner countries. According to economic theory, higher transportation expenses reduce trade volumes for both exports and imports. The variable distance between capitals has a negative effect on Egyptian exports. The study was designed based on the results of the main investigation. Based on the main investigation, the study made several important recommendations, including the need to take several measures to deflect the pace of economic growth of both the Egyptian total and agricultural export variables and rice export value, focusing on countries with high monetary and real GDP and a close geographical distribution. Improve economic relations between Egypt and its trading partners and shift from import-export cooperation to strategic food security cooperation.

Abstract Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p

Fix \(2 < n < \omega\). Let \(L_n\) denote first order logic restricted to the first n variables. Using the machinery of algebraic logic, positive and negative results on omitting types are obtained for \(L_n\) and for infinitary variants and extensions of \(L_{\omega, \omega}\).

Introduction Many factors determine the outcomes of renal transplant, including characteristics of both donors and recipients. Antihuman leukocyte antigen donor-specific antibodies are strongly linked to antibody-mediated rejection and late allograft loss. Aim The aim was to determine the effect of recipient and donor characteristics on kidney transplant graft survival, with special stress on panel-reactive antibodies. Participants and methods This study included 168 adult recipient and donor couples. The authors analyzed data of kidney transplants performed between the years of 2008 and 2018 at National Institute of Urology and Nephrology. Results The authors found a significant increase in renal failure in recipients transplanted with unrelated donor kidney and in positive hepatitis C virus antibodies (HCV Abs) recipients (P = 0.002 and 0.001, respectively) and renal complications (P ≤ 0.001). There was also a significant increase in panel-reactive antibody-positive recipients to get renal complications (P = 0.03). There was a significant increase in renal failure with old-aged recipients (P = 0.008) and with increased duration of transplant (P = 0.003). By multivariate regression, the authors deduced that young age decreases graft loss risk (hazard ratio (HR): 0.88; 95% confidence interval (95% CI): 0.79–0.97; P = 0.017). Recipients of unrelated donor graft and HCV infection were associated with higher hazard ratio graft loss (HR: 13.56; 95% CI: 2.58–71.22; P = 0.002, and HR: 7.96; 95% CI: 1.04–60.44; P = 0.45). Unrelated donors graft were associated with 4 times higher hazard ratio renal complication (HR: 4.18; 95% CI: 2.01–8.72; P = 0.003). HCV infection increases risk three times (HR: 3.24; 95% CI: 1.31–7.99; P = 0.010). Unrelated donor was a significant independent predictor for recipient graft loss risk in a period of more than 5 years after transplantation. Conclusion The authors concluded that recipient and donor characteristics have important roles on kidney transplant graft survival and also on renal complications.

Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke.Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays.Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke.Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.

BackgroundThe role of the long non-coding RNAs (lncRNAs) in the pathogenesis of systemic lupus erythematosus (SLE) is mostly unknown, despite increasing evidence that lncRNAs extensively participate in physiological and pathological conditions.AimTo detect the level of lncRNA-Cox2, HOTAIR, IL-6, and MMP-9 in the serum of SLE patients and to correlate these levels with disease activity and patients' clinical and laboratory data to evaluate the value of these biomarkers for SLE diagnosis and assessment of disease activity.MethodsBlood samples from 58 SLE patients, and 60 healthy controls (HCs) were used for detection of lncRNAs-Cox2 and HOTAIR expression levels by real-time polymerase chain reaction. Both IL-6 and MMP-9 serum levels were assayed by enzyme-linked immunosorbent assay. Lupus activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).ResultsThe serum expression levels of lncRNA-Cox2 and HOTAIR were significantly up-regulated in SLE patients vs HCs (fold change [median (IQR) was 1.29(0.81-1.71, PConclusionLncRNA-COX2 and HOTAIR can be used as new non-invasive biomarkers for the diagnosis of SLE.

The study aimed to investigate the causative species, antifungal susceptibility, and factors associated with oropharyngeal candidiasis (OPC) among Egyptian COVID-19 patients. This is an observational, case-controlled, single-center study that included three groups: COVID-19 patients (30), COVID-19 patients with OPC (39), and healthy individuals (31). Patients’ demographic data (age, sex), laboratory tests, comorbidities, treatment, and outcomes were included. Candida species were isolated from COVID-OPC patient’s oropharyngeal swabs by convenient microbiological methods. Isolated strains were tested for antimicrobial susceptibility, biofilm production, aspartyl protease, and phospholipase activities. The most common respiratory symptoms reported were dyspnea (36/39; 92.4%) and cough (33/39; 84.7%). Candida albicans was the most common isolated species, accounting for 74.36% (29/39), followed by Candida tropicalis and Candida glabrata (15.38% and 10.26%, respectively). Amphotericin was effective against all isolates, while fluconazole was effective against 61.5%. A total of 53.8% of the isolates were biofilm producers. The phospholipase activity of C. albicans was detected among 58.6% (17/29) of the isolates. Significant variables from this study were used to create two equations from a regression model that can predict the severity of disease course and liability to fungal infection, with a stativity of 87% and 91%, respectively. According to our findings, COVID-19 patients with moderate to severe infection under prolonged use of broad-spectrum antibiotics and corticosteroids should be considered a high-risk group for developing OPC, and prophylactic measures are recommended to be included in the treatment protocols. In addition, due to the increased rate of fluconazole resistance, other new antifungals should be considered.

