Geometric Transformation of Modified Multiwalled Carbon Nanotubes-Based Heterometallic Nanostructured Material: A Model for the Electrochemical Discrimination of Insecticides.

Multifunctional carbon-based materials exhibit a large number of unprecedented active sites via an electron transfer process and act as a desired platform for exploring high-performance electroactive material. Herein, we exemplify the holistic design of a heterometallic nanostructured material (MWCNTs@KR-6/Mn/Sn/Pb) formed by the integration of metals (Mn2+, Sn2+, and Pb2+) and a dipodal ligand (KR-6) at the surface of multiwalled carbon nanotubes (MWCNTs). First, MWCNTs@KR-6 was readily synthesized via a noncovalent approach, which was further sequentially doped by Mn2+, Sn2+, and Pb2+ to give MWCNTs@KR-6/Mn/Sn/Pb. The designed material showed excellent electrochemical activity for the discrimination of insecticides belonging to structurally different classes. In contrast to that of the individual building components, both the stability and electrochemical activity of heterometallic nanostructured material were remarkably enhanced, resulting in a magnificent electrochemical performance of the developed material. Hence, the current work reports a comprehensive synthetic approach for MWCNTs@KR-6/Mn/Sn/Pb synthesis by synergizing unique properties of the heterometallic complex with MWCNTs. This work also offers a new insight into the design of multifunctional carbon-based materials for discrimination of different analytes on the basis of their redox potential.

Bio-mimetic selectivity in Hg2+ sensing developed via electro-copolymerized PEDOT and benzothiazole-Au nanoparticles composite.

To eliminate the potential health risks of mercury, development of stable and selective mercury sensor with high sensitivity is the need of the hour. To address this, a novel PEDOT-AA-BTZ-Au-based Hg2+ selective, hybrid electrochemical sensor has been designed by following a simple protocol for electrode fabrication. The electrode was designed by carefully optimizing the onset oxidation potential of supramolecule 2-(anthracen-9-yl)benzo[d]thiazole (AA-BTZ) and conducting polymer poly-(3,4-ethylenedioxythiophene) (PEDOT), using copolymerization approach followed by dropcasting of gold nanoparticles (AuNPs). The designed electrode offered synergistic effects thus augmenting the electrical conductivity and adsorption capacity as depicted by its porous surface morphology. The highly sensitive analytical signal was generated by sulphur pockets present in AA-BTZ and PEDOT conducting framework. This is further complemented by the selectivity offered by the soft interactions between AuNPs and Hg2+ resulting in a low detection limit of 0.60 nM. The prepared system was further utilized for sensing Hg2+ ion in real systems including lake water and cosmetic samples. Low interference from other ions and better reproducibility further established the suitability of the designed transducer system for future on-site sensing.

Studies on Structural Changes of Modified MWCNTs: Material for Electrochemical Monitoring of Antiviral Drug in Human Serum Samples.

The development of a universal approach for precisely tuning the electrochemical characteristics of conducting carbon nanotubes for tracking harmful agents in the human body with high selectivity and sensitivity remains a challenge. Herein, we describe a simplistic, versatile, and general approach to the construction of functionalized electrochemical material. The design of electrochemical material consists of (i) modification of multiwalled carbon nanotubes (MWCNT) with dipodal naphthyl-based dipodal urea (KR-1) through non-covalent functionalization (KR-1@MWCNT) which enhances the dispersibility of MWCNT and hence conductivity, (ii) complexation of KR-1@MWCNT with Hg2+ accelerate the electron transfer in the material which amplify the detection response of functionalized material (i. e., Hg/KR-1@MWCNT) towards various thymidine analogues. Further, the application of functionalized electrochemical material (Hg/KR-1@MWCNT) achieves real-time electrochemical monitoring of harmful antiviral drug 5-iodo-2'-iododeoxyuridine (IUdR) levels in human serum for the first time.

A high-performance Calix@ZnO based bifunctional nanomaterial for selective detection and degradation of toxic azinphos methyl in environmental samples.

One of the key tenets of sustainable agriculture and food safety is the removal of toxic pesticides from the environment. However, developing reliable, affordable, and efficient methods for detecting and degrading pesticides into non-toxic degradable products remains an immediate matter of concern. Herein, we attempt to develop a strategy for the detection as well as degradation of highly toxic phosphorodithioate pesticide, Azinphos methyl (AZM), using hybrid zinc oxide nanoparticles (ZnO NPs). Considering the non-selectivity of bare ZnO and receptor R1, we have fabricated the heterocalixarene-based Calix (R1) over zinc oxide (ZnO) surface in situ via the sol-gel process. The synthesized heterocaliaxrene-modified ZnO (R1@ZnO) NPs show an excellent affinity for the selective and sensitive detection of AZM with a tremendously low limit of detection (68 mg L-1) and no interference from other pesticides. Degradation of AZM was fully supported by fluorescence spectroscopy, scanning electron microscopy (SEM), 1H NMR titrations, FTIR spectroscopy, cyclic voltammetry, and mass spectroscopy, which unequivocally confirmed the formation of non-toxic products. According to our findings, R1@ZnO NPs are sustainable nanomaterials that can be employed for environmental remediation since they operate in an aqueous medium.

Gold nanoparticles capped DHPMs for meliorate detection of antiretroviral drug: Azidothymidine.

Anti-human immunodeficiency (HIV)-drug azidothymidine interferes with the reverse transcriptase enzyme, which results in reduced activity of HIV thereby inhibiting the growth of the virus. Owing to the side effects of high doses and short half-life of this antiviral drug azidothymidine (AZT): a fast and convenient method for its detection would be helpful for HIV patients getting treated with AZT. Referring to this, we synthesized a Biginelli based receptor R1 and evaluated its sensing properties towards AZT with different techniques (UV-Visible, circular dichroism (CD), cyclic voltammetry (CV) by preparing its organic nanoparticles (ONPs) and gold-coated ONPs (AuNP@ONP). The formation of AuNP@ONP was confirmed by UV-Visible spectroscopy, cyclic voltammetry, and HRTEM. It was observed that both the probes selectively sense AZT among various thymidine analogs but AuNP@ONP showed better response on CV, Differential pulse voltammetry (DPV) and, linear sweep voltammetry (LSV) with a detection limit of 6 nM. Proton NMR (1H NMR) reveals that the azide group present at the 3' position is responsible for the selective response of AZT with probes. Quantitative determination by the probes in the pharmaceutical sample gives the recovery percentage above 97%. Hence, economic, affordable, ready-to-use chemosensor for AZT (in an aqueous medium) with low detection limit having satisfactory utility for HIV supplements have been developed.

Risk factors associated with adenoma recurrence following cold snare endoscopic mucosal resection of polyps ≥ 20 mm: a retrospective chart review.

Background and study aims Cold snare endoscopic mucosal resection (EMR) is being increasingly utilized for non-pedunculated polyps ≥ 20 mm due to adverse events associated with use of cautery. Larger studies evaluating adenoma recurrence rate (ARR) and risk factors for recurrence following cold snare EMR of large polyps are lacking. The aim of this study was to define ARR for polyps ≥ 20 mm removed by cold snare EMR and to identify risk factors for recurrence. Patients and methods A retrospective chart review of colon cold snare EMR procedures performed between January 2015 and July 2019 at a tertiary care medical center was performed. During this period, 310 non-pedunculated polyps ≥ 20 mm were excised using cold snare EMR with follow-up surveillance colonoscopy. Patient demographic data as well as polyp characteristics at the time of index and surveillance colonoscopy were collected and analyzed. Results A total of 108 of 310 polyps (34.8 %) demonstrated adenoma recurrence at follow-up colonoscopy. Patients with a higher ARR were older ( P  = 0.008), had endoscopic clips placed at index procedure ( P  = 0.017), and were more likely to be Asian and African American ( P  = 0.02). ARR was higher in larger polyps ( P  < 0.001), tubulovillous adenomas ( P  < 0.001), and polyps with high-grade dysplasia ( P  = 0.003). Conclusions Although cold snare EMR remains a feasible alternative to hot snare polypectomy for resection of non-pedunculated polyps ≥ 20 mm, endoscopists must also carefully consider factors associated with increased ARR when utilizing this technique.

