Parkinson's disease pathology is directly correlated to SIRT3 in human subjects and animal models: Implications for AAV.SIRT3-myc as a disease-modifying therapy.

In Parkinson's disease (PD), post-mortem studies in affected brain regions have demonstrated a decline in mitochondrial number and function. This combined with many studies in cell and animal models suggest that mitochondrial dysfunction is central to PD pathology. We and others have shown that the mitochondrial protein deacetylase, SIRT3, has neurorestorative effects in PD models. In this study, to determine whether there is a link between PD pathology and SIRT3, we analysed SIRT3 levels in human subjects with PD, and compared to age-matched controls. In the SNc of PD subjects, SIRT3 was reduced by 56.8 ± 15.5% compared to control, regardless of age (p < 0.05, R = 0.6539). Given that age is the primary risk factor for PD, this finding suggests that reduced SIRT3 may contribute to PD pathology. Next, we measured whether there was a correlation between α-synuclein and SIRT3. In a parallel study, we assessed the disease-modifying potential of SIRT3 over-expression in a seeding model of α-synuclein. In PFF rats, infusion of rAAV1.SIRT3-myc reduced abundance of α-synuclein inclusions by 30.1 ± 18.5%. This was not observed when deacetylation deficient SIRT3H248Y was transduced, demonstrating the importance of SIRT3 deacetylation in reducing α-synuclein aggregation. These studies confirm that there is a clear difference in SIRT3 levels in subjects with PD compared to age-matched controls, suggesting a link between SIRT3 and the progression of PD. We also demonstrate that over-expression of SIRT3 reduces α-synuclein aggregation, further validating AAV.SIRT3-myc as a potential disease-modifying solution for PD.

Modulating the growth of chemically deposited ZnO nanowires and the formation of nitrogen- and hydrogen-related defects using pH adjustment.

ZnO nanowires (NWs) grown by chemical bath deposition (CBD) have received great interest for nanoscale engineering devices, but their formation in aqueous solution containing many impurities needs to be carefully addressed. In particular, the pH of the CBD solution and its effect on the formation mechanisms of ZnO NWs and of nitrogen- and hydrogen-related defects in their center are still unexplored. By adjusting its value in a low- and high-pH region, we show the latent evolution of the morphological and optical properties of ZnO NWs, as well as the modulated incorporation of nitrogen- and hydrogen-related defects in their center using Raman and cathodoluminescence spectroscopy. The increase in pH is related to the increase in the oxygen chemical potential (µ O), for which the formation energy of hydrogen in bond-centered sites (HBC) and VZn-NO-H defect complexes is found to be unchanged, whereas the formation energy of zinc vacancy (VZn) and zinc vacancy-hydrogen (VZn-nH) complexes steadily decreases as shown from density-functional theory calculations. Revealing that these VZn-related defects are energetically favorable to form as µ O is increased, ZnO NWs grown in the high-pH region are found to exhibit a higher density of VZn-nH defect complexes than ZnO NWs grown in the low-pH region. Annealing at 450 °C under an oxygen atmosphere helps tuning the optical properties of ZnO NWs by reducing the density of HBC and VZn-related defects, while activating the formation of VZn-NO-H defect complexes. These findings show the influence of pH on the nature of Zn(ii) species, the electrostatic interactions between these species and ZnO NW surfaces, and the formation energy of the involved defects. They emphasize the crucial role of the pH of the CBD solution and open new possibilities for simultaneously engineering the morphology of ZnO NWs and the formation of nitrogen- and hydrogen-related defects.

Optimization Strategies Used for Boosting Piezoelectric Response of Biosensor Based on Flexible Micro-ZnO Composites.

Piezoelectric ZnO-based composites have been explored as a flexible and compact sensor for the implantable biomedical systems used in cardio surgery. In this work, a progressive development route was investigated to enhance the performance of piezoelectric composites incorporated with different shape, concentration and connectivity of ZnO fillers. ZnO microrods (MRs) have been successfully synthesized homogeneously in aqueous solution using a novel process-based on chemical bath deposition (CBD) method. The morphological analysis along with Raman scattering and cathodoluminescence spectroscopy of ZnO MRs confirm their high crystalline quality, their orientation along the polar c-axis and the presence of hydrogen-related defects acting as shallow donors in their center. The experimental characterizations highlight that ZnO MR-based composites, with a higher aspect ratio (AR), lead to a significant improvement in the mechanical, dielectric and piezoelectric properties as opposed to the ZnO microparticles (MP) counterparts. The dielectrophoretic (DEP) process is then subjected to both ZnO MP- and MR-based composites, whose performance is expected to be improved as compared to the randomly dispersed composites, thanks to the creation of chain-like structures along the electric field direction. Furthermore, a numerical simulation using COMSOL software is developed to evaluate the influence of the material structuration as well as the filler's shape on the electric field distribution within different phases (filler, matrix and interface) of the composites. Finally, the aligned MR piezoelectric composites are revealed to be high potential in the development of innovative compact and biocompatible force-sensing devices. Such a technological breakthrough allows the achievement of a real-time precise characterization of mitral valve (MV) coaptation to assist surgeons during MV repair surgery.

