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Biomedical subjects

Andrew Day

Publications and source records attributed to Andrew Day.

At least 19 recordsLinked to original sources
PubMed2026

Regulation and function of the HPV16 CircE7 RNA.

High-risk human papillomaviruses (HPV), including HPV16, produce circular RNA that encompasses the E7 oncogene (circE7). CircE7 can be detected in HPV16-positive cells and tumors, is preferentially localized to the cytoplasm, is N6-methyladenosine (m6A)-modified, and can be translated into the E7 oncoprotein. Here, we explored the regulation and function of circE7. Mutation of m6A motifs flanking the backsplice junction revealed a single m6A motif to be essential for circE7 formation. Mutation of this m6A motif promoted linear splicing of the E6*I splice site (226^409), suggesting that linear and circular E7 splicing are inversely regulated. Additionally, mutation of an IRES-like motif in circE7 significantly decreased E7 protein expression, without having significant effects on circE7 RNA levels. Knockdown of YTHDC1, but not other m6A-binding proteins, decreased both circE7 RNA and protein expression. BaseScope ISH was used to confirm the expression of circE7 in head and neck squamous cell carcinoma cell lines and tumors. Using both qRT-PCR and BaseScope ISH, we found that serum and amino acid starvation significantly increased circE7. Finally, we generated an HPV16 genome with mutations in the circE7 m6A motif (Mut2). Stable transduction of primary keratinocytes with Mut2 confirmed the loss of circE7 and increased expression of E6*I. The Mut2 HPV16 genome exhibited significantly decreased viral replication but an increased ability to transform primary keratinocytes. Our studies reveal that the precise regulation of circE7 and E6*I by m6A is critical for the ability of HPV16 to infect and transform keratinocytes.IMPORTANCEHigh-risk human papillomaviruses (HPVs), such as HPV16, must carefully control how much E6 and E7 proteins they make. This study shows that HPV16 toggles a single chemical tag on the viral RNA (an m⁶A mark) to control the production of early region RNAs, including a circular RNA called circE7. The same site coordinately regulates splicing of the E6*I isoform. CircE7 uses m⁶A-binding proteins to control its production and a specific sequence to promote its translation. It is present in HPV-positive cancers and can respond to nutrient starvation. Regulation of circE7 through this m6A site also impacted viral replication and transformation capacity, indicating that this regulatory mechanism is critical for HPV biology.

RNA splicing↗
PubMed2006

A randomized controlled trial of supervised versus unsupervised exercise programs for ambulatory stroke survivors.

BACKGROUND AND PURPOSE: Little is known about the relative efficacy of supervised versus unsupervised community exercise programs for stroke survivors. This study compared the effectiveness of a 10-week supervised strengthening and conditioning program (supervised) with a 1-week supervised instruction program followed by a 9-week unsupervised home program (unsupervised) and evaluated retention of changes at 6 months and 1 year after program completion. METHODS: Seventy-two subjects retained at baseline (27 women, 45 men; mean+/-SD age, 64.6+/-11.8 years) were randomly allocated to receive the supervised or unsupervised program. The primary outcome was walking speed over 6 minutes, and secondary outcome measures were Human Activity Profile, Medical Outcome Study 36-Item Short-Form survey (SF-36), Physiological Cost Index, and lower extremity muscle strength. RESULTS: The 6-minute walking speed increased significantly in both groups and remained significantly improved by 1 year. The Human Activity Profile demonstrated an increasing trend only in the supervised group that was significant by 1 year. The SF-36 Physical Component summary score increased significantly in the supervised group and remained improved by 1 year; the unsupervised group showed significant improvement at 1 year. Women made greater gains in supervised programs, but men made greater gains in unsupervised programs. CONCLUSIONS: Supervised exercise programs and unsupervised programs after initial supervised instruction were both associated with physical benefits that were retained for 1 year, although supervised programs showed trends to greater improvements in self-reported gains. Gender differences require further research.