Development of mirtazapine loaded solid lipid nanoparticles for topical delivery: Optimization, characterization and cytotoxicity evaluation.

Mirtazapine, an antidepressant drug has been proved to exert antipruritic effect upon oral administration in numerous clinical trial studies. The objective of the current study was to develop mirtazapine loaded solid lipid nanoparticles (SLNs) and evaluate its potential as a topical drug delivery system for management of pruritus. Mirtazapine loaded SLNs were successfully developed and optimized applying Box-Behnken design. The optimized mirtazapine loaded SLNs were characterized for physicochemical parameters and morphology. The in vitro cytotoxicity and cellular uptake studies of optimized SLNs were performed in human epithelial A-431 cell line. Further, the optimized mirtazapine loaded SLNs dispersion was incorporated into gel and characterized for rheology and texture analysis. The particle size and PDI of optimized mirtazapine loaded was found to be 180.3 nm and 0.209 respectively. The cytotoxicity studies revealed the safety of mirtazapine loaded SLNs on topical administration. The developed gel showed pseudoplastic flow behavior and good textural profile. The in vitro drug release studies showed that the developed mirtazapine loaded SLNs dispersion and its gel followed Korsmeyer-Peppas model (R2 = 0.905) and Higuchi model (R2 = 0.928) respectively. The ex vivo drug permeation studies showed higher values for mean cumulative amount of drug released (548.25 ± 29.29 µg/cm2), permeation flux (45.10 ± 0.78 µg/cm2/h) and skin retention (11.33 ± 0.85%) of SLNs gel in comparison to pure drug gel. The stability studies indicate the stability of SLNs gel for three months at refrigerated and ambient temperatures. Therefore, abovementioned findings suggest that mirtazapine loaded SLNs could be a potential system for topical management of pruritus.

Use of thermal and non thermal techniques for assessing compatibility between mirtazapine and solid lipids.

The present investigation was aimed at the evaluation of possible interactions between mirtazapine and selected solid lipids that are commonly used to develop solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs). The solids lipids explored were palmitic acid, stearic acid, glycerylmonostearate, cutina CPPH, sterotex NF, gelucire 50/13, hydrogenated castor oil and compritol 888 ATO. The techniques used were Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Hot Stage Microscopy (HSM) and Isothermal Stress Testing (IST) studies. In some cases, the DSC results indicated the possibility of drug-solid lipid interactions which was further ruled out by performing HSM studies. Moreover, IST studies were also used to further confirm the compatibility between the drug and selected solid lipids. And the findings from these studies indicated compatibility between mirtazapine and solid lipids that can further be used to develop SLNs or NLCs.

A comparison of methods used to unveil the genetic and metabolic pool in the built environment.

BACKGROUND: A majority of indoor residential microbes originate from humans, pets, and outdoor air and are not adapted to the built environment (BE). Consequently, a large portion of the microbes identified by DNA-based methods are either dead or metabolically inactive. Although many exceptions have been noted, the ribosomal RNA fraction of the sample is more likely to represent either viable or metabolically active cells. We examined methodological variations in sample processing using a defined, mock BE microbial community to better understand the scope of technique-based vs. biological-based differences in both ribosomal transcript (rRNA) and gene (DNA) sequence community analysis. Based on in vitro tests, a protocol was adopted for the analysis of the genetic and metabolic pool (DNA vs. rRNA) of air and surface microbiomes within a residential setting. RESULTS: We observed differences in DNA/RNA co-extraction efficiency for individual microbes, but overall, a greater recovery of rRNA using FastPrep (> 50%). Samples stored with various preservation methods at - 80°C experienced a rapid decline in nucleic acid recovery starting within the first week, although post-extraction rRNA had no significant degradation when treated with RNAStable. We recommend that co-extraction samples be processed as quickly as possible after collection. The in vivo analysis revealed significant differences in the two components (genetic and metabolic pool) in terms of taxonomy, community structure, and microbial association networks. Rare taxa present in the genetic pool showed higher metabolic potential (RNA:DNA ratio), whereas commonly detected taxa of outdoor origins based on DNA sequencing, especially taxa of the Sphingomonadales order, were present in lower relative abundances in the viable community. CONCLUSIONS: Although methodological variations in sample preparations are high, large differences between the DNA and RNA fractions of the total microbial community demonstrate that direct examination of rRNA isolated from a residential BE microbiome has the potential to identify the more likely viable or active portion of the microbial community. In an environment that has primarily dead and metabolically inactive cells, we suggest that the rRNA fraction of BE samples is capable of providing a more ecologically relevant insight into the factors that drive indoor microbial community dynamics.

