Role of miRNAs and alternative mRNA 3'-end cleavage and polyadenylation of their mRNA targets in cardiomyocyte hypertrophy.

miRNAs play critical roles in heart disease. In addition to differential miRNA expression, miRNA-mediated control is also affected by variable miRNA processing or alternative 3'-end cleavage and polyadenylation (APA) of their mRNA targets. To what extent these phenomena play a role in the heart remains unclear. We sought to explore miRNA processing and mRNA APA in cardiomyocytes, and whether these change during cardiac hypertrophy. Thoracic aortic constriction (TAC) was performed to induce hypertrophy in C57BL/6J mice. RNA extracted from cardiomyocytes of sham-treated, pre-hypertrophic (2 days post-TAC), and hypertrophic (7 days post-TAC) mice was subjected to small RNA- and poly(A)-test sequencing (PAT-Seq). Differential expression analysis matched expectations; nevertheless we identified ~400 mRNAs and hundreds of noncoding RNA loci as altered with hypertrophy for the first time. Although multiple processing variants were observed for many miRNAs, there was little change in their relative proportions during hypertrophy. PAT-Seq mapped ~48,000 mRNA 3'-ends, identifying novel 3' untranslated regions (3'UTRs) for over 7000 genes. Importantly, hypertrophy was associated with marked changes in APA with a net shift from distal to more proximal mRNA 3'-ends, which is predicted to decrease overall miRNA repression strength. We independently validated several examples of 3'UTR proportion change and showed that alternative 3'UTRs associate with differences in mRNA translation. Our work suggests that APA contributes to altered gene expression with the development of cardiomyocyte hypertrophy and provides a rich resource for a systems-level understanding of miRNA-mediated regulation in physiological and pathological states of the heart.

Accelerated resolution therapy: an innovative mental health intervention to treat post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a disabling trauma and stress-related disorder that may occur after a person experiences a traumatic event, and evokes a combination of intrusion and avoidance symptoms, negative alterations in cognitions and mood, and alterations in arousal and reactivity. Accelerated resolution therapy (ART) is an emerging psychotherapy that provides fast and lasting resolution for mental health problems such as PTSD. ART has been shown to achieve a positive result in one to five sessions, typically over a 2-week period, and requires no homework, skills practice or repeated exposure to targeted events. Initial research, including one randomised control trial, has demonstrated that ART interventions can significantly reduce symptoms of psychological trauma in both civilians and US service members and veterans. These results suggest that ART be considered as either a primary treatment option or for refractory PTSD in those with a suboptimal response to endorsed first-line therapies. Conservative estimates indicate substantial potential cost savings in PTSD treatment. Despite the need for more definitive clinical trials, there is increasing interest in ART in the USA, including in the US Army. The growing positive empirical evidence is compelling, and there appears to be sufficient evidence to warrant UK researchers undertaking ART research. The armed forces offer the potential for comparative international trials. However, equally important are veterans, emergency services personnel and those subjected to violence. ART appears to also have application in other conditions, including depression, anxiety disorders, and alcohol or drug misuse. ART can potentially help personnel traumatised by the unique challenges of war and conflict zones by providing brief psychotherapy in a readily accessible and culturally competent manner. ART facilitates the provision of interventions and resolutions in theatre, thus enhancing forces' fighting capability.

Ultrasound screening of paediatric non-alcoholic fatty liver disease (NAFLD): A critical literature review.

