Rapamycin induces transactivation of the EGFR and increases cell survival.

The mammalian target of rapamycin (mTOR) signaling network regulates cell growth, proliferation and cell survival. Deregulated activation of this pathway is a common event in diverse human diseases such as cancers, cardiac hypertrophy, vascular restenosis and nephrotic hypertrophy. Although mTOR inhibitor, rapamycin, has been widely used to inhibit the aberrant signaling due to mTOR activation that plays a major role in hyperproliferative diseases, in some cases rapamycin does not attenuate the cell proliferation and survival. Thus, we studied the mechanism(s) by which cells may confer resistance to rapamycin. Our data show that in a variety of cell types the mTOR inhibitor rapamycin activates extracellularly regulated kinases (Erk1/2) signaling. Rapamycin-mediated activation of the Erk1/2 signaling requires (a) the epidermal growth factor receptor (EGFR), (b) its tyrosine kinase activity and (c) intact autophosphorylation sites on the receptor. Rapamycin treatment increases tyrosine phosphorylation of EGFR without the addition of growth factor and this transactivation of receptor involves activation of c-Src. We also show that rapamycin treatment triggers activation of cell survival signaling pathway by activating the prosurvival kinases Erk1/2 and p90RSK. These studies provide a novel paradigm by which cells escape the apoptotic actions of rapamycin and its derivatives that inhibit the mTOR pathway

Understanding Differences in Medical Versus Surgical Patients Alerted by the Modified Early Warning Score (MEWS) at Jefferson Hospital

An Early Warning Score (EWS) is a risk-management tool to identify patients experiencing clinical deterioration early, therefore allowing timely treatment to occur. Although EWS scores are recommended for all in-patients, more data is available for patients under general medical services compared to surgical services. This study aims to understand differences between medical versus surgical in-patients who receive a red alert from the Modified Early Warning Score (MEWS) at Jefferson hospital. Patients who received a red MEWS alert during admission and discharged between June 2017 to March 2018 (N=812) were categorized as medical or surgical patients. Patient characteristics were compared using an independent samples t-test (age, alert count) or chi-square test (sex, race, admission source, insurance). Patient outcomes were compared using a binary logistic regression (in-hospital mortality, RRT, sepsis diagnosis, ICU transfer, intubation, discharge to hospice) or a Cox regression model (length of stay), controlling for age, sex, and race. Compared to medical patients, surgical patients were younger by 2.7 years (p=0.026) and more likely to have a Commercial and/or Medicare category of insurance (OR=1.568, p=0.005). Surgical patients were more likely to have ICU transfer (OR=1.487, p=0.013) and intubation post-alert (OR=2.470, p=0.006), while less likely to be discharged early (HR=0.675,

Accounting B

Exam paper for second semeste

Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration

BACKGROUND: The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). METHODS: A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. RESULTS: 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). CONCLUSIONS: This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD

“A descriptive study to assess level of academic stress and anxiety of science stream students among selected higher secondary school at Kheda District.”

The words "Stress" and " anxiety" have permeated every aspect of our generation today.In order to function properly, every student has to experience pleasant academic stress and anxiety,also known as eustress.When a student is unable to study or cope with a circumstance, they experience negative stress,also known as distress.Stress is a condition where a student's usal state of equilibrium is altered.By the year 2020, according to the WHO ,that will be one of the main causes of disability.The concern over academic stress and anxiety among science students has grown in recent years.According to estimates, academic stress and anxiety connect to annual performance and result impair the overall performance of 10% to 30% of School students of science stream. AIM:The study aims are to assess academic stress and anxiety regarding school, education system and examination to improve level of knowledge and to reduce stressors, in higher secondary school students of science stream. METHODOLOGY: Non- experimental research design with quantitative research approach was used for research study. The researcher used purposive sampling technique for selecting 300 samples. The tools used, Section 1: socio-demographic data Section 2: structured perceived academic stress scale questionnaires regarding stress. Section 3: Anxiety scale to assess the attitude by anxiety scale. Validity of tool was assessed by 11 experts.Assessment was ascertained by the chi-square formula

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung