Occupational balance: What tips the scales for new students?

The open question, ‘What prevents you from reaching occupational balance?’, was posed within a questionnaire aimed at exploring the meanings of occupation, health and wellbeing with a cohort of first-year occupational therapy students during their initial few weeks at university. Their written responses to the question about occupational balance were analysed and are discussed in this paper. Not surprisingly, occupational balance appeared to be achieved by only a few and more by chance than design. People, time and money factors were identified as the main impediments to achieving occupational balance, with psychological and emotional pressures being at the forefront. Interestingly, despite these barriers, the overall educational benefit of considering the occupational balance question in this way raised the students’ awareness of its relationship to health and wellbeing. This increased awareness might have longer-term health benefits, both personally and professionally, which would be worthy of further research

The impact of pre-restoration land-use and disturbance on sediment structure, hydrology and the sediment geochemical environment in restored saltmarshes

Saltmarshes are being lost or degraded as a result of human activity resulting in loss of critical ecosystem services including the provision of wild species diversity, water quality regulation and flood regulation. To compensate, saltmarshes are being restored or re-created, usually driven by legislative requirements for increased habitat diversity, flood regulation and sustainable coastal defense. Yet, there is increasing evidence that restoration may not deliver anticipated ecosystem services; this is frequently attributed to poor drainage and sediment anoxia. However, physical sediment characteristics, hydrology and the sediment geochemical environment are rarely examined in restoration schemes, despite such factors being critical for plant succession. This study presents the novel integration of 3D-computed X-ray microtomography to quantify sediment structure and porosity, with water level and geochemical data to understand the impact of pre-restoration land use and disturbance on the structure and functioning of restored saltmarshes. The study combines a broad-scale investigation of physical sediment characteristics in nine de-embanked saltmarshes across SE England, with an intensive study at one site examining water levels, sediment structure and the sediment geochemical environment. De-embankment does not restore the hydrological regime, or the physical/chemical framework in the saltmarshes and evidence of disturbance includes a reduction in microporosity, pore connectivity and water storage capacity, a lack of connectivity between the sub-surface environment and overlying floodwaters, and impeded sub-surface water flow and drainage. This has significant consequences for the sediment geochemical environment. This disturbance is evident for at least two decades following restoration and is likely to be irreversible. It has important implications for plant establishment in particular, ecosystem services including flood regulation, nutrient cycling and wild species diversity and for future restoration design

Solubility evaluation of murine hybridoma antibodies

The successful development of antibody therapeutics depends on the molecules having properties that are suitable for manufacturing, as well as use by patients. Because high solubility is a desirable property for antibodies, screening for solubility has become an essential step during the early candidate selection process. In considering the screening process, we formed a hypothesis that hybridoma antibodies are filtered by nature to possess high solubility and tested this hypothesis using a large number of murine hybridoma-derived antibodies. Using the cross-interaction chromatography (CIC) method, we screened the solubility of 92 murine hybridoma-derived monoclonal antibodies and found that all of these molecules exhibited CIC profiles that are indicative of high solubility (>100mg/mL). Further investigations revealed that variable region N-linked glycosylation or isoelectric parameters are unlikely to contribute to the high solubility of these antibodies. These results support the general hypothesis that hybridoma monoclonal antibodies are highly soluble

Roles of Coactivators in Hypoxic Induction of the Erythropoietin Gene

Hypoxia-inducible expression of the erythropoietin (EPO) gene is mediated principally by hypoxia-inducible factor 2alpha (HIF-2alpha) in Hep3B cells under physiologic conditions. How/whether p300/CBP and the members of p160 coactivator family potentiate hypoxic induction of endogenous EPO and other HIF-2alpha and hypoxia-inducible factor 1alpha (HIF-1alpha) target genes remains unclear.We demonstrate, using chromatin immunoprecipitation (ChIP) analysis, that the histone acetyl transferase (HAT) coactivators p300, SRC-1 and SRC-3 are recruited to the 3' enhancer of the EPO gene upon hypoxic stimulation, and that each associates with the enhancer in a periodic fashion. Hypoxia induced acetylation of the EPO gene 5' promoter at histone 4 and lysine 23 of histone 3. Knocking down SRC-3, but not SRC-1 or SRC-2, using short interfering RNAs (siRNAs), reduced EPO transcriptional activity. Knocking down p300 resulted in dramatic down-regulation of hypoxic stimulation of EPO gene transcription, negated recruitment of RNA polymerase II to the gene's promoter, and eliminated hypoxia-stimulated acetylation at the promoter and recruitments of SRC-1 and SRC-3 to the enhancer. The inhibitory effects of knocking down p300 and the chromatin remodeling coactivator, Brm/Brg-1, on EPO transcription were additive, suggesting that p300 and Brm/Brg-1 act independently. p300 was also required for hypoxia induced transcription of the HIF-1alpha target gene, VEGF, but was dispensable for induction of two other HIF-1alpha target genes, PGK and LDHA. Knocking down CBP, a homolog of p300, augmented hypoxic induction of VEGF, LDHA and PGK. Different HIF target genes also exhibited different requirements for members of the p160 coactivator family.p300 plays a central coactivator role in hypoxic induction of EPO. The coactivators exhibit different specificities for different HIF target genes and each can behave differently in transcriptional regulation of different target genes mediated by the same transcription factor

Elucidating the aetiology of human Campylobacter coli infections

Peer reviewedPublisher PD

Schwannoma-like pleomorphic adenoma of the parotid

Pleomorphic adenoma is the most common benign salivary gland tumour. It can occur in any salivary gland, but is most frequently found in the parotid gland. Chondroid metaplasia is a frequent finding in pleomorphic adenoma. Other forms of metaplasia have been described, but are encountered less frequently. We report a rare case of unusual pleomorphic adenoma of the parotid gland with schwannoma-like feature

The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease

Author Correction: The future of Blue Carbon science.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants.</p> <p>Studies in adult and newborn animals have shown that a reduction of body temperature of 3–4°C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5°C have been reported. No complications were noted but the group sizes were too small to evaluate benefit.</p> <p>Methods/Design</p> <p>TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling".</p> <p>Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2°C or to whole body cooling, with rectal temperature kept at 33–34°C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods.</p> <p>Sample size</p> <p>At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months.</p> <p>Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited.</p> <p>Primary outcome</p> <p>Combined rate of mortality and severe neurodevelopmental impairment in survivors at 18 months of age. Neurodevelopmental impairment will be defined as any of:</p> <p>• Bayley mental developmental scale score less than 70</p> <p>• Gross Motor Function Classification System Levels III – V</p> <p>• Bilateral cortical visual impairments</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN89547571</p