Structure–activity relationships of the antimalarial agent artemisinin 10. Synthesis and antimalarial activity of enantiomers of rac-5β-hydroxy-d-secoartemisinin and analogs: Implications regarding the mechanism of action

An efficient synthesis of rac-6-desmethyl-5β–hydroxy-D-secoartemisinin 2, a tricyclic analog of R-(+)-artemisinin 1, was accomplished and the racemate was resolved into the (+)-2b and (−)-2a enantiomers via their Mosher Ester diastereomers. Antimalarial activity resided with only the artemisinin-like enantiomer R-(−)-2a. Several new compounds 9–16, 19a, 19b, 22 and 29 were synthesized from rac-2 but the C-5 secondary hydroxyl group was surprisingly unreactive. For example, the formation of carbamates and Mitsunobu reactions were unsuccessful. In order to assess the unusual reactivity of 2, a single crystal X-ray crystallographic analysis revealed a close intramolecular hydrogen bond from the C-5 alcohol to the oxepane ether oxygen (O-11). All products were tested in vitro against the W-2 and D-6 strains of Plasmodium falciparum. Several of the analogs had moderate activity in comparison to the natural product 1. Iron (II) bromide-promoted rearrangement of 2 gave, in 50% yield, the ring-contracted tetrahydrofuran 22, while the 5-ketone 15 provided a monocyclic methyl ketone 29 (50%). Neither 22 nor 29 possessed in vitro antimalarial activity. These results have implications in regard to the antimalarial mechanism of action of artemisinin

Influence of Annealing Temperature on Structural, Electrical, and Magnetic Properties of Nd0.7Ca0.3MnO3

In this paper, we investigated the effect of annealing temperature on the electrical and magnetic properties of polycrystalline Nd0.7Ca0.3MnO3 synthesized using the well-known solid-state reaction technique. After the formation of the required Perovskite crystal structure phase, another annealing treatment has been done. The selected annealing temperatures are 700, 800, and 900°C for 12 hours. Structural refinement of the X-ray diffraction patterns showed the formation of a single orthorhombic crystal structure phase the of P b n m space group in Nd0.7Ca0.3MnO3 without any impurity peaks. From magneto-resistance measurements, we found that NCMO samples have high-colossal magnetoresistance (CMR). Moreover, the under-investigated NCMO samples showed a high power factor. The resistivity data in the insulating region (T \u3eTMI) were analyzed by considering, the Mott-variable range hopping model. The phase transition temperature showed dependence on the grain size, where Curie temperature (TC) increases with an increase in the grain size

Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systemic Review and Meta-Analysis

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. Results. Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; ), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, and OR 1.23; CI: 0.96-1.58, , respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, and 4.88: 95% CI 0.756 to 9.0133, , respectively). Conclusions. Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients

Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families.

BackgroundThe causes for thousands of individually rare recessive diseases have been discovered since the adoption of next generation sequencing (NGS). Following the molecular diagnosis in older children in a family, parents could use this information to opt for fetal genotyping in subsequent pregnancies, which could inform decisions about elective termination of pregnancy. The use of NGS diagnostic sequencing in families has not been demonstrated to yield benefit in subsequent pregnancies to reduce recurrence. Here we evaluated whether genetic diagnosis in older children in families supports reduction in recurrence of recessive neurogenetic disease.MethodsRetrospective study involving families with a child with a recessive pediatric brain disease (rPBD) that underwent NGS-based molecular diagnosis. Prenatal molecular testing was offered to couples in which a molecular diagnosis was made, to help couples seeking to prevent recurrence. With this information, families made decisions about elective termination. Pregnancies that were carried to term were assessed for the health of child and mother, and compared with historic recurrence risk of recessive disease.ResultsBetween 2010 and 2016, 1172 families presented with a child a likely rPBD, 526 families received a molecular diagnosis, 91 families returned to the clinic with 101 subsequent pregnancies, and 84 opted for fetal genotyping. Sixty tested negative for recurrence for the biallelic mutation in the fetus, and all, except for one spontaneous abortion, carried to term, and were unaffected at follow-up. Of 24 that genotyped positive for the biallelic mutation, 16 were electively terminated, and 8 were carried to term and showed features of disease similar to that of the older affected sibling(s). Among the 101 pregnancies, disease recurrence in living offspring deviated from the expected 25% to the observed 12% ([95% CI 0·04 to 0·20], p = 0·011).ConclusionsMolecular diagnosis in an older child, coupled with prenatal fetal genotyping in subsequent pregnancies and genetic counselling, allows families to make informed decisions to reduce recessive neurogenetic disease recurrence

