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Lung cancer maintains a relatively small survival rate (~19%) over a 5-year period and up to 80–85% of all lung cancer diagnoses are Non-Small Cell Lung Cancer (NSCLC). To determine whether metformin reduces non-small cell lung cancer (NSCLC) LL/2 cell growth, cells were grown in vitro and treated with metformin for 48 h. qPCR was used to assess genes related to cell cycle regulation and pro-apoptotic markers, namely Cyclin D, CDK4, p27, p21, and HES1. Treatment with 10 mM metformin significantly reduced HES1 expression (p = 0.011). Furthermore, 10 mM metformin treatment significantly decreased REDD1 (p = 0.0082) and increased p-mTOR Ser2448 (p = 0.003) protein expression. Control cells showed significant reductions in phosphorylated p53 protein expression (p = 0.0367), whereas metformin treated cells exhibited reduced total p53 protein expression (p = 0.0078). There were no significant reductions in AMPK, PKB/AKT, or STAT3. In addition, NSCLC cells were treated for 48 h. with 10 mM metformin, 4 µM gamma-secretase inhibitor (GSI), or the combination of metformin (10 mM) and GSI (4 µM) to determine the contribution of respective signaling pathways. Metformin treatment significantly reduced total nucleus expression of the proliferation maker Ki-67 with an above 65% reduction in Ki-67 expression between control and metformin-treated cells (p = 0.0021). GSI (4 µM) treatment significantly reduced Ki-67 expression by ~20% over 48 h (p = 0.0028). Combination treatment (10 mM metformin and 4 µM GSI) significantly reduced Ki-67 expression by more than 50% over 48 h (p = 0.0245). As such, direct administration of metformin (10 mM for 48 h) proved to be an effective pharmaceutical agent in reducing the proliferation of cultured non-small cell cancer cells. These intriguing in vitro results, therefore, support the further study of metformin in appropriate in vivo models as an anti-oncogenic agent and/or an adjunctive therapy. [ABSTRACT FROM AUTHOR]

Objective Large-for-gestational-age (LGA) is associated with both fetal and maternal complications. One of the few modifiable risk factors for LGA is Gestational Diabetes Mellitus (GDM); for this reason, fetal growth is usually monitored by ultrasound in the third trimester. This prospective study compared a panel of ten established biomarkers measured at the time of selective screening for GDM at 26–28 weeks gestation with the ultrasound prediction of LGA. Method Women were recruited using convenience sampling and consented at the first antenatal visit. Women with maternal risk factors for GDM attended for the one-step 75 g oral glucose tolerance test. An additional blood sample was taken for biomarker measurement. GDM was diagnosed according to the 2013 World Health Organization (WHO) criteria. Fetal biometry, including the abdominal circumference (AC) and the fetal abdominal subcutaneous tissue (FAST) thickness, were measured at 37 weeks gestation. Results Of the 195 women included, 105 (53.8%) had GDM. Of the 195 babies, 36 (18.5%) were LGA. Whether the woman had GDM or not, fetal biometry was strongly predictive of LGA but none of the following biomarkers measured at 26–28 weeks gestation alone or in combination were predictive: c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin. Conclusions In women diagnosed with GDM, surveillance of fetal growth to identify LGA by ultrasound should continue in the third trimester. None of the ten established maternal biomarkers measured at the time of the OGTT was as strongly predictive of LGA as ultrasound. [ABSTRACT FROM AUTHOR]

To determine differences in physiologic responses and perceived discomfort during maximal and submaximal exercise with 2 common exercise modalities, the elliptical cross-trainer (ECT) and the arc trainer (ARC) were used, which undergoes an excursion of motion using an arc pathway. Eighteen subjects (10 male and 8 female; age = 24.7 [+ or -] 2.6 yr, height = 172.2 [+ or -] 10.3 cm, mass = 69.8 [+ or -] 14.9 kg, %fat = 22.5 [+ or -] 8.1%; mean [+ or -] SD) performed maximal exercise protocols on a treadmill (TML), the ECT, and ARC. Subjects also performed 3 10-minute submaximal exercise bouts on the ECT and ARC at 55%, 65%, and 75% of TML maximal oxygen uptake ([??}[o.sub.2]max) in which heart rate (HR), [??|[o.sub.2], ventilation, respiratory exchange ratio, and hip, knee, and low-back discomfort were monitored. All testing on the ECT and ARC were performed in a counterbalanced order. The [??][o.sub.2]max was greater during TML exercise compared with ECT (p = 0.007) but similar to the ARC. Both ECT and ARC elicited lower maximal HR values compared with maximal TML exercise (p = 0.0001). No difference was observed between ECT and ARC for [??][o.sub.2] during the submaximal exercise bouts (p > 0.05). However, HR was greater during submaximal ECT exercise (p < 0.0001). Perception of discomfort was not different between ECT and ARC for knees (p > 0.05) and lower back (p > 0.05) but different for the hips (p = 0.02). Similar [??}[o.sub.2]max values were observed with ARC and TML modalities. Greater perceptions of discomfort were observed with ECT compared with ARC at similar submaximal exercise intensities, suggesting individuals with, or at risk for, lower-extremity joint pathology may benefit from exercise with modalities other than the ECT. KEY WORDS maximal exercise, submaximal exercise, [??][o.sub.2]; heart rate, joint discomfort

This case illustrates capital budgeting in a service industry context. Three features should make this case attractive to instructors. First, the firm's rationing of capital means that students must select one investment among competing investment alternatives. Second, the project involves renovation of an existing hotel. Most cases analyze a business expansion by estimating the net present value of a single series of cash flows (i.e., either future cash flows occur or do not occur). In this case, students model cash flows if the project is accepted, comparing those cash flows to a model of cash flows if the hotel continues without renovation. Third, we introduce Monte Carlo analysis, which is an advanced technique for assessing uncertainty. The extensive data students use in this case are from an actual hotel chain's project database. The case has been used in undergraduate and graduate managerial accounting classes. Data Availability: Available as downloadable supplemental material files. [ABSTRACT FROM AUTHOR]