A comparative study of the effect of supplementing citicoline with fluoxetine and amitriptyline on learning and memory in albino rats

Background: The prevalence of psychosomatic complaints in children and adolescents has been reported to be between 10% and 25%. In addition, these problems present in a wide range of people across different age groups. Complaints of impaired learning and memory are common in patients treated with drugs acting on the central nervous system including the prototypical antidepressant drugs (AAD) such as fluoxetine and amitriptyline. Concomitant administration of the nootropic drug citicoline may help in the maintenance of cognition through the retention of memory and learning capacity.Methods: Albino rats were used for this study as they are the most standardized of all experimental animals and divided into five groups of six rats each including the control group. The test apparatus used was the Morris water maze which is one of the most widely used tasks in behavioral neuroscience for studying the psychological processes and neural mechanisms of spatial learning and memory. The drugs used in the study were fluoxetine amitriptyline and citicoline. All the rats received respective treatment for the period of 20 days. The experiment was conducted during the last week. During this period, the rats were simultaneously trained and tested for 4 days for learning behavior (i.e. from 14th to 17th day of the study) designated as day 1, day 2, day 3, and day 4. After a gap of 2 days, i.e. on day 20, the rats were tested for the retention of memory on Morris water maze (designated as day 6).Results: There was a statistically significant impairment in learning behavior of the rats in fluoxetine and amitriptyline group when compared to control group (p<0.01 is highly significant) but no such significance was obtained when the groups containing the AADs was supplemented with citicoline. In addition, fluoxetine caused more impairment than amitriptyline and supplemental citicoline was beneficial in retaining the memory and preventing learning impairment, but the combination is more beneficial in the amitriptyline group as compared to the fluoxetine group.Conclusions: Cognition in individuals with depression may be influenced by several factors, including basic neuropathology and the frequency and severity of depressive episodes. The major finding of the present study is that learning was impaired by both the antidepressants, i.e., fluoxetine and amitriptyline but was reversed by citicoline which has a novel mechanism of action

A comparative single dose study of oral acetaminophen 650 mg to its standard 500 mg dose in adult pyrexia patients in a tertiary care hospital

Background: Acetaminophen commonly called as paracetamol is the most used ‘over-the-counter’ analgesic for headache, musculoskeletal pain, dysmenorrhoea etc. It is the best drug to be used as antipyretic for fever due to any cause and safest to be prescribed in all age groups. Antipyretic dose of acetaminophen is 325 to 650 mg; 3 to 4 times a day and is available in the strength of 650 mg and 500 mg tablets. This study was conducted to analyse the antipyretic efficacy and safety profile of two different doses of acetaminophen in patients with low grade fever.Methods: 300 hospitalised patients aged more than 18 years, in department of General Medicine, having low grade fever (38º to 39º C) were randomly allocated into two groups of 150 each, group A received 500 mg and group B received 650 mg of single oral dose of acetaminophen tablets. Oral temperature was measured before dosing, 30 minutes after dosing, one hour, two hourlies thereafter for 6 hours after the dose. Safety was assessed by monitoring for adverse effects during the study and 24 hours after administration of the assigned drug.Results: There was a statistically significant decrease in temperature in group B patients from baseline 39.06±0.87º C to 37.02±0.89º C at the end of 6th hour as compared with 39.18±0.80º C to 38.03±0.77º C in Group A patients (p=0.031).Conclusions: Our study concluded that acetaminophen in a dose of 650 mg is highly efficacious antipyretic drug compared to acetaminophen 500 mg with no adverse effects

A Comparative study to assess the effectiveness and safety of cilnidipine versus amlodipine in patients with newly diagnosed essential hypertension: insights from a single centre prospective observational study

