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.

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.

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.

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.

A randomised comparative study between low-dose intravenous magnesium sulphate and standard intramuscular regimen for treatment of eclampsia.

In a randomised control study, we evaluated the efficacy of intravenous low-dose magnesium sulphate for the management of eclampsia. A total of 144 women with eclampsia were divided into a study group and a control group of 72 women each. The study group received 0.75 g/h of magnesium sulphate intravenously after a loading intravenous dose of 4 g and the control group was given the standard intramuscular regimen as advocated by Pritchard. The primary outcome measure was recurrence rate of the seizures. The secondary outcome measures were development of magnesium toxicity if any, and maternal and perinatal outcomes. The difference in the incidence of fit recurrence was statistically insignificant when both groups were compared (7.46% vs 8.57%, p = 0.939). The total dose of magnesium sulphate was significantly lower in the intravenous group (p < 0.0001), in which no patient developed magnesium toxicity. Low-dose intravenous magnesium sulphate was found to be as effective as the standard intramuscular regimen, while maintaining a high safety margin.

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.

Functional analysis of the cis-acting elements responsible for the induction of the Cyp6a8 and Cyp6g1 genes of Drosophila melanogaster by DDT, phenobarbital and caffeine.

Many Drosophila cytochrome P450 or Cyp genes are induced by caffeine and phenobarbital (PB). To understand the induction mechanism, we created Drosophila S2 cell lines stably transformed with different luciferase reporter plasmids carrying upstream DNAs of Cyp6a8 allele of the resistant 91-R strain, and the 1.1-kb upstream DNAs of Cyp6g1 of the 91-R and the susceptible 91-C strains. Following 24 h treatment with dichlorodiphenyltrichloroethane (DDT), caffeine or PB, luciferase activity of all cell lines was determined. Results showed that the 0.1-kb DNA of Cyp6a8 and the upstream DNAs of Cyp6g1 from both strains are not induced by these chemicals in S2 cells. However, the 0.2-, 0.5- and 0.8-kb DNAs of Cyp6a8 showed 13-24-, 4-5- and 2.2-2.7-fold induction with caffeine, PB and DDT, respectively. These DNAs also showed a 2-3-fold synergistic effect of caffeine and PB but not of caffeine and DDT. The results suggest that the cis-regulatory elements for all three chemicals are located within the -11/-199 DNA of Cyp6a8. Furthermore, caffeine and PB inductions appear to be mediated via different cis-elements, whereas caffeine and DDT induction may involve common regulatory elements. These stably transformed cell lines should help understand the mechanism of resistance-associated Cyp gene overexpression in Drosophila.

Time dependent growth of the block copolymer P123 micelles near cloud point: employing heat cycling as a tool to form kinetically stable wormlike micelles.

The sphere-to-rod growth behavior of the triblock copolymer EO(20)PO(70)EO(20) (P123) micelles has been studied in an aqueous medium by dynamic light scattering (DLS), viscometry, and small angle neutron scattering (SANS) techniques. Unlike the other aqueous pluronic systems, the P123 solutions show a time dependent sphere-to-rod micellar growth in the aqueous medium on approaching their cloud points. The rate of micellar growth increases with increase in temperature, but quite interestingly, it improves rather dramatically when the copolymer solutions are subjected to heat cycling, i.e., heating them to the phase separation and subsequently cooling them back to below their cloud points. The observed kinetically restricted micellar growth has been attributed to the slow dynamics of the micellar restructuring processes essential to arrive at the temperature dependent equilibrium structure. It has been suggested that the improvement in the micellar growth rate upon heat cycling is due to overcoming of the activation energy associated with the micellar restructuring process. In the presence of water-structure-making salts like NaCl, such heat cycling produces kinetically stable wormlike micelles at room temperature, which is observed for the first time in the aqueous pluronic systems.

Pluronic L64 micelles near cloud point: investigating the role of micellar growth and interaction in critical concentration fluctuation and percolation.