Genetic variants in microRNAs (miRNAs) can alter the miRNAs expression and/or function, accordingly, affecting the related biological pathways and disease risk. Dysregulation of miR-155 and miR-146a expression levels has been well-described in viral hepatitis B (HBV). In the current study, we aimed to assess rs767649 T/A and rs57095329 A/G polymorphisms in miR-155, and miR-146a genes, respectively, as risk factors for Chronic HBV (CHBV) in the Egyptian population. Also, we aimed to do in silico analysis to investigate the molecules that primarily target these miRNAs. One hundred patients diagnosed as CHBV and one hundred age and sex-matched controls with evidence of past HBV infection were genotyped for miR-155 (rs767649) and miR-146a (rs57095329) using real-time polymerase chain reaction. The rs767649 AT and AA genotypes in CHBV patients confer four folds and ten folds risk respectively, as compared to control subjects [(AOR = 4.245 (95%CI 2.009-8.970), p

Aim of work To determine level of ischemia-modified albumin (IMA) in patients with Behçet’s disease (BD) and to assess its role in disease manifestations and activity. Patients and methods The study included 48 patients with BD and 38 matched controls. Disease activity was estimated by the BD current activity form. Serum IMA was measured. Results Mean age of the patients was 33.8±7.9 years. There were 42 males and six females, and the disease duration was 52.9±48.8 months. The serum IMA level was significantly increased in the patients with BD (50.9±12.9 U/ml) compared with the control (7.76±1.6 U/ml) (P

Aims Esophagogastroduodenoscopy is the commonest diagnostic procedure performed to evaluate upper gastrointestinal tract. However, there are limited data on the differences in endoscopic findings in different populations. Therefore, we conducted this study to compare the frequencies of endoscopic findings in two different populations. Patients and methods We used a large endoscopic database to retrieve the data of patients who underwent esophagogastroduodenoscopy at Fayoum University Hospital, Egypt and Ansh Clinic, Ahmadabad, India in the year of 2016. Results A total of 7107 patients were included in the final analysis: 5527 from India and 1580 from Egypt. Indian patients were more likely to present with normal finding (54.6 vs. 22.7%, P0.001). Overall, varices are most common in older male patients (>20 years), gastroesophageal reflux in males, and gastritis in females. Conclusion Further research is needed to validate our findings regarding the effect of age and sex on the frequency of endoscopic findings.

Hematopoietic stem cell transplantation (HSCT) is now an established treatment modality with definitive indications for many hematological disorders. However, this line of treatment requires tremendous resources, and it becomes increasingly difficult for transplanters practicing in the developing world to reconcile the difference between what is possible and what is available. On the basis of 30 years of experience and more than 4250 transplants , this article will focus on the challenges faced our HSCT program and how they were solved. The HSCT program in Egypt started in 1989 on a narrow scale and since that time we faced many challenges.In 1997, the transplant rate increased dramatically with the opening of many HSCT units distributed allover Egypt. Our team is registered in the Center for International Blood and Marrow Transplant Research ,and the number of transplants performed till December 2019 exceeded 4000 cases (60% allogeneic and 40% autologous).

This study considers sodium-alginate (C6H9NaO7) fluid over an accelerated vertical plate. The plate is heated from the bottom. A non-Newtonian model of C6H9NaO7 is considered. The convection term in the momentum equations is also considered. The dimensionless form of the problem is constructed based on dimensionless variables. The integral transformation of Laplace is used to develop the exact solution to the problem. Explicit expressions are obtained for the velocity field and temperature distribution. The corresponding skin-friction and Nusselt number results are computed based on this. Equations for entropy generation (EG) and Bejan number (BN) are developed. The results are plotted and discussed for embedded parameters. Most significantly, the results for EG and BN are computed and discussed.

