A Simplified Approach for the Aqueous Synthesis of Luminescent CdSe/ZnS Core/Shell Quantum Dots and Their Applications in Ultrasensitive Determination of the Biomarker 3-Nitro-l-tyrosine.

In contrast to the hot-injection organometallic routes, synthesizing stable and highly luminescent core/shell nanocrystals with encapsulation of biocompatible groups through an aqueous route is a long-standing challenge. In recent years, relatively high quantum efficiency and unique properties of core/shell nanostructured materials (quantum dots) have contributed toward enhancement in sensing capability. The present work reports a facile aqueous synthesis process of core/shell CdSe/ZnS quantum dots (QDs) with encapsulation of glutathione (GSH). The optimal conditions for the synthesis of the most stable particles were ascertained, and the different experimental analyses suggest that the stable core/shell QDs in question have good crystallinity with a size around 4.7 nm with a shell thickness of 0.7 nm and a photoluminescence quantum yield of about 35%. Further, it is demonstrated that the as-synthesized material has great potential in detecting as low as 0.28 nM 3-nitro-l-tyrosine (3-NT), an important marker for oxidative stress, the level of which in our body signals several chronically diseased conditions. The enthalpy-driven interactions of CdSe/ZnS-GSH QDs with 3-NT were characterized through steady-state and time-resolved luminescence spectroscopy and isothermal microcalorimetry. The devised method of probing 3-NT was further validated with human serum samples. Thus, the proposed strategy may provide a protocol for selective determination of 3-NT under different pathological conditions.

Review on the Use of Heavy Metal Deposits from Water Treatment Waste towards Catalytic Chemical Syntheses.

The toxicity and persistence of heavy metals has become a serious problem for humans. These heavy metals accumulate mainly in wastewater from various industries' discharged effluents. The recent trends in research are now focused not only on the removal efficiency of toxic metal particles, but also on their effective reuse as catalysts. This review discusses the types of heavy metals obtained from wastewater and their recovery through commonly practiced physico-chemical pathways. In addition, it covers the advantages of the new system for capturing heavy metals from wastewater, as compared to older conventional technologies. The discussion also includes the various structural aspects of trapping systems and their hypothesized mechanistic approaches to immobilization and further rejuvenation of catalysts. Finally, it concludes with the challenges and future prospects of this research to help protect the ecosystem.

Synthesis of Excitation Independent Highly Luminescent Graphene Quantum Dots through Perchloric Acid Oxidation.

We demonstrate a facile liquid phase exfoliation method by only using perchloric acid to synthesize graphene quantum dots (GQDs) having excitation independent strong emission with a quantum yield of about 14%. The proposed simplified synthesis strategy can help in overcoming the limitations of existing aqueous routes which produce GQDs with excitation dependent emission and of low quantum efficiency. Photoluminescence (PL) properties of GQDs have been studied in detail to understand the origin of emission. As-synthesized GQDs show excitation independent photoluminesce (PL) which suggests that the synthesized materials do not have any significant defects. Spectral analysis suggests that the PL emission of the well-defined GQDs originates mainly from the peripheral functional groups conjugated with carbon backbone planes. We also demonstrate a relatively longer PL lifetime (average lifetime of about 10 ns) of the synthesized GQDs determined by time correlated single photon counting (TCSPC) measurement and this high lifetime suggests that the synthesized GQDs may be suitable for biomacromolecular probing. In addition, as-synthesized GQDs interestingly show delayed fluorescence and steady state anisotropy, which make the material an appropriate candidate for application in sensing and bioimaging of cells and organisms.

Exploiting the biomimetic and luminescence properties of multivalent dendrimer-semiconductor nanohybrid materials in the ultra-low level determination of folic acid.

