Using Personal Activity Intelligence With Patients in a Clinic Setting: A Feasibility Study.

BACKGROUND: Personal Activity Intelligence (PAI) is a novel heart-rate-based metric used to assess cardiorespiratory fitness and quantify physical activity. OBJECTIVE: The aim of this study was to examine the feasibility, acceptability, and effectiveness of PAI with patients in a clinic setting. METHODS: Patients (n = 25) from 2 clinics underwent 12 weeks of heart-rate-monitored physical activity interfaced with aPAI Health phone app. We used a pre-post design with the Physical Activity Vital Sign and the International Physical Activity Questionnaire. Feasibility, acceptability, and PAI measures were used to evaluate the objectives. RESULTS: Twenty-two patients (88%) completed the study. There were significant improvements in International Physical Activity Questionnaire metabolic equivalent task minutes per week ( P = .046) and a decrease in sitting hours ( P = .0001). The Physical Activity Vital Sign activity increase in minutes per week was not significant ( P = .214). Patients achieved a mean PAI score of 116 ± 81.1 and 100 or greater 71% of the days. Most patients (81%) expressed satisfaction with PAI. CONCLUSIONS: Personal Activity Intelligence is feasible, acceptable, and effective when used with patients in a clinic setting.

Trends in Quantification of HbA1c Using Electrochemical and Point-of-Care Analyzers.

Glycated hemoglobin (HbA1c), one of the many variants of hemoglobin (Hb), serves as a standard biomarker of diabetes, as it assesses the long-term glycemic status of the individual for the previous 90-120 days. HbA1c levels in blood are stable and do not fluctuate when compared to the random blood glucose levels. The normal level of HbA1c is 4-6.0%, while concentrations > 6.5% denote diabetes. Conventionally, HbA1c is measured using techniques such as chromatography, spectroscopy, immunoassays, capillary electrophoresis, fluorometry, etc., that are time-consuming, expensive, and involve complex procedures and skilled personnel. These limitations have spurred development of sensors incorporating nanostructured materials that can aid in specific and accurate quantification of HbA1c. Various chemical and biological sensing elements with and without nanoparticle interfaces have been explored for HbA1c detection. Attempts are underway to improve the detection speed, increase accuracy, and reduce sample volumes and detection costs through different combinations of nanomaterials, interfaces, capture elements, and measurement techniques. This review elaborates on the recent advances in the realm of electrochemical detection for HbA1c detection. It also discusses the emerging trends and challenges in the fabrication of effective, accurate, and cost-effective point-of-care (PoC) devices for HbA1c and the potential way forward.

Vaginosis: Advances in new therapeutic development and microbiome restoration.

Vaginosis is a condition experienced by most women at least once in their lifetime. This condition arises due to the imbalance in the microbiome of the vaginal ecosystem. Most of the pathogens of this disease are organisms which are commonly found in a normal healthy vagina. The vaginal microbiome is important as they act as a primary defence against secondary infections and Sexually transmitted diseases and infections (STDs and STIs). The vagina is mostly dominated by Lactobacillus along with other microbes including Gardnerella vaginalis, Atopobium vaginae., Prevotella spp., Mobiluncus spp., etc. Vaginal microbiome also includes Candida albicans and other species of the genus. The ratio in which these species are present varies from person to person and the dominant species decides the whether a vagina is "normal" or not. Lactobacillus dominated vagina is considered normal and if dominated by Gardnerella and such it is considered to be Bacterial vaginosis (BV) and similarly for Vulvovaginal Candidiasis (VVC). The microbiome also undergoes changes during menstrual cycles and menopausal stages. Due to the dynamic nature of this microbiome, it is tough to perfectly restore the balance. But several treatments are currently available with antibiotics like Clindamycin and derivatives of 5-nitroimidazole drugs like Metronidazole. The extensive use and the non-adherence to the treatment regimen has led to drug resistance through biofilm formation, efflux pumps, single nucleotide polymorphisms and resulting recurrent episode of vaginosis in women. Alternative medicines, preparations from plant sources, anti-microbial peptides and nano formulations are also being explored. Most of these medicines tend to focus on reducing the pathogen load rather than restoring the balance of the ecosystem. Vaginal microbiome transplant, an effort to restore the normalcy in the vaginal environment is becoming a popular treatment. In this review we discuss about the types of vaginosis, available treatments, challenges in treating the condition and the new drugs that are under investigation.