Background: Calcium channel blockers (CCBs) are proposed to play a pivotal role for the management and control of hypertension. Dihydropyridine-type calcium channel blockers (CCBs) like Amlodipine are frequently used because for their strong antihypertensive and minimal adverse side effects. However, it is commonly associated with the causation of pedal edema among the patients. Cilnidipine, which is a novel new generation calcium channel blocker, is presumed to cause lesser pedal edema with a satisfactory clinical control of hypertension along with negligible side effects. This study was carried out to compare clinical effectiveness and safety profile between Amlodipine and Cilnidipine.Methods: A prospective, randomized, open label study of 12 weeks’ duration was conducted amongst 60 patients with newly diagnosed essential hypertension. 30 patients of one group received Tab. Amlodipine 5 mg and 30 patients of same age groups received Tab. Cilnidipine 10mg.Results: There was a highly statistically significant decrease in the level of blood pressure in the Cilnidipine group compared to the Amlodipine group mainly at day 90 (P<0.001). Cilnidipine treated group had a fall in blood pressure of 23 ± 8 mmHg and the Amlodipine group had a decrease in the blood pressure of 12±7mmHg. Additionally, there was also significant reduction in pulse rate in the cilnidipine group. Only 4 patients in the Cilnidipine group developed ankle edema which completely disappeared at the end of 12 weeks of therapy compared to 9 patients in the Amlodipine group which persistently worsened at the completion of the study.Conclusions: Our study concluded that cilnidipine was a well-tolerated anti-hypertensive drug amongst patients with newly diagnosed essential hypertension and associated with minor adverse effects

Estimation of polarization aberrations and their effect on the coronagraphic performance for future space telescopes

A major goal of proposed future space observatories, such as the Habitable World Observatory, is to directly image and characterize Earth-like planets around Sun-like stars to search for habitability signatures requiring the starlight suppression (contrast) of 1e-10. One of the significant aspects affecting this contrast is the polarization aberrations generated from the reflection from mirror surfaces. The polarization aberrations are the phase-dependent amplitude and phase patterns originating from the Fresnel reflections of the mirror surfaces. These aberrations depend on the angle of incidence and coating parameters of the surface. This paper simulates the polarization aberrations for an on-axis and off-axis TMA telescope of a 6.5 m monolithic primary mirror. We analyze the polarization aberrations and their effect on the coronagraphic performance for eight different recipes of mirror coatings for Astronomical filter bands g-I: three single-layer metal coatings and five recipes of protective coatings. First, the Jones pupils are estimated for each coating and filter band using the polarization ray tracing in Zemax. Then, we propagate these Jones pupils through a Vector Vortex Coronagraph and Perfect Coronagraphs using hcipy, a physical optics-based simulation framework. The analysis shows that the two main polarization aberrations generated from the four mirrors are the retardance-defocus and retardance-tilt. The simulations also show that the coating plays a significant role in determining the strength of the aberrations. The bare/oxi-aluminum and Al+18nm LiF coating outperforms all the other coatings by one order of magnitude.Comment: 13 pages, 11 figures, SPIE Optics+Photonics 2023 proceeding, Paper no: 12680-2

The ALMaQUEST Survey: The Molecular Gas Main Sequence and the Origin of the Star-forming Main Sequence

The origin of the star forming main sequence ( i.e., the relation between star formation rate and stellar mass, globally or on kpc-scales; hereafter SFMS) remains a hotly debated topic in galaxy evolution. Using the ALMA-MaNGA QUEnching and STar formation (ALMaQUEST) survey, we show that for star forming spaxels in the main sequence galaxies, the three local quantities, star-formation rate surface density (\sigsfr), stellar mass surface density (\sigsm), and the \h2~mass surface density (\sigh2), are strongly correlated with one another and form a 3D linear (in log) relation with dispersion. In addition to the two well known scaling relations, the resolved SFMS (\sigsfr~ vs. \sigsm) and the Schmidt-Kennicutt relation (\sigsfr~ vs. \sigh2; SK relation), there is a third scaling relation between \sigh2~ and \sigsm, which we refer to as the `molecular gas main sequence' (MGMS). The latter indicates that either the local gas mass traces the gravitational potential set by the local stellar mass or both quantities follow the underlying total mass distributions. The scatter of the resolved SFMS ($\sigma \sim 0.25$ dex) is the largest compared to those of the SK and MGMS relations ($\sigma \sim$ 0.2 dex). A Pearson correlation test also indicates that the SK and MGMS relations are more strongly correlated than the resolved SFMS. Our result suggests a scenario in which the resolved SFMS is the least physically fundamental and is the consequence of the combination of the SK and the MGMS relations

Polarization aberrations in next-generation giant segmented mirror telescopes (GSMTs) I. Effect on the coronagraphic performance

