Fostering and evaluating learner engagement with academic literacy support: making the most of Moodle

This paper reports on the evaluation of an ambitious attempt to embed academic literacy support within a core content course for first-year students at the University of the South Pacific. The course is offered in both blended and online modes, catering for on-campus and off-campus students, respectively, using Moodle as the virtual learning environment (VLE). We begin by explaining how we have made the most of Moodle as a learning platform, enabling us to supplement the core content resources with additional components that support students’ academic literacy development, rather than sacrificing content to create this space. Since the additional material is embedded into the main learning design of the course, students acquire academic literacy within the disciplinary context of their academic programme, rather than through standalone ‘study skills’ provision that is devoid of content. We then devote the majority of the paper to discussing the evaluation of this course design, again explaining how we have made the most of Moodle to do so. We have used learning analytics data from Moodle tracking and completion reports to calculate engagement scores for each student, focusing on a composite of their access to resources, their compliance with sequencing and timing, their investment in activities, and their overall achievement. We have then examined the extent to which the different elements of engagement appear to impact achievement in assignments, demonstrating that the students who achieved the highest grades were those who accessed more materials, kept up with the intended schedule, and invested more than they needed to in activities, despite no immediate rewards for doing so

Influence of Impurity on the Properties of Chemically Synthesized Calcium Hydroxide

Here we report synthesis and characterization of chemically synthesized calcium hydroxide (Ca(OH)2) with and without deliberate presence of NaNO3 as an impurity. Calcium nitrate tetrahydrate (Ca(NO3)2.4H2O) is used as precursor and alkaline NaOH solution is used as precipitant to synthesize the Ca(OH)2 samples. The samples were characterized by XRD, FESEM, FTIR spectroscopy, DTA, TGA and UV-Vis spectroscopy techniques. From the UV-Vis spectroscopy results, it is found that the Ca(OH)2 with NaNO3 impurity has higher bandgap than the sample without NaNO3. The weight loss in TGA is also more for the Ca(OH)2 with impurity than the one for without impurity. The results are discussed in terms of composition formed during synthesis process

3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR

An HLA-G/SPAG9/STAT3 axis promotes brain metastases

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade-the "premetastatic" or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used to obtain the transcriptional profiles of premetastatic and macrometastatic (non-premetastatic) lung, breast, and melanoma BMICs. We identified that lung, breast, and melanoma premetastatic BMICs share a common transcriptomic signature that is distinct from their non-premetastatic counterparts. Importantly, we show that premetastatic BMICs exhibit increased expression of HLA-G, which we further demonstrate functions in an HLA-G/SPAG9/STAT3 axis to promote the establishment of brain metastatic lesions. Our findings suggest that unraveling the molecular landscape of premetastatic BMICs allows for the identification of clinically relevant targets that can possibly inform the development of preventive and/or more efficacious BM therapies

Epigenetic reprogramming of breast cancer cells with oocyte extracts

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.</p> <p>Results</p> <p>We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts.</p> <p>Conclusions</p> <p>This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.</p

Mechanism and disease-association of E2 conjugating enzymes:lessons from UBE2T and UBE2L3

Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus. However, recent evidence demonstrates that mutations or impairment of the E2s can lead to severe disease states, including chromosome instability syndromes, cancer predisposition, and immunological disorders. Given their relevance to diseases, E2s may represent an important class of therapeutic targets. In the present study, we review the current understanding of the mechanism of this important family of enzymes, and the role of selected E2s in disease

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

P2Y receptor regulation of mitogenesis in vascular smooth muscle cells

This study investigates the effects of nucleotides on the regulation of mitogenesis in explant cultures of human saphenous vein (SV) VSM both in the presence and absence of PDGF at several levels in the mitogenic pathway.;[3H]-thymidine incorporation was used as an index of DNA synthesis and proliferation. PDGF induced increases in proliferation of SV VSMCs. Increases in ERK and JNK activation, but not p38 MAPK, were also observed using phospho-specific antibodies in Western blotting. MEK inhibitors, PD98059 and U0126, attenuated both PDGF-induced ERK activation and DNA synthesis. The activation of JNK was also found to be dependent upon ERK activation when these inhibitors were used. SB203580, LY294002 and Y27632, which were inhibitors of p38 MAPK, P13K and ROCK respectively, attenuated the PDGF-induced increase in DNA synthesis but did not block ERK or JNK activation.;Nucleotides such as ATP, ADP, UTP, UDP, 2MeSATP and ATPgS per se did not induce increases in [3H]-thymidine incorporation in SV cells. However, ATP in the presence of PDGF synergistically enhanced DNA synthesis in SV VSMCs, whereas UTP and UDP inhibited the PDGF-mediated DNA synthesis response. Other nucleotides had no effect. This suggested an antipropliferative role for UTP and UDP and a proliferative role for ATP. Neither ATP or UTP alone or with PDGF stimulated a detectable accumulation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) although ATP, UTP and PDGF elevated intracellular calcium levels.;ATP was found to increase the activation of ERK to the same extent as PDGF when incubated on cells for longer than 10 minutes. In the presence of PDGF, ATP synergistically enhanced the PDGF-induced ERK response. UTP and UDP alone did not increase the activation of ERK. Nucleotides did not increase the activation of JNK or p38 MAPK. However, in the presence of PDGF, UTP attenuated the PDGF-induced activation of JNK

Role of Karanjadi Ghrita for the Management of Bhagandara (Fistula-in-Ano)

In Ayurveda, fistula-in-ano is known as Bhagandara which considered in Asta Mahagada. This disease has been considered in Asta Mahagada in Ayurvedic classics due to its complications and more recurrence rate. Nowadays this disease is increasing due to more prone to sedentary life style. Using of Kshara Sutra therapy in case of Bhagandara is for a long time. Kshar Sutra therapy is big revolution in the case of this disease, but it has still challenges for finding satisfactory cure. It has some complications like severe post-procedural pain, burning sensation, inflammation, discharge, itching and enhances the Pitta Dosha. To overcome these complications of Kshara Sutra, a clinical study was conducted that using of Karanjadi Ghrita by their local application after the therapy of Kshara Sutra. Mainly, the contents of Karanjadi Ghrita have cleaning and healing properties. Maximum ingredients of this medicine were having Tikta and Kashaya in Rasa. Tikta and Kashaya rasa promote the ulcer healing by his Shodhana and Ropana properties. Some of the drugs of Karanjadi Ghrita have analgesic properties, reduce inflammation qualities and reduces burning sensation properties. Karanjadi Ghrita has stopped bacterial growth and their toxicity by the reduce infection and reduce toxicity properties of ingredients. It proves that Karanjadi Ghrita reduces the Pitta Dosha and overcome the complications. It was found that Karanjadi Ghrita with Kshara Sutra was more efficient and can be considered a better method