Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology

Tumour necrosis factor (TNF) is a pleiotropic cytokine with dual roles in cancer biology including prostate cancer (PCa). On the one hand, there is evidence that it stimulates tumour angiogenesis, is involved in the initiation of PCa from an androgen-dependent to a castrate resistant state, plays a role in epithelial to mesenchymal plasiticity, and may contribute to the aberrant regulation of eicosanoid pathways. On the other hand, TNF has also been reported to inhibit neovascularisation, induce apoptosis of PCa cells, and stimulate anti-tumour immunity. Much of the confusion surrounding its seemingly paradoxical roles in cancer biology stems from the dependence of its effects on the biological model within which TNF is investigated. This review will address some of these issues, and also discuss on the therapeutic implications.

Scaffolds for growth factor delivery as applied to bone tissue engineering

There remains a substantial shortfall in treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient, has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors; which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However cost and potential complications associated with growth factors means controlled release is an important consideration in the design of new bone tissue engineering strategies. This review will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure

Critically ill patients receiving extracorporeal membrane oxygenation (ECMO) are often noted to have increased sedation requirements. However, data related to sedation in this complex group of patients is limited. The aim of our study was to characterise the sedation requirements in adult patients receiving ECMO for cardiorespiratory failure. A retrospective chart review was performed to collect sedation data for 30 consecutive patients who received venovenous or venoarterial ECMO between April 2009 and March 2011. To test for a difference in doses over time we used a regression model. The dose of midazolam received on ECMO support increased by an average of 18 mg per day (95% confidence interval 8, 29 mg, P=0.001), while the dose of morphine increased by 29 mg per day (95% confidence interval 4, 53 mg, P=0.021) The venovenous group received a daily midazolam dose that was 157 mg higher than the venoarterial group (95% confidence interval 53, 261 mg, P=0.005). We did not observe any significant increase in fentanyl doses over time (95% confidence interval 1269, 4337 µg, P=0.94). There is a significant increase in dose requirement for morphine and midazolam during ECMO. Patients on venovenous ECMO received higher sedative doses as compared to patients on venoarterial ECMO. Future research should focus on mechanisms behind these changes and also identify drugs that are most suitable for sedation during ECMO.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

The factor structure of the COPE Questionnaire in a sample of clinically depressed and anxious adults

The Coping Orientation to Problems Experienced is a multidimensional scale designed to assess how people respond to stress. The COPE has been validated in a variety of populations displaying variations in factor structure. However, in terms of mental health populations, it has only been validated in alcohol-dependent samples. This paper investigated the factor structure of the COPE in a sample of adults diagnosed with depression and anxiety. Two hundred and seventy-one patients attending cognitive behaviour therapy for anxiety and depression completed the COPE. Confirmatory factor analysis found a poor fit for both lower order and higher order factors based upon the Lyne and Roger (2000) study. Exploratory factor analyses identified six primary subscales (Active Planning, Social Support, Denial, Acceptance, Disengagement, Restraint) which explained approximately 60% of the variance in coping. These 6 subscales may assist researchers and clinicians to validly measure coping in anxious and depressed adults.

Teacher Reporting Attitudes Scale (TRAS): confirmatory and exploratory factor analyses with a Malaysian sample.

The Teacher Reporting Attitude Scale (TRAS) is a newly developed tool to assess teachers’ attitudes toward reporting child abuse and neglect. This article reports on an investigation of the factor structure and psychometric properties of the short form Malay version of the TRAS. A self-report cross-sectional survey was conducted with 667 teachers in 14 randomly selected schools in Selangor state, Malaysia. Analyses were conducted in a 3-stage process using both confirmatory (stages 1 and 3) and exploratory factor analyses (stage 2) to test, modify, and confirm the underlying factor structure of the TRAS in a non-Western teacher sample. Confirmatory factor analysis did not support a 3-factor model previously reported in the original TRAS study. Exploratory factor analysis revealed an 8-item, 4-factor structure. Further confirmatory factor analysis demonstrated appropriateness of the 4-factor structure. Reliability estimates for the four factors—commitment, value, concern, and confidence—were moderate. The modified short form TRAS (Malay version) has potential to be used as a simple tool for relatively quick assessment of teachers’ attitudes toward reporting child abuse and neglect. Cross-cultural differences in attitudes toward reporting may exist and the transferability of newly developed instruments to other populations should be evaluated.

A confirmatory factor analysis of the Observer Alexithymia Scale in treatment seeking alcohol-dependent patients

Confirmatory factor analyses evaluated the factorial validity of the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample. Observation was conducted by clinical psychologists. All models examined were rejected, given their poor fit. Given the psychometric limitations of the OAS shown in this study, the OAS may not be the most appropriate measure to use early in treatment among alcohol-dependent individuals.