Activities of Daily Living↗
PubMed2006

Nongastric Helicobacter species detected in the intestinal tract of children.

The presence of members of the family Helicobacteraceae in the colon of children was investigated using PCR, denaturing gradient gel electrophoresis, and fluorescent in situ hybridization. The rate of detection of species belonging to the Helicobacteraceae family in children with inflammatory bowel disease (92%) and irritable bowel syndrome (100%) was found to be significantly higher than that in healthy children (25%) (P < 0.05).

Adolescent↗
PubMed2006

Affective determinants of treatment engagement in violent offenders.

Affective factors are likely to play a major role in determining the extent to which offenders are able to engage with, and benefit from, treatment. In this article, it is argued that the relationship between affect and treatment engagement may be understood in three ways: the access the client has to emotional states, the ability to express such states, and the willingness of the client to do this in the therapeutic session. It is suggested that affective determinants of treatment readiness can be understood with reference to models of emotional regulation and that attention to these affective factors in the early stages of treatment is likely to promote engagement, reduce attrition, and consequently improve treatment outcomes for violent offenders.

Adult↗
PubMed2006

The meaning of anger for Australian Indigenous offenders: the significance of context.

The problem of overrepresentation of Indigenous offenders in Australian prisons highlights the need for effective tertiary intervention programs within correctional settings as a way of reducing Indigenous reincarceration. This study seeks to explore meanings of anger within an Indigenous context that might inform the development of more acceptable and potentially more effective rehabilitation programs. A methodology that acknowledges the importance of narrative, context, and culture was devised to explore how anger as an emotion is understood and experienced by a group of Indigenous men in a South Australian prison. Although some of the major themes reflected experiences of anger common to many offenders, it was evident that for these Indigenous men, anger was experienced within a broad social and political context that imbued the experience of anger with layers of culturally specific meaning. It is suggested that these layers of meaning constitute sufficient difference to warrant further exploration.

Adult↗
PubMed2006

Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials.

INTRODUCTION: Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia. METHODS: Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 mug/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20. RESULTS: The patients, 42 +/- 15 years old, were burned on 46% +/- 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 +/- 1.2 to 2.0 +/- 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023). CONCLUSION: Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.

Adult↗
PubMed2005

Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma.

BACKGROUND AND PURPOSE: This study compared late radiation morbidity in patients with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities evaluated included fibrosis, joint stiffness and edema at 2 years following treatment. The impact of morbidity on patient function as measured by the Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS) was also evaluated. PATIENTS AND METHODS: 129 patients were evaluated. Toxicity rates were compared by treatment arm using the Fisher's exact test. Function scores by toxicity were analyzed using the Wilcoxon rank sum test. Multivariate logistic regression was used to evaluate the joint effect of treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint stiffness and edema. RESULTS: 27 of 56 patients (48.2%) in the postoperative arm compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater fibrosis (P = 0.07). Although not statistically significant, edema was more frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.5%) in the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73 (17.8%). Patients with significant fibrosis, joint stiffness or edema had significantly lower function scores on both measures (all P-values < 0.01). Field size was predictive of greater rates of fibrosis (P = 0.002) and joint stiffness (P = 0.006) and marginally predictive of edema (P = 0.06). CONCLUSIONS: Patients treated with postoperative radiotherapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function.

Adolescent↗
PubMed2005

Indicators of functional status for primary malignant brain tumour patients.

