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Mitochondrial DNA (mtDNA) deletions which clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impair mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these mtDNA deletions arise and accumulate in perinuclear mitochondria causing localised mitochondrial dysfunction before spreading through the muscle fibre. We believe that mito-nuclear signalling is a key contributor in the accumulation and spread of mtDNA deletions, and that knowledge of how muscle fibres respond to mitochondrial dysfunction is key to our understanding of disease mechanisms. To understand the contribution of mito-nuclear signalling to the spread of mitochondrial dysfunction, we use imaging mass cytometry. We characterise the levels of mitochondrial Oxidative Phosphorylation proteins alongside a mitochondrial mass marker, in a cohort of patients with mtDNA maintenance disorders. Our expanded panel included protein markers of key signalling pathways, allowing us to investigate cellular responses to different combinations of oxidative phosphorylation dysfunction and ragged red fibres. We find combined Complex I and IV deficiency to be most common. Interestingly, in fibres deficient for one or more complexes, the remaining complexes are often upregulated beyond the increase of mitochondrial mass typically observed in ragged red fibres. We further find that oxidative phosphorylation deficient fibres exhibit an increase in the abundance of proteins involved in proteostasis, e.g. HSP60 and LONP1, and regulation of mitochondrial metabolism (including oxidative phosphorylation and proteolysis, e.g. PHB1). Our analysis suggests that the cellular response to mitochondrial dysfunction changes depending on the combination of deficient oxidative phosphorylation complexes in each fibre., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael F. Marusich declares receipt of licensing revenues from Abcam and EMD/Millipore on sales of anti-mtDNA-encoded protein antibodies. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Obesity is a significant global health issue, especially for reproductive-aged women. Women who enter pregnancy overweight or obese are at increased risk of a range of adverse reproductive, maternal, and child health outcomes. The preconception period has been recognised as a critical time to intervene to improve health outcomes for women and their children. Despite this recognition, adequate information is significantly lacking in relation to women's health experiences, behaviours, and information preferences to inform the development of high-quality preconception intervention strategies., Aim: This study aimed to examine women's perspectives of barriers, enablers, and strategies for addressing overweight and obesity before conception., Method: Using a qualitative research design, twelve multiparous women, aged between 32 and 43 years, who considered themselves to be overweight or obese were interviewed. Data were analysed using thematic analysis., Findings: Three themes were identified in relation to barriers: lack of information and knowledge, time constraints, and affordability. The following four themes emerged with respect to enablers and strategies: knowledge provision, accountability and motivation, regular contact, and habit formation., Conclusion: Key factors to incorporate in women-centred interventions for preconception weight loss include multi-faceted knowledge provision and practical affordable methods for supporting healthy behaviours. Interventions should integrate techniques for ensuring regular contact with support networks, to enhance accountability, motivation, and facilitate habit formation. Further research is now being conducted by our team to co-design interventions and strategies informed by these findings., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Benzoic acid (BA) was administered in the diet to male and female Sprague Dawley Crl:CD(SD) rats in an OECD Test Guideline 443 Extended One-Generation Reproductive Toxicity (EOGRT) study to test for effects that may occur as a result of pre- and postnatal exposure. The study included cohorts of F 1 offspring to evaluate potential effects of benzoic acid on reproduction, the developing immune system, and the developing neurological system with the inclusion of learning and memory assessments. Benzoic acid was incorporated in the diet at concentrations of 0, 7,500, 11,500, and 15,000 mg/kg diet (ppm). These concentrations were selected based on the results of preliminary studies, and, based on average food consumption, were intended to supply BA doses of approximately 0, 500, 750, and 1000 mg/kg bw/day. To avoid exceeding these target dose levels, the dietary concentrations were adjusted (based on historical control body weight and food consumption data) to maintain the target mg/kg bw/day dose levels during those life periods when food intake per unit of body weight was increased to support milk production by females (gestation and lactation) and rapid pup growth (post-weaning). In the parental (F 0 ) generation, survival, clinical observations, organ weights, pathology, hematology, serum chemistry, urinalysis, and bile acids were unaffected by BA administration. Reproductive parameters were also unaffected by BA administration. In the F 1 generation, survival, growth and developmental landmarks, organ weights, pathology, immunotoxicity assessment, and neurotoxicity and neurobehavioral parameters such as auditory startle response, locomotor activity, learning and memory assessments were unaffected by BA administration, as were clinical pathology (hematology, serum chemistry, urinalysis, bile acids and thyroid hormones) and reproductive performance. Similarly, no adverse effects or systemic toxicity were observed in the F 2 generation. Overall, the highest dietary concentration (15,000 ppm), providing a dosage of approximately 1000 mg/kg bw/day, was the NOAEL for benzoic acid in this EOGRT study., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: This study explored the extent to which disaggregated support from family, peers, close friendships, teachers, and schools predicted membership into identified, sex-specific trajectories of depressed mood in 3210 Australian adolescents (49% females) based on self-report data collected at four annual time points from school Grade 6 to 9 (ages 10-16)., Methods: The sample was initially split by sex. Group-Based Trajectory Modelling was used to identify the trajectory groups using a Censored Normal model, starting with a two-group model and increasing group size in increments of one, up to a six-group model. Overall model-fit and specific model-fit criteria were examined, and participants were allocated to best-fit groups. Multinomial Logistic Regression examined the associations between baseline social supports and allocated trajectory group membership., Results: For boys, four trajectory groups were identified which were given the qualitative labels; Low Stable, Moderate Stable, Moderate Decreasing, and High Stable. Regression analysis showed that higher rates of peer belonging were associated with membership in the low and moderate groups compared to the High Stable group. For girls, four trajectory groups were identified and labelled as Low Stable, Moderate Decreasing, Moderate Increasing and High Increasing. Regression analysis showed that higher rates of family support, school climate, and peer belonging were associated with membership in the low and moderate groups compared to the High Increasing group., Conclusions: Implications included the need for school-based early intervention programs to consider disaggregated supports and vary their interventions by sex. Limitations and directions for future research are discussed., (Copyright © 2020 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Objective: Parental cancer is a significant problem for adolescent and young adult offspring. To understand the extent of the problem of parental cancer for Australian offspring, data regarding those impacted are required. The aim of this study was to enumerate and describe the characteristics of Western Australian adolescent and young adult offspring (12-24 years) and their parents with cancer using linked population data., Methods: A retrospective cohort study was conducted using data from the Western Australia Data Linkage System, which provided results generalisable at a national level., Results: Between 1982 and 2015, 57,708 offspring were impacted by 34,600 parents' incident malignant cancer diagnoses. The most common diagnosis was breast cancer. Of the 36.4% of parents who died, this was mostly a result of cancer. Most families resided in regional areas and were of high or middle socioeconomic status. Significant predictors of earlier parent death included low socioeconomic status, remoteness, age, having more children and having older children., Conclusion: A considerable number of adolescent and young adult offspring are impacted by parental cancer at a potentially vulnerable age. This research provides knowledge to better understand who is affected by parental cancer in Australia. Implications for public health: These results may be useful for planning and implementation of Australian supportive services., (© 2019 The Authors.)