In view of the enhanced generation of folate receptors in cancerous cells and diseases linked to the deficiency of folic acid, such as anemia, mental devolution, congenital malformation, etc., the development of a simple method for the ultra-sensitive determination of folic acid remains a long-standing issue for practical applications in medicine and biotechnology. Thus, the proposed luminescence based strategy involving multifunctional poly(amidoamine) (PAMAM) dendrimer encapsulated quantum dots (QDs) as a probe provides a simple, fast and efficient method for the selective determination of folic acid at the nano-molar level. Absorption and Fourier transform infra-red (FTIR) spectroscopy provide evidence of the binding of folic acid with dendrimer amine groups. The emission quenching of dendrimer encapsulated CdS QDs follows a linear Stern-Volmer plot with an exceedingly high value of the Stern-Volmer constant (KSV = 8.4 × 106 M-1) facilitating a higher detection efficiency. Similar quenching analysis with dendrimer-ZnS QDs showed a slightly lower Stern-Volmer constant (KSV = 2.29 × 106 M-1). The lower probing efficiency of the protein or amino acid capping of QDs has been explained through zeta potential measurements. The solvent polarity dependence suggests a charge transfer process responsible for the emission quenching of CdS QDs, which is static in nature as revealed by lifetime measurements. The determination of folic acid at this low level is not affected by possible interfering molecules, such as vitamin C, vitamin B12 and uric acid. Calorimetric measurements showed that the exothermic binding of folic acid with a dendrimer follows enthalpy-entropy compensation. The detailed mechanistic aspect of interactions of folic acid with the QD probe helps in a better understanding of the detection process, which in turn can assist in developing a dendrimer based material for image analysis and drug delivery in folate receptor rich cells.

Injectable biocompatible RAFT mediated nitroxide nanogels: A robust ROS-reduction antioxidant approach.

This work introduces novel nitroxide-based nanogels (NGs) crafted through controlled RAFT (Reversible Addition Fragmentation chain Transfer) polymerization, showcasing over 85% improved shelf-life compared to native superoxide dismutase (SOD) enzymes. These 30-40 nm NGs hold great promise for injectable delivery, effectively reducing foam cell formation and displaying potent antioxidant behavior against various reactive oxygen species (ROS), revolutionizing antioxidant therapy. Featuring a meticulously designed core-shell structure via precise RAFT polymerization, these NGs mimic SOD enzymatic activity with nitroxide-based antioxidants, providing unprecedented defense against ROS. Combining methacrylated 2,2,6,6-Tetramethyl-4-piperidyl methacrylate (PMA) and Glycidyl methacrylate (GMA) monomers with precisely synthesized nitroxyl radicals results in exceptional properties. Validated through comprehensive analytical methods, these NGs exhibit remarkable stability, halting foam cell formation even at high concentrations, and demonstrate notable biocompatibility. Their ability to protect low density lipoprotein (LDL) from oxidation for up to a month positions them at the forefront of combating cardiovascular diseases, especially atherosclerosis. This study pioneers injectable antioxidant therapy, offering an innovative approach to cardiovascular ailments. Targeting narrow plaques signifies a promising intervention, reshaping cardiovascular disease treatments. It highlights the potential of advanced drug delivery in biomedicine, promising more effective cardiovascular disease treatments.

Revolutionizing Food Safety with Quantum Dot-Polymer Nanocomposites: From Monitoring to Sensing Applications.

The present review article investigates the prospective utilisation of quantum dot-polymer nanocomposites in the context of ensuring food safety. The text pertains to the advancement of nanocomposites, encompassing their distinctive optical and electrical characteristics, and their prospective to transform the detection and perception of food safety risks. The article explores diverse methodologies for producing nanocomposites and underscores their potential utility in identifying impurities, microorganisms, and harmful substances in food. The article provides an overview of the challenges and limitations associated with the utilisation of nanocomposites in food safety applications, encompassing concerns regarding toxicity and the necessity for standardised protocols. The review article presents a comprehensive examination of the present research status in this area and underscores the potential of quantum dots-polymer nanocomposites in transforming food safety monitoring and sensing.

Catalytic polymer nanocomposites for environmental remediation of wastewater.