Evaluation of the Anticancer Activity of pH-Sensitive Polyketal Nanoparticles for Acute Myeloid Leukemia.

Polyketals are a class of acid-responsive polymers that have been relatively less explored for drug delivery applications compared to polyesters. The degradation of these polymers is accelerated in an acidic medium and does not result in acidic byproducts. Their biocompatibility depends on the diol used for the synthesis. The present work aims to synthesize, characterize, and fabricate nanospheres of an aliphatic polyketal for delivery of the nucleotide analogue cytarabine toward the treatment of acute myeloid leukemia (AML). The internalization mechanism of the nanospheres was probed, and its implication on the nuclear localization and escape from the endo-lysosomal compartments were studied. The drug-loaded polyketal nanoparticles reduced the cell viability to a greater extent compared with the free drug. The effect of the drug-loaded polyketal nanoparticles on the differential gene expression of leukemic cells was investigated for the first time to understand their therapeutic implications. It was found that treatment with drug-loaded polyketal nanoparticles downregulated AML-specific genes involved in cell proliferation and recurrence compared to the free drug. The protein expression studies were performed for selected genes obtained from gene expression analysis. Biodistribution studies showed that the poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) nanoparticles exhibit prolonged circulation time. Overall, our results suggest that polyketal-based delivery of cytarabine represents a more effective alternative strategy for AML therapy.

Multifunctional Traceable Liposomes with Temperature-Triggered Drug Release and Neovasculature-Targeting Properties for Improved Cancer Chemotherapy.

Poor distribution of nanocarriers at the tumor site and insufficient drug penetration into the tissue are major challenges in the development of effective and safe cancer therapy. Here, we aim to enhance the therapeutic effect of liposomes by accumulating doxorubicin-loaded liposomes at high concentrations in and around the tumor, followed by heat-triggered drug release to facilitate low-molecular-weight drug penetration throughout the tumor. A cyclic RGD peptide (cRGD) was incorporated into liposomes decorated with a thermosensitive polymer that allowed precise tuning of drug release temperature (i.e., Polymer-lip) to develop a targeted thermosensitive liposome (cRGD-Polymer-lip). Compared with conventional thermosensitive liposomes, cRGD-Polymer-lip enhanced the binding of liposomes to endothelial cells, leading to their accumulation at the tumor site upon intravenous administration in tumor-bearing mice. Drug release triggered by local heating strongly inhibited tumor growth. Notably, tumor remission was achieved via multiple administrations of cRGD-Polymer-lip and heat treatments. Thus, combining the advantages of tumor neovascular targeting and heat-triggered drug release, these liposomes offer high potential for minimally invasive and effective cancer chemotherapy.

An open-source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing.

BACKGROUND AND OBJECTIVES: Next generation sequencing (NGS) has promising applications in transfusion medicine. Exome sequencing (ES) is increasingly used in the clinical setting, and blood group interpretation is an additional value that could be extracted from existing data sets. We provide the first release of an open-source software tailored for this purpose and describe its validation with three blood group systems. MATERIALS AND METHODS: The DTM-Tools algorithm was designed and used to analyse 1018 ES NGS files from the ClinSeq® cohort. Predictions were correlated with serology for 5 antigens in a subset of 108 blood samples. Discrepancies were investigated with alternative phenotyping and genotyping methods, including a long-read NGS platform. RESULTS: Of 116 genomic variants queried, those corresponding to 18 known KEL, FY and JK alleles were identified in this cohort. 596 additional exonic variants were identified KEL, ACKR1 and SLC14A1, including 58 predicted frameshifts. Software predictions were validated by serology in 108 participants; one case in the FY blood group and three cases in the JK blood group were discrepant. Investigation revealed that these discrepancies resulted from (1) clerical error, (2) serologic failure to detect weak antigenic expression and (3) a frameshift variant absent in blood group databases. CONCLUSION: DTM-Tools can be employed for rapid Kell, Duffy and Kidd blood group antigen prediction from existing ES data sets; for discrepancies detected in the validation data set, software predictions proved accurate. DTM-Tools is open-source and in continuous development.

