Search Results (11)

The key challenges to treating glioblastoma multiforme (GBM) are the heterogeneous and complex nature of the GBM tumour microenvironment (TME) and difficulty of drug delivery across the blood–brain barrier (BBB). The TME is composed of various neuronal and immune cells, as well as non-cellular components, including metabolic products, cellular interactions, and chemical compositions, all of which play a critical role in GBM development and therapeutic resistance. In this review, we aim to unravel the complexity of the GBM TME, evaluate current therapeutics targeting this microenvironment, and lastly identify potential targets and therapeutic delivery vehicles for the treatment of GBM. Specifically, we explore the potential of aptamer-targeted delivery as a successful approach to treating brain cancers. Aptamers have emerged as promising therapeutic drug delivery vehicles with the potential to cross the BBB and deliver payloads to GBM and brain metastases. By targeting specific ligands within the TME, aptamers could potentially improve treatment outcomes and overcome the challenges associated with larger therapies such as antibodies. Full article

Background: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents’ experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. Methods: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child’s sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. Results: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child’s future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent–infant bonding, and reported variable impact on their feelings of guilt. Conclusion: Parents reported that GS during the neonatal period was useful because it provided a “backbone” for their child’s care. Parents did not consistently endorse negative impacts like interference with parent–infant bonding. Full article

The duration of inter-speaker pauses is a pragmatically salient aspect of conversation that is affected by linguistic and non-linguistic context. Theories of conversational turn-taking imply that, due to listener entrainment to the flow of syllables, a higher speech rate will be associated with shorter turn-transition times (TTT). Previous studies have found conflicting evidence, however, some of which may be due to methodological differences. In order to test the relationship between speech rate and TTT, and how this may be modulated by other dialogue factors, we used question-answer sequences from spontaneous conversational corpora in Dutch and English. As utterance-final lengthening is a local cue to turn endings, we also examined the impact of utterance-final syllable rhyme duration on TTT. Using mixed-effect linear regression models, we observed evidence for a positive relationship between speech rate and TTT: thus, a higher speech rate is associated with longer TTT, contrary to most theoretical predictions. Moreover, for answers following a pause (“gaps”) there was a marginal interaction between speech rate and final rhyme duration, such that relatively long final rhymes are associated with shorter TTT when foregoing speech rate is high. We also found evidence that polar (yes/no) questions are responded to with shorter TTT than open questions, and that direct answers have shorter TTT than responses that do not directly answer the questions. Moreover, the effect of speech rate on TTT was modulated by question type. We found no predictors of the (negative) TTT for answers that overlap with the foregoing questions. Overall, these observations suggest that TTT is governed by multiple dialogue factors, potentially including the salience of utterance-final timing cues. Contrary to some theoretical accounts, there is no strong evidence that higher speech rates are consistently associated with shorter TTT. Full article

Viruses are important constituents of ecosystems, with the capacity to alter host phenotype and performance. However, virus discovery cued by disease symptoms overlooks latent or beneficial viruses, which are best detected using targeted virus detection or discovered by non-targeted methods, e.g., high-throughput sequencing (HTS). To date, in 64 publications, 701 viruses have been described associated with indigenous species of Aotearoa New Zealand. Viruses were identified in indigenous birds (189 viruses), bats (13 viruses), starfish (4 viruses), insects (280 viruses), and plants (126 viruses). HTS gave rise to a 21.9-fold increase in virus discovery rate over the targeted methods, and 72.7-fold over symptom-based methods. The average number of viruses reported per publication has also increased proportionally over time. The use of HTS has driven the described national virome recently by 549 new-to-science viruses; all are indigenous. This report represents the first catalogue of viruses associated with indigenous species of a country. We provide evidence that the application of HTS to samples of Aotearoa New Zealand’s unique fauna and flora has driven indigenous virus discovery, a key step in the process to understand the role of viruses in the biological diversity and ecology of the land, sea, and air environments of a country. Full article

The aroma profile is a key component of Pinot noir wine quality, and this is influenced by the diversity, quantity, and typicity of volatile compounds present. Volatile concentrations are largely determined by the grape itself and by microbial communities that produce volatiles during fermentation, either from grape-derived precursors or as byproducts of secondary metabolism. The relative degree of aroma production from grape skins compared to the juice itself, and the impact on different yeasts on this production, has not been investigated for Pinot noir. The influence of fermentation media (Pinot noir juice or synthetic grape must (SGM), with and without inclusion of grape skins) and yeast choice (commercial Saccharomyces cerevisiae EC1118, a single vineyard mixed community (MSPC), or uninoculated) on aroma chemistry was determined by measuring 39 volatiles in finished wines using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC-MS). Fermentation medium clearly differentiated the volatile profile of wines with and without yeast, while differences between EC1118 and MSPC wines were only distinct for Pinot noir juice without skins. SGM with skins produced a similar aroma profile to Pinot noir with skins, suggesting that grape skins, and not the pulp, largely determine the aroma of Pinot noir wines. Full article

