The transformative effect of a foundation year: ‘I’m a totally changed person’

Developing academic skills and preparing students for university-level study areonly two important outcomes of a foundation year programme. Drawing on thework of Mezirow, this paper will, with a focus on five students, consider thetransformative element of adult learning through transforming previousassumptions and beliefs. The qualitative research was based on a university insouth west England and consisted of several interviews over a four-yearlongitudinal research project, tracking the experiences of five foundation yearstudents, assessing how well it prepared them for university-level study. Thisarticle will consider the transformative nature of the foundation year, highlightingspecific changes in students’ self-belief, agency, power and confidence. Drawing onthe voices of the participants, the findings revealed that there are two mainconditions which support transformation: firstly, having a sense of belongingthrough finding supportive social networks, and secondly, developing confidence intheir educational ability. Additionally, the ways in which universities can getinvolved are explored, including ways in which lecturing teams can support theseconditions for transformation and assist with any obstacles students may faceduring their foundation year. These insights may be useful in the design ordevelopment of other Foundation Year programmes, or in the wider context ofsupporting widening participation students with transformation

Choice of Bacterial Growth Medium Alters the Transcriptome and Phenotype of Salmonella enterica Serovar Typhimurium

The type of bacterial culture medium is an important consideration during design of any experimental protocol. The aim of this study was to understand the impact of medium choice on bacterial gene expression and physiology by comparing the transcriptome of Salmonella enterica SL1344 after growth in the widely used LB broth or the rationally designed MOPS minimal medium. Transcriptomics showed that after growth in MOPS minimal media, compared to LB, there was increased expression of 42 genes involved in amino acid synthesis and 23 genes coding for ABC transporters. Seven flagellar genes had decreased expression after growth in MOPS minimal medium and this correlated with a decreased motility. In both MOPS minimal medium and MEM expression of genes from SPI-2 was increased and the adhesion of S. Typhimurium to intestinal epithelial cells was higher compared to the levels after growth in LB. However, SL1344 invasion was not significantly altered by growth in either MOPs minimal media or MEM. Expression of SPI-2 was also measured using chromosomal GFP reporter fusions followed by flow cytometry which showed, for the first time, that the reduction in SPI-2 transcript after growth in different media related to a reduction in the proportion of the bacterial population expressing SPI-2. These data highlight the profound differences in the global transcriptome after in vitro growth in different media and show that choice of medium should be considered carefully during experimental design, particularly when virulence related phenotypes are being measured

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Maine’s Potential to Be a Global Leader in Sustainable Seaweed Harvesting and Management

A multitude of macroalgae (i.e., seaweed) species that are harvested in Maine are economically and ecologically important. Currently, management of these resources in Maine is focused on rockweed (Ascophyllum nodosum). This seaweed grows in abundance along intertidal rocky shores and provides a number of benefits including serving as habitat and nursery for many species including fin-fish, coastal protection from storms and sea level rise, carbon sequestration, and is a harvestable natural resource used primarily in fertilizer and animal feed production. It is critical that these functions and benefits are maintained and harvesting activities managed to ensure a sustainable fishery and healthy ecosystem. In 2014, Maine drafted a rockweed fisheries management plan; however, this plan has yet to be adopted. The delay in adoption is now an opportunity to re-examine the plan from an ecosystem-based management (EBM) perspective. We compare EBM strategies to the existing rockweed fisheries management plan, and identify areas of synergy as well as gaps in the management of Maine’s seaweeds and harvesting activities. Based on this analysis we propose Maine adopt an EBM approach and strategies for wild as well as farmed seaweeds

Nitrite-derived nitric oxide reduces hypoxia-inducible factor 1α-mediated extracellular vesicle production by endothelial cells

Introduction Extracellular vesicles (EVs) are small, spherical particles enclosed by a phospholipid bilayer (∼30–1000 nm) released from multiple cell types, and have been shown to have pathophysiological roles in a plethora of disease states. The transcription factor hypoxia-inducible factor-1 (HIF-1) allows for adaptation of cellular physiology in hypoxia and may permit the enhanced release of EVs under such conditions. Nitric oxide (NO) plays a pivotal role in vascular homeostasis, and can modulate the cellular response to hypoxia by preventing HIF-1 accumulation. We aimed to selectively target HIF-1 via sodium nitrite (NaNO2) addition, and examine the effect on endothelial EV, size, concentration and function, and delineate the role of HIF-1 in EV biogenesis. Methods Endothelial (HECV) cells were exposed to hypoxic conditions (1% O2, 24 h) and compared to endothelial cells exposed to normoxia (21% O2) with and without the presence of sodium nitrite (NaNO2) (30 μM). Allopurinol (100 μM), an inhibitor of xanthine oxidoreductase, was added both alone and in combination with NaNO2 to cells exposed to hypoxia. EV and cell preparations were quantified by nanoparticle tracking analysis and confirmed by electron microscopy. Western blotting and siRNA were used to confirm the role of HIF-1α and HIF-2α in EV biogenesis. Flow cytometry and time-resolved fluorescence were used to assess the surface and intravesicular protein content. Results Endothelial (HECV) cells exposed to hypoxia (1% O2) produced higher levels of EVs compared to cells exposed to normoxia. This increase was confirmed using the hypoxia-mimetic agent desferrioxamine. Treatment of cells with sodium nitrite (NaNO2) reduced the hypoxic enhancement of EV production. Treatment of cells with the xanthine oxidoreductase inhibitor allopurinol, in addition to NaNO2 attenuated the NaNO2-attributed suppression of hypoxia-mediated EV release. Transfection of cells with HIF-1α siRNA, but not HIF-2α siRNA, prior to hypoxic exposure prevented the enhancement of EV release. Conclusion These data provide evidence that hypoxia enhances the release of EVs in endothelial cells, and that this is mediated by HIF-1α, but not HIF-2α. Furthermore, the reduction of NO2− to NO via xanthine oxidoreductase during hypoxia appears to inhibit HIF-1α-mediated EV production