Background: Coronary tortuosity (CT) had different definitions and scores in literature with unclear pathophysiological impact. Objectives: To study degree of CT and it's relation to ischemic changes in patients with angina but normal coronary angiography (CA). Methods: We conducted a prospective study at University hospitals between May 2016 and January 2017. We included 200 consecutive patients who underwent CA due to chest pain assumed to be of cardiac origin, and their CA was normal (no diameter stenosis >30%, nor myocardial bridging). Patients were prospectively divided into 2 groups based on the presence (n = 113) or absence (n = 87) of ischemic changes during stress study and compared for clinical, echocardiographic and CA characteristics. A newly proposed Tortuosity Severity Index (TSI) was developed into significant (mild/moderate CT with more than 4 curvatures in total, or severe/extreme CT with any number of curvatures) or not significant TSI (mild CT with curvatures less than or equal to 4 curvatures in total). Results: Patients with ischemic changes had the highest rate of CT (76.5 vs 18%, p = 0.004) compared to those without. CT mostly affects the left anterior descending (LAD) coronary artery in mid and distal segments. Females, elderly, and hypertensives with left ventricular hypertrophy were strongly related to CT. Multivariate logistic regression analysis identified CT with significant TSI as the only predictor of ischemic changes in these patients (OR = 6.2, CI = 2.5–15.3, P =

This article aims to study the mixed convection heat transfer in non-Newtonian nanofluids over an infinite vertical plate. Mixed convection is caused due to buoyancy force and sudden plate motion. Sodium alginate (SA-NaAlg) is considered as non-Newtonian base fluid and molybdenum disulphide (MoS2) as nanoparticles are suspended in it. The effective thermal conductivity and viscosity of nanofluid are calculated using the Maxwell–Garnetts (MG) and Brinkman models, respectively. The flow is modeled in the form of partial differential equations with imposed physical conditions. Exact solutions for velocity and temperature fields are developed by means of the Laplace transform technique. Numerical computations are performed for different governing parameters such as non-Newtonian parameter, Grashof number and nanoparticle volume fraction and the results are plotted in various graphs. Results for skin friction and Nusselt number are presented in tabular form which show that increasing nanoparticle volume fraction leads to heat transfer enhancement and increasing skin friction. Keywords: Molybdenum disulphide, Sodium alginate, Enhanced heat transfer, Mixed convection, Exact solutions

Introduction and aim Neuropsychiatric complications that develop after living donor liver transplantation (LT) are frequently encountered, though not adequately estimated among Egyptian recipients. We aimed to estimate the frequency of neuropsychiatric manifestations and neurocognitive functional changes after living donor LT. Patients and methods A prospective observational cohort study was conducted to evaluate 30 adult patients with end-stage liver disease preoperatively in a single Egyptian Transplant Center from November 2012 till January 2014. Relevant preoperative, intraoperative, and postoperative data were recorded and recollected and at 3 and 6 months of follow-up. The assessment included neurologic evaluation, Child–Turcotte–Pugh score, model of end-stage liver disease score, clinical hepatic encephalopathy staging scale, West Haven criteria, and International Society for Hepatic Encephalopathy and Nitrogen Metabolism score for semiquantitative assessment of encephalopathy. Results Hepatitis C virus was the main etiology for liver disease in 27 (90%) patients. Overt hepatic encephalopathy was seen in 26.6%, whereas covert hepatic encephalopathy occurred in 43.3%. Postoperatively, 76.7% of the patients demonstrated neuropsychiatric manifestations, with 50% of them showing mainly early major events, namely, encephalopathy. Late minor manifestation rates were 50%. Early cyclosporine administration and cold ischemia time longer than 40 min were significant predictors of occurrence of early neurologic events postoperatively (P=0.031 and 0.025, respectively). Both risk factors were associated with earlier and higher rates of neurologic complications. Conclusion Patients of living donor LT are at increased risk of developing early postoperative major neurologic sequelae, which become of less clinical significance later on. The patients’ cognitive functions improve with time after transplant.