Microfluidic electrochemical immunosensor for the determination of cystatin C in human serum.

The fabrication of a nanointerfaced electrochemical immunosensor is described for the rapid determination of cystatin C, a biomarker that is elevated in diabetic retinopathy. A dispersion of graphene oxide-chitosan (GO-Chit) nanocomposite was used to modify the carbon working electrode, allowing for a high conjugation of anti-cystatin C antibody. This modified sensor was characterized both morphologically and electrochemically, and the sensor performance was evaluated towards selective quantification of cystatin C in simulated as well as serum samples using cyclic voltammetry and differential pulse voltammetry. The sensor was able to detect cystatin C in the concentration range1 - 10 mg/L with a detection limit of 0.0078 mg/L. The preparation time of the sensor was 420 s, which was faster than that of conventional ELISA and other electrochemical sensors reported in literature. The clinical applicability of the proposed electrochemical biosensor was demonstrated through quantification of cystatin C in human serum samples and identification of diabetic retinopathy. A cutoff value of 1.2 mg/L of cystatin C was used beyond which the samples were classified as positive for diabetic retinopathy. Two different working electrodes, namely a glassy carbon electrode (GCE) and paper electrodes, were used in the study. The working potential was set to 0.25 V vs. Ag/AgCl for experiments with the GCE and 0.15 V for the paper electrodes. The prediction was validated by clinical diagnosis wherein the prediction accuracy of the sensor exceeded 85%. The sensor platform was translated onto a paper substrate and characterized for achieving an optimum sensing performance. This work is the first attempt to employ an electrochemical cystatin C sensor for the diagnosis of diabetic retinopathy from serum samples. Graphical abstract.

Correction to: Axially aligned electrically conducting biodegradable nanofibers for neural regeneration.

The original version of this article unfortunately contained a mistake. The presentation of Fig. 2e was incorrect. The corrected version of Fig. 2E1 is given below.

Recent advances in molybdenum disulfide-based electrode materials for electroanalytical applications.

The primary objective of this review article is to summarize the development and structural diversity of 2D/3D molybdenum disulfide (MoS2) based modified electrodes for electrochemical sensors and biosensor applications. Hydrothermal, mechanical, and ultrasonic techniques and solution-based exfoliation have been used to synthesize graphene-like 2D MoS2 layers. The unique physicochemical properties of MoS2 and its nanocomposites, including high mechanical strength, high carrier transport, large surface area, excellent electrical conductivity, and rapid electron transport rate, render them useful as efficient transducers in various electrochemical applications. The present review summarizes 2D/3D MoS2-based nanomaterials as an electrochemical platform for the detection and analysis of various biomolecules (e.g., neurotransmitters, NADH, glucose, antibiotics, DNA, proteins, and bacteria) and hazardous chemicals (e.g., heavy metal ions, organic compounds, and pesticides). The substantial improvements that have been achieved in the performance of enzyme-based amperometry, chemiluminescence, and nucleic acid sensors incorporating MoS2-based chemically modified electrodes are also addressed. We also summarize key sensor parameters such as limits of detection (LODs), sensitivity, selectivity, response time, and durability, as well as real applications of the sensing systems in the environmental, pharmaceutical, chemical, industrial, and food analysis fields. Finally, the remaining challenges in designing MoS2 nanostructures suitable for electroanalytical applications are outlined. Graphical abstract • MoS2 based materials exhibit high conductivity and improved electrochemical performance with great potential as a sensing electrode. • The role of MoS2 nanocomposite films and their detection strategies were reviewed. • Biomarkers detection for disease identification and respective clinical treatments were discussed. • Future Challenges, as well as possible research development for "MoS2 nanocomposites", are suggested.

Correction to: Recent advances in molybdenum disulfide-based electrode materials for electroanalytical applications.

The original version of this article unfortunately missed Prof. A.T. Ezhil Vilian's project number in Acknowledgements. The missing project number is 2017R1D1A1B03034977.