Does Delay in the Diagnosis of Rudimentary Horn Pregnancy in Patients with Unicornuate Uteri Impact Treatment Outcomes?

OBJECTIVE: Rudimentary horn pregnancy (RHP) is a very rare form of ectopic pregnancy (EP) that tends to rupture in the second trimester. Similar to other EPs, the treatment of RHPs is excision, hence delay in diagnosis (DID) can be detrimental. Our objective is to determine whether DID of RHP in patients with unicornuate uteri (UCU) impacts the treatment outcome. DESIGN: Retrospective cohort study of published case reports in PubMed database. MATERIALS AND METHODS: A computerized PubMed search of case reports of RHP from 2007 to 2020 was performed using the key words; unicornuate uterus, rudimentary horn, pregnancy, case. Data was analyzed with SPSS version 26. RESULTS: Of the 97 published cases, due to limited information available, 95 cases were included, 40 (42.1%) in which the diagnosis of RHP was made at first encounter and 55 (57.9%) in which the diagnosis was delayed. Out of these cases, it was possible to calculate the median [range] length of delay (35 [1-1825] days) in only 32 cases. Of 95 cases, 27 (28.4%), 5 (5.3%), 61 (64.2%), 1 (1.1%), underwent laparoscopy, laparoscopy converted to laparotomy, laparotomy, and methotrexate injection respectively. Diagnosis was made at autopsy in one case. CONCLUSIONS: Diagnosis of RHP was significantly more likely to be made at first encounter when patients were known to have a uterine anomaly. DID was associated with a significantly higher GA at the time of treatment but there was no significant difference in the proportion of fetuses that were alive upon entrance to the abdomen, rate of ruptured RH and hemoperitoneum. Out of all of the cases, only one maternal death was reported. Therefore, delaying surgery to confirm a diagnosis of RHP does not adversely impact the maternal fetal outcome

Elucidating cannabinoids’ effects on Ewing’s sarcoma tumor vasculature

To elucidate the mechanism by which AJA affects Ewing’s Sarcoma cellular pathways, we conducted an angiogenic array to observe AJA’s effects on fifty-five different angiogenic proteins. The angiogenic array showed potential upregulation of TIMP-1, an angiogenic inhibitor, but similar results have yet to be replicated in subsequent ELISA’s. Solid tumors commonly have high vascular densities and increased interstitial fluid pressures (IFP), which reduce the efficacy of treatments by inhibiting the absorption of therapeutic drugs. To determine the effects of AJA and CBD on IFP, and thus on vasculature in vivo, we measured IFP levels in mouse xenograft ES tumors. AJA and CBD both produced significant decreases in IFP within thirty minutes of injection, affirming their potential as legitimate cancer treatments

Interpreting Cancer Genomes Using Systematic Host Perturbations by Tumour Virus Proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations. However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer

“Nobody knows, or seems to know how rheumatology and breastfeeding works”: Women's experiences of breastfeeding whilst managing a long-term limiting condition – A qualitative visual methods study

Background Only around 1% of babies in the UK are breastfed exclusively until six months of age as recommended by the World Health Organisation. One in ten women who have recently given birth in the UK have a long-term illness and they are at increased risk of stopping breastfeeding early. We considered women with autoimmune rheumatic diseases as an exemplar group of long term illnesses, to explore the barriers and enablers to breastfeeding Aim To understand the experiences of infant feeding among women with autoimmune rheumatic diseases and to identify potential barriers and enablers. Design Qualitative visual timeline-facilitated interviews. Participants and setting 128 women with autoimmune rheumatic diseases who were considering pregnancy, pregnant, or had young children took part in an online survey as part of the STAR Family Study. Of these, 13 women who had children were purposefully sampled to be interviewed. Interviews took place in person or on the telephone. Timeline-facilitated interviews were used to focus on lived experiences and topics important to the women, including early parenting. We conducted a focused thematic analysis of women's lived experiences of infant feeding. Results Three main themes were identified in relation to breastfeeding: lack of information about medication safety, lack of support in decision-making and maintaining breastfeeding, and maternal guilt. Conclusions Women with autoimmune rheumatic diseases found it difficult to access the information they needed about medications to make informed decisions about breastfeeding. They often also felt pressurised into breastfeeding and experienced feelings of guilt if they were unable, or did not wish to breastfeed. Tailored interventions are required that adopt a non-judgmental and person-centred approach to support decision-making in regard to infant feeding, providing women with information that can best enable them to make infant feeding choices