Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study.

PURPOSE: Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD. METHODS: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient. RESULTS: Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score. CONCLUSIONS: Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD. CLINICAL TRIAL REGISTRATION NUMBER: NCT01374906.

Low Surface Energy and pH Effect on SnO2 Nanoparticles Formation for Supercapacitor Applications.

The SnO2 nanoparticles formation by hydrothermal method at different experimental conditions such as temperature, pH, reaction time, and capping agent (cetyltrimethylammonium bromide), was studied. X-ray diffraction results confirmed regular rutile crystal structure of SnO2. The characteristic Raman peak observed at 635 cm-1 corresponded to A1g modes of Sn-O vibrations. The study of optical property using photoluminescence confirmed the emissive spectra of SnO2. The infrared peak observed at 618 cm-1 corresponded to Eu modes of Sn-O vibrations of TO phonon because of E⊥ to c-axis. Scanning electron microscope images clearly revealed the formation of complete SnO2 nanoparticles. The unique SnO2 nanoparticles stacked together to form microspheres at pH-5 showed high specific capacitance of 274.8 F/g at a current density of 0.5 A/g. The observed results confirmed the feasibility of SnO2 nanoparticles being used as appropriate positive electrode candidate for supercapacitor applications.

Identification and functional characterization of antimicrobial peptide from the marine crab Dromia dehaani.

Many naturally occurring biologically active compounds are derived from marine organisms. Brachyuran crab Dromia dehaani is also known as sponge crab. Hence, this study was undertaken to isolate and characterize the antimicrobial peptide from the marine crab hemolymph. Therefore the objectives of this research work was to high light the functions of biologically active peptide Dromidin. Dromidin was identified and confirmed as a new antimicrobial peptide in the hemolymph of the crab D. dehaani. Antimicrobial peptide was characterized and confirmed by using various analytical techniques. ESI-MS analysis of the active antimicrobial hemolymph fraction resulted in the value 513.0 Da. In addition, current findings strongly suggest that this peptide is functionally important against the pathogens.

Efficacy of phenyl quinoline phenol derivatives as COX-2 inhibitors; an approach to emergent the small molecules as the anti-inflammatory and analgesic therapeutics.

2-(4-phenylquinoline-2-yl)phenol derivatives (4a-l) with COX-2 enzyme inhibition, analgesic, anti-inflammatory and antipyretic potentials were executed and reported. From the in vitro COX-2 enzyme inhibition assay, compounds 4 h (IC50 0.026 µM) and 4j (IC50 0.102 µM) were found as most potent COX-2 inhibitors. Consequently, to get more insight into the binding mode with COX-2, compounds 4a-l were docked into the COX-2 (PDB ID: 1CX2) active site. In the Human Red Blood Cells (HRBC) membrane stabilization assay (in vitro anti-inflammatory), compounds 4f (IC50 0.064 µM) substituted with -OH (R1) and -3Cl (R2), 4 h (IC50 0.021 µM), 4i (IC50 0.484 µg/ml) and 4j (IC50 0.092 µM) with -CHO containing alkanol and ether group at R1 and -4F, -4Br and -OMe at R2 (C2) were showed most potent anti-inflammatory activity. Eventually, acute toxicity studies revealed that 2-(4-phenylquinoline-2-yl)phenol derivatives (4a-l) are safe up to a toleration dose limit of 100 µg/kg body weight. In the Backer's yeast intraperitoneal injection test, compounds 4f, 4 h and 4j produced significant (p < 0.05) antipyretic activity at 1, 1.5, 2 and 2.5 h, whereas test compound 4j and the reference drug indomethacin showed significant antipyretic activity throughout the observation period up to 2.5 h. Promising in vivo results obtained were correlated with the standard non-steroidal anti-inflammatory drugs and the compounds 4f, 4 h, 4i, 4j, and 4 l were efficiently identified as therapeutically potent/fortune moieties as non-steroidal anti-inflammatory agents/analgesics. At the end, ulcerogenic study result ensured that the tested 2-(4-phenylquinoline-2-yl)phenol derivatives created no side-effect.

Long-term 4-year safety of saxagliptin in drug-naive and metformin-treated patients with Type 2 diabetes.