Metabolic Syndrome-An Emerging Constellation of Risk Factors: Electrochemical Detection Strategies.

Metabolic syndrome is a condition that results from dysfunction of different metabolic pathways leading to increased risk of disorders such as hyperglycemia, atherosclerosis, cardiovascular diseases, cancer, neurodegenerative disorders etc. As this condition cannot be diagnosed based on a single marker, multiple markers need to be detected and quantified to assess the risk facing an individual of metabolic syndrome. In this context, chemical- and bio-sensors capable of detecting multiple analytes may provide an appropriate diagnostic strategy. Research in this field has resulted in the evolution of sensors from the first generation to a fourth generation of 'smart' sensors. A shift in the sensing paradigm involving the sensing element and transduction strategy has also resulted in remarkable advancements in biomedical diagnostics particularly in terms of higher sensitivity and selectivity towards analyte molecule and rapid response time. This review encapsulates the significant advancements reported so far in the field of sensors developed for biomarkers of metabolic syndrome.

Polymer-coated viral vectors: hybrid nanosystems for gene therapy.

The advantages and critical aspects of nanodimensional polymer-coated viral vector systems potentially applicable for gene delivery are reviewed. Various viral and nonviral vectors have been explored for gene therapy. Viral gene transfer methods, although highly efficient, are limited by their immunogenicity. Nonviral vectors have a lower transfection efficiency as a result of their inability to escape from the endosome. To overcome these drawbacks, novel nanotechnology-mediated interventions that involve the coating or modification of virus using polymers have emerged as a new paradigm in gene therapy. These alterations not only modify the tropism of the virus, but also reduce their undesirable interactions with the biological system. Also, co-encapsulation of other therapeutic agents in the polymeric coating may serve to augment the treatment efficacy. The viral particles can aid endosomal escape, as well as nuclear targeting, thereby enhancing the transfection efficiency. The integration of the desirable properties of both viral and nonviral vectors has been found beneficial for gene therapy by enhancing the transduction efficiency and minimizing the immune response. However, it is essential to ensure that these attempts should not compromise on the inherent ability of viruses to target and internalize into the cells and escape the endosomes.

SurR9C84A protects and recovers human cardiomyocytes from hypoxia induced apoptosis.

Survivin, as an anti-apoptotic protein and a cell cycle regulator, is recently gaining importance for its regenerative potential in salvaging injured hypoxic cells of vital organs such as heart. Different strategies are being employed to upregulate survivin expression in dying hypoxic cardiomyocytes. We investigated the cardioprotective potential of a cell permeable survivin mutant protein SurR9C84A, for the management of hypoxia mediated cardiomyocyte apoptosis, in a novel and clinically relevant model employing primary human cardiomyocytes (HCM). The aim of this research work was to study the efficacy and mechanism of SurR9C84A facilitated cardioprotection and regeneration in hypoxic HCM. To mimic hypoxic microenvironment in vitro, well characterized HCM were treated with 100µm (48h) cobalt chloride to induce hypoxia. Hypoxia induced (HI) HCM were further treated with SurR9C84A (1µg/mL) in order to analyse its cardioprotective efficacy. Confocal microscopy showed rapid internalization of SurR9C84A and scanning electron microscopy revealed the reinstatement of cytoskeleton projections in HI HCM. SurR9C84A treatment increased cell viability, reduced cell death via, apoptosis (Annexin-V assay), and downregulated free cardiac troponin T and MMP-9 expression. SurR9C84A also upregulated the expression of proliferation markers (PCNA and Ki-67) and downregulated mitochondrial depolarization and ROS levels thereby, impeding cell death. Human Apoptosis Array further revealed that SurR9C84A downregulated expression of pro-apoptotic markers and augmented expression of HSPs and HTRA2/Omi. SurR9C84A treatment led to enhanced levels of survivin, VEGF, PI3K and pAkt. SurR9C84A proved non-toxic to normoxic HCM, as validated through unaltered cell proliferation and other marker levels. Its pre-treatment exhibited lesser susceptibility to hypoxia/damage. SurR9C84A holds a promising clinical potential for human cardiomyocyte survival and proliferation following hypoxic injury.