The structure and the properties of the (Ethylene Oxide)(13)(Propylene Oxide)(30)(Ethylene Oxide)(13) (Pluronic L64, MW approximately 2900) micelles have been studied in the aqueous medium by small angle neutron scattering (SANS), dynamic light scattering (DLS) and viscometry measurements. The aqueous solutions of this triblock copolymer are unique among the pluronic solutions in showing critical concentration fluctuations and a concomitant enhancement in viscosity on approaching their cloud point. So far these results have been attributed solely to the presence of attractive interaction between the spherical L64 micelles. Recent theoretical studies, on the other hand, suggest that L64 micelles prefer a prolate ellipsoidal structure to sphere (Bedrov et al. Langmuir 2007, 23, 12032) and have a predominantly repulsive intermicellar interaction. A comparative analysis of our SANS data based on the spherical and prolate ellipsoidal structure shows that the L64 micelles can be best described by a prolate ellipsoidal structure, the aspect ratios of which increase progressively with increase in temperature. This, together with our viscosity and DLS studies, suggests that the enhanced viscosity of the copolymer solution near the cloud point arises largely due to the anisotropic growth of the micelles to the worm-like structures. The role of the intermicellar attractive interaction has thus been limited to the observed critical concentration fluctuation, and its effect decreases progressively with increase in copolymer concentration. It has also been shown that the water structure making salts like NaCl reduces the micellar growth temperature and helps in forming worm-like micelles at the room temperature. These studies thus identify the effect of micellar growth and interaction in determining the properties of the copolymer solution near the cloud point, which are the first of its kind in the case of the pluronics.

Effectiveness of introducing blood culture collection packs to reduce contamination rates.

Contaminated blood cultures result in a significant waste of healthcare resources and can lead to inappropriate antibiotic therapy. Practitioners have taken measures to reduce contamination rates. These include thorough skin disinfection, effective hand decontamination, introduction of a standardised approach to collection, and the introduction of blood culture collection packs (BCCP). This study aims to assess the impact of introducing BCCP and staff training on the rate of contamination. The study demonstrated that contamination rates are greatest in high patient throughput units where practitioners are under most pressure. The introduction of blood culture packs and staff training has reduced contamination rate significantly from 43% to 25% of the total number of positives, equating to an overall reduction of 42%. Thus, there is a demonstrable benefit in the purchase of commercially produced blood culture packs and the investment in staff training.

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.

Improved micellar hydration and gelation characteristics of PEO-PPO-PEO triblock copolymer solutions in the presence of LiCl.

LiCl-induced changes in the micellar hydration and gelation characteristics of aqueous solutions of the two triblock copolymers F127 (EO(100)PO(70)EO(100)) and P123 (EO(20)PO(70)EO(20)) (where EO represents the ethylene oxide block and PO represents the propylene oxide block) have been studied by small-angle neutron scattering (SANS) and viscometry. The effect of LiCl was found to be significantly different from those observed for other alkali metal chloride salts such as NaCl and KCl. This can be explained on the basis of the complexation of hydrated Li(+) ions with the PEO chains in the micellar corona region. The interaction between the chains and the ions is more significant in the case F127 because of its larger PEO block size, and therefore, micelles of this copolymer show an enhanced degree of hydration in the presence of LiCl. The presence of the hydrated Li(+) ions in the micellar corona increases the amount of mechanically trapped water there and compensates more than the water molecules lost through the dehydration of the PEO chains in the presence of the Cl(-) ions. The enhancement in micellar hydration leads to a decrease in the minimum concentration required for the F127 solution to form a room-temperature cubic gel phase from 18% to 14%. Moreover, for both copolymers, the temperature range of stability of the cubic gel phase also increases with increasing LiCl concentration, presumably because of the ability of the Li(+) ions to reduce micellar dehydration with increasing temperature. Viscosity studies on a poly(ethylene glycol) (PEG) homopolymer with a size equivalent to that of the PEO block in F127 (4000 g/mol) also suggest that the dehydrating effect of the Cl(-) ion on the PEG chain is compensated by its interaction with the hydrated Li(+) ions.

Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera.