AIMS: To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus. METHODS: Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.5, 5 or 10 mg/day. Patients rescued during or completing 24 weeks of treatment could continue in a 42-month long-term blinded phase, for which the primary goal was assessment of safety and tolerability. Between-group efficacy was not evaluated in the long-term phase of study 11. Time to rescue or discontinuation because of inadequate glycaemic control, change from baseline in HbA(1c) and percentages of patients achieving HbA(1c) < 53 mmol/mol (< 7.0%) were assessed in study 14. RESULTS: No new safety findings were noted during the long-term phase. Most adverse events were mild or moderate, with slightly greater frequency of upper respiratory infections with saxagliptin. Hypoglycaemic event rates were similar with saxagliptin and placebo. In study 14, time to rescue or discontinuation because of inadequate glycaemic control was longer with saxagliptin plus metformin than for placebo plus metformin. From baseline to week 154, HbA(1c) decreased with saxagliptin but increased with placebo. CONCLUSION: Saxagliptin monotherapy or add-on to metformin is generally safe and well tolerated, with no increased risk of hypoglycaemia, for up to 4 years.

Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin.

BACKGROUND: In four 24-week controlled studies, the antihyperglycaemic efficacy of saxagliptin was demonstrated in patients with type 2 diabetes mellitus as add-on therapy to glyburide, a thiazolidinedione, or metformin, and when used in initial combination with metformin vs. metformin monotherapy in drug-naive patients. METHODS: Data from these studies were analysed to compare the proportions of patients who achieved specific reductions from baseline in glycated haemoglobin [HbA(1c); reductions of ≥ 0.5% and ≥ 0.7% in all studies (prespecified); reductions ≥ 1.0% in the add-on studies and ≥ 1.0% to ≥ 2.5% in the initial combination study (post hoc)] for saxagliptin vs. comparator at week 24. We report overall rates of glycaemic response defined by these reductions in HbA(1c) and rates of response without experiencing hypoglycaemia. RESULTS: Large glycaemic response rates were higher with saxagliptin 2.5 and 5 mg/day than with comparator (HbA(1c) ≥ 1.0%, 31.7-50.3% vs. 10.3-20.0%) as add-on therapy and higher with saxagliptin 5 mg/day as initial combination with metformin than with metformin monotherapy (HbA(1c) ≥ 2.0%, 68.3% vs. 49.8%) in drug-naive patients. Addition of saxagliptin was associated with a low incidence of hypoglycaemia; overall response rates and response rates excluding patients who experienced hypoglycaemia were similar. Analysis of several demographic and baseline clinical variables revealed no consistent correlations with response to saxagliptin. CONCLUSIONS: Whether receiving saxagliptin as an add-on therapy to glyburide, a thiazolidinedione, or metformin or in initial combination with metformin, a greater percentage of patients achieve clinically relevant large reductions in HbA(1c) vs. comparator, with a low incidence of hypoglycaemia.

Characterizing melanoma in the setting of oculocutaneous albinism: an analysis of the literature.

Although it is established that individuals with albinism have increased risks for nonmelanoma skin cancers, melanomas occurring in the setting of albinism are rare. PubMed and Google Scholar were searched for individual case reports describing melanoma in individuals with oculocutaneous albinism (OCA). All published cases characterizing individuals with albinism and melanoma in the medical literature were gathered to evaluate any epidemiologic or histologic differences from melanomas arising in the general population. Frequencies of melanoma characteristics between the OCA literature cohort and general population were compared using Clopper-Pearson confidence intervals. From 1952 to 2018, at least 64 cases of melanoma in 56 individuals with albinism were reported in the global medical literature. The median age of diagnosis for melanoma in individuals with albinism was 41 years, and the median Breslow depth at diagnosis was 2.0 mm. The subtypes of melanoma were nodular in 33% and superficial spreading in 46% of these cases, respectively. Amelanotic melanomas comprised 65% of the cases in our OCA cohort; however, histologic subtypes were only available for fourteen of the amelanotic cases. Finally, 17% of melanomas in patients with albinism arose from preexisting lesions. Despite their rarity, melanomas arising in oculocutaneous albinism have distinct characteristics from melanomas arising in the general population. Clinicians should consider a differential diagnosis of melanoma for any potential skin malignancies in individuals with albinism.

Rapid biological synthesis of platinum nanoparticles using Ocimum sanctum for water electrolysis applications.