This study reviewed the literature regarding the psychological, social, and behavioural impact of parental cancer on offspring aged 10-24 years, at the time of the parent's first diagnosis. A systematic literature review was conducted following 2015 PRISMA guidelines. Seven studies met inclusion criteria. Offspring were impacted by their parent's cancer and experienced psychological and behavioural problems. Daughters and offspring who experienced more problems at their parent's diagnosis appeared to be most impacted. Offspring refrained from communicating their disease-related concerns, but expected their parents to communicate openly. Turning to oneself and peer-support were coping strategies used by offspring. The majority of offspring were significantly impacted by their parent's cancer. The paucity of literature focusing on offspring aged 10-24 years at the time of their parent's incident cancer diagnosis indicates that research has overlooked offspring age at their parent's cancer onset as a factor that may influence their future outcomes., (Copyright © 2018. Published by Elsevier Ltd.)

This report evaluates the scientific literature on caffeine with respect to potential cardiovascular outcomes, specifically relative risks of total cardiovascular disease (CVD), coronary heart disease (CHD) and acute myocardial infarction (AMI), effects on arrhythmia, heart failure, sudden cardiac arrest, stroke, blood pressure, hypertension, and other biomarkers of effect, including heart rate, cerebral blood flow, cardiac output, plasma homocysteine levels, serum cholesterol levels, electrocardiogram (EKG) parameters, heart rate variability, endothelial/platelet function and plasma/urine catecholamine levels. Caffeine intake has been associated with a range of reversible and transient physiological effects broadly and cardiovascular effects specifically. This report attempts to understand where the delineations exist in caffeine intake and corresponding cardiovascular effects among various subpopulations. The available literature suggests that cardiovascular effects experienced by caffeine consumers at levels up to 600 mg/day are in most cases mild, transient, and reversible, with no lasting adverse effect. The point at which caffeine intake may cause harm to the cardiovascular system is not readily identifiable in part because data on the effects of daily intakes greater than 600 mg is limited. However, the evidence considered within this review suggests that typical moderate caffeine intake is not associated with increased risks of total cardiovascular disease; arrhythmia; heart failure; blood pressure changes among regular coffee drinkers; or hypertension in baseline populations., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

