Distribution of cardiomyocyte-selective adeno-associated virus serotype 9 vectors in swine following intracoronary and intravenous infusion.

Limited reports exist regarding adeno-associated virus (AAV) biodistribution in swine. This study assessed biodistribution following antegrade intracoronary and intravenous delivery of two self-complementary serotype 9 AAV (AAV9sc) biologics designed to target signaling in the cardiomyocyte considered important for the development of heart failure. Under the control of a cardiomyocyte-specific promoter, AAV9sc.shmAKAP and AAV9sc.RBD express a small hairpin RNA for the perinuclear scaffold protein muscle A-kinase anchoring protein ß (mAKAPß) and an anchoring disruptor peptide for p90 ribosomal S6 kinase type 3 (RSK3), respectively. Quantitative PCR was used to assess viral genome (vg) delivery and transcript expression in Ossabaw and Yorkshire swine tissues. Myocardial viral delivery was 2-5 × 105 vg/µg genomic DNA (gDNA) for both infusion techniques at a dose ∼1013 vg/kg body wt, demonstrating delivery of ∼1-3 viral particles per cardiac diploid genome. Myocardial RNA levels for each expressed transgene were generally proportional to dose and genomic delivery, and comparable with levels for moderately expressed endogenous genes. Despite significant AAV9sc delivery to other tissues, including the liver, neither biologic induced toxic effects as assessed using functional, structural, and circulating cardiac and systemic markers. These results indicate successful targeted delivery of cardiomyocyte-selective viral vectors in swine without negative side effects, an important step in establishing efficacy in a preclinical experimental setting.

Zinc ferrite nanoparticles from industrial waste for Se (IV) elimination from wastewater.

The presence of high concentrations of selenium ions in wastewater is considered an environmental problem. However, the mechanism of selenium ions (Se (IV)) removal by the adsorption process has not been investigated in-depth so far. Also, the recovery and conversion of the industrial waste materials into valuable materials is a vital issue. Therefore, in this study, zinc ferrite nanopowders are economically synthesized from steel-making wastes by co-precipitation method for investigating as adsorbents of selenium species. The produced nanopowders were annealed at 150, 300, 500, and 850 °C for 5 h to scrutinize the impact of annealing temperature on their crystallite size. The compositional, optical, and magnetic features of the nanopowders were defined by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM), UV-Vis. spectrophotometer along with vibrating sample magnetometer (VSM). Optical absorbance spectra were found characteristic due to the electronic structure of Fe3+ (3d5) considering the C3v local symmetry of Fe3+ ions. The prepared nanopowders demonstrated good adsorption capacity toward selenium ions (43.67 mg/g at pH 2.5) from an aqueous medium. Adsorption data were found fitting to Freundlich isotherm model. Thus, ZnFe2O4 can be recommended to effectively eliminate selenium ions from aqueous solutions.

Western diet-induced obesity results in brain mitochondrial dysfunction in female Ossabaw swine.

Diet-induced obesity is implicated in the development of a variety of neurodegenerative disorders. Concurrently, the loss of mitochondrial Complex I protein or function is emerging as a key phenotype across an array of neurodegenerative disorders. Therefore, the objective of this study was to determine if Western diet (WD) feeding in swine [carbohydrate = 40.8% kCal (17.8% of total calories from high fructose corn syrup), protein = 16.2% kcal, fat = 42.9% kCal, and 2% cholesterol] would result in Complex I syndrome pathology. To characterize the effects of WD-induced obesity on brain mitochondria in swine, high resolution respirometry measurements from isolated brain mitochondria, oxidative phosphorylation Complex expression, and indices of oxidative stress and mitochondrial biogenesis were assessed in female Ossabaw swine fed a WD for 6-months. In line with Complex I syndrome, WD feeding severely reduced State 3 Complex I, State 3 Complex I and II, and uncoupled mitochondrial respiration in the hippocampus and prefrontal cortex (PFC). State 3 Complex I mitochondrial respiration in the PFC inversely correlated with serum total cholesterol. WD feeding also significantly reduced protein expression of oxidative phosphorylation Complexes I-V in the PFC. WD feeding significantly increased markers of antioxidant defense and mitochondrial biogenesis in the hippocampi and PFC. These data suggest WD-induced obesity may contribute to Complex I syndrome pathology by increasing oxidative stress, decreasing oxidative phosphorylation Complex protein expression, and reducing brain mitochondrial respiration. Furthermore, these findings provide mechanistic insight into the clinical link between obesity and mitochondrial Complex I related neurodegenerative disorders.

Synthesis of new Cr2O3/Fe2O3/glass composites from industrial wastes; from undesired to advanced optical products.

