Deformed graphene FET biosensor on textured glass coupled with dielectrophoretic trapping for ultrasensitive detection of GFAP.

Numerous efforts have been undertaken to mitigate the Debye screening effect of FET biosensors for achieving higher sensitivity. There are few reports that show sub-femtomolar detection of biomolecules by FET mechanisms but they either suffer from significant background noise or lack robust control. In this aspect, deformed/crumpled graphene has been recently deployed by other researchers for various biomolecule detection like DNA, COVID-19 spike proteins and immunity markers like IL-6 at sub-femtomolar levels. However, the chemical vapor deposition (CVD) approach for graphene fabrication suffers from various surface contamination while the transfer process induces structural defects. In this paper, an alternative fabrication methodology has been proposed where glass substrate has been initially texturized by wet chemical etching through the sacrificial layer of synthesized silver nanoparticles, obtained by annealing of thin silver films leading to solid state dewetting. Graphene has been subsequently deposited by thermal reduction technique from graphene oxide solution. The resulting deformed graphene structure exhibits higher sensor response towards glial fibrillary acidic protein (GFAP) detection with respect to flat graphene owing to the combined effect of reduced Debye screening and higher surface area for receptor immobilization. Additionally, another interesting aspect of the reported work lies in the biomolecule capture by dielectrophoretic (DEP) transport on the crests of the convex surfaces of graphene in a coplanar gated topology structure which has resulted in 10 aM and 28 aM detection limits of GFAP in buffer and undiluted plasma respectively, within 15 min of application of analyte. The detection limit in buffer is almost four decades lower than that documented for GFAP using biosensors which is is expected to pave way for advancing graphene FET based sensors towards ultrasensitive point-of-care diagnosis of GFAP, a biomarker for traumatic brain injury.

Disorder-to-order transition of long fibers contained in evaporating sessile drops.

A liquid drop containing a long fiber is a complex system whose configuration is determined by an interplay of elastic stresses in the fiber and capillary forces due to the liquid. We study the morphological evolution of fibers that are much longer than the drop diameter in evaporating sessile drops. After insertion, the fibers are either found in an ordered or disordered state, with increasing disorder for increasing fiber length. Upon evaporation, the order increases, in such a way that the final configuration deposited on the solid surface is either a circle, an ellipse, or 8-shaped. The morphology of the deposit depends on the fiber length and the elastocapillary length, both non-dimensionalized with the characteristic drop size, which we classify in a morphology regime map. The disorder-to-order transition allows depositing ordered fiber structures on solid surfaces even in cases of a strongly disordered state after fiber insertion. Combined with technologies such as inkjet printing, this process could open new avenues to decorate surfaces with filamental structures whose morphology can be controlled by varying the fiber length.

Structural and therapeutic properties of salicylic acid-solubilized Pluronic solutions and hydrogels.

Salicylic acid (SA) finds extensive applications in the treatment of rheumatic and skin diseases because of its analgesic, anti-inflammatory and exfoliating properties. As it is lipophilic in nature, there is a need for appropriate delivery systems to harness these properties for different applications. Herein, we examined the suitability of Pluronic P123/F127 micellar systems as delivery media by investigating the structural, flow and antimicrobial properties of P123/F127-SA solutions and hydrogels using DLS, SANS, rheological and zone inhibition measurement techniques. SA modulates the aggregation characteristics of these surfactant systems and brings about spherical-to-worm-like micelle-to-vesicular structural transitions in the hydrophobic Pluronic P123 system, a spherical-to-worm-like micellar transition in the mixed P123/F127 system and an onset of inter-micellar attraction in the hydrophilic Pluronic F127 system. SA-solubilized systems of both hydrophobic and hydrophilic Pluronics inhibit the growth of Gram-positive and Gram-negative bacteria with comparable MIC values. This suggests that the interaction of SA molecules with the bacterial cell membrane remains unobstructed upon encapsulation in Pluronic micelles. F127 hydrogel-based SA formulations with rheological properties suitable for topical applications and up to 15% SA loading were prepared. These will be useful SA ointments as F127 is an FDA-approved excipient for topical drug delivery applications. The results indicate that Pluronics remain effective as delivery agents for SA and exhibit interesting structural polymorphism upon its solubilization.

