Patients often approach a pharmacist instead of visiting a doctor for minor ailments such as cough, cold, allergies, pain, fever, acidity, diarrhea, and skin-related conditions. Purchase of specific ...medicines over the counter is legally recognized in most countries. 'Over-the-Counter (OTC) Medicines' means drugs which are legally allowed to be sold by pharmacists without need for a prescription. The term does not have a legal definition in India. Technically, drugs are OTC unless they are specifically stated as prescription only drugs. OTC drugs allow faster and cheaper access to healthcare; however, their misuse and adverse health effects cause concerns. This article describes concept of OTC medicines and practices in India against the background of globally prevalent regulations and practices. A recognized category of OTC medicines by law, patient awareness programs, and support of pharmacists and pharmaceutical companies are required to optimize the use of OTC medicines in India.
Our goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer's-related pathology. We assessed the effect of 52 weeks of a ...supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging.
This 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs. education control intervention. A total of 117 underactive older adults (mean age 72.9 7.7) without evidence of cognitive impairment, with elevated (n = 79) or subthreshold (n = 38) levels of cerebral amyloid were randomized, and 110 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. We conducted 18F-AV45 PET imaging of cerebral amyloid and anatomical MRI for whole brain and hippocampal volume at baseline and Week 52 follow-up to index brain health. Neuropsychological tests were conducted at baseline, Week 26, and Week 52 to assess executive function, verbal memory, and visuospatial cognitive domains. Cardiorespiratory fitness testing was performed at baseline and Week 52 to assess response to exercise. The aerobic exercise group significantly improved cardiorespiratory fitness (11% vs. 1% in the control group) but there were no differences in change measures of amyloid, brain volume, or cognitive performance compared to control.
Aerobic exercise was not associated with reduced amyloid accumulation in cognitively normal older adults with cerebral amyloid. In spite of strong systemic cardiorespiratory effects of the intervention, the observed lack of cognitive or brain structure benefits suggests brain benefits of exercise reported in other studies are likely to be related to non-amyloid effects.
NCT02000583; ClinicalTrials.gov.
•The influence of boron in Co2FeSi1−xBx (x = 0–0.5) Heusler alloys was systematically investigated.•The x-ray diffraction and microstructural analysis confirmed the presence of second phase.•The ...melting point decreases with increasing boron and merges with ordering temperature at x = 0.5.•The observed compositional shift with boron content is attributed to the formation of second phase.
The influence of partial substitution of boron on the structural, microstructure, magnetic and calorimetric properties of Co2FeSi1−xBx (x = 0–0.5) alloys was systematically investigated. The x-ray powder diffraction and microstructural analysis confirmed the presence of second phase in the alloys. From calorimetric studies, it was observed that L21–B2 ordering temperature remain constant whereas the melting point decreases with increasing boron content and merges with ordering temperature at x = 0.5. The Curie temperature (TC) for the alloys x ≥ 0.25 has shown a linear increase with boron concentration. The saturation magnetic moment exhibits a linear decrease and confirms the substitutional effect of boron for Si. With increase in boron content, a compositional shift has been observed which may be attributed to the formation of second phase at the grain boundaries.
Phagocytosis is an evolutionarily conserved biological process where pathogens or cellular debris are cleared by engulfing them in a membrane-enclosed cellular compartment called the phagosome. The ...formation, maturation, and subsequent degradation of a phagosome is an important immune response essential for protection against many pathogens. Yet, the global lipid profile of phagosomes remains unknown, especially as a function of their maturation in immune cells. Here, we show using mass spectrometry based quantitative lipidomics that the ceramide class of lipids, especially very long chain ceramides, are enriched on maturing phagosomes with a concomitant decrease in the biosynthetic precursors of ceramides. We thus posit a new function for the enzyme ceramide synthase during phagocytosis in mammalian macrophages. Biochemical assays, cellular lipid feeding experiments, and pharmacological blockade of ceramide synthase together show that this enzyme indeed controls the flux of ceramides on maturing phagosomes. We also find similar results in the primitive eukaryote Dictyostelium discoideum, suggesting that ceramide enrichment may be evolutionarily conserved and likely an indispensible step in phagosome maturation.
•Thickness dependent magnetic anisotropy in Tb-Fe thin films studied.•Formation of nano-columnar structures aid perpendicular magnetic anisotropy.•The magnetic energetics changes from surface ...dominated to bulk-lie properties with increase in film thicknesses.
In this paper, we have attempted to understand the magnetic behaviour of Tb-Fe thin films grown with different thicknesses through detailed electron microscopy, magnetization measurements and magnetic domain imaging studies. Tb-Fe thin films over a range of thicknesses such as 50, 100, 200, 400, 600 and 800 nm were deposited on Si substrates using electron beam evaporation technique. Grazing incidence X-ray diffraction studies revealed that all the films were amorphous in nature. Microstructural studies using transmission electron microscopy showed columnar channel of voids extending from substrate to film surface. Magnetization measurements along the in-plane and out-of-plane direction indicated presence of out-of-plane magnetic anisotropy in all the films. Saturation magnetization and coercivity measured along the out-of-plane direction were found to vary with the thickness of the films. A very high coercivity of ~2000 mT was obtained for the film having thickness of 400 nm. Magnetic anisotropy calculations indicated a strong perpendicular magnetic anisotropy for the 400 nm thick film. The variation of magnetic anisotropy with film thickness was correlated with the magnetic domain patterns observed in the films using magnetic force microscopy.