Characterizing and Optimizing Piezoelectric Response of ZnO Nanowire/PMMA Composite-Based Sensor.

Due to the outstanding coupling between piezoelectric and semiconducting properties of zinc oxide nanowires, ZnO NW-based structures have been demonstrating promising potential with respect to their applicability in piezoelectric, piezotronic and piezo-phototronic devices. Particularly considering their biocompatibility and biosafety for applications regarding implantable medical detection, this paper proposed a new concept of piezoelectric composite, i.e., one consisting of vertically aligned ZnO NW arrays and an insulating polymer matrix. First, the finite element method (FEM) was employed to drive optimization strategies through adjustment of the key parameters such as Young's modules and the dielectric constant of the dielectric constituents, together with the density and dimension of nanowire (NW) itself. Second, to investigate the functionality of each individual layer of composite, different designed structures were fabricated and characterized in terms of electrical and piezoelectric properties. Next, experimental and simulation tests were performed, indicating that the decreasing thickness of the top poly(methyl methacrylate) layer (PMMA) can substantially enhance the piezoelectric sensitivity of the ZnO NW composite. Besides the further benefit of no polarization being needed, our material has a comparable charge coefficient (d33) with respect to other lead-free alternatives (e.g., BaTiO3), confirming the high sensing abilities of the developed structure based on vertically aligned ZnO NW arrays. Finally, a time-varying model combining piezoelectricity and electric circuit modules was investigated in detail, giving rise to an estimation of the d33 coefficient for ZnO NWs. Based on this study, the developed material is revealed to be highly promising in medical applications, particularly regarding the FFR technique, where coronary pressure can be measured through a piezoelectric sensor.

[Evaluation of the impact of multiple micronutrient powders on children anemia in three Andean regiones in Peru]. / Evaluación del impacto de los multimicronutrientes en polvo sobre la anemia infantil en tres regiones andinas del Perú

The aim of this research was to determine the impact of the strategy of multi-micronutrient supplementation (MMN) on the childhood anemia in three Andean regions of Peru. A sentinel surveillance system was established in 29 health centers of Andahuaylas, Ayacucho and Huancavelica (Peru) to monitor a cohort of children of 6 to 35 months of age whom been received MMM for a period of 12 months. Data regarding hemoglobin levels were gathered at the beginning and at the end of the research; they included consumption of MMN, and other data from clinical records and from growth and development charts. Between the child who completed the supplementation, the prevalence of anemia decreased from 70.2% to 36.6% (p value <0.01). 55,0% and 69,1% of children with mild and moderate anemia at the beginning of the supplementation got cured. This research shows that supplementation with MMN could be a valuable strategy to fight anemia.

Evaluación del impacto de los multimicronutrientes en polvo sobre la anemia infantil en tres regiones andinas del Perú / Evaluation of the impact of multiple micronutrient powders on children anemia in three andean regiones in Peru

Con el objetivo de determinar el impacto de la administración con multimicronutrientes (MMN) en polvo sobre la anemia infantil en tres regiones andinas del Perú, se estableció un sistema de vigilancia centinela en 29 establecimientos de Andahuaylas, Ayacucho y Huancavelica, en niños de 6 a 35 meses de edad, a quienes se les indicó MMN por un periodo de 12 meses, entre el 2009 y 2011. Además de los datos sociodemográficos de los menores y las madres, se determinó los niveles de hemoglobina al inicio y al final del estudio. Entre los menores que culminaron la suplementación, la prevalencia de anemia se redujo de 70,2 a 36,6% (p<0,01), y se evidenció que el 55,0% y el 69,1% de niños con anemia leve y moderada al inicio del estudio, la habían superado al término del mismo. Se concluye que la suplementación con MMN en polvo puede ser una estrategia efectiva en la lucha contra la anemia.

The aim of this research was to determine the impact of the strategy of multi-micronutrient supplementation (MMN) on the childhood anemia in three Andean regions of Peru. A sentinel surveillance system was established in 29 health centers of Andahuaylas, Ayacucho and Huancavelica (Peru) to monitor a cohort of children of 6 to 35 months of age whom been received MMM for a period of 12 months. Data regarding hemoglobin levels were gathered at the beginning and at the end of the research; they included consumption of MMN, and other data from clinical records and from growth and development charts. Between the child who completed the supplementation, the prevalence of anemia decreased from 70.2% to 36.6% (p value <0.01). 55,0% and 69,1% of children with mild and moderate anemia at the beginning of the supplementation got cured. This research shows that supplementation with MMN could be a valuable strategy to fight anemia.