Pluronic Induced Interparticle Attraction and Re-entrant Liquid-Liquid Phase Separation in Charged Silica Nanoparticle Suspensions.

Tuning surface properties of nanoparticles by introducing charge, surface functionalization, or polymer grafting is central to their stability and applications. Here, we show that introducing non-DLVO forces like steric and hydrophobic effects in charged silica nanoparticle suspensions through interaction with a nonionic surfactant brings about interesting modulations in their interparticle interaction and phase behavior. The Ludox TM-40 negatively charged silica suspensions thus exhibit liquid-liquid phase separation driven by the onset of interparticle attraction in the system in the presence of the triblock copolymer Pluronic P123. The observed phase separations are thermoresponsive in nature, as they are associated with lower consolute temperatures and a re-entrant behavior as a function of temperature. The nanoparticle-Pluronic system thus undergoes transformation from one-phase to two-phase and then back to one-phase with monotonic increase in temperature. Evolution of the interparticle interaction in the composite system is investigated by dynamic light scattering (DLS), small angle neutron scattering (SANS), zeta potential, rheological, and fluorescence spectroscopy studies. Zeta potential studies show that the charge interaction in the system is partially mitigated through adsorption of a Pluronic micellar layer on the nanoparticle surfaces. Contrast-matching SANS studies suggest that hydrophobic interactions between the adsorbed micellar layer bring about the onset of interparticle attraction in the system. The results are unique and not reported hitherto in charged silica nanoparticle systems.

Unusual Growth and Hydration Characteristics of Oil Solubilized Micelles in Aqueous Pluronic Systems.

Lipophile induced modulations of self-assembly characteristics in aqueous Pluronic systems merit attention because of wide-ranging uses of Pluronics as solubilizing agents of lipophilic substances. In this paper, we report unusual evolutions of structural and hydration properties in lavender essential oil (LO) solubilized Pluronic P85 aqueous micellar systems as a function of micellar volume fraction and temperature. Our DLS, SANS, and viscometry studies show that the spherical-to-wormlike micellar structural transition observed in 1% P85 solutions upon solubilization of LO quite unexpectedly gets suppressed with increased P85 concentration to ≥5%. Detailed SANS studies reveal that the core sizes of the oil solubilized micelles cannot attain the threshold value required for the onset of structural transition at higher copolymer concentrations due to their progressive shrinking with an increase in P85 concentration. Oil solubilized P85 solutions show two cloud points and very interestingly exhibit micellar growth upon cooling to their lower cloud points. Steady state fluorescence studies explain this based on increasing dehydration of micellar corona with a decrease in temperature, very much opposite to what is observed in pure aqueous Pluronic systems. The results give new insight into viscous flow properties and low temperature storage possibilities of oil solubilized aqueous Pluronic systems.

Intensification patterns and the probability of HbA1c goal attainment in Type 2 diabetes mellitus: real-world evidence for the concept of 'intensification inertia'.

