Preferences and Perspectives of Specialist Multiple Sclerosis Nurses and Patients with Multiple Sclerosis Regarding the New RebiSmart® 3.0 Autoinjector versus Other Assistive Devices.

Purpose: RebiSmart® is an electromechanical multidose autoinjector developed for administering subcutaneous interferon beta-1a in patients with multiple sclerosis (pwMS). This online survey aimed to understand MS nurses' and pwMS preferences and perceptions regarding the features of an upgraded version of the RebiSmart device (RebiSmart 3.0) compared to other assistive devices used for multiple sclerosis (MS) therapy. Patients and Methods: Eligible MS nurses and pwMS from Germany, Italy, and the United Kingdom completed a double-blind, 30-minute online self-administered questionnaire, including a 10-minute video describing the features of RebiSmart 3.0 and its use in administering interferon beta-1a. Results: In total, 102 participants (MS nurses, n=52; patients, n=50) completed the survey. Overall, 70% respondents found the RebiSmart 3.0 device "very"/"extremely" appealing, 53% were "very"/"extremely" interested in learning more, and 71% stated they would be "very"/"extremely" comfortable using (pwMS) or educating (MS nurses) on it. Among current or recent RebiSmart 2.0 users (vs RebiSmart 2.0 nonusers), 67% (vs 52%) rated RebiSmart 3.0 "very" or "extremely" appealing, 52% (vs 43%) were "very" or "extremely" interested in learning more about the device, and 67% (vs 48%) stated they would be "very" or "extremely" comfortable using the RebiSmart 3.0 device. Respondents ranked customizable injection process (including injection speed, hold time, depth and rotation guide), self-injection process, and hidden needle as the most important self-assistive device features. RebiSmart 3.0 was rated higher than other self-injecting devices on all tested features. Overall, with respect to the top three features, 89% of the MS nurses and 73% of PwMS rated RebiSmart 3.0 "very good" or "excellent". After reviewing the video, 52% respondents had no questions, 67% nurses recommended providing more information on the customizable injection process feature of RebiSmart 3.0 to patients, and 88% nurses considered patient demonstration materials to be the most helpful type of information for them when initiating and educating pwMS on self-assistive devices. Conclusion: The overall reactions of MS nurses and pwMS to the RebiSmart 3.0 device features were positive. The incremental advances over previous versions of the device as well as in comparison with other currently available assistive devices were welcomed. The MS nurses identified key needs for patient education on the use of the device and the suitable approaches (training videos and educational leaflets) to support MS nurses and pwMS.

Recalibrating the Non-Communicable Diseases risk prediction tools for the rural population of Western India.

BACKGROUND: The aim of the present study was to recalibrate the effectiveness of Indian Diabetes Risk Score (IDRS) and Community-Based Assessment Checklist (CBAC) by opportunistic screening of Diabetes Mellitus (DM) and Hypertension (HT) among the people attending health centres, and estimating the risk of fatal and non-fatal Cardio-Vascular Diseases (CVDs) among them using WHO/ISH charts. METHODS: All the people aged ≥ 30 years attending the health centers were screened for DM and HT. Weight, height, waist circumference, and hip circumferences were measured, and BMI and Waist-Hip Ratio (WHR) were calculated. Risk categorization of all participants was done using IDRS, CBAC, and WHO/ISH risk prediction charts. Individuals diagnosed with DM or HT were started on treatment. The data was recorded using Epicollect5 and was analyzed using SPSS v.23 and MedCalc v.19.8. ROC curves were plotted for DM and HT with the IDRS, CBAC score, and anthropometric parameters. Sensitivity (SN), specificity (SP), Positive Predictive Value (PPV), Negative Predictive Value (NPV), Accuracy and Youden's index were calculated for different cut-offs of IDRS and CBAC scores. RESULTS: A total of 942 participants were included for the screening, out of them, 9.2% (95% CI: 7.45-11.31) were diagnosed with DM for the first time. Hypertension was detected among 25.7% (95% CI: 22.9-28.5) of the participants. A total of 447 (47.3%) participants were found with IDRS score ≥ 60, and 276 (29.3%) with CBAC score > 4. As much as 26.1% were at moderate to higher risk (≥ 10%) of developing CVDs. Area Under the Curve (AUC) for IDRS in predicting DM was 0.64 (0.58-0.70), with 67.1% SN and 55.2% SP (Youden's Index 0.22). While the AUC for CBAC was 0.59 (0.53-0.65). For hypertension both the AUCs were 0.66 (0.62-0.71) and 0.63 (0.59-0.67), respectively. CONCLUSIONS: IDRS was found to have the maximum AUC and sensitivity thereby demonstrating its usefulness as compared to other tools for screening of both diabetes and hypertension. It thus has the potential to expose the hidden NCD iceberg. Hence, we propose IDRS as a useful tool in screening of Diabetes and Hypertension in rural India.

Assessment of Obstructive Sleep Apnea in Association with Severity of COVID-19: A Prospective Observational Study.

INTRODUCTION: OSA has been postulated to be associated with mortality in COVID-19, but studies are lacking thereof. This study was done to estimate the prevalence of OSA in patients with COVID-19 using various screening questionnaires and to assess effect of OSA on outcome of disease. METHODOLOGY: In this prospective observational study, consecutive patients with RT-PCR confirmed COVID-19 were screened for OSA by different questionnaires (STOPBANG, Berlin Questionnaire, NoSAS, and Epworth Scale). Association between OSA, outcome (mortality) and requirement for respiratory support was assessed. RESULTS: In study of 213 patients; screening questionnaires for OSA [STOPBANG, Berlin Questionnaire (BQ), NoSAS] were more likely to be positive in patients who died compared to patients who survived. On binary logistic regression analysis, age ≥ 55 and STOPBANG score ≥ 5 were found to have small positive but independent effect on mortality even after adjusting for other variables. Proportion of patients who were classified as high risk for OSA by various OSA screening tools significantly increased with increasing respiratory support (p < 0.001 for STOPBANG, BQ, ESS and p = 0.004 for NoSAS). CONCLUSION: This is one of the first prospective studies of sequentially hospitalized patients with confirmed COVID-19 status who were screened for possible OSA could be an independent risk factor for poor outcome in patients with COVID-19.

Fabrication of nanopatterned PLGA films of curcumin and TPGS for skin cancer.

Squamous cell carcinoma treatment has limited therapeutic options and the incidence rate is increasing recently. In the present investigation, we developed poly(lactic-co-glycolic acid) (PLGA) nanopatterned films (NPFs) through poly dimethyl siloxane (PDMS) cast molding technique and explored its therapeutic efficacy in combination with curcumin and tocopherol poly (ethylene glycol) 1000 succinate (TPGS). Herein, we demonstrate the preparation and characterization of curcumin loaded tocopherol polyethylene glycol 1000 succinate stabilized poly (lactic-co-glycolic) acid nanopatterned films (CTP-NPFs). CTP-NPFs showed good in vitro cytotoxicity towards human skin cancer cell line (A431) when compared to that of unpattern films. CTP-NPFs effectively inhibited the progression of 7, 12-Dimethylbenz[a]anthracene (DMBA)/croton oil induced skin cancer in Swiss albino mice. The nanopatterned films could be used as an alternate treatment for skin cancer.

Optical detection of glucose and glycated hemoglobin using etched fiber Bragg gratings coated with functionalized reduced graphene oxide.

An enhanced optical detection of D-glucose and glycated hemoglobin (HbA1c ) has been established in this study using etched fiber Bragg gratings (eFBG) coated with aminophenylboronic acid (APBA)-functionalized reduced graphene oxide (RGO). The read out, namely the shift in Bragg wavelength (ΔλB ) is highly sensitive to changes that occur due to the adsorption of glucose (or HbA1c ) molecules on the eFBG sensor coated with APBA-RGO complex through a five-membered cyclic ester bond formation between glucose and APBA molecules. A limit of detection of 1 nM is achieved with a linear range of detection from 1 nM to 10 mM in the case of D-glucose detection experiments. For HbA1c , a linear range of detection varying from 86 nM to 0.23 mM is achieved. The observation of only 4 pm (picometer) change in ΔλB even for the 10 mM lactose solution confirms the specificity of the APBA-RGO complex coated eFBG sensors to glucose molecules.

Sensitive detection of C-reactive protein using optical fiber Bragg gratings.

An accurate and highly sensitive sensor platform has been demonstrated for the detection of C-reactive protein (CRP) using optical fiber Bragg gratings (FBGs). The CRP detection has been carried out by monitoring the shift in Bragg wavelength (ΔλB) of an etched FBG (eFBG) coated with an anti-CRP antibody (aCRP)-graphene oxide (GO) complex. The complex is characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy. A limit of detection of 0.01mg/L has been achieved with a linear range of detection from 0.01mg/L to 100mg/L which includes clinical range of CRP. The eFBG sensor coated with only aCRP (without GO) show much less sensitivity than that of aCRP-GO complex coated eFBG. The eFBG sensors show high specificity to CRP even in the presence of other interfering factors such as urea, creatinine and glucose. The affinity constant of ∼1.1×10(10)M(-1) has been extracted from the data of normalized shift (ΔλB/λB) as a function of CRP concentration.

