Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample.

OBJECTIVE: To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old). METHOD: Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores. RESULTS: Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores. CONCLUSION: The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use's impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.

Proficient mycogenic synthesis of silver nanoparticles by soil derived fungus Aspergillus melleus SSS-10 with cytotoxic and antibacterial potency.

The present study aimed at evaluating the extracellular synthesis of silver nanoparticles by soil fungus Aspergillus melleus SSS-10 for antibacterial and cytotoxic activity. In this study, the formation of silver nanoparticles (AgNPs) was estimated by the colour change in cell free extract from pale yellow to golden yellow after 24 h of the reaction. UV-Vis study showed the absorbance maxima at 410 nm. Tauc plot analysis revealed the band gap energy as 2.34 eV. Dynamic Light Scattering (DLS) data revealed polydisperse anisotropic silver nanoparticles with average hydrodynamic diameter of 92.006 nm. Zeta potential of - 19.6 mV provided evidence of stable silver nanoparticles. X-ray diffraction (XRD) analysis revealed four prominent Bragg peaks corresponding to (111), (200), (220) and (311) planes characteristic of silver (Ag) in FCC structural configuration. Average crystallite size was found to be 87.3 nm from Scherrer equation. Scanning Electron Microscope (SEM) analysis revealed irregular morphology of silver nanoparticles. EDS analysis displayed characteristic energy peaks of silver from 2.72 keV to 3.52 keV confirming the presence of silver nanoparticles. Biosynthesized AgNPs exhibited strong cytotoxic potential on MG-63 cells. AgNPs also showed antibacterial activity against both Staphylococcus aureus and Escherichia coli. In conclusion, this study provides a platform to explore the utility of fungal mediated silver nanoparticles synthesized for various pharmaceutical and cosmeceutical applications.

Downregulation of PTEN Promotes Autophagy via Concurrent Reduction in Apoptosis in Cardiac Hypertrophy in PPAR α-/- Mice.

Cardiac hypertrophy is characterized by an increase in the size of the cardiomyocytes which is initially triggered as an adaptive response but ultimately becomes maladaptive with chronic exposure to different hypertrophic stimuli. Prolonged cardiac hypertrophy is often associated with mitochondrial dysfunctions and cardiomyocyte cell death. Peroxisome proliferator activated receptor alpha (PPAR α), which is critical for mitochondrial biogenesis and fatty acid oxidation, is down regulated in hypertrophied cardiomyocytes. Yet, the role of PPAR α in cardiomyocyte death is largely unknown. To assess the role of PPAR α in chronic hypertrophy, isoproterenol, a ß-adrenergic receptor agonist was administered in PPAR α knock out (PPAR α-/-) mice for 2 weeks and hypertrophy associated changes in cardiac tissues were observed. Echocardiographic analysis ensured the development of cardiac hypertrophy and compromised hemodynamics in PPAR α-/- mice. Proteomic analysis using high resolution mass spectrometer identified about 1,200 proteins enriched in heart tissue. Proteins were classified according to biological pathway and molecular functions. We observed an unexpected down regulation of apoptotic markers, Annexin V and p53 in hypertrophied heart tissue. Further validation revealed a significant down regulation of apoptosis regulator, PTEN, along with other apoptosis markers like p53, Caspase 9 and c-PARP. The autophagy markers Atg3, Atg5, Atg7, p62, Beclin1 and LC3 A/B were up regulated in PPAR α-/- mice indicating an increase in autophagy. Similar observations were made in a high cholesterol diet fed PPAR α-/-mice. The results were further validated in vitro using NRVMs and H9C2 cell line by blocking PPAR α that resulted in enhanced autophagosome formation upon hypertrophic stimulation. The results demonstrate that in the absence of PPAR α apoptotic pathway is inhibited while autophagy is enhanced. The data suggest that PPAR α signaling might act as a molecular switch between apoptosis and autophagy thereby playing a critical role in adaptive process in cardiac hypertrophy.

Synergistic effect of trivalent (Gd3+, Sm3+) and high-valent (Ti4+) co-doping on antiferromagnetic YFeO3.