Next-generation large segmented mirror telescopes are expected to perform direct imaging and characterization of Earth-like rocky planets, which requires contrast limits of $10^{-7}$ to $10^{-8}$ at wavelengths from I to J band. One critical aspect affecting the raw on-sky contrast are polarization aberrations arising from the reflection from the telescope's mirror surfaces and instrument optics. We simulate the polarization aberrations and estimate their effect on the achievable contrast for three next-generation ground-based large segmented mirror telescopes. We performed ray-tracing in Zemax and computed the polarization aberrations and Jones pupil maps using the polarization ray-tracing algorithm. The impact of these aberrations on the contrast is estimated by propagating the Jones pupil maps through a set of idealized coronagraphs using hcipy, a physical optics-based simulation framework. The optical modeling of the giant segmented mirror telescopes (GSMTs) shows that polarization aberrations create significant leakage through a coronagraphic system. The dominant aberration is retardance defocus, which originates from the steep angles on the primary and secondary mirrors. The retardance defocus limits the contrast to $10^{-5}$ to $10^{-4}$ at 1 $\lambda/D$ at visible wavelengths, and $10^{-5}$ to $10^{-6}$ at infrared wavelengths. The simulations also show that the coating plays a major role in determining the strength of the aberrations. Polarization aberrations will need to be considered during the design of high-contrast imaging instruments for the next generation of extremely large telescopes. This can be achieved either through compensation optics, robust coronagraphs, specialized coatings, calibration, and data analysis approaches or by incorporating polarimetry with high-contrast imaging to measure these effects.Comment: 18 pages, 12 figures, Accepted in Astronomy & Astrophysics manuscript no. aa45651-2

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

Aims/hypothesis: $FTO$ harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for $FTO$ in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the $FTO$ locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods: All studies published on the association between $FTO$-rs9939609 (or proxy [r$^2$ > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results: The $FTO$-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10$^{−19}$), overweight by 1.13-fold/allele (p = 1.0 × 10$^{−11}$) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10$^{−8}$). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10$^{−5}$). The $FTO$-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10$^{−17}$), WHR by 0.003/allele (p = 1.2 × 10$^{−6}$), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of $FTO$ variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation: $FTO$ is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, $FTO$ is also associated with type 2 diabetes independently of BMI. Electronic supplementary material The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Expression of a malarial Hsp70 improves defects in chaperone-dependent activities in ssa1 mutant yeast

Plasmodium falciparum causes the most virulent form of malaria and encodes a large number of molecular chaperones. Because the parasite encounters radically different environments during its lifecycle, many members of this chaperone ensemble may be essential for P. falciparum survival. Therefore, Plasmodium chaperones represent novel therapeutic targets, but to establish the mechanism of action of any developed therapeutics, it is critical to ascertain the functions of these chaperones. To this end, we report the development of a yeast expression system for PfHsp70-1, a P. falciparum cytoplasmic chaperone. We found that PfHsp70-1 repairs mutant growth phenotypes in yeast strains lacking the two primary cytosolic Hsp70s, SSA1 and SSA2, and in strains harboring a temperature sensitive SSA1 allele. PfHsp70-1 also supported chaperone-dependent processes such as protein translocation and ER associated degradation, and ameliorated the toxic effects of oxidative stress. By introducing engineered forms of PfHsp70-1 into the mutant strains, we discovered that rescue requires PfHsp70-1 ATPase activity. Together, we conclude that yeast can be co-opted to rapidly uncover specific cellular activities mediated by malarial chaperones. © 2011 Bell et al

Approaches to lowering the cost of large space telescopes

New development approaches, including launch vehicles and advances in sensors, computing, and software, have lowered the cost of entry into space, and have enabled a revolution in low-cost, high-risk Small Satellite (SmallSat) missions. To bring about a similar transformation in larger space telescopes, it is necessary to reconsider the full paradigm of space observatories. Here we will review the history of space telescope development and cost drivers, and describe an example conceptual design for a low cost 6.5 m optical telescope to enable new science when operated in space at room temperature. It uses a monolithic primary mirror of borosilicate glass, drawing on lessons and tools from decades of experience with ground-based observatories and instruments, as well as flagship space missions. It takes advantage, as do large launch vehicles, of increased computing power and space-worthy commercial electronics in low-cost active predictive control systems to maintain stability. We will describe an approach that incorporates science and trade study results that address driving requirements such as integration and testing costs, reliability, spacecraft jitter, and wavefront stability in this new risk-tolerant "LargeSat" context.Comment: Presented at SPIE, Optics+Photonics 2023, Astronomical Optics: Design, Manufacture, and Test of Space and Ground Systems IV in San Diego, CA, US