AIMS: To assess the effects of 'clinical' and 'intensification inertia' by evaluating the impact of different intensification interventions on the probability of HbA1c goal attainment using real-world data. METHODS: Electronic health records (Cleveland Clinic, 2005-2016) were used to identify 7389 people with Type 2 diabetes mellitus and HbA1c ≥53 mmol/mol (≥7.0%), despite a stable regimen of two oral antihyperglycaemic drugs for ≥6 months. The participants were stratified by index HbA1c and analysed over a 6-month period for pharmacological intensification, and then for 12 additional months for HbA1c goal attainment (<53 mmol/mol). RESULTS: The probability of HbA1c goal attainment (Kaplan-Meier analysis) in the group with index HbA1c 53-63 mmol/mol (7.0-7.9%) was highest with the addition of oral antidiabetic drugs [57.3% (95% CI 52.1, 62.0)] or glucagon-like peptide-1 receptor agonists [56.7% (95% CI 40.4, 68.6)], in the 64-74 mmol/mol (8.0-8.9%) group with the addition of oral antidiabetic drugs [31.9% (95% CI 25.1, 38.1)] or insulin [30.6% (95% CI 18.3, 41.0)], and in the ≥75 mmol/mol (≥9.0%) group with the addition of glucagon-like peptide-1 receptor agonists [53.0% (95% CI 31.8, 67.6)] or insulin [43.5% (95% CI 36.4, 49.8)]. CONCLUSIONS: Numerical, but not statistically significant, differences in HbA1c goal attainment probability by type of intensification were most marked in people with the highest index HbA1c [≥75 mmol/mol (≥9.0%)]; in this group, injectable therapy showed trends toward greater glycaemic control benefits. Additional research into the phenomenon of intensification inertia is warranted.

Salt and phytochemical assisted modulation of self-assembly characteristics of Polysorbate-80 in aqueous medium.

Polysorbate 80 is one of the most widely used solubilizing agents in food, cosmetic and pharmaceutical industries. Influences of different classes of solubilizates and additives on its self-assembly characteristics are however, not sufficiently understood yet. In this manuscript, we show how common water structure making salt NaCl, and lipophilic phytochemicals like curcumin and lavender oil help in modulating the structure of Polysorbate 80 micelles in aqueous medium. Our DLS, SANS and rheological studies show that NaCl induces sphere-to-rod growth of polysorbate 80 micelles at the room temperature. Micellar solubilizations of the phytochemicals, which were found to be facilitated with increase in temperature, induce only a marginal growth of the micelles up to the highest level of solubilization. Their presence however, helps in modulating the NaCl induced micellar growth behavior in the tween 80 solutions leading to observation of micelle-to-vesicle structural transition at 2% lavender oil concentration. The phytochemical solubilized micellar solutions could be converted to alginate based hydrogel beads and patches that can freely release micellar phytochemical in aqueous medium. Our results shed light on possible ways of modulating the solubilization behavior, self-assembly characteristics and rheological properties of aqueous system of polysorbate 80, which could be important for their applications.

Overt bleeding in complicated P. falciparum malaria: An experience from east coast of India.

Delay in diagnosis of falciparum may result in complicated, life-threatening conditions. Though haematological abnormalities and coagulopathy are common complications that occur in malaria but complications with rare manifestations like overt bleeding do pose challenges for the clinicians worldwide. This study reports the incidence and prognosis of overt bleeding from the east coast of India and makes an attempt to relate it with the pathogenesis of the disease in severe Plasmodium falciparum malaria patients. This study was conducted in Sriram Chandra Bhanj Medical College Hospital, Cuttack, Odisha, India. A total of 120 complicated (multi organ dysfunction) malaria cases were included in this study. Amongst them 54 (45.0%) showed signs of overt bleeding and clinically the bleeding was either from one or multiple sites. Out of the total overt bleeding cases, 79.6% had elongated prothrombin time (PT), activated partial prothrombin time (aPTT) and elevated D-dimer with thrombocytopenia indicating disseminated intravascular coagulopathy (DIC). It was observed that case fatality rate was very high in coagulopathy group than the non coagulopathy group. Our observations highlight that awareness of overt bleeding in P. falcipatum infection is necessary for general practitioners in endemic areas for malaria like in Odisha for effective and timely management of complicated patients.Timely diagnosis and treatment of DIC with appropriate prescribed drugs can prevent and cure the complications of severe falciparum malaria with anti-malarial treatment.

Lymphocyte subtypes in relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.