INTRODUCTION: Paediatric NAFLD is an increasing global health concern, which can be effectively managed with early detection. Screening, using accurate, affordable, and accessible tests is recommended, however, there is currently no consensus on the most appropriate tests. Although ultrasound techniques are widely used, their performance against reference tests have not been fully assessed. METHODS: A literature search of related databases for peer-reviewed original articles published from January 2010-March 2024 was conducted. Appropriate tools were used to systematise and document the search results and selected studies were quality assessed and critically appraised. Extracted data was subjected to thematic analysis and narrative synthesis. RESULTS: Eighteen articles met the inclusion criteria. B-mode and Quantitative ultrasound techniques were compared against MR spectroscopy, MRI-PDFF and Liver biopsy. CONCLUSION: Liver echogenicity and Steato-scores were the B-mode methods used. The former was less effective, with a maximum reported sensitivity of 70%. The latter reached up to 100% sensitivity, and >80% specificity. Ultrasound performed better with moderate-severe steatosis. There was not enough evidence to support steatosis grading, possibly due to small sample sizes and lack of established cut-off values. QUS (Quantitative Ultrasound)) methods including Continuous Attenuation Parameter (CAP), Attenuation Coefficient (AC), Ultrasound derived fat fraction (UDFF), Tissue Scatter Imaging (TSI) Hepato-Renal Index (HRI), Heterogeneity Index (HIA), Computer Assisted Ultrasound (CAUS) and Picture Archiving and Communication System (PACS-based Image analysis performed better than B-mode methods. Although QUS demonstrated excellent performance, with sensitivity and specificity of up to 100%, this will require further verification before implementation in practice. PRACTICE IMPLICATIONS: Ultrasound techniques can effectively be used for paediatric NAFLD screening, especially in higher-risk subjects. The steato-scores method is currently recommendable for this, with excellent potential for the use of QUS, after cut-off values and validation requirements have been addressed.

Factors influencing sonographer-led bowel ultrasound services in the UK.

INTRODUCTION: There is a growing understanding of the potency of bowel ultrasound leading to an increasing application of ultrasound in examining different bowel conditions. However, sonographers' involvement in bowel ultrasound is under-researched. This study investigated the factors influencing sonographers' experience in adult bowel ultrasound. METHODS: A convenience sampling method was used to promote the study in April 2021. A mixed methods online questionnaire was utilised to explore the participants' views. Quantitative data were analysed using descriptive analysis on Excel, while qualitative data were analysed using inductive thematic analysis. RESULTS: Almost half of the participants (53%; n = 16) indicated low confidence in using ultrasound to examine the bowel for abnormalities. While 63% of the participants reported having high confidence in examining the bowel for suspected appendicitis, 70% (n = 21) reported low confidence in carrying out ultrasound in examining Inflammatory bowel disease. Furthermore, 23 participants (77%) indicated a high interest in bowel ultrasound training. Qualitative findings revealed mixed opinions on bowel ultrasound practice. Factors influencing sonographers' experience are the need for more training opportunities, preference for other imaging modalities, management challenges, radiologists' influence, sonographers' perspectives, and positive perspectives. CONCLUSION: Several factors influence sonographers' confidence in using ultrasound for bowel abnormalities. However, the findings emphasise the need for more research into the future design and implementation of sonographers' bowel ultrasound training. IMPLICATION FOR PRACTICE: This study brings new insight to an under-researched area on the scope of sonography practice, highlighting some sonographers' experience, opinions, and involvement in bowel ultrasound. It further strengthens the argument for more training to be made available to sonographers on bowel ultrasound.

A seafood risk tool for assessing and mitigating chemical and pathogen hazards in the aquaculture supply chain.

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets.

Baseline survey of marine sediments collected from the Kingdom of Bahrain: PAHs, PCBs, organochlorine pesticides, perfluoroalkyl substances, dioxins, brominated flame retardants and metal contamination.

A baseline survey of sediment contamination was undertaken at 14 locations around the coastline of Bahrain in May 2017, followed by a focused survey of 20 sites, in November 2019. Samples were assessed for industrial pollutants, including metals, PAHs and a suite of organohalogen compounds. The data generated indicated that levels of chemical contaminants were generally low and did not pose a toxicological risk when assessed against commonly applied sediment quality guidelines (SQG). The highest concentrations of PAHs and PCBs were identified in samples collected at coastal sites adjacent to a refinery area known to contain a diverse mix of industry. Tubli Bay, a heavily stressed small bay receiving high loads of sewage effluent, was also identified as an area warranting further investigation with elevated concentrations of BDE209, PFOS and metal contamination. Such data provides a useful baseline assessment of sediment contamination, against which management control measures can be assessed.

Impact of injections during diagnostic coronary arteriography on coronary patency in the setting of acute myocardial infarction from the TIMI trials. Thrombolysis In Myocardial Infarction.