The leaf extract of Ocimum sanctum was used as a reducing agent for the synthesis of platinum nanoparticles from an aqueous chloroplatinic acid (H(2)PtCl(6)·6H(2)O). A greater conversion of platinum ions to nanoparticles was achieved by employing a tulsi leaf broth with a reaction temperature of 100 °C. Energy-dispersive absorption X-ray spectroscopy confirmed the platinum particles as major constituent in the reduction process. It is evident from scanning electron microscopy that the reduced platinum particles were found as aggregates with irregular shape. Fourier-transform infrared spectroscopy revealed that the compounds such as ascorbic acid, gallic acid, terpenoids, certain proteins and amino acids act as reducing agents for platinum ions reduction. X-ray diffraction spectroscopy suggested the associated forms of platinum with other molecules and the average particle size of platinum nanoparticle was 23 nm, calculated using Scherer equation. The reduced platinum showed similar hydrogen evolution potential and catalytic activity like pure platinum using linear scan voltammetry. This environmentally friendly method of biological platinum nanoparticles production increases the rates of synthesis faster which can potentially be used in water electrolysis applications.

Observation on an isopod parasitizing the edible fish Parastromateus niger in the Parangipettai coast of India.

Cymothoidae are big parasites on fishes and often they are host specific. This study reports that in India, the Black pomfret (Parastromateus niger), a highly edible marine fish belonging to the family Carangidae, is the type host of Cymothoa eremita (Isopoda, Cymothoidae). Among one hundred and sixty fish examined from April to July, 2010 in Parangipettai coastal waters, only three female specimens were infested in June, 2010. It seems that such parasitism depends particularly on the season and on the host sex.

Assessment of soft bottom polychaete diversity in Thondi, Palk Bay, India.

Polychaete assemblages are relatively poorly known in comparison to other components from Indian waters. In the present study, the spatial and seasonal distributions of polychaetes were investigated in the Thondi coastal area. Polychaete assemblage structure seems to be influenced by environmental parameters, such as temperature, salinity, pH, dissolved oxygen and total organic carbon. A total of 34 polychaete species were found, of which 26 species were in station I while 22 species in station II. There was a pronounced variation in diversity of polychaetes between the studied sites. Among the families maximum percentage of species constituted by Glyceridae (12%) and minimum Owenidae (4%) at station I and in station II, the Eunicidae (14%) was maximum and Pisinidae as (4%) minimum. The population density varied from 1456 to 2456 no m(-2) in station I; 2120 to 4424 in station II and diversity index varied from 1.96 to 2.48 in station I; 2.01 to 2.53 in station II. Species richness varied from 1.21 to 1.65 in station I; 1.36 to 1.69 in station II and evenness index varied from 0.9 to 0.97 in station I; 0.91 to 0.98 in station II. BIO-ENV analysis showed that salinity, TOC and temperature as the key variables in influencing the faunal distribution.

Transport of condensing droplets in Taylor-Green vortex flow in the presence of thermal noise.

We study the role of phase change and thermal noise in particle transport in turbulent flows. We employ a toy model to extract the main physics: Condensing droplets are modelled as heavy particles which grow in size, the ambient flow is modelled as a two-dimensional Taylor-Green flow consisting of an array of vortices delineated by separatrices, and thermal noise are modelled as uncorrelated Gaussian white noise. In general, heavy inertial particles are centrifuged out of regions of high vorticity and into regions of high strain. In cellular flows, we find, in agreement with earlier results, that droplets with Stokes numbers smaller than a critical value, St

Novel study on improvement of plastics properties by blending of waste micro plastics into ABS plastics.

Occupancy of waste micro plastic particles in the beach sand is found hazardous sea livings as well as creates the environmental issues. Many research attempts have been made to short out them. This investigation focuses on utilizing such micro plastic to produce cost effective ABS plasticproducts including toys manufacturing. The screened out micro plastic particles were chemically refined to obtain the pro form of Polypropylene (PP) and Polystyrene (PS) and then they used (10 wt%, 15 wt%, 20 wt%and 25 wt%) with raw ABS plastic and prepared billets by injection moulding. The moulding parameters like melting temperature (230 °C, 240 °C, 250 °C and 260 °C), injection pressure (1300 bar, 1400 bar, 1500 bar and 1600 bar) and injection time (0.4s, 0.8s, 1.2s and 1.6s) to maximize the Impact, tensile and flexural strengths of proposed plastic with Taguchi method. The results reveal that 25% micro plastic reinforced specimen prepared at 250 °C, 1400 bar and 1.6s, is outperformed.

Do wind and brass players snore less? A cross-sectional study of snoring and daytime fatigue in professional orchestral musicians.

OBJECTIVES: To determine whether playing a wind or brass musical instrument is associated with reduced snoring or daytime fatigue. DESIGN: Cross-sectional, controlled, anonymous, questionnaire-based observational study. SETTING: Rehearsal and performance halls. PARTICIPANTS: Three hundred and forty musicians from Scotland's five professional orchestras. MAIN OUTCOME MEASURES: Snore Outcomes Survey questionnaire and the Epworth Sleepiness Score. STATISTICAL METHOD: Hierarchical linear regression analysis. RESULTS: No significant difference was found between the snoring severity (Snore Outcomes Survey score) or daytime sleepiness (Epworth score) of wind/brass and other professional musicians. A regression model with snoring severity (Snore Outcomes Survey score) as the dependent variable and the three covariates of gender, age and body mass index as independent variables was significant [F(3, 206) = 28.77, P < 0.01, adjusted r(2) = 0.285]. Increasing age, body mass index and male gender were all significantly associated with lower Snore Outcomes Survey scores (i.e. worse snoring).The addition of instrument type did not significantly increase the fit of the model, and the regression coefficient for instrument type was not significant. There were similar results when the Epworth Sleepiness Score was used as the dependent variable. CONCLUSIONS: This study demonstrated no significant difference between the snoring severity or daytime sleepiness of brass/wind players and other professional orchestral musicians. This result may have been attributed to comparatively low levels of snoring/daytime sleepiness in the population studied. The findings contrast with previous studies examining the effects of singing and didgeridoo playing but concur with a recent similar study of orchestral musicians. A prospective interventional study would be required to determine whether playing a wind or brass instrument improves these variables in patients complaining of disruptive snoring.

Antimicrobial activity of marine sponge Clathria indica (Dendy, 1889).

Sponges are sessile filter feeders that have developed efficient defense mechanisms against foreign invaders such as viruses, bacteria or eukaryotic organisms. Antimicrobial peptides are known as major components of the innate immune defense system in marine invertebrates. The aim of the present work was to study the antimicrobial properties of the Indian sponge Clathria indica with special reference to the identification of antimicrobial peptides. Crude methanolic extract and its chloroform, n-butanol and aqueous fractions were tested against 16 human pathogens which include eleven bacteria with four of them being multidrug resistant and five pathogenic fungi. All fractions showed effective antibacterial activity against common and multidrug-resistant Salmonella typhi and antifungal activity against C. albicans and C. neoformans. However, they were ineffective against Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Staphylococcus aureus. Chloroform fraction being the most potent among the fractions tested on chemical investigation was indicative of the presence of peptides as evidenced by ninhydrin positive spots on TLC and presence of peptide bonds by NMR. Its ESI-MS showed presence of several peptides in the range of m/z 850 to 980. Structure of three peptides has been tentatively assigned by ESI-MS/MS or tandem mass analysis, on the basis of the amino acid sequence established. The results clearly show that the sponge C. indica represent an interesting source of marine invertebrates-derived antimicrobial peptides in the development of new strategies to treat various infectious diseases.

Stereoselective binding of chiral ligands to single nucleotide polymorphisms of the human organic cation transporter-1 determined using cellular membrane affinity chromatography.

Membranes from stably transfected cell lines that express two point mutations of the human organic cation transporter-1 (hOCT1), R488M and G465R, have been immobilized on the immobilized artificial membrane (IAM) liquid chromatographic stationary phase to form two cellular membrane affinity chromatography (CMAC) columns, CMAC(hOCT1(G465R)) and CMAC(hOCT1(R488M)). Columns were created using both stationary phases, and frontal displacement chromatography experiments were conducted using [(3)H] MMP(+) (1-methyl-4-phenylpyridinium) as the marker ligand and various displacers, including the single enantiomers of verapamil, fenoterol, and isoproterenol. The chromatographic data obtained were used to refine a previously developed pharmacophore for hOCT1.

Understanding Transmission Dynamics of COVID-19-Type Infections by Direct Numerical Simulations of Cough/Sneeze Flows.

The transmission dynamics of highly contagious respiratory diseases like COVID-19 (through coughing/sneezing) is an open problem in the epidemiological studies of such diseases (Bourouiba, JAMA. https://doi.org/10.1001/jama.2020.4756. 2020). The problem is basically the fluid dynamics of a transient turbulent jet/puff with buoyancy, laden with evaporating droplets carrying the pathogen. A turbulent flow of this nature does not lend itself to reliable estimates through modeling approaches such as RANS (Reynolds-Averaged Navier-Stokes equations) or other droplet-based models. However, direct numerical simulations (DNS) of what may be called "cough/sneeze flows" can play an important role in understanding the spread of the contagion. The objective of this work is to develop a DNS code for studying cough/sneeze flows by a suitable combination of the DNS codes available with the authors (developed to study cumulus cloud flows including thermodynamics of phase change and the dynamics of small water droplets) and to generate useful data on these flows. Recent results from the cumulus cloud simulations are included to highlight the effect of turbulent entrainment (which is one of the key processes in determining the spread of the expiratory flows) on the distribution of liquid water content in a moist plume. Furthermore, preliminary results on the temperature distribution in a "dry cough" (i.e., without inclusion of liquid droplets) are reported to illustrate the large spatial extent and time duration over which the cough flow can persist after the coughing has stopped. We believe that simulations of this kind can help to devise more accurate guidelines for separation distances between neighbors in a group, design better masks, and minimize the spread of respiratory diseases of the COVID-19 type.

Morphology-Dependent Photoelectrochemical and Photocatalytic Performance of γ-Bi2O3 Nanostructures.

Simple one-step solvothermal route was used to synthesize γ-Bi2O3 nanostructures. Well-defined nanoflowers and finite nanorods surface morphology of the samples were revealed. The physical characterization and material confirmation was explored by employing X-ray diffraction (XRD), Raman, photoluminescence (PL), and Fourier transform infrared (FTIR) studies. The optical bandgap of about 2.71 and 2.72 eV was observed for nanoflower and nanorods, respectively. The highest specific surface area of 0.877 m²/g with mesoporous feature was reported for nanoflower sample. The improved photocurrent of 12.47 µA/cm² was observed for the nanoflower photoanode with lowest internal resistance and the highest stability over 3600 s, with 87% retention in photocurrent was estimated from chronoamperometry (CA) study. The effective methyl orange degradation of MO as 94% was investigated by nanoflower photocatalyst. The synthesis of metastable γ-Bi2O3 nanostructures with hierarchical morphology to adapt as an efficient photoanode for solar water splitting and pollutant degradation applications was reported.

Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial.

AIMS: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. METHODS AND PATIENTS: A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to

Identification of Parapenaeopsis stylifera, a new host for Epipenaeon ingens.

Epipenaeon ingens (Isopoda: Bopyridae) is reported for the first time from Parapenaeopsis stylifera (Decapoda: Penaeidae) in South India. According to the month the parasitic prevalence ranged from 0.0 to 2.9%. A characteristic bulge of the branchial chamber growth retardation and degenerated sex organs were observed in the infested shrimp.

A taxonomic review of the fish parasitic isopod family Cymothoidae Leach, 1818 (Crustacea: Isopoda: Cymothooidea) of India.

The parasitic isopod family Cymothoidae Leach, 1818 of the India exclusive economic zone is reviewed. A total of 56 nominal species corresponding to 48 valid species belonging to sixteen genera are reviewed from 73 host species belonging to 35 families. Mothocya plagulophora (Haller, 1880), Nerocila depressa Milne Edwards, 1840, Nerocila loveni Bovallius, 1887, Nerocila trichiura (Miers, 1877), Norileca triangulata (Richardson, 1910) and Ryukyua globosa Williams Bunkley-Williams, 1994 are redescribed. Indusa pustulosa Pillai, 1954 is synonymised with Agarna malayi Tiwari, 1952; Cymothoa krishnai Jayadev Babu Sanjeeva Raj, 1984 is synonymised with Cymothoa eremita (Brünnich, 1783) and Nerocila priacanthusi Kumari, Rao Shyamasundari, 1987 is synonymised with Nerocila arres Bowman Tareen, 1983. Ourozeuktes bopyroides (Lesueur, 1814) is revised and excluded from the Indian fauna. The Indian cymothoid species Agarna bengalensis Kumari, Rao Shaymasundari, 1990, Cymothoa asymmetrica Pillai, 1954 and Nerocila hemirhamphusi Shyamasundari, Rao Kumari, 1990 are regarded here as species inquirenda. A key to the Indian genera of the family Cymothoidae and keys to the Indian species of the genera Cymothoa, Joryma, Mothocya, and Nerocila are presented. A checklist of the valid Cymothoidae species until now reported from Indian marine fishes are compiled. Host preferences, morphological variability and distribution are discussed.