The removal of harmful chemicals and species from water, soil, and air is a major challenge in environmental remediation, and a wide range of materials have been studied in this regard. To identify the optimal material for particular applications, research is still ongoing. Polymer nanocomposites (PNCs), which combine the benefits of nanoparticles with polymers, an alternative to conventional materials, may open up new possibilities to overcome this difficulty. They have remarkable mechanical capabilities and compatibility due to their polymer matrix with a very high surface area to volume ratio brought about by their special physical and chemical properties, and the extremely reactive surfaces of the nanofillers. Composites also provide a viable answer to the separation and reuse problems that hinder nanoparticles in routine use. Understanding these PNCs materials in depth and using them in practical environmental applications is still in the early stages of development. The review article demonstrates a crisp introduction to the PNCs with their advantageous properties as a catalyst in environmental remediation. It also provides a comprehensive explanation of the design procedure and synthesis methods for fabricating PNCs and examines in depth the design methods, principles, and design techniques that guide proper design. Current developments in the use of polymer nanocomposites for the pollutant treatment using three commonly used catalytic processes (catalytic and redox degradation, electrocatalytic degradation, and biocatalytic degradation) are demonstrated in detail. Additionally, significant advances in research on the aforementioned catalytic process and the mechanism by which contaminants are degraded are also amply illustrated. Finally, there is a summary of the research challenges and future prospects of catalytic PNCs in environmental remediation.

Common Signaling Pathways Involved in Alzheimer's Disease and Stroke: Two Faces of the Same Coin.

Alzheimer's disease (AD) and stroke are two interrelated neurodegenerative disorders which are the leading cause of death and affect the neurons in the brain and central nervous system. Although amyloid-ß aggregation, tau hyperphosphorylation, and inflammation are the hallmarks of AD, the exact cause and origin of AD are still undefined. Recent enormous fundamental discoveries suggest that the amyloid hypothesis of AD has not been proven and anti-amyloid therapies that remove amyloid deposition have not yet slowed cognitive decline. However, stroke, mainly ischemic stroke (IS), is caused by an interruption in the cerebral blood flow. Significant features of both disorders are the disruption of neuronal circuitry at different levels of cellular signaling, leading to the death of neurons and glial cells in the brain. Therefore, it is necessary to find out the common molecular mechanisms of these two diseases to understand their etiological connections. Here, we summarized the most common signaling cascades including autotoxicity, ApoE4, insulin signaling, inflammation, mTOR-autophagy, notch signaling, and microbiota-gut-brain axis, present in both AD and IS. These targeted signaling pathways reveal a better understanding of AD and IS and could provide a distinguished platform to develop improved therapeutics for these diseases.

SbI3·3S8: A Novel Promising Inorganic Adducts Crystal for Second Harmonic Generation.

In the past twenty years, the basic investigation of innovative Non-Linear Optical (NLO) crystals has received significant attention, which has built the crucial heritage for the use of NLO materials. Fundamental research is essential given the scarcity of materials for NLO compounds, especially in the deep ultraviolet (DUV) and middle- and far-infrared (MFIR) regions. In the present work, we synthesized high-quality MFIR SbI3·3S8 NLO crystals having a length in the range of 1-5 mm through rapid facile liquid phase ultrasonic reaction followed by the assistance of instantaneous natural evaporation phenomenon of the solvent at room temperature. X-ray diffraction (XRD) results ratify the hexagonal R3m structure of SbI3·3S8 crystal, and energy-dispersive X-ray spectroscopy (EDX) demonstrates that the elemental composition of SbI3·3S8 crystal is similar to that of its theoretical composition. The direct and indirect forbidden energy gaps of SbI3·3S8 were measured from the optical transmittance spectra and they were shown to be 2.893 eV and 1.986 eV, respectively. The green sparkling signal has been observed from the crystal during the second harmonic generation (SHG) experiment. Therefore, as inorganic adducts are often explored as NLO crystals, this work on the MFIR SbI3·3S8 NLO crystal can bring about additional investigations on this hot topic in the near future.

Bismuth sulfoiodide (BiSI) nanorods: synthesis, characterization, and photodetector application.

The nanorods of bismuth sulfoiodide (BiSI) were synthesized at relatively low temperature (393 K) through a wet chemical method. The crystalline one-dimensional (1D) structure of the BiSI nanorods was confirmed using high resolution transmission microscopy (HRTEM). The morphology and chemical composition of the material were examined by applying scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. The average diameter of 126(3) nm and length of 1.9(1) µm of the BiSI nanorods were determined. X-ray diffraction (XRD) revealed that prepared material consists of a major orthorhombic BiSI phase (87%) and a minor amount of hexagonal Bi13S18I2 phase (13%) with no presence of other residual phases. The direct energy band gap of 1.67(1)  eV was determined for BiSI film using diffuse reflectance spectroscopy (DRS). Two types of photodetectors were constructed from BiSI nanorods. The first one was traditional photoconductive device based on BiSI film on stiff glass substrate equipped with Au electrodes. An influence of light intensity on photocurrent response to monochromatic light (λ = 488 nm) illumination was studied at a constant bias voltage. The novel flexible photo-chargeable device was the second type of prepared photodetectors. It consisted of BiSI film and gel electrolyte layer sandwiched between polyethylene terephthalate (PET) substrates coated with indium tin oxide (ITO) electrodes. The flexible self-powered BiSI photodetector exhibited open-circuit photovoltage of 68 mV and short-circuit photocurrent density of 0.11 nA/cm2 under light illumination with intensity of 0.127 W/cm2. These results confirmed high potential of BiSI nanorods for use in self-powered photodetectors and photo-chargeable capacitors.

Non-coding RNAs and their bioengineering applications for neurological diseases.

Engineering of cellular biomolecules is an emerging landscape presenting creative therapeutic opportunities. Recently, several strategies such as biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems have been developed to improve specific biological functions, however, have been confounded with fundamental and technical roadblocks. Rapidly emerging investigations on the bioengineering prospects of mammalian ribonucleic acid (RNA) is expected to result in significant biomedical advances. More specifically, the current trend focuses on devising non-coding (nc) RNAs as therapeutic candidates for complex neurological diseases. Given the pleiotropic and regulatory role, ncRNAs such as microRNAs and long non-coding RNAs are deemed as attractive therapeutic candidates. Currently, the list of non-coding RNAs in mammals is evolving, which presents the plethora of hidden possibilities including their scope in biomedicine. Herein, we critically review on the emerging repertoire of ncRNAs in neurological diseases such as Alzheimer's disease, Parkinson's disease, neuroinflammation and drug abuse disorders. Importantly, we present the advances in engineering of ncRNAs to improve their biocompatibility and therapeutic feasibility as well as provide key insights into the applications of bioengineered non-coding RNAs that are investigated for neurological diseases.

Physicochemical Understanding of Protein-Bound Quantum Dot-Based Sensitive Probing of Bilirubin: Validation with Real Samples and Implications of Protein Conformation in Sensing.

Precise and rapid determination of free bilirubin (BR), a key biomarker of pathological conditions of the liver, is important clinical issue. The present study demonstrates that the combination of the strong specific affinic properties of protein, bovine serum albumin (BSA), toward bilirubin and luminescence of well-characterized semiconductor quantum dots (QDs) can offer a simple, fast, and sensitive technique for the determination of free bilirubin through quenching analysis. Here, BSA molecule not only stabilizes the quantum dots in an aqueous environment but also helps bring BR closer to QDs during the interactions of CdSe-BSA QDs with BR. Further, it is revealed through photophysical investigation that the conformation of protein molecule may play an important role in biomolecular sensing considering bilirubin as a model target molecule. The luminescence of CdSe-BSA QDs was highly responsive toward bilirubin, where nearly 90% of emission intensity was quenched on adding only 40 µM bilirubin, suggesting strong interactions involved between synthesized QDs and bilirubin. Solvent polarity dependence on luminescence changes confirms strong electrostatic interaction between the QDs and BR. The applicability of the synthesized quantum dots in sensing bilirubin has been checked in the presence of different possible interfering agents and also with plasma isolated from real blood samples of both normal and hepatitis patients. It was observed that bilirubin as control sample as well as in human serum sample can be optimally measured at pH 7.5, 25 °C. Thus, the proposed strategy being able to measure free BR even at least two orders of magnitude lower than bilirubin level in normal blood may provide a reasonable protocol to determine BR in the pathophysiology of many critical human diseases, like hepatitis and Gilbert's syndrome in the near future.

Room temperature synthesis of NIR emitting Ag2S nanoparticles through aqueous route and its influence on structural modulation of DNA.