Antidepressants as antipruritic agents: A review.

Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin. Many natural as well as, antipruritic therapies are usually practiced in the treatment of pruritus including general preventive measures, topical therapies such as cooling agents, antihistamines, anesthetics, capsaicin, corticosteroids, immunomodulators and; systemic therapies including administration of antihistamines, opioid antagonists/agonists, antiepileptic drugs/neuroleptics (e.g., gabapentin and pregabalin), antidepressants (e.g., doxepin, amitriptyline, paroxetine, fluvoxamine, sertraline, escitalopram and mirtazapine) (Patel and Yosipovitch, 2010; Reich et al., 2011; Martín and Padilla, 2015; Eskeland et al., 2016). Topical therapies are the mainstay of treatment of delicate and localized pruritus while other systemic drug therapies are used to treat stern and generalized pruritus. The reported antipruritic activity of some antidepressant drugs has intrigued this review to focus on the types of pruritus, pruritus mechanism, the antipruritic mechanism of antidepressants and to comprehend the role of antidepressants in the management of pruritus.

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application.

PURPOSE: Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. METHODS: lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. RESULTS: Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization of lys-NDs was confirmed by various techniques such as confocal microscopy, soft X-ray spectroscopy, and flow cytometry. CONCLUSION: This study establishes that dispersion of lys-NDs in aqueous medium maintains long-term stability and also provides evidence that lysine functionalization enables NDs to interact effectively with the biological system to be used for RNAi therapeutics.

An ionic liquid-in-water microemulsion as a potential carrier for topical delivery of poorly water soluble drug: Development, ex-vivo and in-vivo evaluation.

In this paper, we report an ionic liquid-in-water (IL/w) microemulsion (ME) formulation which is able to solubilize etodolac (ETO), a poorly water soluble drug for topical delivery using BMIMPF6 (1-butyl-3-methylimidazolium hexafluorophosphate) as IL, Tween 80 as surfactant and ethanol as co-surfactant. The prepared ME was characterized for physicochemical parameters, subjected to ex-vivo permeation studies as well as in-vivo pharmacodynamic evaluation. The ex-vivo drug permeation studies through rat skin was performed using Franz-diffusion cell and the IL/w based ME showed maximum mean cumulative percent permeation of 99.030±0.921% in comparison to oil-in-water (o/w) ME (61.548±1.875%) and oily solution (48.830±2.488%) of ETO. In-vivo anti-arthritic and anti-inflammatory activities of the prepared formulations were evaluated using different rodent models and the results revealed that ETO loaded IL/w based ME was found to be more effective in controlling inflammation than oily solution, o/w ME and marketed formulation of ETO. Histopathological studies also demonstrated that IL/w based ME caused no anatomical and pathological changes in the skin.

Non Diabetic and Stress Induced Hyperglycemia [SIH] in Orthopaedic Practice What do we know so Far?

Hyperglycemia is also seen amongst non-diabetics and can cause significant morbidity and mortality. SIH has been reported in literature and studied in relation to trauma and critically ill patients. However, literature specific to orthopaedics on this topic is very small. Further, management of hyperglycemia in such patients is still a matter of debate and no universal consensus exists regarding its management. Future studies are needed on this topic to provide appropriate management guidelines and optimal patient outcomes.