Higher topoisomerase 2 alpha gene transcript levels predict better prognosis in GBM patients receiving temozolomide chemotherapy: identification of temozolomide as a TOP2A inhibitor.

The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.

Critical behavior of three organosiloxane de Vries-type liquid crystals observed via the dielectric response.

Dielectric measurements have been made on three organosiloxane liquid crystal compounds exhibiting a smectic A (SmA) to smectic C* (SmC*) transition, the SmA phase being of the de Vries type. The electroclinic response of the molecules in the de Vries phase of these compounds exhibits a double-peak profile, and is thus different from the conventional chiral SmA phase, a feature explained on the basis of an antiferroelectric (AF) block model (Krishna Prasad et al 2009 Phys. Rev. Lett. 102 147802). The differential interactions arising from the different molecular ends of these siloxane-based compounds, which are the basis for the AF block model, can also be expected to enhance the layer translational order. We present x-ray integrated intensity data that show a high (~0.9) translational order in the SmA phase. Dielectric relaxation spectra bring out the fact that the magnitude of the soft mode relaxation parameters is dependent on the number of siloxane groups in the terminal part of the molecule. A range-shrinking analysis of the temperature-dependent dielectric relaxation strength has been carried out, using a power-law expression. The characteristic exponent shows a systematic growth with range shrinking and reaches limiting values comparable to that predicted for the 2D Ising universality class.

Diminution of the ordering in plastic and liquid crystalline phases by confinement.

In a compound exhibiting plastic (crystal B) and liquid crystalline (smectic A) phases, we report calorimetric and X-ray features that are drastically affected by confinement and orientation in Anopore membranes. Data on the untreated membranes in which the molecules aligned parallel to the pore axes, show a significant diminution in the correlation length corresponding to the positional order of the plastic phase suggesting that finite size effects can perhaps transform the plastic phase to a hexatic one. In the orthogonal case, having the molecules in the plane of the membrane, a new phase is induced, whose structural possibilities are discussed. Calorimetric measurements corroborate these results and also bring out the different thermal behaviors, not only between the bulk and the confined cases, but also between the situations wherein the orientations of the molecules are different. These findings are expected to open up a new path to understand the melting phenomenon, especially that which occurs in lower dimensions.

A computationally efficient method for nonparametric modeling of neural spiking activity with point processes.

Point-process models have been shown to be useful in characterizing neural spiking activity as a function of extrinsic and intrinsic factors. Most point-process models of neural activity are parametric, as they are often efficiently computable. However, if the actual point process does not lie in the assumed parametric class of functions, misleading inferences can arise. Nonparametric methods are attractive due to fewer assumptions, but computation in general grows with the size of the data. We propose a computationally efficient method for nonparametric maximum likelihood estimation when the conditional intensity function, which characterizes the point process in its entirety, is assumed to be a Lipschitz continuous function but otherwise arbitrary. We show that by exploiting much structure, the problem becomes efficiently solvable. We next demonstrate a model selection procedure to estimate the Lipshitz parameter from data, akin to the minimum description length principle and demonstrate consistency of our estimator under appropriate assumptions. Finally, we illustrate the effectiveness of our method with simulated neural spiking data, goldfish retinal ganglion neural data, and activity recorded in CA1 hippocampal neurons from an awake behaving rat. For the simulated data set, our method uncovers a more compact representation of the conditional intensity function when it exists. For the goldfish and rat neural data sets, we show that our nonparametric method gives a superior absolute goodness-of-fit measure used for point processes than the most common parametric and splines-based approaches.

Freeman-Sheldon syndrome--prenatal and postnatal diagnosis.

A six-day-old girl, born to normal non-consanguineous parents presented with mask like facies with a small mouth giving a 'whistling' appearance. Other dysmorphic features include deep set eyes, broad nasal bridge, long philtrum and 'H' shaped cutaneous dimple on the chin. There was congenital windmill vane hand position and severe talipes equinovarus deformity. The above features are characteristic of Freeman-Sheldon syndrome also known as Whistling Face syndrome. Ultrasound scanning during 8(th) month of the pregnancy showed the fetus to have facial abnormality and bilateral clenched hand and talipes with extension contractures of knees. Provisional diagnosis of FSS was made which was confirmed after the birth. Thus all cases of Arthrogryposis during prenatal scan should be carefully looked for the facial abnormality in the fetus.

Electric-field-dictated phase diagram and accelerated dynamics of a reentrant nematic liquid crystal under photostimulation.