BACKGROUND & OBJECTIVES: The monoaminergic systems which exert a modulatory role in memory processing, are disturbed in Alzheimer's disease (AD) and Moringa oleifera (MO) has been shown to exert its effect in CNS by altering the brain monoamines. The present study aims to see whether chronic oral treatment of ethanolic extract of MO leaves can alter the brain monoamines (norepinephrine, dopamine and serotonin) in distinct areas of brain in rat model of AD caused by intracerebroverticle (ICV) infusion of colchicine and hence can provide protection against monoaminergic deficits associated with AD. METHODS: Rats were given ICV infusion of colchicine (15 microg/5microl) and MO leaf alcoholic extract was given in various doses. The effective dose was standardized by radial arm maze (RAM) training. From the selected dose of 250 mg/kg body weight, the biochemical estimations and EEG studies were performed. RESULTS: Stereotaxic ICV infusion of colchicine significantly impaired the RAM performance together with decrease in norepinephrine (NE) level in cerebral cortex (CC), hippocampus (HC) and caudate nucleus (CN). Dopamine (DA) and serotonin (5-HT) levels were decreased in CC, HC and CN. The EEG studies showed a decrease in beta and alpha waves and increase in biphasic spike wave pattern in experimental Alzheimer rat model. Treatment with MO extract markedly increased the number of correct choices in a RAM task with variable alteration of brain monoamines. The EEG studies showed an increase in beta waves and a decrease in spike wave discharges. INTERPRETATION & CONCLUSION: Our results showed that brain monoamines were altered discreetly in different brain areas after colchicine infusion in brain. After treatment with MO, leaf extract the monoamine levels of brain regions were restored to near control levels. Our findings indicated that MO might have a role in providing protection against AD in rat model by altering brain menoamine levels and electrical activity.

Castlemans disease in HIV infected patient from eastern India.

Castlemans disease is a rare lymphoproliferative disorder. We report a patient of Castlemans disease with advanced HIV infection who responded well to conventional HAART. This case is interesting because of the rarity of the disease in the eastern part of India and its good out come with antiretroviral therapy.

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.

Mathematical model for chemotherapeutic drug efficacy in arresting tumour growth based on the cancer stem cell hypothesis.

OBJECTIVE: Cancer stem cells have been identified as the growth root for various malignant tumours and are thought to be responsible for cancer recurrence following treatment. MATERIALS AND METHODS: Here, a predictive mathematical model for the cancer stem cell hypothesis is used to understand tumour responses to chemotherapeutic drugs and judge the efficacy of treatments in arresting tumour growth. The impact of varying drug efficacies on different abnormal cell populations is investigated through the kinetics associated with their decline in response to therapy. RESULTS AND CONCLUSIONS: The model predicts the clinically established 'dandelion phenomenon' and suggests that the best response to chemotherapy occurs when a drug targets abnormal stem cells. We compare continuous and periodic drug infusion. For the latter, we examine the relative importance of the drug cell-kill rate and the mean time between successive therapies, to identify the key attributes for successful treatment.

Room temperature sphere-to-rod growth and gelation of PEO-PPO-PEO triblock copolymers in aqueous salt solutions.

The effects of NaCl and KF on the sphere-to-rod micellar growth behavior of triblock copolymers having two different compositions, (EO)20(PO)70(EO)20 (P123) and (EO)26(PO)40(EO)26 (P85), have been studied by dynamic light scattering (DLS), small angle neutron scattering (SANS) and dilute solution viscometry. NaCl can effectively tune the sphere-to-rod growth temperature of the micelles of both these copolymers and induce micellar growth down to the room temperature and below. The growth behavior is found to be dependent on the composition of the copolymer as P123 being more hydrophobic shows the room temperature growth in the presence of ethanol at significantly lesser NaCl concentration than the less hydrophobic copolymer P85. DLS studies depict for the first time the growth driven transition of the copolymer solutions from dilute to semi-dilute regime as a function of copolymer and salt concentrations. KF can also induce room temperature growth of the P123 micelles at lesser salt concentration than NaCl but it fails to induce any such growth of the P85 micelles. A pseudo-binary temperature-concentration phase diagram on 15% copolymer solutions shows the variation of the sphere-to-rod transition temperature and the cloud point of the copolymer solutions as a function of salt concentration.