Monophasic polycrystalline powders of Y1-x R x Fe1-(4/3)y Ti y O3 (R = Sm, Gd; x = 0.05, 0.10, 0.15; y = 0.05) were successfully synthesized via a low temperature solid-state synthesis route. The X-ray diffraction and Raman spectroscopy studies indicate that all the calcined powders with R3+ (Gd3+, Sm3+) at Y3+ and Ti4+ at Fe3+ sites were crystallized in an orthorhombic phase associated with a change in lattice parameters. The Williamson-Hall method employed to calculate the strain revealed that the strain increased with the increased concentration of dopants ((Gd3+, Sm3+) at Y3+) compared to an increase in the size of crystallites, corroborating the findings of SEM. Analysis of diffuse reflectance spectra indicated a drop in bandgap from 1.93 eV to 1.86 eV and 1.96 eV to 1.91 eV for Gd, Ti co-doping and Sm, Ti co-doping respectively, demonstrating the capacity of the synthesized powders to absorb visible light. Absorbance spectra also revealed the existence of mixed states of Fe3+ and Fe4+ which was corroborated by XPS studies. The magnetic hysteresis loop analysis at room temperature illustrated that with co-doping, there is a strong enhancement in magnetization as well as coercivity, suggesting a strong transition from anti-ferromagnetic behaviour to ferromagnetic behaviour. Pertaining to the greatly improved optical and magnetic properties with the addition of (Gd3+, Sm3+) at Y3+ and Ti4+ at Fe3+ sites, these materials are anticipated to be of potential use in various applications.

Structural, optical and magnetic properties of Sm3+ doped yttrium orthoferrite (YFeO3) obtained by sol-gel synthesis route.

Fine powders of Y1-x Sm x FeO3 (x = 0, 0.05, 0.10, 0.15) were synthesized via citrate based sol-gel route. While the as synthesized powders were amorphous, the calcined (900 °C/8 h) powders were confirmed to be polycrystalline by x-ray powder diffraction (XRD) studies. The calcined powders were found to crystallize in an orthorhombic structure associated with the lattice parameters a = 5.59 Å, b = 7.60 Å, c = 5.28 Å. These lattice parameters increased with the increase in Sm3+ content at yttrium sites. The strain that was obtained by the Williamson-Hall method increased with the increase in dopant (Sm3+) concentration vis-à-vis a decrease in crystallite size. Diffuse reflectance spectroscopic studies suggest an increase in band gap as Sm doping level increased. Significant enhancement in magnetization associated with a decrease in coercive field accompanied by a transition from anti-ferromagnetic to soft ferromagnetic behaviour in Sm doped YFeO3 were encountered. It is hoped that these materials with the enhanced magnetic properties could be of potential use for multifarious applications.

Risk factors for degenerative aortic valve disease in India: A case control study.

BACKGROUND: Degenerative aortic valve disease often co-exists with coronary artery disease (CAD) and studies done in western populations have shown that it shares the same risk factors which cause CAD. However little is known in this context among Asian Indians. The current study looks into the risk factors of degenerative aortic valve disease in Asian Indian population. METHODS: Ninety-one consecutive patients with severe aortic stenosis (AS) reporting for left heart catheterization prior to valve replacement surgery at a tertiary care centre were recruited for the study. They were compared with age and sex matched controls selected from a database of 3200 patients referred for elective diagnostic left heart catheterization for suspected CAD. Following traditional cardiovascular risk factors were assessed in all patients: age, gender, family history of CAD, smoking history, presence of diabetes, hypertension and dyslipidemia. RESULTS: The mean age of the study population was 57.8 ± 8.2 years (range, 40-80 years). Smoking, family history of CAD and hypercholesterolemia were significantly more prevalent in patients with degenerative AS compared to those with normal valves. No significant difference was noted in the presence of diabetes mellitus. On multivariate logistic regression, family history of premature CAD (OR 3.68; CI 1.38-9.78) smoking history (OR, 2.56; CI, 1.21-5.39), and raised LDL levels (OR, 5.55; CI, 2.63-11.69) were independently associated with the aortic stenosis patient cohort. CONCLUSIONS: The study showed a significant association of cardiovascular risk factors with aortic stenosis independent of age and gender in Asian Indian patients.