Efficient framework for brain tumor detection using different deep learning techniques

The brain tumor is an urgent malignancy caused by unregulated cell division. Tumors are classified using a biopsy, which is normally performed after the final brain surgery. Deep learning technology advancements have assisted the health professionals in medical imaging for the medical diagnosis of several symptoms. In this paper, transfer-learning-based models in addition to a Convolutional Neural Network (CNN) called BRAIN-TUMOR-net trained from scratch are introduced to classify brain magnetic resonance images into tumor or normal cases. A comparison between the pre-trained InceptionResNetv2, Inceptionv3, and ResNet50 models and the proposed BRAIN-TUMOR-net is introduced. The performance of the proposed model is tested on three publicly available Magnetic Resonance Imaging (MRI) datasets. The simulation results show that the BRAIN-TUMOR-net achieves the highest accuracy compared to other models. It achieves 100%, 97%, and 84.78% accuracy levels for three different MRI datasets. In addition, the k-fold cross-validation technique is used to allow robust classification. Moreover, three different unsupervised clustering techniques are utilized for segmentation

TRANSETHOSOMES AS BREAKTHROUGH TOOL FOR CONTROLLED TRANSDERMAL DELIVERY OF DEXKETOPROFEN TROMETAMOL: DESIGN, FABRICATION, STATISTICAL OPTIMIZATION, IN VITRO, AND EX VIVO CHARACTERIZATION

Objective: Transethosomes (TEs) have introduced an emerging avenue of interest in vesicular research for transdermal delivery of drugs and can be a proper delivery system for painkillers like NSAIDS. This study aimed to formulate and characterize the potential of TE to enhance the transdermal transport of Dexketoprofen trometamol (DKT) to achieve controlled pain management compared to DKT solution. Methods: Factorial design (23) was adopted to appraise the influence of independent variables, namely, Lipoid S100 and surfactant concentrations and surfactant type (X3) on the % solubilization efficiency (% SE), vesicle size (VS), and % release efficiency (% RE). Thin film hydration was the preferred approach for preparing TEs where vesicle size, zeta potential, polydispersity index, %SE and %RE were investigated. The optimized formula was nominated and subjected to several studies. For the permeation study, optimum TE was incorporated into carbapol gel base for comparison with DKT solution. Also, an accelerated stability study was assessed for optimized formula. Results: All the prepared DKT-loaded TEs revealed acceptable VS, PDI, and ZP. The highest %SE (86.08±1.05 %) and lowest %RE (44.62±1.36 %) were observed in case of F1. The optimized formula (F1) displayed VS of 133.2±1.62 nm, PDI of 0.342±0.03 and ZP of-21.6±2.45 mV. F1 revealed enhanced skin permeation of a 2.6-fold increase compared with DKT solution. Moreover, F1 was stable upon storage and a non-significant change (P>0.05) was observed. Conclusion: DKT was successfully incorporated into vesicle carrier and can signify an alternative option for providing this therapy, bypassing the poor bioavailability and considerable adverse consequences of using the oral route besides improved patient compliance

Surfactant-Free Peroxidase-Mediated Enzymatic Polymerization of a Biorenewable Butyrolactone Monomer via a Green Approach:Synthesis of Sustainable Biobased Latexes

A green surfactant-free one-pot horseradish peroxidase-mediated enzymatic polymerization is successfully applied to produce a sustainable and thermally stable biobased high average molar mass poly(α-methylene-γ-butyrolactone) (PMBL) at ambient conditions in water for the first time. The initiation step required only very low concentrations of hydrogen peroxide and 2,4-pentanedione water-soluble initiator to generate the keto-enoxy radicals responsible for forming the primary latex particles. The polymer nanoparticles can be seen as monodisperse, and the biobased latexes are colloidally stable and likely stabilized by the adsorption of 2,4-pentanedione moieties on the particle surfaces. Polymerizations in air produced a 98% yield of PMBL after only 3 h, highlighting the relevance of molecular oxygen. An array of characterization techniques such as dynamic light scattering (DLS), Fourier transform infrared (FTIR), 1H, 13C, and HSQC two-dimensional (2D) nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and size-exclusion chromatography (SEC) are used to confirm the properties of the synthesized latexes. The PMBL exhibited high thermal stability, with only a 5% weight loss at 340 °C and a glass-transition temperature of 200 °C, which is double that of polymethyl methacrylate (PMMA). This research provides an interesting pathway for the synthesis of sustainable biobased latexes via enzymes in a green environment using just water at ambient conditions and the potential use of the polymer in high-temperature applications.</p

Surfactant-Free Peroxidase-Mediated Enzymatic Polymerization of a Biorenewable Butyrolactone Monomer via a Green Approach:Synthesis of Sustainable Biobased Latexes

A green surfactant-free one-pot horseradish peroxidase-mediated enzymatic polymerization is successfully applied to produce a sustainable and thermally stable biobased high average molar mass poly(α-methylene-γ-butyrolactone) (PMBL) at ambient conditions in water for the first time. The initiation step required only very low concentrations of hydrogen peroxide and 2,4-pentanedione water-soluble initiator to generate the keto-enoxy radicals responsible for forming the primary latex particles. The polymer nanoparticles can be seen as monodisperse, and the biobased latexes are colloidally stable and likely stabilized by the adsorption of 2,4-pentanedione moieties on the particle surfaces. Polymerizations in air produced a 98% yield of PMBL after only 3 h, highlighting the relevance of molecular oxygen. An array of characterization techniques such as dynamic light scattering (DLS), Fourier transform infrared (FTIR), 1H, 13C, and HSQC two-dimensional (2D) nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and size-exclusion chromatography (SEC) are used to confirm the properties of the synthesized latexes. The PMBL exhibited high thermal stability, with only a 5% weight loss at 340 °C and a glass-transition temperature of 200 °C, which is double that of polymethyl methacrylate (PMMA). This research provides an interesting pathway for the synthesis of sustainable biobased latexes via enzymes in a green environment using just water at ambient conditions and the potential use of the polymer in high-temperature applications.</p

The impact of Oligo-miocene basaltic intrusions on the petroleum system in Gulf of Suez rift basin, Egypt: new insights into tikhermal maturity and reservoir quality

In recent years, the petroleum industry has prioritized the exploration of new and unconventional petroleum reservoirs. As a result, this study assessed the significance of basaltic intrusions from two key aspects: their impact on the thermal maturity of pre-rift source rocks and their potentiality as reservoirs. The present study attempts to integrate surface field investigations of basaltic dykes in Wadi Nukhul and Wadi Matulla as surface analogs with petroleum system modeling of pre-rift source rocks containing subsurface basaltic intrusions in the Abu Rudeis-Sidri field. Therefore, the fracture networks were observed in Wadi Nukhul and Wadi Matulla, suggesting that both the basaltic dykes and host rocks have interconnected fractures, which is critical for a high-quality reservoir of the dykes and efficient oil expulsion. As a result, the analysis of burial history, temperature, maturity, generation, transformation ratio, and expelled oil quantity revealed a significantly high value for basaltic intrusions. Moreover, the Abu Rudeis-Sidri field had a good petroleum system with thermally mature source rocks by basaltic intrusions. Furthermore, the fractured basaltic intrusions presented a high-quality oil reservoir well-sealed by the thick Rudeis Formation. Oil production has doubled since the discovery of this reservoir. This study introduces a novel approach to understanding the distribution pattern of basaltic intrusions in subsurface and surface analogs, which can serve as a model for exploring new potential unconventional basaltic reservoirs in the Gulf of Suez rift basin