Background: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1–5 years) from diagnosis. Objectives were to (a) examine changes over time in health and psychological wellbeing, (b) track ME/CFS symptomatology and fulfillment of paediatric ME/CFS diagnostic criteria over time, and (c) determine baseline predictors of ME/CFS criteria fulfilment at follow-up. Methods: 34 participants aged 13–18 years (25 ME/CFS, 23 controls) completed standardised questionnaires at diagnosis (baseline) and follow-up assessing fatigue, sleep quality and hygiene, pain, anxiety, depression, and health-related quality of life. ME/CFS symptomatology and diagnostic criteria fulfilment was also recorded. Results: ME/CFS patients showed significant improvement in most health and psychological wellbeing domains over time, compared with controls who remained relatively stable. However, fatigue, pain, and health-related quality of life remained significantly poorer amongst ME/CFS patients compared with controls at follow-up. Sixty-five percent of ME/CFS patients at baseline continued to fulfil ME/CFS diagnostic criteria at follow-up, with pain the most frequently experienced symptom. Eighty-two percent of patients at follow-up self-reported that they still had ME/CFS, with 79% of these patients fulfilling criteria. No significant baseline predictors of ME/CFS criteria fulfilment at follow-up were observed, although pain experienced at baseline was significantly associated with criteria fulfilment at follow-up (R = 0.6, p = 0.02). Conclusions: The majority of Australian adolescents with ME/CFS continue to fulfil diagnostic criteria at follow-up, with fatigue, pain, and health-related quality of life representing domains particularly relevant to perpetuation of ME/CFS symptoms in the early years following diagnosis. This has direct clinical impact for treating clinicians in providing a more realistic prognosis and highlighting the need for intervention with young people with ME/CFS at the initial diagnosis and start of treatment. Full article

Wetland managers, citizens and government leaders are observing rapid changes in coastal wetlands and associated habitats around the Great Lakes Basin due to human activity and climate variability. SAR and optical satellite sensors offer cost effective management tools that can be used to monitor wetlands over time, covering large areas like the Great Lakes and providing information to those making management and policy decisions. In this paper we describe ongoing efforts to monitor dynamic changes in wetland vegetation, surface water extent, and water level change. Included are assessments of simulated Radarsat Constellation Mission data to determine feasibility of continued monitoring into the future. Results show that integration of data from multiple sensors is most effective for monitoring coastal wetlands in the Great Lakes region. While products developed using methods described in this article provide valuable management tools, more effort is needed to reach the goal of establishing a dynamic, near-real-time, remote sensing-based monitoring program for the basin. Full article

Ricin, produced from the castor beans of Ricinus communis, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of concern from a public health perspective and no current licensed medical interventions exist to protect from the action of the toxin. Therefore, we examined the oral toxicity of ricin in Balb/C mice and developed a robust food deprivation model of ricin oral intoxication that has enabled the assessment of potential antitoxin treatments. A lethal oral dose was identified and mice were found to succumb to the toxin within 48 h of exposure. We then examined whether a despeciated ovine F(ab′)₂ antibody fragment, that had previously been demonstrated to protect mice from exposure to aerosolised ricin, could also protect against oral intoxication. Mice were challenged orally with an LD₉₉ of ricin, and 89 and 44% of mice exposed to this otherwise lethal exposure survived after receiving either the parent anti-ricin IgG or F(ab′)₂, respectively. Combined with our previous work, these results further highlight the benefit of ovine-derived polyclonal antibody antitoxin in providing post-exposure protection against ricin intoxication. Full article

Spinal cord stimulation may enable recovery of volitional motor control in people with chronic Spinal Cord Injury (SCI). In this study we explored the effects of adding SCS, applied transcutaneously (tSCS) at vertebral levels T10/11, to a sit-to-stand training intervention in people with motor complete and incomplete SCI. Nine people with chronic SCI (six motor complete; three motor incomplete) participated in an 8-week intervention, incorporating three training sessions per week. Participants received either tSCS combined with sit-to-stand training (STIM) or sit-to-stand training alone (NON-STIM). Outcome measures were carried out before and after the intervention. Seven participants completed the intervention (STIM N = 5; NON-STIM N = 2). Post training, improvements in International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor scores were noted in three STIM participants (range 1.0–7.0), with no change in NON-STIM participants. Recovery of volitional lower limb muscle activity and/or movement (with tSCS off) was noted in three STIM participants. Unassisted standing was not achieved in any participant, although standing with minimal assistance was achieved in one STIM participant. This pilot study has shown that the recruitment of participants, intervention and outcome measures were all feasible in this study design. However, some modifications are recommended for a larger trial. Full article

One of the most challenging components of the UK nuclear legacy is Magnox sludge, arising from the corrosion of Mg alloy-clad irradiated metallic U fuel that has been stored in high pH ponds. The sludges mainly comprise Mg hydroxide and carbonate phases, contaminated with fission products and actinides, including Pu. Cementation and deep geological disposal is one option for the long-term management of this material, but there is a need to understand how Pu may be leached from the waste, if it is exposed to groundwater. Here, we show that cemented Mg(OH)₂ powder prepared with Pu(IV)_aq is altered on contact with water to produce a visibly altered ‘leached zone’, which penetrates several hundred microns into the sample. In turn, this zone shows slow leaching of Pu, with long-term leaching rates between 1.8–4.4 × 10⁻⁵% of total Pu per day. Synchrotron micro-focus X-ray fluorescence mapping identified decreased Pu concentration within the ‘leached zone’. A comparison of micro-focus X-ray absorption spectroscopy (µ-XAS) spectra collected across both leached and unleached samples showed little variation, and indicated that Pu was present in a similar oxidation state and coordination environment. Fitting of the XANES spectra between single oxidation state standards and EXAFS modeling showed that Pu was present as a mixture of Pu(IV) and Pu(V). The change in Pu oxidation from the stock solution suggests that partial Pu oxidation occurred during sample ageing. Similarity in the XAS spectra from all samples, with different local chemistries, indicated that the Pu oxidation state was not perturbed by macro-scale variations in cement chemistry, surface oxidation, sample aging, or the leaching treatment. These experiments have demonstrated the potential for leaching of Pu from cementitious waste forms, and its underlying significance requires further investigation. Full article

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05). Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044). Tea consumption had no effect (p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease. Full article