Direct acting oral anticoagulant: Bench to bedside.

Vitamin K antagonists are an effective group of oral anticoagulants. However because of genetic variability in their metabolism and multiple food and drug interactions, these drugs have narrow therapeutic window with unpredictable anticoagulant effects requiring constant monitoring. Several newer direct acting oral anticoagulants have been approved for prevention of stroke in patients with nonvalvular atrial fibrillation and treatment or prevention of venous thromboembolism. The direct acting oral anticoagulants include the direct thrombin inhibitor (dabigatran) and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban). These have a better safety and efficacy profile compared to Vitamin K antagonists. Some of the limitations of these drugs include increased risk of gastrointestinal bleeding (except apixaban), increased risk for thrombotic complication upon sudden cessation of therapy and inability to monitor the anticoagulation efficacy. Recent availability of the antidote to these drugs has further strengthened their safety profile. In the current review we will discuss these agents with focus on their potential clinical uses and limitations.

Design improvement and performance evaluation of solar photocatalytic reactor for industrial effluent treatment.

This work reports the details of the design components and materials used in a linear compound parabolic trough reactor constructed with an aim to use the photocatalyst for solar photocatalytic applications. A compound parabolic trough reactor has been designed and engineered to exploit both UV and visible part of the solar irradiation. The developed compound parabolic trough reactor could receive almost 88% of UV radiation along with a major part of visible radiation. The performance of the reactor has been evaluated in terms of degradation of a probe pollutant using the parameters such as rate constant, residence time and photonic efficiency. An attempt has been made to assess the performance in different ranges of solar spectrum. Finally the developed reactor has been employed for the photocatalytic treatment of a paper mill effluent using Degussa P25 as the photocatalyst. The paper mill effluent collected from Nagaon paper mill, Assam, India has been treated under both batch mode and continuous mode using Degussa P25 photocatalyst under artificial and natural solar radiation, respectively. The photocatalytic degradation kinetics of the paper mill effluent has been determined using the reduction in total organic carbon (TOC) values of the effluent.

Antenna-coupled photon emission from hexagonal boron nitride tunnel junctions.

The ultrafast conversion of electrical signals to optical signals at the nanoscale is of fundamental interest for data processing, telecommunication and optical interconnects. However, the modulation bandwidths of semiconductor light-emitting diodes are limited by the spontaneous recombination rate of electron-hole pairs, and the footprint of electrically driven ultrafast lasers is too large for practical on-chip integration. A metal-insulator-metal tunnel junction approaches the ultimate size limit of electronic devices and its operating speed is fundamentally limited only by the tunnelling time. Here, we study the conversion of electrons (localized in vertical gold-hexagonal boron nitride-gold tunnel junctions) to free-space photons, mediated by resonant slot antennas. Optical antennas efficiently bridge the size mismatch between nanoscale volumes and far-field radiation and strongly enhance the electron-photon conversion efficiency. We achieve polarized, directional and resonantly enhanced light emission from inelastic electron tunnelling and establish a novel platform for studying the interaction of electrons with strongly localized electromagnetic fields.

Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer's and other neurodegenerative diseases.

Latrepirdine (Dimebon(TM)) was originally marketed as a non-selective antihistamine in Russia. It was repurposed as an effective treatment for patients suffering from Alzheimer's disease (AD) and Huntington's disease (HD) following preliminary reports showing its neuroprotective functions and ability to enhance cognition in AD and HD models. However, latrepirdine failed to show efficacy in phase III trials in AD and HD patients following encouraging phase II trials. The failure of latrepirdine in the clinical trials has highlighted the importance of understanding the precise mechanism underlying its cognitive benefits in neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to affect a number of cellular functions including multireceptor activity, mitochondrial function, calcium influx and intracellular catabolic pathways; however, it is unclear how these properties contribute to its clinical benefits. Here, we review the studies investigating latrepirdine in cellular and animal models to provide a complete evaluation of its mechanisms of action in the central nervous system. In addition, we review recent studies that demonstrate neuroprotective functions for latrepirdine-related class of molecules including the ß-carbolines and aminopropyl carbazoles in AD, Parkinson's disease and amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects and underlying biological functions presents obvious value for developing structural analogues of latrepirdine for dementia treatment.

Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain.

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including Aß42 and γ-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae. We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including α-synuclein (α-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on α-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wild-type mice. Latrepirdine only protected yeast against the cytotoxicity associated with α-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of α-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate α-syn accumulation in transgenic mouse models of α-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust pro-autophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.

Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model.

Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aß42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities.

Ag(I) induced emission with azines having donor-acceptor-donor chromophore.

Two azine molecules, [3-{4-(dimethylamino)phenyl}prop-2-en-1-ylidene]hydrazone (HL) and [4-(dimethylamino)benzylidene]hydrazone (LL) synthesized via Schiff base condensation, show an absorption band due to intra-ligand charge transfer (ILCT). Both ligands show weak emission in the absence of a metal ion as input. When Ag(+) ions are added to either compound in THF, the metal ion gets bonded to the azine moiety resulting in a high intensity emission (approximately 400 fold). While Cu(+) shows a slight enhancement of emission, other first-row transition, alkali or alkaline-earth metal ions do not show any emission allowing Ag(+) ions to be detected in the presence of these metal ions. Both the Ag(+) complexes were characterised by X-ray crystallography and show solid-state spectra similar to their solution spectra. Time-resolved fluorescence measurements done on the complexes show two excited-state lifetimes.

A coumarin-derived fluorescence probe selective for magnesium.

Two different coumarin derivatives have been connected via an imine linkage to obtain a new fluorescence signaling system. This compound itself does not show any emission due to rapid isomerization around the C[double bond]N bond. However, in the presence of a Mg(II) ion, this isomerization is stopped because of bonding to the metal ion resulting in high-intensity (approximately 550-fold) emission. Other metal ions like Li(I), Ca(II), and Zn(II) show very little emission, while biologically relevant transition-metal ions do not show any emission. In this way, the Mg(II) ion can be detected in the presence of these ions.

Percutaneous Closure of Perimembranous Ventricular Septal Defect with Amplatzer Device.

BACKGROUND: The Amplatzer perimembranous ventricular septal occluder is an innovative device for percutaneous closure of perimembranous ventricular septal defects (PMVSD). In appropriately selected cases this procedure is safe and effective. METHODS: Fourteen patients with the mean age 10.53 years (range 18 months to 55 years) and mean body weight 20.64 kg (range 6 to 52 kg) underwent PMVSD closure. RESULT: The PMVSD mean diameter was 5.28 mm (range from 4 to 9 mm). Implantation was successful in 92% of the cases and all patients had complete occlusion of the shunt within three months. CONCLUSION: Device orientation was excellent in all cases. Device-related aortic insufficiency, tricuspid insufficiency or left ventricular dysfunction was not observed. One patient had embolisation of the device and another had complete heart block which required a permanent pacemaker implantation. The excellent short term results need to be confirmed over long-term follow-up.

Coronary Artery Revascularisation : Past, Present and Future.

The high prevalence of coronary artery disease has inspired the development of technologies and techniques for coronary revascularisation, including coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). PCI have witnessed the impact of innovation with newer hardware and drug eluting stents (DES). DES have indisputably reduced restenosis, however there is an emerging concern over the risk of late stent thrombosis associated with their use. We discuss the limitations of the current generation DES and review advances in the stent technology. The technology used in CABG has improved, resulting in off-pump coronary artery bypass (OPCAB), endoscopic, video-assisted, and robot-assisted CABG with automated one-shot distal anastomotic devices being used increasingly. The difference in adverse outcomes between CABG and PCI continues to decline and the future may witness a close collaboration between the two.