Background: The treatment of patients with repeated drug-eluting stent–in stent restenosis (DES-ISR) remains a challenge and a burdensome clinical problem. Methods: Over a 3-year period, 130 lesions in 123 patients who underwent target lesion revascularization (TLR) for DES restenosis were included in the study. They were classified into two main groups: the first group having first-time DES-ISR (n = 84), and the second group having rerestenosis of DES-treated DES-ISR (n = 39). Further classification according to the treatment strategy yielded four subgroups: balloon angioplasty (BA) in first-time DES-ISR (n = 66), re-DES in the same group (n = 22), BA in rerestenosis of DES-treated DES-ISR (n = 30), and re-DES in the same group (n = 10). Angiographic follow-up was planned at 1 year, and clinical follow-up for re-TLR up to 2 years later. Results: The mean duration of clinical follow-up was 24.8 ± 9.7 months. The angiographic follow-up data were obtained for 108 patients (87.8%) at 1 year. Among patients treated for first-time DES-ISR, late lumen loss (0.65 ± 0.83 mm and 1.02 ± 0.52 mm, p = 0.02) and binary restenosis rates (25% and 49.1%, p = 0.05) were significantly less in those undergoing re-DES compared with BA. This benefit was not evident in patients having rerestenosis of DES-treated DES-ISR. Re-TLR at 2 years was significantly less in the re-DES group compared with BA (log rank p = 0.038) in first-time DES-ISR patients, while no significant difference (log rank p = 0.58) was observed in those having rerestenosis of DES-treated DES-ISR. Conclusion: While a strategy of re-DES would be better than BA in first-time DES-ISR, this could not be extrapolated to rerestenosis cases.

Radiation safety is an important counterpart in all facilities utilizing ionizing radiations. The concept of radiation safety has always been a hot topic, especially with the late reports pointing to increased hazards with chronic radiation exposure. Adopting a nationwide radiation safety program is considered one of the most urging topics, and is a conjoint responsibility of multiple disciplines within the health facility.

Background: Coronary steal is an often encountered clinical condition attributable to multiple etiologies. Diverse treatment modalities have been previously elucidated. Aim: To elucidate the potential role of interventional approach using N-butyl Cyanoacrylate (Histoacryl®) to treat coronary steal. Material and methods: We present four patients with coronary steal due to different causes. Three patients had coronary arterial fistulas, and the fourth patient underwent prior Coronary Artery Bypass Graft (CABG) surgery with a patent unligated Left Internal Mammary Artery (LIMA) side-branch. We report the attempted trans-catheter closure of the fistulas and LIMA side-branch using n-butyl cyanoacrylate as an embolic agent. Results: In our series, Coronary angiography was the imaging modality used for diagnosing and guiding the treatment of all cases. Multi-detector CT was used to track the pathway and termination of the fistula in one case only. From the three fistula cases, two originated from the left anterior descending (LAD) coronary artery and one from the left circumflex (LCX) coronary artery. We accomplished successful occlusion in two of the three fistula cases and in the LIMA side-branch case as well. Conclusion: N-butyl Cyanoacrylate (Histoacryl®) is a useful interventional embolic agent that could be used to treat coronary steal of diverse etiology.

Background: Rectal cancer is one of the most common tumors in industrialized countries and one of the most common malignant tumors of the gastrointestinal tract. MR imaging has become the most accurate technique in local staging of rectal cancer; this is due to advances in terms of imaging equipment, coils, and sequences that have progressively improved the technique, with a parallel increase in accuracy. Objective: To assess the role of magnetic resonance imaging with diffusion in staging of rectal carcinoma before and after chemo and radiation therapy in relation to histopathological findings. Materials and methods: The studied group included 19 patients proved to be rectal carcinoma by colonoscopy between October 2011 and December 2013. All patients were evaluated with conventional MRI and diffusion weighted images. Our population which was staged as Tx N2 M0 and T3–T4 Nx M0 stage, underwent MR and diffusion weighted imaging (DWI) before neoadjuvant chemo and radiation therapy and later 6–8 wks. After the end of the treatment they performed again MR for the re-staging of disease. The sensitivity, specificity and diagnostic accuracy for both examinations were calculated. Our gold standard was the histopathology. Results: For T stage conventional MRI showed 60% sensitivity and 33% specificity with overall diagnostic accuracy 46.5% which increased after adding DWI to 87% sensitivity and 80% specificity with an overall accuracy 83.5%. N stage prediction by conventional MRI was 74% sensitivity and 80% specificity with an overall accuracy 78%. This increased after adding DWI to 83% sensitivity and 83% specificity with an overall accuracy 83%. MRI with DWI showed diagnostic accuracy 94.7%, and without DWI the diagnostic accuracy was 84.2%. Conclusion: The use of additional DWI yields better diagnostic accuracy than does use of conventional MR imaging alone in the evaluation of complete response to neoadjuvant chemo radiotherapy in patients with locally advanced rectal cancer.

The notion of neat reducts is an old venerable notion in cylindric algebra theory invented by Henkin. This notion is regaining momentum. In this paper we explain why. This notion is discussed in connection to the algebraic notions of representability and complete representability, and the corresponding metalogical ones of completeness and omitting types, particularly for finite variable fragments. Also it is shown how such a notion has found intersection with non-trivial topics in model theory (like finite forcing) and set theory (forcing).