BACKGROUND: Recent data suggest that lymphopenia is more prevalent than reported in relapsing-remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF). OBJECTIVE: The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia. METHOD: A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1, n = 35) and normal lymphocyte counts (G2, n = 24). RESULTS: Fifty-nine patients were identified, with mean age 49, 71.2% females, and average DMF duration 20 months. Age, sex, baseline white blood count, disease and treatment durations were similar between groups. Prior interferon therapy and baseline lower normal lymphocyte counts were more frequent in G1. Mean lymphocyte counts were 0.8 ± 0.2 × 109/L in G1 and 1.6 ± 0.3 × 109/L in G2. CD3+, CD4+, and CD8+ T cell mean counts were lower (p < 0.0001), while CD4/CD8 ratio higher (p = 0.03) in G1 than G2. Mean CD19 + B cell counts were normal; however, values were lower in G1 (p = 0.04). After adjusting for confounders, significantly positive correlations were noted between lymphocyte counts and CD3 + , CD4+, CD8+ T, and B cell counts. Negative correlation was observed between lymphocyte counts and CD4/CD8 ratio driven by low CD8+ T cell counts. CONCLUSION: DMF treatment predominantly impacts T cells, in particular CD8+ subtype. This finding may have implications in this population's immunocompetence.

Heat-induced solubilization of curcumin in kinetically stable pluronic P123 micelles and vesicles: An exploit of slow dynamics of the micellar restructuring processes in the aqueous pluronic system.

Wide therapeutic potential combined with low cost and negligible toxicity makes curcumin one of the most sought after drugs in recent times. Its poor aqueous solubility and low bioavailability are often overcome by using micelles and vesicles as its carriers. The substances that are commonly used for this purpose are a class of nonionic surfactants called pluronics. Solubilization of curcumin in aqueous systems of these surfactants is carried out by thin film hydration method presumably because slow dynamics of micellar restructuring processes in them creates hindrance for direct solubilization. In this manuscript, we show that this problem can be overcome and curcumin can be solubilized directly in pluronic P123 micellar solutions by heating them to the phase separation temperature in the presence of curcumin. The obtained curcumin containing micellar solutions show cytotoxicity on human breast carcinoma (MCF7) cells with IC50 values similar to that shown by free curcumin solution. Addition of mucoadhesive polymer κ-Carrageenan into these solutions converts them to curcumin containing gels and patches with rheological properties suitable for topical application. These solutions also exhibit systematic spherical-to-worm like micellar-to-vesicular structural transitions in the presence of NaCl. The large curcumin containing aggregates thus formed show kinetic stability with respect to dilution, which is an important attribute for drug delivery application. Characterization of the micellar and vesicular systems and gels were carried out by SANS, DLS and rheological measurements. The obtained results represent first systematic study on solubilization of curcumin in pluronic aggregates of various shapes and size.

Clinical performance of cuffed versus uncuffed preformed endotracheal tube in pediatric patients undergoing cleft palate surgery.

BACKGROUND: Uncuffed endotracheal tubes are commonly used in children but due to several decade preferred in paediatric oral surgery. Due to lack of conclusive evidences in this regard, we have conducted this study to compare post-operative morbidity following use of cuffed and uncuffed endotracheal tubes in paediatric patients undergoing cleft lip-palate surgery. METHODS: This randomised controlled trial was conducted on children aged 2 to 12 years.110 patients were allocated in two parallel groups using computer generated list of random numbers. Post operative extubation stridor, sore throat, time to first oral intake and regaining of normal voice were compared between two groups. RESULTS: The incidence of sore throat was significantly more (P value > 0.005) in patients of uncuffed group compared to cuffed group. The time to first oral intake and time to regain normal voice were significantly earlier in cuffed group compared to the other. CONCLUSION: With standard care, preformed cuffed ET tube has shown reduced incidence of post operative sore throat. Cuffed group has earlier oral intake and normal voice regain compared to uncuffed group.

Phase separations in aerosol OT reverse micellar solutions in dodecane: a curious case of polar domain composition driven transition from lower consolute temperature (LCT) to upper consolute temperature (UCT) regime.

