The application of metabolomics to ascertain the significance of prolonged maturation in the production of lager-style beers

NMR-focused metabolomic analysis has been employed to ascertain the extent to which a diversity of non-volatile substances change in level during maturation and storage on a pilot and commercial scale. No substantive changes were observed, leading to the conclusion that, once materials such as vicinal diketones and acetaldehyde have been dealt with, there is no merit in the prolonged storage of beer. © 2019 The Institute of Brewing & Distilling

Incidence, time course and predictors of impairments relating to caring for the profoundly affected arm after stroke: A systematic review

Background and purpose - A significant number of stroke survivors will not recover the use of their affected arm. A proportion will experience pain, stiffness and difficulty with basic care activities. The purpose of the review was to identify predictors of difficulty caring for the profoundly affected arm and establish the incidence and time-course of the related impairments of pain, spasticity and contracture. Method - Data sources: Databases (PubMED, MEDLINE, AMED, EMBASE, CINAHL and the Cochrane Controlled Trials Register) were searched from inception to December 2013. Additional studies were identified from citation tracking. Review methods: Independent reviewers used pre-defined criteria to identify eligible studies. Quality assessment and risk of bias were assessed using the McMasters Assessment Tool. A narrative evidence synthesis was performed. Results - Thirty-nine articles reporting 34 studies were included. No studies formally measured difficulty caring for the arm, but related impairments were common. Incidence of spasticity in those with weakness ranged from 33% to 78%, shoulder pain affected 22% to 90% and contracture was present in at least 50%. Spasticity and pain appear within 1 week of stroke, and contracture within two weeks. Impairments continued to develop over at least 3–6 months. The most frequent predictors of spasticity and contracture were weakness and reduced motor control, and the risk of pain is most commonly predicted by reduced sensation, shoulder subluxation, weakness and stroke severity. Discussion - There is no published evidence on predicting the likelihood of difficulty caring for the arm following stroke. However, the related impairments of spasticity, pain and contracture are common. Given the time-course of development, clinicians may need not only to intervene early but also be prepared to act over a longer time period. Further research is needed to examine difficulty caring for the arm and the relationship with associated impairments to enable researchers and clinicians to develop targeted interventions

Asking the right questions to get the right answers: Using cognitive interviews to review the acceptability, comprehension and clinical meaningfulness of patient self-report adverse event items in oncology patients

Background: Standardized reporting of treatment-related adverse events (AE) is essential in clinical trials, usually achieved by using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) reported by clinicians. Patient-reported adverse events (PRAE) may add value to clinician assessments, providing patient perspective on subjective toxicity. We developed an online patient symptom report and self-management system for real-time reporting and managing AE during cancer treatment integrated with electronic patient records (eRAPID). As part of this program we developed a patient version of the CTCAE (version 4.0), rephrasing terminology into a self-report format. We explored patient understanding of these items via cognitive interviews. Material and method: Sixty patients (33 female, 27 male) undergoing treatment were purposively sampled by age, gender and tumor group (median age 61.5, range 35–84, 12 breast, 12 gynecological, 13 colorectal, 12 lung and 11 renal). Twenty-one PRAE items were completed on a touch-screen computer. Subsequent audio-recorded cognitive interviews and thematic analysis explored patients’ comprehension of items via verbal probing techniques during three interview rounds (n = 20 patients/round). Results: In total 33 item amendments were made; 29% related to question comprehension, 73% response option and 3% order effects. These amendments to phrasing and language improved patient understanding but maintained CTCAE grading and key medical information. Changes were endorsed by members of a patient advisory group (N = 11). Conclusion: Item adaptations resulted in a bank of consistently interpreted self-report AE items for use in future research program. In-depth analysis of items through cognitive interviews is an important step towards developing an internationally valid system for PRAE, thus improving patient safety and experiences during cancer treatment

Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants

Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of Cited2-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate cited2 function during development. Indeed, the microinjection of morpholinos targeting cited2 transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-cited2 morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of Cited2 at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.Agência financiadora: Fundação para a Ciência e a Tecnologia (FCT) Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve) ALG-01-0145-FEDER-28044; DFG 568/17-2 Algarve Biomedical Center (ABC) Municipio de Louléinfo:eu-repo/semantics/publishedVersio

Effect of vessel wettability on the foamability of "ideal" surfactants and "real-world" beer heads

The ability to tailor the foaming properties of a solution by controlling its chemical composition is highly desirable and has been the subject of extensive research driven by a range of applications. However, the control of foams by varying the wettability of the foaming vessel has been less widely reported. This work investigates the effect of the wettability of the side walls of vessels used for the in situ generation of foam by shaking aqueous solutions of three different types of model surfactant systems (non-ionic, anionic and cationic surfactants) along with four different beers (Guinness Original, Banks’s Bitter, Bass No 1 and Harvest Pale). We found that hydrophilic vials increased the foamability only for the three model systems but increased foam stability for all foams except the model cationic system. We then compared stability of beer foams produced by shaking and pouring and demonstrated weak qualitative agreement between both foam methods. We also showed how wettability of the glass controls bubble nucleation for beers and champagne and used this effect to control exactly where bubbles form using simple wettability patterns

Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left–right patterning defects

Deficiency of the transcription factor Cited2 in mice results in cardiac malformation, adrenal agenesis, neural tube, placental defects and partially penetrant cardiopulmonary laterality defects resulting from an abnormal Nodal->Pitx2c pathway. Here we show that a maternal high-fat diet more than doubles the penetrance of laterality defects and, surprisingly, induces palatal clefting in Cited2-deficient embryos. Both maternal diet and Cited2 deletion reduce embryo weight and kidney and thymus volume. Expression profiling identified 40 embryonic transcripts including Pitx2 that were significantly affected by embryonic genotype-maternal diet interaction. We show that a high-fat diet reduces Pitx2c levels >2-fold in Cited2-deficient embryos. Taken together, these results define a novel interaction between maternal high-fat diet and embryonic Cited2 deficiency that affects Pitx2c expression and results in abnormal laterality. They suggest that appropriate modifications of maternal diet may prevent such defects in humans