Fabrication of Electrochemical Biosensor with ZnO-PVA Nanocomposite Interface for the Detection of Hydrogen Peroxide.

Hydrogen peroxide (H2O2) is considered to be highly toxic and its increased concentration in human body may lead to diseases like alzheimer's, parkinson's, cardiovascular, tumor and cancer. Hence, there is an increasing demand for the detection of H2O2 in human blood serum. In this context, an electrochemical sensor was developed using zinc oxide-polyvinyl alcohol (ZnO-PVA) nanocomposite as a nano-interface. The fabricated Au/ZnO-PVA/CAT/Chitosan bio-electrode exhibited a well-defined redox peak with anodic and cathodic peak potential of -0.408 V and 0.259 V for Fe(III):Fe(II) and H2O2:1/2 O2 redox couples respectively. The developed biosensor exhibited a linear range of 1 µM-17 µM with a sensitivity of 210.49 µA µM-1 cm-2, response time of less than 1 s, limit of detection of 9.13 nM and a limit of quantification of 30.13 nM. The developed bio-electrode showed a Michaelis-Menten constant (KM) of 0.39 µM and dry stability of 93% up to 20 days. The obtained biosensor was successfully utilized to determine the H2O2 concentration in human blood serum sample.

Amperometric determination of As(III) and Cd(II) using a platinum electrode modified with acetylcholinesterase, ruthenium(II)-tris(bipyridine) and graphene oxide.

The authors describe an amperometric biosensor for the determination As(III) and Cd(II) based on the inhibition of the enzyme acetylcholineesterase (AChE). A platinum electrode was modified with ruthenium(II)-tris(bipyridyl), graphene oxide and AChE and then showed redox peaks at 0.06 and 0.2 V vs Ag/AgCl in the presence of acetylthiocholine chloride (ATChCl). Amperometry unveiled a steady-state turnover rate with the release of thiocholine. In the presence of arsenic(III) and cadmium(II), AChE showed an inhibitive response at 0.214 and 0.233 V vs Ag/AgCl, respectively. The electrode exhibits a detection limit and linear range of 0.03 µM and 0.05-0.8 µM for As(III) and 0.07 µM and 0.02-0.7 µM for Cd(II), respectively. Type of inhibition and inhibition constants induced by As(III) and Cd(II) on the catalytic sites of AChE were determined from Dixon and Lineweaver-Burk plots. The modified electrode was applied to the determination of As3+ and Cd2+ in river, tap and waste water, and the results proved that the method is sensitive and can be an alternative to chromatographic and spectroscopic techniques. Graphical abstract Schematic presentation of Pt/Ru(II)-tris(bipy)-GO/AChE electrode in absence and presence of metal ions (As3+/Cd2+).

Phosphoproteomics of Retinoblastoma: A Pilot Study Identifies Aberrant Kinases.

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer. Over 350 proteins showed differential phosphorylation in RB compared to control retina. Our study identified stress response proteins to be hyperphosphorylated in RB which included H2A histone family member X (H2AFX) and sirtuin 1. In particular, Ser140 of H2AFX also known as gamma-H2AX was found to be hyperphosphorylated in retinoblastoma, which indicated the activation of DNA damage response pathways. We also observed the activation of anti-apoptosis in retinoblastoma compared to control. These observations showed the activation of survival pathways in retinoblastoma. The identification of hyperphosphorylated protein kinases including Bromodomain containing 4 (BRD4), Lysine deficient protein kinase 1 (WNK1), and Cyclin-dependent kinase 1 (CDK1) in RB opens new avenues for the treatment of RB. These kinases can be considered as probable therapeutic targets for RB, as small-molecule inhibitors for some of these kinases are already in clinical trials for the treatment other cancers.

Injectable and 3D Bioprinted Polysaccharide Hydrogels: From Cartilage to Osteochondral Tissue Engineering.