AOT-based microemulsions have been studied quite extensively on account of their numerous industrial applications and their existence as simple ternary phases. Properties of these microemulsions with higher alkanes as the oil continuous phase are governed by the presence of a strong inter micellar attractive interaction. In water in oil (w/o) microemulsions the inter micellar attraction strengthens with increase in temperature and leads to the observation of critical behavior on approaching the lower consolute temperature (LCT). In this manuscript we show that the phase behavior of AOT-based reverse micellar solutions in dodecane transforms dramatically when the polar domain is changed from water to formamide (FA) and even to aqueous solution of urea and NaCl. In all these cases the temperatures dependence of the microemulsion properties undergo complete reversal, which brings about a transition in their phase separation characteristics from lower consolute temperature (LCT) to upper consolute temperature (UCT) regime. Such systematic transformation in the phase behavior as a function of polar domain composition, which has been explained based on the influence of the polar domain on the properties of the interfacial AOT layer, is first of its kind in any reverse micellar system.

Butanol solubilization in aqueous F127 solution: investigating the enhanced micellar solvation and consequent improvement in gelation characteristics.

Pluronics(®) are an important class of non-ionic surfactants because of their rich phase behavior and numerous industrial and biomedical applications. F127, an FDA approved Pluronic(®) is the most prominent member amongst them owing to its potential uses as vehicle for drug delivery and template for the fabrication of mesoporous materials. A cubic micellar gel formed by this copolymer above 15 wt% concentration is the commonly used form of self assembled structure for these applications. In this manuscript we report SANS, fluorescence and rheological studies on the effect of n-butanol on gelation characteristics of aqueous F127 solutions. The studies show that solubilization of n-butanol results in a large increase in viscosity of micellar solution at a fixed copolymer concentration, and leads to the formation of stiff gel at F127 concentration as low as 9 wt%. SANS and fluorescence studies attribute this to enhancement in micellar solvation due to solubilization of n-butanol. Quite interestingly, SANS studies show that n-butanol induced F127 gels form at significantly lower micellar volume fraction than the pure F127 gels. The observed improvement in gelation characteristics can have important bearing with the application in making mesoporous materials since n-butanol is used as co-surfactant to control pore size of such structures formed with F127 gels as template.

Additive induced core and corona specific dehydration and ensuing growth and interaction of Pluronic F127 micelles.

Pluronic F127 is considered to be the most prominent member amongst Pluronics owing to its uses in the fields of drug delivery and fabrication of mesoporous materials. Though extensive studies were carried out on the phase behavior of this copolymer, the effect of additives on restructuring and growth processes of its micelles is not understood yet. In this manuscript we report DLS, SANS, fluorescence and rheological studies on the effects of NaCl and butan-1-ol on the properties of Pluronic F127 micelles in the aqueous medium. The studies show that corona specific micellar dehydration by NaCl induces inter micellar attraction and consequent formation of micellar clusters. Core specific micellar dehydration by butan-1-ol on the other hand, brings about sphere-to-rod micellar shape transition on approaching the cloud point of copolymer solutions. A room temperature sphere-to-rod shape transition of Pluronic F127 micelles can also be induced in the combined presence of butan-1-ol and NaCl. Observation of such micellar shape transition in aqueous Pluronic F127 system is first of its kind, which can have important bearing with their application in mesoporous structure formation and drug delivery.

Solubilization of parabens in aqueous Pluronic solutions: investigating the micellar growth and interaction as a function of paraben composition.

The influence of methyl paraben (MP) and butyl paraben (BP) on the aggregation characteristics of Pluronics in an aqueous medium has been investigated by DLS, SANS, viscometry, and fluorescence measurement techniques. Parabens are extensively used as preservatives in cosmetic, pharmaceutical, and food products. In this paper, we show that their influence on the restructuring and growth of Pluronics micelles vary quite significantly with their aqueous solubility and with the composition of Pluronics. In the case of P105 and P104, MP reduces the sphere-to-rod transition temperature down to room temperature, but BP with significantly less aqueous solubility than MP suppresses such micellar transition and leads to the formation of micellar clusters due to the onset of intermicellar attractive interaction. In the case of more hydrophobic Pluronic P103, on the other hand, both MP and BP are able to induce rapid room temperature sphere-to-rod micellar growth, which is not observed in the presence of water structure making salts like NaCl and Na(3)PO(4). These observations have been attributed to modulation of growth and restructuring processes of the Pluronic micelles arising due to different locations of parabens within the micellar corona as determined by their aqueous solubility and the hydrophobicity of the Pluronics.