FATCO Syndrome Variant - Fibular Hypoplasia, Tibial Campomelia and Oligosyndactyly -- A Case Report.

The word aplasia/hypoplasia is used for partial or total absence of a bone. Fibula, a lower limb bone is one of the most common to be involved with this and its incidence is amongst the highest in long bone deficiencies. FATCO syndrome consisting of fibular aplasia, tibial campomelia and oligosyndactyly has been described in the literature but only one has been reported from India as per our literature review. However, it is important to know multiple regional involvement can occur along with this syndrome and prove to be a major difficulty for the child and the parents both. Due to the rarity of reports on this rare syndrome and difficulty in treatment it is important that each such case should be described to make the management easier.

Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.

Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.

Mechanical and infectious complications of central venous catheterizations in a tertiary-level intensive care unit in northern India.

BACKGROUND: Central venous catheters (CVC) are associated with mechanical, infectious and thrombotic complications. AIMS: To study (a) the incidence of mechanical and infectious complications of CVC insertions and to compare, (b) the rates of these complications between the internal jugular venous (IJV) and the subclavian venous (SCV) accesses. SETTINGS AND DESIGN: An adult intensive care unit of a tertiary care hospital. Prospective, observational study. METHODS: All landmark-based CVC insertions performed between 1(st) October 2008 and 30(th) September 2009 were prospectively studied for mechanical and infectious complications. STATISTICAL ANALYSIS: SPSS software for Windows, Version SPSS 16.0, and Epi Info (3.5.1) software. RESULTS: Four hundred and eighty central venous catheterizations were studied (IJV route, 241 and SCV route, 239). Mechanical complications occurred in 86 patients (17.9%, bleeding complications-48, catheter-related complications-27 and pneumothorax-11). The IJV route was associated with a significantly higher incidence of bleeding complications (P=0.009). Forty-seven patients had infectious complications (9.79%), like exit site infections (n=17), catheter tip infections (n=22) and catheter-related bloodstream infections (CRBSIs) (n=8). The risks of infectious complications increased significantly if the CVC was in situ for longer than 7 days (P=0.009), especially with IJV cannulae. The incidence density of CVC tip infections was 7.67 per 1000 catheter days and of CRBSIs was 2.79 per 1000 catheter days. CONCLUSIONS: Bleeding complications occurred more frequently with IJV insertions and infectious complications occurred more commonly in cannulae that were left in situ for longer than 7 days.

Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies.

PURPOSE: Detonation nanodiamonds (NDs) are carbon-based nanomaterials that, because of their size (4-5 nm), stable inert core, alterable surface chemistry, fluorescence, and biocompatibility, are emerging as bioimaging agents and promising tools for the delivery of biochemical molecules into cellular systems. However, diamond particles possess a strong propensity to aggregate in liquid formulation media, restricting their applicability in biomedical sciences. Here, the authors describe the covalent functionalization of NDs with lysine in an attempt to develop nanoparticles able to act as suitable nonviral vectors for transferring genetic materials across cellular membranes. METHODS: NDs were oxidized and functionalized by binding lysine moieties attached to a three-carbon-length linker (1,3-diaminopropane) to their surfaces through amide bonds. Raman and Fourier transform infrared spectroscopy, zeta potential measurement, dynamic light scattering, atomic force microscopic imaging, and thermogravimetric analysis were used to characterize the lysine-functionalized NDs. Finally, the ability of the functionalized diamonds to bind plasmid DNA and small interfering RNA was investigated by gel electrophoresis assay and through size and zeta potential measurements. RESULTS: NDs were successfully functionalized with the lysine linker, producing surface loading of 1.7 mmol g(-1) of ND. These modified NDs formed highly stable aqueous dispersions with a zeta potential of 49 mV and particle size of approximately 20 nm. The functionalized NDs were found to be able to bind plasmid DNA and small interfering RNA by forming nanosized "diamoplexes". CONCLUSION: The lysine-substituted ND particles generated in this study exhibit stable aqueous formulations and show potential for use as carriers for genetic materials.