Biomechanical performance of functional cartilage is executed by the exclusive anisotropic composition and spatially varying intricate architecture in articulating ends of diarthrodial joint. Osteochondral tissue constituting the articulating ends comprise superfical soft cartilage over hard subchondral bone sandwiching interfacial soft-hard tissue. The shock-absorbent, lubricating property of cartilage and mechanical stability of subchondral bone regions are rendered by extended chemical structure of glycosaminoglycans and mineral deposition, respectively. Extracellular matrix glycosaminoglycans analogous polysaccharides are major class of hydrogels investigated for restoration of functional cartilage. Recently, injectable hydrogels have gained momentum as it offers patient compliance, tunable mechanical properties, cell deliverability, and facile administration at physiological condition with long-term functionality and hyaline cartilage construction. Interestingly, facile modifiable functional groups in carbohydrate polymers impart tailorability of desired physicochemical properties and versatile injectable chemistry for the development of highly potent biomimetic in situ forming scaffold. The scaffold design strategies have also evolved from single component to bi- or multilayered and graded constructs with osteogenic properties for deep subchondral regeneration. This review highlights the significance of polysaccharide structure-based functions in engineering cartilage tissue, injectable chemistries, strategies for combining analogous matrices with cells/stem cells and biomolecules and multicomponent approaches for osteochondral mimetic constructs. Further, the rheology and precise spatiotemporal positioning of cells in hydrogel bioink for rapid prototyping of complex three-dimensional anisotropic cartilage have also been discussed.

Correction: Self-assembly of peptides: influence of substrate, pH and medium on the formation of supramolecular assemblies.

Correction for 'Self-assembly of peptides: influence of substrate, pH and medium on the formation of supramolecular assemblies' by Priyadharshini Kumaraswamy et al., Soft Matter, 2011, 7, 2744-2754.

Design and development of amperometric biosensor for the detection of lead and mercury ions in water matrix-a permeability approach.

Intake of water contaminated with lead (Pb2+) and mercury (Hg2+) ions leads to various toxic effects and health issues. In this context, an amperometric urease inhibition-based biosensor was developed to detect Pb2+ and Hg2+ ions in water matrix. The modified Pt/CeO2/urease electrode was fabricated by immobilizing CeO2 nanoparticles and urease using a semi-permeable adsorption layer of nafion. With urea as a substrate, urease catalytic activity was examined through cyclic voltammetry. Further, maximum amperometric inhibitive response of the modified Pt/CeO2/urease electrode was observed in the presence of Pb2+ and Hg2+ ions due to the urease inhibition at specific potentials of -0.03 and 0 V, respectively. The developed sensor exhibited a detection limit of 0.019 ± 0.001 µM with a sensitivity of 89.2 × 10-3 µA µM-1 for Pb2+ ions. A detection limit of 0.018 ± 0.003 with a sensitivity of 94.1 × 10-3 µA µM-1 was achieved in detecting Hg2+ ions. The developed biosensor showed a fast response time (<1 s) with a linear range of 0.5-2.2 and 0.02-0.8 µM for Pb2+ and Hg2+ ions, respectively. The modified electrode offered a good stability for 20 days with a good repeatability and reproducibility. The developed sensor was used to detect Pb2+ and Hg2+ ions contaminating Cauvery river water and the observed results were in good co-ordination with atomic absorption spectroscopic data.

Design and Development of Acetylthiocholine Electrochemical Biosensor Based on Zinc Oxide-Cerium Oxide Nanohybrid Modified Platinum Electrode.

Acetylcholinesterase (AChE) enzyme has been predominantly used for the detection of pesticides and metal ions. But, these sensors respond to pesticides as well as metal ions at certain concentration, which results in poor selectivity. Hence in this work, the amount of thiocholine produced during AChE inhibition has been estimated to detect the residual activity of AChE enzyme in-turn to enhance the efficiency of the biosensor. In this context, Pt/ZnO-CeO2/AChE/Chitosan based biosensor has been developed for sensitive voltammetric quantification of thiocholine in AChE. The sensor exhibited enhanced electron transfer rate, good conductivity and biocompatibility. Both the intrinsic and extrinsic parameters were simultaneously optimized using second order polynomial regression to get the best conditions for ATCh determination. Under optimized experimental conditions, the redox peak current was linear over the concentration range of 0.1-1.5 mM with detection and quantification limit of 0.05 and 0.15 µM respectively and the sensitivity of 1.47 µA mM-1.