In a system consisting of photoactive molecules that exhibit light-driven isomerization transformations, actinic light can diminish or enhance ordering to the extent that transitions from the equilibrium to a more disordered phase can be brought about isothermally. This feature enables light to be used as a thermodynamiclike parameter to investigate phase behavior and adds another dimension to the studies owing to the nonequilibrium character of the isothermal transitions. We have carried out experiments which exploit the combination of two recent findings, viz., an electric field can accelerate the return to the nematic liquid crystalline phase from a photodriven isotropic phase; and in a reentrant mesogen, the photoinduced phase can be more ordered. To photostimulate the nonequilibrium transitions a low power uv radiation (0.1 mW cm(-2)) has been used. Unique temperature-electric-field phase diagrams of a liquid crystal exhibiting isotropic-nematic-smectic- A -reentrant nematic sequence, mapped using light transmission as probe reveal that the electric field influences all the transitions, but the effect is maximum on the equilibrium reentrant nematic to the photoinduced smectic- A transition. Temporal measurements have been performed under nonequilibrium conditions to study the dynamics of both the photochemical and the back relaxation processes across the different transitions. The electric field is indeed observed to accelerate the thermal back relaxation in each case, and especially the recovery of the reentrant phase is hastened by three orders of magnitude in time. We explore possible causes for the acceleration and present a finding which can be associated with one of the predictions of density-functional calculations for isomerization of azobenzenes.

Unusual dielectric and electrical switching behavior in the de Vries smectic A phase of two organosiloxane derivatives.

X-ray, electrical, electro-optical, and dielectric studies in the de Vries smectic A (SmA) phase of organosiloxane derivatives exhibit features surprisingly different from that of a conventional SmA phase. The switching data show a double peak profile, characteristic of an antiferroelectric (AF) structure. A model with the adjacent smectic layers having an AF-like arrangement and no global tilt correlation is proposed. Observed in molecules with differential interactions between the two termini, these findings have wide ramifications in understanding the minimum layer shrinkage of such systems.

Pretransitional behaviour in the vicinity of the isotropic-nematic transition of strongly polar compounds.

The isotropic-nematic transition, being weakly first order, exhibits pretransitional effects signifying the appearance of the nematic-like regions in the isotropic phase. In the isotropic phase, strongly polar liquid crystals, such as the popular alkyl and alkoxy cyano biphenyl behave in a non-standard fashion: whereas far away from the transition the dielectric constant ε(iso) has a 1/T dependence (a feature also commonly seen in polar liquids), on approaching the nematic phase the trend reverses resulting in a maximum in ε(iso), at a temperature slightly above the transition, an effect explained on the basis of short-range correlations with an antiparallel association of the neighbouring molecules. Recently, there has been a revival in studies on this behaviour to possibly associate it with the order of transition. Here we report dielectric measurements carried in the vicinity of this transition for a number of compounds having different molecular structures including a bent core system, but with a common feature that the molecules possess a strong terminal polar group, nitro in one case and cyano in the rest. Surprisingly, the convex shape of the thermal variation of ε(iso) was more an exception than the rule. In materials that exhibit such an anomaly we find a linear correlation between δε = (ε(peak)-ε(IN))/ε(IN) and δT = T(peak)-T(IN), where ε(peak) is the maximum value of the dielectric constant in the isotropic phase, ε(IN) the value at the transition, and T(peak) and T(IN) the corresponding temperatures.

Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-beta-cyclodextrin.

The virtual insolubility of gliquidone in water results in poor wettability and dissolution characteristics, which may lead to a variation in bioavailability. To improve these characteristics of gliquidone, binary systems with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were prepared by classical methods such as physical mixing, kneading, co-evaporation and co-lyophilization. The solid state interaction between the drug and HP-beta-CD was assessed by evaluating the binary systems with X-ray diffraction, differential scanning calorimetry and IR- spectroscopy. The results establish the molecular encapsulation and amorphization of gliquidone. The phase solubility profile of gliquidone in aqueous HP-beta-CD vehicle resulted in an A(L) type curve with a stability constant of 1625 M(-1). The dissolution rate of binary systems was greater than that of pure drug and was significantly higher in the case of co-lyophilized and co-evaporated systems. Upon oral administration, [AUC]-alpha was significantly higher in case of co-lyophilized (2 times) and co-evaporated systems (1.5 times) compared to pure drug suspension while other binary systems showed only a marginal improvement. The study ascertained the utility of HP-beta-CD in enhancing the oral bioavailability of gliquidone, and points towards a strong influence of the preparation method on the physicochemical properties.

Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin.