The mechanical force of injection at 90 minutes opens 13.4% of occluded arteries, but overall, only 2.4% of all culprit arteries (already open and occluded combined) are opened. Thus, although some arteries are opened by the force of hand injection, the frequency of mechanical opening among all arteries is low, and hand injections appear to alter current 80% patency rates by approximately 2.5%.

Spatial disorientation blocks reliable goal location on a plus maze but does not prevent goal location in the Morris maze.

Cue control in spatial learning was investigated in a plus maze and a Morris maze. Rats transported in opaque containers with prior rotation to a plus maze, but not a Morris maze, could not find a goal defined by external cues. Rats transported in clear containers without rotation found the goal in both mazes. In the Morris maze, goal location was readily relearned following cue removal by rats in clear containers but not by rats in the opaque/rotation group. B. L. McNaughton et al.'s (1996) theory that during spatial learning sensory information is bound to preconfigured internal maps in the hippocampus, whose metric is self-motion and whose orientation depends on input from an inertial based head direction system, may explain this study's findings.

Multiple points of entry into a circular enclosure prevent place learning despite normal vestibular orientation and cue arrays: evidence for map resetting.

This study identified sources of map orientation critical for successful spatial problem solving by rats of a plus maze embedded in water. Disorientation slowed, but it did not prevent acquisition of goal location. Use of a circular enclosure with multiple points of entry prevented reliable goal location. A single entry point enabled the rats to locate a fixed goal. A cue array within the enclosure was ineffective in providing orientation. These data suggest that stable map orientation can be derived from entry location when enclosure geometry is uniformative, but is not readily taken from cue arrays. They further suggest that map orientation is reset when rats enter an enclosure.

Characterization of proliposomes.

Photographic evidence of the process of proliposome hydration is provided together with comprehensive particle size analysis of both hydrated dimyristoylphosphatidylcholine: dimyristoylphosphatidylglycerol:ergosterol:amphotericin B proliposomes and egg lecithin:ergosterol:amphotericin B proliposomes using photon correlation spectroscopy and Coulter Counter analysis. Proliposome particle size and the temperature during hydration have been shown to have little effect on subsequent liposome size. A short term stability study of proliposomes indicated that only minor changes in the size distribution profile of the hydrated product are apparent after storage at 20 degrees C for 9 months. Furthermore, no drop in amphotericin B potency was noticed over a 6-month period.

Using the patchwork text assessment as a vehicle for evaluating students' perceptions of their clinical leadership development.

A shift in universities world wide in providing theoretical post graduate programmes of study underpinned by traditional assessment strategies to work based learning programmes supported by innovative assessment strategies is required if Higher education institutions are to effectively educate contemporary healthcare leaders. Concurrently generating the evidence to evaluate the effectiveness of educational programmes is required by commissioners of healthcare education (DH, 2010). This paper reports on the perceptions of twelve post graduate students attending a clinical leadership masters programme of their leadership development through analysis of the critical commentary provided by students as part of assessment strategy that utilised the Patchwork Text Assessment. Following a thematic content analysis six themes emerged: programme philosophy and its impact on the success of the Patchwork Text Assessment; leadership development targeted against leadership frameworks; application and applicability of learning to the students own healthcare organisation; integrating theory to practice through theoretical development and work based activities; the value of networking; and the importance of multi-professional reflective groups. This study has clearly demonstrated how the success of the Patchwork Text Assessment in promoting deep learning is determined by its integration into the overall philosophy of the programme. Concurrently systems needed to be in place to ensure that Patchwork text Assessment is operationalised effectively and embedded within the day to day management of the programme.

Chemical mutagenesis of human interferon-beta: construction, expression in E. coli, and biological activity of sodium bisulfite-induced mutations.

A series of modified human interferon-beta (IFN-beta) genes was produced by sodium bisulfite treatment of the IFN-beta gene cloned in M13. A library of mutated sequences was generated from which subgenomic fragments containing one or a small number of coding alterations were isolated and substituted into the IFN-beta gene in an E. coli expression vector. A number of modified genes and their expression products were evaluated. In several instances levels of expression and biological activity profiles are altered compared to the parental gene product. A number of key amino acids can be identified, whose substitutions have marked effects on biological activity of IFN-beta.