A REVIEW ON PHARMACO KINETIC DRUG INTERACTIONS OF STATINS

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT- -P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review aim is to summarize the most important interactions of statins

Investigation of Thermal Conductivity of water with Al2O3 Nanoparticles

In Thermal systems, Heat transfer fluids play a significant role. But conventional temperature transfer fluids have poor temperature transfer features. Many researches are created in order to improve the thermal properties of regular fluids. The improvement of thermal conductivity of regular fluids by micro-sized solid particles will not result in a valuable change. Therefore, Nanoparticles are put into it to create sizeable heat transfer liquids. Metal oxide nanoparticles i.e. Al2O3 is confusing with water and thermal conductivity of the blend is certainly investigated at different temperature ranges. It is discovered that the thermal conductivity boosts by 5%. The evaluation summarizes that the effective thermal conductivity of the Nano fluids boosts beyond 55°C

Self-similar shear-thickening behavior in CTAB/NaSal surfactant solutions

The effect of salt concentration Cs on the critical shear rate required for the onset of shear thickening and apparent relaxation time of the shear-thickened phase, has been investigated systematically for dilute CTAB/NaSal solutions. Experimental data suggest a self-similar behavior of the critical shear rate and relaxation time as functions of Cs. Specifically, the former ~ Cs^(-6) whereas the latter ~ Cs^(6) such that an effective Weissenberg number for the onset of the shear thickened phase is only weakly dependent on Cs. A procedure has been developed to collapse the apparent shear viscosity versus shear rate data obtained for various values of Cs into a single master curve. The effect of Cs on the elastic modulus and mesh size of the shear-induced gel phase for different surfactant concentrations is discussed. Experiments performed using different flow cells (Couette and cone-and-plate) show that the critical shear rate, relaxation time and the maximum viscosity attained are geometry-independent. The elastic modulus of the gel phase inferred indirectly by employing simplified hydrodynamic instability analysis of a sheared gel-fluid interface is in qualitative agreement with that predicted for an entangled phase of living polymers. A qualitative mechanism that combines the effect of Cs on average micelle length and Debye parameter with shear-induced configurational changes of rod-like micelles is proposed to rationalize the self-similarity of SIS formation.Comment: 27 pages, 17 figure

Megaesophagus in a Line of Transgenic Rats: A Model of Achalasia

Megaesophagus is defined as the abnormal enlargement or dilatation of the esophagus, characterized by a lack of normal contraction of the esophageal walls. This is called achalasia when associated with reduced or no relaxation of the lower esophageal sphincter (LES). To date, there are few naturally occurring models for this disease. A colony of transgenic (Pvrl3-Cre) rats presented with megaesophagus at 3 to 4 months of age; further breeding studies revealed a prevalence of 90% of transgene-positive animals having megaesophagus. Affected rats could be maintained on a total liquid diet long term and were shown to display the classic features of dilated esophagus, closed lower esophageal sphincter, and abnormal contractions on contrast radiography and fluoroscopy. Histologically, the findings of muscle degeneration, inflammation, and a reduced number of myenteric ganglia in the esophagus combined with ultrastructural lesions of muscle fiber disarray and mitochondrial changes in the striated muscle of these animals closely mimic that seen in the human condition. Muscle contractile studies looking at the response of the lower esophageal sphincter and fundus to electrical field stimulation, sodium nitroprusside, and L-nitro-L-arginine methyl ester also demonstrate the similarity between megaesophagus in the transgenic rats and patients with achalasia. No primary cause for megaesophagus was found, but the close parallel to the human form of the disease, as well as ease of care and manipulation of these rats, makes this a suitable model to better understand the etiology of achalasia as well as study new management and treatment options for this incurable condition.National Institutes of Health (U.S.) (Grant T32OD011141)National Institutes of Health (U.S.) (Grant P30ES002109

Beneficial health effects of cumin (Cuminum cyminum) seeds upon incorporation as a potential feed additive in livestock and poultry: A mini-review

Cumin (Cuminum cyminum Linn) is an annual plant of the family Umbelliferae, with its use dating back to ancient times when it was cultivated for its medicinal and culinary potential. Cumin seeds could contain a wide variety of phytochemicals, including alkaloids, coumarins, anthraquinones, flavonoids, glycosides, proteins, resins, saponins, tannins, and steroids. In particular, linoleic acid, one of the unsaturated fatty acids found in abundance in cumin oleoresin, is credited with promoting good health. Many of cumin's purported biological actions in livestock and poultry have been attributed to flavonoids such as apigenin, luteolin, and glycosides. Cumin has several healthful qualities, such as antibacterial, insecticidal, anti-inflammatory, analgesic, antioxidant, anticancer, anti-diabetic, anti-platelet aggregation, hypotensive, bronchodilatory, immunological, anti-amyloidogenic, and anti-osteoporotic properties. Cumin supplementation may improve milk production and reproductive function in dairy cows by altering the feeding pattern of bacteria in the rumen, encouraging the growth of beneficial microbes, or stimulating the secretion of certain digestive enzymes. Because of the low price of cumin seed, it could be concluded that its inclusion in the diet might be beneficial to the commercial poultry industry and reduce the overall cost of egg and meat production. In recent years a rise in cumin's popularity has been seen as a result of the herbal movement spearheaded by naturopaths, yoga gurus, advocates of alternative medicine, and manufacturers of feed additives. Animal nutritionists are exploring the use of cumin for its potential to boost growth, improve nutrient usage efficiency, and reduce greenhouse gas emissions. This mini-review discusses how cumin could be used as a feed ingredient to boost productivity and ensure healthy animal reproduction

Quantifying tropical cyclone's effect on the biogeochemical processes using profiling float observations in the Bay of Bengal