University Student Depression Inventory (USDI) : confirmatory factor analysis and review of psychometric properties

Background: The 30-item USDI is a self-report measure that assesses depressive symptoms among university students. It consists of three correlated three factors: Lethargy, Cognitive-Emotional and Academic motivation. The current research used confirmatory factor analysis to asses construct validity and determine whether the original factor structure would be replicated in a different sample. Psychometric properties were also examined. Method: Participants were 1148 students (mean age 22.84 years, SD = 6.85) across all faculties from a large Australian metropolitan university. Students completed a questionnaire comprising of the USDI, the Depression Anxiety Stress Scale (DASS) and Life Satisfaction Scale (LSS). Results: The three correlated factor model was shown to be an acceptable fit to the data, indicating sound construct validity. Internal consistency of the scale was also demonstrated to be sound, with high Cronbach Alpha values. Temporal stability of the scale was also shown to be strong through test-retest analysis. Finally, concurrent and discriminant validity was examined with correlations between the USDI and DASS subscales as well as the LSS, with sound results contributing to further support the construct validity of the scale. Cut-off points were also developed to aid total score interpretation. Limitations: Response rates are unclear. In addition, the representativeness of the sample could be improved potentially through targeted recruitment (i.e. reviewing the online sample statistics during data collection, examining the representativeness trends and addressing particular faculties within the university that were underrepresented). Conclusions: The USDI provides a valid and reliable method of assessing depressive symptoms found among university students.

To separate or not to separate? Parental decision-making regarding the separation of twins in the early years of schooling

In recent times concerns about possible adverse effects of early separation and advocacy for individual rights have resulted in a movement away from organizational level policies about the separation of twin children as they enter school. Instead, individualized approaches that focus on the twin children’s characteristics and family perspectives have been proposed. This study, conducted in Australia where all but a few families had choice about the class placement of their twin children, questioned parents (N = 156) about their placement decisions. Results indicated that most parents opted for placement together in the early years of schooling. The choice to separate twins at school entry was associated with parent identification of risk in the twin relationship, while being kept together was associated with parent identification of absence of such risk. The findings are discussed in light of the current evidence against separation, and suggest that parent choices regarding the separation of twin children in the early years are informative to educational policy and practice.

Advanced practice nursing role development : factor analysis of a modified role delineation tool

Aim his study reports the use of exploratory factor analysis to determine construct validity of a modified advanced practice role delineation tool. Background Little research exists on specific activities and domains of practice within advanced practice nursing roles, making it difficult to define service parameters of this level of nursing practice. A valid and reliable tool would assist those responsible for employing or deploying advanced practice nurses by identifying and defining their service profile. This is the third paper from a multi-phase Australian study aimed at assigning advanced practice roles. Methods A postal survey was conducted of a random sample of state government employed Registered nurses and midwives, across various levels and grades of practice in the state of Queensland, Australia, using the modified Advanced Practice Role Delineation tool. Exploratory factor analysis, using principal axis factoring was undertaken to examine factors in the modified tool. Cronbach’s alpha coefficient determined reliability of the overall scale and identified factors. Results There were 658 responses (42% response rate). The five factors found with loadings of ≥.400 for 40 of the 41 APN activities were similar to the five domains in the Strong model. Cronbach’s alpha coefficient was .94 overall and for the factors ranged from 0.83 to 0.95. Conclusion Exploratory factor analysis of the modified tool supports validity of the five domains of the original tool. Further investigation will identify use of the tool in a broader healthcare environment.

Preparation of porous nanofibers from electrospun polyacrylonitrile/calcium carbonate composite nanofibers using porogen leaching technique

Production of nanofibrous polyacrylonitrile/calcium carbonate (PAN/CaCO3) nanocomposite web was carried out through solution electrospinning process. Pore generating nanoparticles were leached from the PAN matrices in hydrochloric acid bath with the purpose of producing an ultimate nanoporous structure. The possible interaction between CaCO3 nanoparticles and PAN functional groups was investigated. Atomic absorption method was used to measure the amount of extracted CaCO3 nanoparticles. Morphological observation showed nanofibers of 270–720 nm in diameter containing nanopores of 50–130 nm. Monitoring the governing parameters statistically, it was found that the amount of extraction (ε) of CaCO3was increased when the web surface area (a) was broadened according to a simple scaling law (ε = 3.18 a0.4). The leaching process was maximized in the presence of 5% v/v of acid in the extraction bath and 5 wt % of CaCO3 in the polymer solution. Collateral effects of the extraction time and temperature showed exponential growth within a favorable extremum at 50°C for 72 h. Concentration of dimethylformamide as the solvent had no significant impact on the extraction level.

A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis

The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear. Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor (IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof during insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measured using qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolonged euglycaemic, hyperinsulinaemic clamp (p-EHC), during the mid-developmental (24 h) and acute (46 h) phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13–32-fold (P < 0.05) at both time-points in the insulin-treated horses. A second aim was to determine if the down-regulation of the receptor genes could be accounted for by an increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horses given a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution. There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulation of both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriate lamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemic laminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapy for hyperinsulinaemic laminitis.

Child mental health after parental separation: The impact of resident/non-resident parenting, parent mental health, conflict and socioeconomics

Children of separated parents tend to have poorer mental health than children of intact families. Explanations to date have tended to focus on resident mothers, neglecting the potential importance of non-resident fathers. Using recent data from the Longitudinal Study of Australian Children, and independent teacher-reports of child mental health, this study 1) compares the mental health of children with resident and non-resident fathers and 2) explores predictors of poor mental health among children with a non-resident father. Children with a non-resident father had poorer mental health than those with a resident father, but this difference was explained fully by exposure to parental conflict, and to a lesser extent by socioeconomic status, parenting, and parent mental health. For children with a non-resident father, the strongest predictors of child mental health were mothers' employment and maternal parenting consistency. Policy implications are discussed.