Near infra-red (NIR) light emitting nanomaterials had shown great promise in clinical imaging in view of negligible absorption by skin or tissue of mammalian. Thus, it demands for synthesizing stable NIR emitting nanomaterials in water environment. The present work presents synthesis of biologically acceptable luminescent near-IR emitting silver sulfide nanoparticles through an aqueous route using 2-mercaptoethanol. The prepared as-synthesized Ag2S nanoparticles exhibited bright photoluminescence with quantum yield of ca. 4%. X-ray diffraction (XRD) analysis indicated that the products were monoclinic α-Ag2S. Fourier transform infrared spectral analysis revealed that the stretching vibration at 2560 cm-1 responsible for S-H bond of thiol group disappeared suggesting the conjugation of 2-mercaptoethanol with Ag2S nanoparticles. In view of investigating any possible effect on genetic materials, interactions of the synthesized particles with calf thymus DNA was investigated employing Ethidium bromide (EB) as structural probe. To understand the binding mechanism, the UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopic, as well as DNA melting studies measurements were carried out. The observed results confirm that nanoparticles interact with DNA through groove binding.

Acoustic cavitation assisted destratified clay tactoid reinforced in situ elastomer-mimetic semi-IPN hydrogel for catalytic and bactericidal application.

Ultrasonicaion is non-chemical process where acoustic waves have been targeted to aqueous medium dispersed precursor materials. In situ synthesis of silver nanoparticles anchored in hydrogel matrix has been opted via ~20 kHz frequency assisted (bath sonication) synthesis having the ultrasonication power intensity (UPI) of ~106 J/m2. Power intensity is inversely proportional to the surface area of the clay tactoids. The hydrogel have been prepared by in situ 20 kHz assisted sonochemical destratification of laponite clay tactoids which could be terminologically stated as 'top-down method'. Silver nanoparticles (AgNPs) have been deposited in the surfaces of the porous matrix of hydrogel via 'soak and irradiate' method. Soaking of silver ions into the gel matrix is welcomed due to their efficient stabilization and fast transformation towards AgNPs. AgNPs played the key role in catalytic reduction and bactericidal activity. Moreover, the prepared hydrogel has enough robust to withstand cyclic stress, uniaxial stress and oscillatory stress which have been extensively justified by the physico-mechanical characterizations. The gel supported catalyst showed first order reaction kinetics and less time consuming period during reduction of 4-nitrophenol as a model pollutant.

A Multifunctional Smart Textile Derived from Merino Wool/Nylon Polymer Nanocomposites as Next Generation Microwave Absorber and Soft Touch Sensor.

In recent times e-textiles have emerged as wonder safeguards due to the great potential background in space, military, healthcare, or portable electronics. As a result, widespread research and development have been done to make significant advancement in this field, but it still remains a key challenge to use one single product with multifunctional attributes with the past performance of key characteristics. In this work, phase-separated PEDOT:PSS ornamented with reduced graphene oxide (rGO) nanosheets, deposited on the newly fabricated ultralightweight, superhydrophobic, and mechanically enriched merino wool/nylon (W-N) composite textile followed by the dipping and drying strategy. The open edges-layered structure of rGO helping uniform deposition of PEDOTs clusters, which allows the formation of a stacked layer of PEDOTs/rGO-PEDOTs/PEDOTs for robust three-dimensional electrical transforming channel network within the W-N textile surface. These dip-coated multifunctional textiles show high electrical conductivities up to 90.5 S cm-1 conjugated with a flexible electromagnetic interference shielding efficiency of 73.8 dB (in X-band) and in-plane thermal conductivity of 0.81 W/mK with a minimum thickness of 0.84 mm. This thin coating maintained the hydrophobicity (water contact angle of ∼150°) leading to an excellent EM protective cloth combined with real-life antenna performance under high mechanical or chemical tolerance. Interestingly, this multiuse textile can also act as an exceptional TASER Proof Textile (TPT) due to a short out of the electrical shock coming from the TASER by its unique conducting network architecture. Remarkably, this coated textile can get a response by the soft touch to lighten up the household bulb and could establish wireless communication via an HC-05 Bluetooth module as a textile-based touch switch. This developed fabric could perform as a new potentially scalable single product in intelligent smart garments, portable next-generation electronics, and the growing threat of EM pollution.

Curcumin Downregulates GSK3 and Cdk5 in Scopolamine-Induced Alzheimer's Disease Rats Abrogating Aß40/42 and Tau Hyperphosphorylation.

Alzheimer's disease (AD) is the most common form of dementia. Extracellular amyloid-ß (Aß) aggregation and tau hyperphosphorylation are the key drivers of AD. Glycogen synthase kinase 3 (GSK3) and cyclin dependent kinase 5 (Cdk5) have been known as leading applicants arbitrating abnormal tau hyperphosphorylation. Thus, we evaluated the efficacy and underlying mechanism of action of curcumin in scopolamine-induced AD rats in our study. We found that curcumin-treated AD rats markedly reduced the levels of Aß40 and Aß42 in the brain and in the plasma in comparison to untreated AD rats. Moreover, the levels of phosphorylated tau at Ser396 (PHF13), Ser202/Thr205 (AT8), and Aß40/42 (MOAB2) were decreased significantly in AD rats treated with curcumin. Phospho-GSK3ß (Tyr216), the active form of GSK3ß, and total GSK3ß were significantly decreased in AD rats treated with curcumin. Furthermore, Cdk5 and its activators p35 and p25 were significantly decreased in curcumin-treated AD rats. The reduced levels of Cdk5, p35, p25, and GSK3ß in curcumin-treated AD rats may result decreased Aß aggregation and tau hyperphosphorylation, thus ameliorating AD. Impaired spatial memory and locomotor activity in AD rats were partially reversed by curcumin. Therefore, curcumin, as a natural compound present in turmeric, may be a more effective therapeutic agent in the treatment of AD in humans.

Curcumin Ameliorates the Impaired Insulin Signaling Involved in the Pathogenesis of Alzheimer's Disease in Rats.

To date, dysregulation of the insulin signaling pathway in the brain has not been demonstrated unequivocally in Alzheimer's disease (AD). The purpose of the study was to examine the possible dysregulation of insulin signaling pathway in an AD rat model. Furthermore, the present study investigated the effect of Donepezil and Curcumin on insulin signaling, insulin, and glucose levels in AD rat brain. The rats were induced to develop AD by intraperitoneal administration of Scopolamine. We found that glucose levels in plasma and brain were decreased in AD rats, whereas the insulin levels was increased in plasma but decreased in brain in AD rats. In addition, insulin signaling proteins IR-ß, IGF-1, IRS-1, IRS-2 p-Akt (Ser473), and Akt were markedly reduced in the AD rats. Furthermore, GLUT3 and GLUT4 levels in the brain were markedly reduced in AD rats. All these data were compared to Saline-treated control rats. Curcumin significantly increased glucose levels in plasma and in brain. However, insulin levels was decreased in plasma and was increased in AD rats' brain. Moreover, GLUT3 and GLUT4 levels were significantly increased in Curcumin-treated AD rats. All these data were compared to Scopolamine- induced AD rats. Thus amelioration of impaired insulin signaling and improved glucose regulation in AD rats by Curcumin may be beneficial in the management of AD.

Antioxidant defense in schizophrenia and bipolar disorder: A meta-analysis of MRS studies of anterior cingulate glutathione.

BACKGROUND: Glutathione [GSH] is a major intracellular antioxidant that disposes peroxides and protects neurons and glial cells from oxidative stress. In both schizophrenia and bipolar disorder, atypical levels of GSH have been demonstrated, particularly in the anterior cingulate cortex (ACC), though no consistent results have emerged due to limitations in sample size. Our objective was to evaluate if GSH levels in the ACC are abnormal in these 2 disorder, when compared to healthy controls. METHODS: We reviewed all 1H-MRS studies reporting GSH values for patients satisfying DSM or ICD based criteria for (1) the psychotic disorders - schizophrenia or schizoaffective disorder or (2) bipolar disorder in comparison to a healthy controls (HC) group in the Anterior Cingulate Cortex (ACC) published until June 2018. A random-effects model was used to calculate the pooled effect size. A meta-regression analysis of moderator variables was also undertaken. RESULTS: The literature search identified 18 studies with a total sample size of 581 controls, 578 patients with schizophrenia or bipolar disorder. There is a small but significant reduction in ACC GSH in patients with schizophrenia compared to HC (N = 13; RFX SMD =0.26; 95% CI [0.07 to 0.44]; p = 0.008; heterogeneity p = 0.11). There is a significant increase in the ACC GSH concentration in bipolar disorder compared to HC (N = 6; RFX SMD = -0.28, 95% CI [-0.09 to -0.47]; p = 0.003; heterogeneity p = 0.95). CONCLUSIONS: We report a small, but significant reduction in GSH concentration in the ACC in schizophrenia, and a similar sized increase in bipolar disorder. A notable limitation is the lack of sufficient data to examine the moderating effect of the symptom profile. Schizophrenia and bipolar disorder have notably different patterns of redox abnormalities in the ACC. Reduced ACC GSH may confer a schizophrenia-like clinical phenotype, while an excess favouring a bipolar disorder-like profile.

Prognostic Utility of Multivariate Morphometry in Schizophrenia.

Background: Voxel-based morphometry studies have repeatedly highlighted the presence of distributed gray matter changes in schizophrenia, but to date, it is not clear if clinically useful prognostic information can be gleaned from structural imaging. The suspected association between gray matter volume (GMV) and duration of psychotic illness, antipsychotic exposure, and symptom severity also limits the prognostic utility of morphometry. We address the question of whether morphometric information from patients with drug-naive first-episode psychosis can predict the linear trajectory of symptoms following early antipsychotic intervention using a longitudinal design. Method: Sixty-two first-episode, drug-naive patients with schizophrenia underwent brain magnetic resonance imaging scans at baseline, treated with antipsychotics, and rescanned after 1-year follow-up. Positive and Negative Syndrome Scale (PANSS) was used to assess their clinical manifestations. A multivariate approach to detect covariance-based network-like spatial components [Source Based Morphometry (SBM)] was performed to analyze the GMV. Paired t tests were used to study changes in the loading coefficients of GMV in the spatial components between two time points. The reduction in PANSS scores between the baseline (T0) and 1-year follow-up (T1) expressed as a ratio of the baseline scores (reduction ratio) was computed for positive, negative, and disorganization symptoms. Separate multiple regression analyses were conducted to predict the longitudinal change in symptoms (treatment response) using the loading coefficients of spatial components that differed between T0 and T1 with age, gender, duration of illness, and antipsychotic dose as covariates. We also tested the putative "toxicity" effects of baseline symptom severity on the GMV at 1 year using multiple regression analysis. Results: Of the 30 spatial components of gray matter extracted using SBM, loading coefficients of anterior cingulate cortex (ACC), insula and inferior frontal gyrus (IFG), superior temporal gyrus (STG), middle temporal gyrus (MTG), precuenus, and dorsolateral prefrontal cortex (DLPFC) reduced with time in patients. Specifically, the lower volume of insula and IFG at baseline predicted a lack of improvement in positive and disorganization symptoms. None of the symptom severity scores (positive, negative, or disorganization) at baseline independently predicted the reduced GMV at 1 year. Conclusions: The baseline deficit in a covariance-based network-like spatial component comprising of insula and IFG is predictive of the clinical course of schizophrenia. We do not find any evidence to support the notion of symptoms per se being neurotoxic to gray matter tissue. If judiciously combined with other available predictors of clinical outcome, multivariate morphometric information can improve our ability to predict prognosis in schizophrenia.

Putative Astroglial Dysfunction in Schizophrenia: A Meta-Analysis of 1H-MRS Studies of Medial Prefrontal Myo-Inositol.

Background: Several lines of evidence support a role for astroglial pathology in schizophrenia. Myo-inositol is particularly abundant in astroglia. Many small sized studies have reported on myo-inositol concentration in schizophrenia, but to date these have not been pooled to estimate a collective effect size. Methods: We reviewed all proton magnetic resonance spectroscopy (1H-MRS) studies reporting myo-inositol values for patients satisfying DSM or ICD based criteria for schizophrenia in comparison to a healthy controls group in the medial prefrontal cortex published until February 2018. A random-effects model was used to calculate the pooled effect size using metafor package. A meta-regression analysis of moderator variables was also undertaken. Results: The literature search identified 19 studies published with a total sample size of 585 controls, 561 patients with schizophrenia. Patients with schizophrenia had significantly reduced medial prefrontal myo-inositol compared to controls (RFX standardized mean difference = 0.19, 95% CI [0.05-0.32], z = 2.72, p = 0.0067; heterogeneity p = 0.09). Studies with more female patients reported more notable schizophrenia-related reduction in myo-inositol (z = 2.53, p = 0.011). Discussion: We report a small, but significant reduction in myo-inositol concentration in the medial prefrontal cortex in schizophrenia. The size of the reported effect indicates that the biological pathways affecting the astroglia are likely to operate only in a subset of patients with schizophrenia. MRS myo-inositol could be a useful tool to stratify and investigate such patients.