Methane is a potent greenhouse gas that is produced in significant quantities by aerobic marine organisms. These bacteria apparently catalyse the formation of methane through the cleavage of the ...highly unreactive carbon-phosphorus bond in methyl phosphonate (MPn), but the biological or terrestrial source of this compound is unclear. However, the ocean-dwelling bacterium Nitrosopumilus maritimus catalyses the biosynthesis of MPn from 2-hydroxyethyl phosphonate and the bacterial C-P lyase complex is known to convert MPn to methane. In addition to MPn, the bacterial C-P lyase complex catalyses C-P bond cleavage of many alkyl phosphonates when the environmental concentration of phosphate is low. PhnJ from the C-P lyase complex catalyses an unprecedented C-P bond cleavage reaction of ribose-1-phosphonate-5-phosphate to methane and ribose-1,2-cyclic-phosphate-5-phosphate. This reaction requires a redox-active 4Fe-4S-cluster and S-adenosyl-L-methionine, which is reductively cleaved to L-methionine and 5'-deoxyadenosine. Here we show that PhnJ is a novel radical S-adenosyl-L-methionine enzyme that catalyses C-P bond cleavage through the initial formation of a 5'-deoxyadenosyl radical and two protein-based radicals localized at Gly 32 and Cys 272. During this transformation, the pro-R hydrogen from Gly 32 is transferred to the 5'-deoxyadenosyl radical to form 5'-deoxyadenosine and the pro-S hydrogen is transferred to the radical intermediate that ultimately generates methane. A comprehensive reaction mechanism is proposed for cleavage of the C-P bond by the C-P lyase complex that uses a covalent thiophosphate intermediate for methane and phosphate formation.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent ...systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 NCT02912468; SINUS-52 NCT02898454) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery.
SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153).
Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test.
Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.
► No improvement in mechanical properties were found on addition of 0.2
wt.% boron in Ti-1100 alloy in the as cast condition even though there was significant refinement in the microstructure. ► ...Ti-1100 alloy with 0.2
wt.% boron exhibited a higher yield strength, ultimate tensile strength and similar ductility as compared to the base alloy at room temperature in the thermomechanically (α–β rolled) and standard heat treatment condition. The results were in-line with the predictions of a model based on treating the material as a metal matrix composite with aligned but fragmented whiskers. ► No discernible trend in the variation of yield strength and UTS in boron containing Ti-1100 alloy was observed with change in heat treatment (i.e. solution treatment condition) either at room temperature or at 600
°C although they broadly follow the change in the matrix yield strength and UTS. ► The mechanical properties of the Ti-1100 alloy with 0.2
wt.% boron was also found to better than that of the base alloy at 600
°C.
The effect of 0.2
wt.% of boron on the mechanical properties of Ti-1100, a near α titanium alloy, was evaluated at room temperature and at 600
°C in the as cast and thermomechanically processed (α–β rolled) condition after subjecting it to different heat treatments. Boron addition in Ti-1100 significantly refined the microstructure in the as cast condition but the mechanical properties did not show any improvement. However, in the thermomechanically processed (α–β rolled) and standard heat treatment condition, the yield strength (YS) and ultimate tensile strength (UTS) of the boron containing alloy increased significantly without any drop in elongation-to-failure as compared to the base alloy at both room temperature and 600
°C. No discernible trend was seen in YS and UTS in boron containing alloy with change in solution treatment temperature either at room temperature or at 600
°C.
The aim of the presented study was to determine the ability of the high pressure processing (HPP) for extraction of bioactive compounds from black carrot pomace and to optimize treatment conditions ...(pressure, temperature, processing time) for obtaining the maximum yield of bioactive compounds. Experiments were conducted using pilot scale high pressure food processors and water as the extraction solution. A set of response surface analysis mathematical models were developed and validated for the extraction of bioactive compounds of black carrot pomace, considering total monomeric anthocyanin contents (TMA), total phenolic compounds (TPC) and antioxidant activity (AA). Quality attributes such as total color difference (ΔE*) and polymeric color ratio (PCR) of the samples were also evaluated. The validation results showed that the error values of the obtained models were lower than 10%, which means acceptable error value in modelling study. Combined pressure–thermal treatment at 266.6 MPa, 78.3 °C for 13.6 min was identified as the optimal process condition for maximum extraction of bioactive compounds.
Graphic Abstract
The effect of strain rate on trigger stress for stress-induced martensitic transformation (SIMT) and yield strength in Ti–18Al–8Nb alloy was investigated in the strain rate range 1.33
×
10
−5 to 1.33
...×
10
−1
s
−1 at room temperature. The alloy exhibited SIMT during tensile testing at all the strain rates tested. The trigger stress for SIMT was found to increase whereas the yield strength was found to remain more or less unchanged with increase in strain rate.
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