The transdermal delivery of aqueous formulations of indomethacin, a model drug, with different concentrations of three types of dendrimer showed a linear increase in flux with increasing concentration of each of the dendrimers. This result was in contrast to phase solubility studies, where Higuchi's A(N) profile was observed. The steady-state flux of the drug increased significantly and was highest with the G4-NH2 dendrimer at 0.2% w/v concentration, which showed an enhancement factor of 4.5 compared to the pure drug suspension. In vivo, a steady-state flux was achieved in 5 h, and the C(max) values were significantly higher with G4-NH2 and G4-OH dendrimer formulations. The [AUC](0-24h) of G4-NH2 (2.27 times) and G4-OH (1.95 times) formulations were significantly higher than that of the pure drug, but was only marginally higher in the case of G-4.5 dendrimer formulation. The % inhibition of paw volume showed a trend comparable to the pharmacokinetic data and a maximum of 1.6- and 1.5-fold increase was found with G4-NH2 and G4-OH formulations, respectively, compared to the pure drug suspension.

Effect of pH and complexation on transdermal permeation of gliquidone.

Gliquidone, a second generation sulfonylurea has been investigated for transdermal delivery. The poor aqueous solubility of the drug prompted the use of hydroxypropyl-beta-cyclodextrin (HP-beta-CD), a cyclic oligosaccharide, which is known to facilitate transdermal permeation of many drugs by enhancing the solubility and thus improving the diffusible species of the drug molecules at the skin-vehicle interface. In order to optimize the transdermal delivery of gliquidone, the effect of pH along with complexation on the solubility and permeation has been investigated. The solubility profiles of the drug, on increasing the concentration of HP-beta-CD were of Higuchi's AL type at the three pH values evaluated. However, the solubilization slope of the drug at pH 7.0 was 22 times that at pH 3.0 as a result of greater intrinsic solubility of the ionized form of the drug at pH 7.0. Transdermal flux of gliquidone at pH 7.0 was significantly greater than the flux at pH 3.0 in the presence of 15% w/v HP-beta-CD, attributable to the better solubility of the drug at pH 7.0 in the presence of HP-beta-CD. The effect of increasing concentrations of HP-beta-CD investigated at variable drug loading in the donor phase at pH 7.4 endorsed the earlier observations from studies on other drugs, that the drug has to be present at saturation in HP-beta-CD aqueous vehicle to achieve an optimized flux. While at saturation, the steady state flux of gliquidone from the aqueous HP-beta-CD (25% w/v) vehicle was enhanced 31 times compared to pure drug suspension at pH 7.4, unsaturation in the donor phase resulted in the decreased flux of gliquidone. It was concluded from the present study that enhanced transdermal flux of gliquidone can be achieved by adjusting the pH and the concentration of HP-beta-CD to achieve a better solubility of the drug.

Acetylcholinesterase mediated susceptibility of soldiers and workers of formosan subterranean termite (Isoptera: Rhinotermitidae) to chlorpyrifos.

Target site studies were undertaken to examine the difference in susceptibility of Formosan subterranean termite, Coptotermes formosanus Shiraki, workers and soldiers to chlorpyrifos. Workers exhibited significantly greater acetylcholinesterase activity per insect than soldiers (118.63 +/- 48.51 versus 47.98 +/- 22.59 mOD/min/insect equivalent). Likewise, enzyme activity (mean +/- SD) per milligram of protein was greater in workers than soldiers (440.30 +/- 267.43 versus 311.53 +/- 149.83 mOD/min/mg protein). The enzyme of soldiers was more sensitive to the acetylcholinesterase (AChE) inhibitors eserine and chlorpyrifos-oxon than that of workers. The I50s of chlorpyrifos-oxon were 2.66 and 4.59 nM for soldiers and workers, respectively, whereas the I50s of eserine were 16.56 and 25.41 nM for soldiers and workers, respectively. The amount of protein was significantly higher in workers than in soldiers with mean values of 0.270 +/- 0.102 and 0.154 +/- 0.054 mg/insect equivalent, respectively. We suggest that the differential response of workers and soldiers to chlorpyrifos may be due to the difference in AChE sensitivity to inhibition and the amount of protein between them.

Plasma protein polymorphisms in Malas and Madigas of coastal Andhra Pradesh, south India.

Four plasma protein polymorphisms: Group specific Component (GC), Haptoglobin (HP), Transferrin (TF) and Caeruloplasmin (CP), have been determined in two endogamous populations (Mala and Madiga) of Visakhapatnam of Coastal Andhra Pradesh, South India. The results were compared between the two caste populations and they revealed no significant differences. The results were also compared with those available from other Andhra populations.