BACKGROUND: We compared the functional status and survival time of patients with malignant gliomas. METHODS: This retrospective review included 143 patients diagnosed with malignant gliomas. Patients were grouped according to histopathological diagnosis. To measure functional status, patients were assigned a Karnofksy performance status (KPS) score at the time of presentation and at one, three, six, nine, 12 months and yearly intervals thereafter. Data were analyzed using descriptive methods as well as Kruskal-Wallis tests, Chi-square tests, Log-Rank tests and Cox's proportional hazards modeling. RESULTS: Eighty-four patients were male. The median age of patients was 63 years. One hundred and seven patients had a histopathological diagnosis of glioblastoma multiforme, 23 of anaplastic astrocytoma and 13 of anaplastic oligodendroglioma. Twenty-nine patients received aggressive multimodal treatment, 83 received intermediate treatment and the remaining 31 patients received conservative therapy. Significant treatment complications occurred in 33% of patients including four post-operative deaths. The anaplastic oligodendroglioma group had lower mortality and maintained better KPS scores over time, as did patients receiving full treatment. The most significant prognostic factors for functional status included age, pretreatment KPS, and type of treatment received. The most significant factors associated with time until death included age, severity of comorbidities, pretreatment KPS, presence of confusion, histopathological diagnosis and type of treatment received. CONCLUSION: In patients with malignant gliomas, younger age, better functional status at presentation and aggressive multimodal treatment were associated with improved longer-term functional status and survival. Confirmation of the effect of multimodal treatment on patient functional status would require a randomised controlled clinical trial.

Adult↗
PubMed2005

A comparison of high and standard blood transfusion volumes in premature infants.

UNLABELLED: We compared high volume (20 ml/kg) with standard volume (15 ml/kg) packed red blood cell (PRBC) transfusions in a randomized trial. Ten high volume babies received a mean of 2.8 transfusions, while 10 standard volume babies received a mean of 3.4 (p=0.58). No adverse events were attributed to the use of the high volume transfusions. CONCLUSION: Higher transfusion volumes appear to be well tolerated. The data can be used in the planning of larger controlled trials in VLBW infants.

Blood Transfusion↗
PubMed2004

Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.

Fostriecin (CI-920) is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosphatase 4(PP4) found to have anticancer activity in preclinical testing. A phase I study was conducted to evaluate the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of this drug. Forty-six patients were treated with escalating doses of fostriecin (2-47 mg/m2) administered as a daily bolus infusion for five consecutive days. PK studies were performed at different time points following administration of fostriecin. Dose-limiting toxicities included: elevation of creatinine, bilirubin, and hepatic transaminases; nausea, anorexia, lethargy, and hypotension. PK studies were compatible with a two-compartment model. Regression analysis revealed a significant relationship between dose and clearance; however, the r2 value was only 0.168 indicating a low predictive value for the model. No significant difference was seen in PK parameters with repeated dosing during the same cycle. Although no tumor responses were seen, 16 patients had stable disease with a median duration response of 2.6 months. The study was closed before reaching MTD due to problems with the supply of fostriecin from the National Cancer Institute of the United States (NCI US). New methods for synthesizing fostriecin have recently been described and therefore further development of this unique anticancer agent may be warranted.

Adult↗
PubMed2004

Validation of the Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients: results of a prospective observational study.

OBJECTIVE: Recently, evidence-based clinical practice guidelines for the provision of nutrition support in the critical care setting have been developed. To validate these guidelines, we hypothesized that intensive care units whose practice, on average, was more consistent with the guidelines would have greater success in providing enteral nutrition. DESIGN: Prospective observational study. SETTING: Fifty-nine intensive care units across Canada. PATIENTS: Consecutive cohort of mechanically ventilated patients. INTERVENTIONS: In May 2003, participating intensive care units recorded nutrition support practices on a consecutive cohort of mechanically ventilated patients who stayed for a minimum of 72 hrs. Sites enrolled an average of 10.8 (range, 4-18) patients for a total of 638. Patients were observed for an average of 10.7 days. MEASUREMENTS AND MAIN RESULTS: We examined the association between five recommendations from the clinical practice guidelines most directly related to the provision of nutrition support (use of parenteral nutrition, feeding protocol, early enteral nutrition, small bowel feedings, and motility agents) and adequacy of enteral nutrition. We defined adequacy of enteral nutrition as the percent of prescribed calories that patients actually received. Across sites, the average adequacy of enteral nutrition over the observed stay in intensive care unit ranged from 1.8% to 76.6% (average 43.0%). Intensive care units with a greater than median utilization of parenteral nutrition (>17.5% patient days) had a much lower adequacy of enteral nutrition (32.9 vs. 52.7%, p < .0001). Intensive care units that used a feeding protocol tended to have a higher adequacy of enteral nutrition than those that did not (44.9 vs. 38.5%, p = .03). Intensive care units that initiated enteral nutrition on >50% of their patients within the first 48 hrs had a higher adequacy of enteral nutrition than those that did not (48.1 vs. 34.4%, p < .0001). Intensive care units that had a >50% utilization of motility agents and/or any small bowel feedings in patients with high gastric residuals tended to have a higher adequacy of enteral nutrition than those intensive care units that did not (45.6 vs. 39.2%, p = .04, and 48.4 vs. 41.8%, p = .16, respectively). CONCLUSIONS: Intensive care units that were more consistent with the Canadian clinical practice guidelines were more likely to successfully feed patients via enteral nutrition. Adoption of the Canadian clinical practice guidelines should lead to improved nutrition support practice in intensive care units. This may translate into better outcomes for critically ill patients receiving nutrition support.

Adolescent↗
PubMed2004

The recruitment and retention of indigenous criminal justice agency staff in an Australian state.

In Australia, as in other countries that have experienced colonisation, indigenous people are massively overrepresented in all stages of the criminal justice system. If criminal justice agencies are to provide culturally responsive and effective services to this group, it is important that they employ significant numbers of indigenous staff across all levels of their organisations. Despite the positive intentions of many justice agencies to increase the proportion of indigenous staff members they employ, the numbers remain low. In this article, we explore some of the possible reasons for this by reporting the results of focus groups conducted with existing indigenous justice agency employees. The employees raised a number of issues relevant to recruitment and retention. These are discussed in terms of their potential value in improving justice agency indigenous recruitment and retention strategies.

Australia↗
PubMed2003

Alcohol use and negative affect in the offence cycle.

INTRODUCTION: It is commonly acknowledged that, for many offenders, alcohol use is strongly associated with criminal behaviour. The belief held by many professionals that the two phenomena are associated, probably in a causal way, has led to the inclusion of alcohol use as a 'criminogenic need' in many settings where rehabilitation programmes are used to reduce recidivism. However, the mechanisms and pathways involved in the alcohol crime link remain poorly understood. ARGUMENT AND CONCLUSION: This paper reviews the literature relating to alcohol offending links and draws some inferences about the role of alcohol use as a criminogenic need in offender rehabilitation. It is proposed that the bi-directional relationship between alcohol use and negative affective states is important in understanding the offence cycle, and that deficits in self-regulation not only characterize both alcohol misuse and negative affect but are also implicated in the offending behaviour itself.

Alcoholic Intoxication↗
PubMed2003

Working with childhood sexual abuse: a survey of mental health professionals.

OBJECTIVE: This study aimed to establish the views of a group of mental health professionals from various disciplines working in mental health service in a British hospital about the needs of clients who had experienced childhood sexual abuse. METHOD: Staff members were asked to complete an anonymous survey which asked questions relating to knowledge of sexual abuse and its effects, and the needs of clients and staff in working with this client group. A total of 54 people responded to the survey, 42 were female, 11 male. Most (72%) reported having over 10 years experience working in mental health, working in both in-patient and out-patient settings. RESULTS: While respondents were reasonably knowledgeable about childhood sexual abuse, they were not very comfortable, competent or supported in their work with this client group. There were no differences in responses according to the age or gender of respondents, but less experienced staff were more likely to feel supported. Those that had received training and/or supervision felt significantly more capable in working with this client group. CONCLUSIONS: The study offers some support for the development of specialist training, consultancy and supervision programs for mental health staff in the area of child sexual abuse.

Adult↗