Physical and biogeochemical observations from an autonomous profiling Argo float in the Bay of Bengal show significant changes in upper ocean structure during the passage of Tropical Cyclone (TC) Hudhud (7–14 October 2014). TC Hudhud mixed water from a depth of about 50 m into the surface layers through a combination of upwelling and turbulent mixing. Mixing was extended into the depth of nutricline, the oxycline and the subsurface‐chlorophyll‐maximum; thus had a strong impact on the biogeochemistry of the upper ocean. Before the storm, the near‐surface layer was nutrient depleted and was thus oligotrophic with the chlorophyll‐a concentration of less than 0.15 mg m‐3. Storm mixing initially increased the chlorophyll by 1.4 mg m‐3, increased the surface nitrate concentration to about 6.6 μM kg‐1, and decreased the sub‐surface dissolved oxygen (30–35 m) to 31 % of saturation (140 μM). These conditions were favorable for phytoplankton growth resulting in an estimated increase in primary productivity averaging 1.5 g C m‐2 day‐1 over 15 days. During this bloom, chlorophyll‐a increased by 3.6 mg m‐3, and dissolved oxygen increased from 111 % to 123 % of saturation. Similar observations during TC Vardah (6–12 December 2016) showed much less mixing. Our analysis suggests that relatively small (high) translation speed and presence of cold (warm) core eddy leads to strong (weak) oceanic response during TC Hudhud (TC Vardah). Thus, although cyclones can cause strong biogeochemical responses in the Bay of Bengal, the strength of response depends on the properties of the storm and the prevailing upper ocean structure such as presence of mesoscale eddies

Core and edge modeling of JT-60SA H-mode highly radiative scenarios using SOLEDGE3X–EIRENE and METIS codes

In its first phase of exploitation, JT-60SA will be equipped with an inertially cooled divertor, which can sustain heat loads of 10 MW/m2 on the targets for a few seconds, which is much shorter than the intended discharge duration. Therefore, in order to maximize the duration of discharges, it is crucial to develop operational scenarios with a high radiated fraction in the plasma edge region without unacceptably compromising the scenario performance. In this study, the core and edge conditions of unseeded and neon-seeded deuterium H-mode scenarios in JT-60SA were investigated using METIS and SOLEDGE3X–EIRENE codes. The aim was to determine whether, and under which operational conditions, it would be possible to achieve heat loads at the targets significantly lower than 10 MW/m2 and potentially establish a divertor-detached regime while keeping favorable plasma core conditions. In first analysis, an investigation of the edge parameter space of unseeded scenarios was carried out. Simulations at an intermediate edge power of 15 MW indicate that, without seeded impurities, the heat loads at the targets are higher than 10 MW/m2 in attached cases, and achieving detachment is challenging, requiring upstream electron densities at least above 4 × 1019 m−3. This points toward the need for impurity injection during the first period of exploitation of the machine. Therefore, neon seeding simulations were carried out, performing a seeding rate scan and an injected power scan while keeping the upstream electron density at the separatrix at 3 × 1019 m−3. They show that at 15 MW of power injected into the edge plasma, the inner target is easily detached and presents low heat loads when neon is injected. However, at the outer target, the heat fluxes are not lowered below 10 MW/m2, even when the power losses in the edge plasma are equal to 50% of the power crossing the separatrix. Therefore, the tokamak will probably need to be operated in a deep detached regime in its first phase of exploitation for discharges longer than a few seconds. In the framework of core–edge integrated modeling, using METIS, the power radiated in the core was computed for the most interesting cases

Whole Genome Characterization of a Few EMS-Induced Mutants of Upland Rice Variety Nagina 22 Reveals a Staggeringly High Frequency of SNPs Which Show High Phenotypic Plasticity Towards the Wild-Type

The Indian initiative, in creating mutant resources for the functional genomics in rice, has been instrumental in the development of 87,000 ethylmethanesulfonate (EMS)-induced mutants, of which 7,000 are in advanced generations. The mutants have been created in the background of Nagina 22, a popular drought- and heat-tolerant upland cultivar. As it is a pregreen revolution cultivar, as many as 573 dwarf mutants identified from this resource could be useful as an alternate source of dwarfing. A total of 541 mutants, including the macromutants and the trait-specific ones, obtained after appropriate screening, are being maintained in the mutant garden. Here, we report on the detailed characterizations of the 541 mutants based on the distinctness, uniformity, and stability (DUS) descriptors at two different locations. About 90% of the mutants were found to be similar to the wild type (WT) with high similarity index (>0.6) at both the locations. All 541 mutants were characterized for chlorophyll and epicuticular wax contents, while a subset of 84 mutants were characterized for their ionomes, namely, phosphorous, silicon, and chloride contents. Genotyping of these mutants with 54 genomewide simple sequence repeat (SSR) markers revealed 93% of the mutants to be either completely identical to WT or nearly identical with just one polymorphic locus. Whole genome resequencing (WGS) of four mutants, which have minimal differences in the SSR fingerprint pattern and DUS characters from the WT, revealed a staggeringly high number of single nucleotide polymorphisms (SNPs) on an average (16,453 per mutant) in the genic sequences. Of these, nearly 50% of the SNPs led to non-synonymous codons, while 30% resulted in synonymous codons. The number of insertions and deletions (InDels) varied from 898 to 2,595, with more than 80% of them being 1–2 bp long. Such a high number of SNPs could pose a serious challenge in identifying gene(s) governing the mutant phenotype by next generation sequencing-based mapping approaches such as Mutmap. From the WGS data of the WT and the mutants, we developed a genic resource of the WT with a novel analysis pipeline. The entire information about this resource along with the panicle architecture of the 493 mutants is made available in a mutant database EMSgardeN22 (http://14.139.229.201/EMSgardeN22)

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks