Class Attendance and Students’ Evaluations of Teaching: Do No-Shows Bias Course Ratings and Rankings?

Background: Many university departments use students’ evaluations of teaching (SET) to compare and rank courses. However, absenteeism from class is often nonrandom and, therefore, SET for different courses might not be comparable. Objective: The present study aims to answer two questions. Are SET positively biased due to absenteeism? Do procedures, which adjust for absenteeism, change course rankings? Research Design: The author discusses the problem from a missing data perspective and present empirical results from regression models to determine which factors are simultaneously associated with students’ class attendance and course ratings. In order to determine the extent of these biases, the author then corrects average ratings for students’ absenteeism and inspect changes in course rankings resulting from this adjustment. Subjects: The author analyzes SET data on the individual level. One or more course ratings are available for each student. Measures: Individual course ratings and absenteeism served as the key outcomes. Results: Absenteeism decreases with rising teaching quality. Furthermore, both factors are systematically related to student and course attributes. Weighting students’ ratings by actual absenteeism leads to mostly small changes in ranks, which follow a power law. Only a few, average courses are disproportionally influenced by the adjustment. Weighting by predicted absenteeism leads to very small changes in ranks. Again, average courses are more strongly affected than courses of very high or low in quality. Conclusions: No-shows bias course ratings and rankings. SET are more appropriate to identify high- and low-quality courses than to determine the exact ranks of average courses

Transvaginal Repair of a Large Chronic Porcine Ventral Hernia with Synthetic Mesh Using NOTES

Transvaginal placement of synthetic mesh to repair large porcine hernia using NOTES technology appears to be a feasible alternative to traditional techniques

Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol

Patients with chronic lung disease, obesity, and other co-morbid conditions are at increased risk of severe illness and death when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hypercapnia, the elevation of CO2 in blood and tissue, commonly occurs in patients with severe acute and chronic lung disease, including those with pulmonary infections, and is also associated with high mortality risk. We previously reported that hypercapnia increases viral replication and mortality of influenza A virus infection in mice. We have also shown that culture in elevated CO2 upregulates expression of cholesterol synthesis genes in primary human bronchial epithelial cells. Interestingly, factors that increase the cholesterol content of lipid rafts and lipid droplets, platforms for viral entry and assembly, enhance SARS-CoV-2 infection. In the current study, we investigated the effects of hypercapnia on ACE2 expression and entry of SARS-CoV-2 pseudovirus (p-SARS-CoV-2) into airway epithelial cells. We found that hypercapnia increased ACE2 expression and p-SARS-CoV-2 uptake by airway epithelium in mice, and in cultured VERO and human bronchial epithelial cells. Hypercapnia also increased total cellular and lipid raft-associated cholesterol in epithelial cells. Moreover, reducing cholesterol synthesis with inhibitors of sterol regulatory element binding protein 2 (SREBP2) or statins, and depletion of cellular cholesterol, each blocked the hypercapnia-induced increases in ACE2 expression and p-SARS-CoV-2 entry into epithelial cells. Cigarette smoke extract (CSE) also increased ACE2 expression, p-SARS-CoV-2 entry and cholesterol accumulation in epithelial cells, an effect not additive to that of hypercapnia, but also inhibited by statins. These findings reveal a mechanism that may account, in part, for poor clinical outcomes of SARS-CoV-2 infection in patients with advanced lung disease and hypercapnia, and in those who smoke cigarettes. Further, our results suggest the possibility that cholesterol-lowering therapies may be of particular benefit in patients with hypercapnia when exposed to or infected with SARS-CoV-2

PPAR-γ: a thrifty transcription factor

The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a prototypical metabolic nuclear receptor that acts as a lipid sensor, integrating the homeostatic control of energy, lipid, and glucose metabolism. This perspective will highlight three lines of evidence which place PPAR-γ as a key player in a feed-forward pathway favoring differentiation and energy storage by adipocytes

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study

Cancer of unknown primary site (CUP) represents up to 5% of all cancer diagnoses and is associated with poor survival. We have performed a prospective multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) for patients with CUP. Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigation and who had ECOG performance status 0–2 were treated with G 1000 mg m−2 intravenously (i.v.) days 1 and 8, and C AUC 5 i.v. on day 8 every 3 weeks to a maximum of nine cycles. The primary end points were response rate, and toxicity, with secondary end points of progression-free survival and overall survival. Fifty-one (23 male, 27 female) patients were enrolled (one patient ineligible), with a median age of 69 years (range 41–83 years). Fifty patients were evaluable for toxicity and 46 patients were evaluable for efficacy. The overall response rate to the GC regimen was 30.5%. With a median follow-up of 24 months, the median progression-free survival was 18 weeks (4.2 months) and the median overall survival was 34 weeks (7.8 months). The frequency of grade 3 or 4 toxicity was low. Nausea/vomiting was the most common side effect, but was usually only mild in severity. Uncomplicated neutropenia (14%), thrombocytopenia (10%) and anaemia (8%) were the most common causes of grade 3–4 toxicity. The regimen was very well tolerated, particularly in the elderly. The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP

Retroviral Expression of Transforming Growth Factor-Alpha Does Not Transform Fibroblasts or Keratinocytes

Transforming growth factor α (TGFα) is a peptide so named because it helps to impart anchorage-independent growth to normal rat kidney (NRK) cells in vitro and is secreted by many rodent and human tumor cells. To directly investigate the transforming properties of this factor, we constructed a replication-defective murine retrovirus that expresses the human sequence coding for TGFα. infection of NIH/3T3 cells with the TGFα retrovirus led to the integration of a transcriptionally active provirus and overexpression of biologically active TGFα, but failed to induce morphologic transformation. Similarly, the TGFα retrovirus failed to induce morphologic transformation of five other types of rodent fibroblasts.We also investigated the effect of TGFα expression on the growth of BALB/MK mouse keratinocytes, which require epidermal growth factor (EGF) for proliferation. We show that exogenously added TGFα is an extremely potent mitogen for BALB/MK cells. However, retroviral expression of TGFa in BALB/MK cells failed to relieve dependence on exogenously added EGF (or TGFα) for cell growth. These results suggest that overexpression of TGFα does not, by itself, transform rodent fibroblasts or keratinocytes