For the tendency toward cleaner production and safe conversion of undesired toxic wastes to highly priced advanced products, this work introduces new ceramics/glass composites of Cr2O3/Fe2O3/lead silicate glass (LSG) from industrial LSG wastes. Both chromia Cr2O3 and hematite Fe2O3 ceramics are added equally to the LSG wastes with different percentages (10, 20, and 30 wt.%) via the pressureless sintering method. The competitiveness of this work is dependent on the conversion of undesired waste materials into advanced/smart optical materials with a low cost and an environmentally friendly method. Hence, the influence of both Cr2O3 and Fe2O3 additions on the behavior and the different characteristics of the lead silicate wastes are comprehensively investigated. Evaluation of the final ceramics/glass composites was achieved through their phase composition, microstructure, optical, and magnetic characteristics. The results verified that the insertion of both chromia and hematite together into the glass waste had a key role in improving its morphological properties and optical and magnetic behaviors. Composite with 30% of Cr2O3/Fe2O3 gave the highest optical absorbance of 90%, the lowest and best band gap energy of 1.68 ev, and the highest refractive index of 2.85. Also, it recorded the best magnetic behavior with the highest saturation magnetization of 139.700 × 10-2A m2 kg-1 and the best coercivity of 190.0 Oe. These findings confirmed the successful clean conversion of the hazardous lead silicate waste into advanced products with promising optoelectronic characteristics.

A multi-criteria decision analysis (MCDA) tool for purchasing off-patent oncology medicines in Egypt.

BACKGROUND: Multi- criteria decision analysis (MCDA) can assist policymakers in objectively choosing between alternative therapeutic options based on multiple value attributes. Our aim was to create an MCDA tool for the national tenders of off-patent oncology medicines in Egypt. METHODS: An initial list of criteria was developed through a literature review complemented by local expert interviews. Price or cost-related criteria were excluded to abide by the national regulations of the tender process. Next, a workshop hosting diversified stakeholders representing different governmental bodies was held. Anonymous voting was used to rank and weigh the criteria as well as assigning scores. Price was added as a separate step to identify best option based on price per point. The tool was then tested on a national tender sample of off-patent oncology medicines to assess its performance, and it was readjusted accordingly in a second workshop. RESULTS: Seven non-price criteria were selected, including use in reference countries (23.49% weight), equivalence with the reference product (18.79%), manufacturing quality (15.53%), provision of pharmacovigilance services (12.94%), supply reliability (10.78%), previous use in local settings (9.8%) and macroeconomic benefit (8.67%). A medicine receives a score ranging from 0 to 100% of each criterion's weight. The aggregated score is calculated on a hundred-point scale. Based on participants' consensus, an overall score of 65 was set as a cut-off for passing the technical eligibility phase of the tendering process. Any product receiving a lower score would be disqualified from the tender. For qualified products, the lower price per point represents preferential option for the national tender. CONCLUSIONS: The created MCDA tool is capable of objectively comparing similar off-patent oncology medicines by considering multiple value attributes and providing reliable scoring functions for each.

Mechanism-Driven Modeling to Aid Non-invasive Monitoring of Cardiac Function via Ballistocardiography.

Left ventricular (LV) catheterization provides LV pressure-volume (P-V) loops and it represents the gold standard for cardiac function monitoring. This technique, however, is invasive and this limits its applicability in clinical and in-home settings. Ballistocardiography (BCG) is a good candidate for non-invasive cardiac monitoring, as it is based on capturing non-invasively the body motion that results from the blood flowing through the cardiovascular system. This work aims at building a mechanistic connection between changes in the BCG signal, changes in the P-V loops and changes in cardiac function. A mechanism-driven model based on cardiovascular physiology has been used as a virtual laboratory to predict how changes in cardiac function will manifest in the BCG waveform. Specifically, model simulations indicate that a decline in LV contractility results in an increase of the relative timing between the ECG and BCG signal and a decrease in BCG amplitude. The predicted changes have subsequently been observed in measurements on three swine serving as pre-clinical models for pre- and post-myocardial infarction conditions. The reproducibility of BCG measurements has been assessed on repeated, consecutive sessions of data acquisitions on three additional swine. Overall, this study provides experimental evidence supporting the utilization of mechanism-driven mathematical modeling as a guide to interpret changes in the BCG signal on the basis of cardiovascular physiology, thereby advancing the BCG technique as an effective method for non-invasive monitoring of cardiac function.

Combined effect of magnesia and zirconia on the bioactivity of calcium silicate ceramics at C\S ratio less than unity.

This paper describes the effect of magnesia in the presence of zirconia on the bioactivity, microstructure and physico-mechanical properties of calcium silicate composition adjusted at calcia/silica ratio(C/S) of 0.5. A mixture from calcium carbonate and silica was conducted at C/S of 0.5. 20wt.% of magnesia and 5-25wt.% of ZrO2 were added. Each mixture was mixed with ethanol in a planetary ball mill, dried, formed and fired at a temperature of 1325±5°C. Phase composition, FE-SEM, and physico-mechanical properties of the fired specimens were determined and explained. The in vitro bioactivities of these specimens were investigated by analysis of their abilities to form apatite in the simulated body fluid (SBF) for a short time (7days) using SEM-EDS. The findings indicated that the surface of the specimens containing 5 and 15wt.% ZrO2 were completely covered by single and multilayered hydroxyapatite (HA) precipitate typical to "cauliflower" morphology, respectively. The surface of the specimen containing 25wt.% ZrO2 did not cover, but there are some scattered HA precipitate. The differences among the results were rationalized based on the phase composition. Vickers hardness and fracture toughness of the specimens of highly promised bioactivity were 2.32-2.57GPa and 1.80-1.50MPa. m1/2, respectively. The properties of these specimens are similar to the properties of human cortical bone. Consequently, these composites might be used as bone implant materials.