Regional odontodysplasia: a case of progressive tooth development.

Regional odontodysplasia (RO) is considered a relatively rare dental anomaly despite increasing numbers of case reports in recent years. It usually presents as a localized anomaly in tooth development affecting a few adjacent teeth in a single maxillary or mandibular quadrant. The purpose of this paper is to describe an uncommon case of regional odotodysplasia involving noncontiguous mandibular teeth, crossing the midline in a male patient, and showing progressive normalization of tooth anatomy over a period of 6 years. Typically, teeth affected with RO become pulpally involved early on and are either extracted or endodontically treated. Such reports of automatic normalization over time in RO is supportive of a more conservative treatment approach.

Phenol solubilization in aqueous Pluronic® solutions: investigating the micellar growth and interaction as a function of Pluronic® composition.

Pluronics® are considered as potential materials for the removal of contaminants like phenol from polluted water sources because of their superior solubilizing capacity of aromatic compounds. Systematic studies on the influence of solubilization of phenol on room temperature aggregation characteristics of Pluronics® in water are, however, conspicuous by their absence. In this manuscript, we thus report DLS, SANS and rheological studies on the influence of phenol on the aggregation characteristics of four Pluronics® viz. F127, P123, P104 and P103. The aim of this study has been to understand the role played by the composition of the Pluronics® in determining growth and interaction of the micelles induced by solubilization of phenol. The study shows that in the case of F127 and P123, phenol solubilization leads to a large increase in light scattering intensity due to an onset of attractive intermicellar interactions and consequent formation of micellar clusters. P123 being smaller than F127 shows a subsequent time dependent micellar growth, leading to a sphere-to-rod shape transitions in micelles. The copolymers P103 and P104, which are smaller and less hydrophobic than P123, respectively, exhibit a large increase in solution viscosity in the presence of phenol owing to a rapid sphere-to-rod micellar growth. The observation of such a fine interplay between the growth and interaction of the pluronic micelles in the presence of a hydrophobic solvent is first of its kind and highlights the role of composition of pluronic in determining the kinetics of the micellar restructuring process.

Investigating the evolution of the phase behavior of AOT-based w/o microemulsions in dodecane as a function of droplet volume fraction.

AOT-based water in oil (w/o) microemulsions are one of the most extensively studied reverse micellar systems because of their rich phase behavior and their ability to form in the absence of any co-surfactant. The aggregation characteristics and interaction of the microemulsion droplets in these systems are known to be governed by AOT-oil compatibility and water to AOT molar ratio (w). In this manuscript by using Dynamic Light Scattering (DLS) and viscometry techniques, we show that droplet volume fraction too plays an important role in shaping the phase behavior of these microemulsions in dodecane. The phase separation characteristics and the evolution of the viscosity and the hydrodynamic radius of the microemulsion droplets on approaching the cloud points have thus been found to undergo complete transformation as one goes from low to high droplet volume fraction even at a fixed 'w'. Modeling of the DLS data attributes this to the weakening of inter droplet attractive interaction caused by the growing dominance of the excluded volume effect with increase in droplet volume fraction. In the literature, the inter droplet attractive interaction driven phase separation in these microemulsions is explained based on gas-liquid type phase transition, conceptualized in the framework of Baxter adhesive hard sphere theory. The modeling of our viscosity data, however, does not support such proposition as the characteristic stickiness parameter (τ(-1)) of the microemulsion droplets in this system remains much lower than the critical value (τ(c)(-1)≈10.25) required to enforce such phase transition.