A quantitative human risk assessment of chloroxylenol was conducted for liquid hand and dishwashing soap products used by consumers and health-care workers. The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity. No observed adverse effect levels (NOAEL) were established from chronic toxicity studies, specifically a carcinogenicity study that found no cancer excess (18 mg/kg-day) and studies of developmental and reproductive toxicity (100 mg/kg-day). Exposure to chloroxylenol for adults and children was estimated for two types of rinse-off cleaning products, one liquid hand soap, and two dishwashing products. The identified NOAELs were used together with exposure estimates to derive margin of exposure (MOE) estimates for chloroxylenol (i.e., estimates of exposure over NOAELs). These estimates were designed with conservative assumptions and likely overestimate exposure and risk (i.e., highest frequency, 100% dermal penetration). The resulting MOEs ranged from 178 to over 100, 000, 000 indicating negligibly small potential for harm related to consumer or health-care worker exposure to chloroxylenol in liquid soaps used in dish washing and hand washing., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Emerging blood-based screening technologies for bowel cancer may improve screening participation compared to at-home stool sampling. This study assessed the impact of different screening delivery scenarios with increasing health system interactions on sampling preferences and likelihood of screening participation., Methods: N=1,561 persons aged 45 to 74 years completed a behavioural survey measuring demographics, readiness to screen, overall collection method preference, and proposed participation in stool and blood methods across four screening scenarios differing in terms of the number of required health system interactions., Results: Overall, respondents preferred a blood test (79.6%) compared to a stool test (20.4%). However, increasing health system interactions had a strong impact on the likelihood of participating in either sampling method (p<0.001). Moreover, likelihood of participating in each of the four blood-screening scenarios was significantly lower than the current at-home stool sampling approach (all p<0.001)., Conclusions: Blood-based screening methods require increased contact with the health system but these interactions have negative impact on screening likelihood. All blood-based scenarios showed lower screening likelihood ratings than the current at-home FIT approach. Thus, blood-based screening may not resolve suboptimal screening participation rates in Australia., (© 2016 Public Health Association of Australia.)

This report evaluates the scientific literature on caffeine with respect to potential central nervous system (CNS) effects, specifically effects on sleep, anxiety, and aggression/risk-taking. Caffeine has been the subject of more scientific safety studies than any other food ingredient. It is important, therefore, to evaluate new studies in the context of this large existing body of knowledge. The safety of caffeine can best be described in a narrative form, and is not usefully expressed in terms of a "bright line" numerical value like an "acceptable daily intake" (ADI). Caffeine intake has been associated with a range of reversible physiological effects, in a few studies at levels of less than 100 mg in sensitive individuals. It is also clear that many people can tolerate much greater levels - perhaps up to 600-800 mg/day or more - without experiencing such effects. The reasons for this type of variability in response are described in this report. Based on all the available evidence, there is no reason to believe that experiencing such effects from caffeine intake has any significant or lasting effect on health. The point at which caffeine intake may cause harm to the CNS is not readily identifiable, in part because data on the effects of daily intakes greater than 600 mg is limited. Effects of caffeine on risk-taking and aggressive behavior in young people have received considerable publicity, yet are the most difficult to study because of ethical concerns and limitations in the ability to design appropriate studies. At present, the weight of available evidence does not support these concerns, yet this should not preclude ongoing careful monitoring of the scientific literature., (Copyright © 2015 Ramboll Environ US Corporation. Published by Elsevier Inc. All rights reserved.)

Objective: To identify subgroups of Australian adults likely to receive physical activity advice from their general practitioner and to evaluate the content of the advice provided., Methods: Participants (n=1,799), recruited from the Australian Health and Social Science panel, completed an online survey. Signal Detection Analysis was used to identify subgroups that were more/less likely to have received physical activity recommendations., Results: Overall, 18% of participants received a physical activity recommendation from their general practitioner in the past 12 months and eight unique subgroups were identified. The subgroup with the highest proportion (54%) of participants reporting that they received a physical activity recommendation was those with poor physical and mental health-related quality of life and an average daily sitting time of <11 hours. Other subgroups with high proportions of individuals receiving recommendations were characterised by higher weight and/or the presence of co-morbidities. The most commonly prescribed physical activity type was aerobic activity. Few participants received specific physical activity advice., Conclusions: General practitioners are incorporating physical activity promotion into their practice, but primarily as a disease management tool and with limited specificity., Implications: Strategies to assist Australian general practitioners to effectively promote physical activity are needed., (© 2015 Public Health Association of Australia.)

Background and Aims: The mechanism of action of spinal cord stimulation (SCS) is poorly understood and the success of treatment can depend on factors beyond the technical aspects of implantation. The aim of this retrospective analysis is the identification of preimplantation psychological values that may predict outcome of SCS treatment., Methods: The retrospective analysis consisted of data from 83 patients who underwent SCS implantation from 2005 to 2013. Preimplantation evaluation included pain severity, sleep interference and distress each recorded with a numeric rating scale (NRS 0-10), depression and anxiety (Hospital Anxiety and Depression Score-HADS), catastrophizing (Pain Catastrophizing Scale-PCS), and patient's confidence in performing daily activity (Pain Self-Efficacy Questionnaire-PSEQ)., Results: A fall in pain score of greater than 50% at one year follow up was the criteria applied to divide patients into two groups. Group A consisted of 39 patients whose pain score fell more than 50% and group B consisted of 44 patients whose pain score fell less than 50% at one year follow up. The median preimplantation pain score was comparable between the two groups. However, the preimplantation scores for sleep interference, HADS-depression, PCS and PSEQ, were significantly worse in group B. Receiver operating characteristic (ROC) curve analysis and univariate regression show that HADS-depression >10 and PSEQ ≤18 are risk factors for failure of SCS treatment, but only sleep interference, assessed with NRS >7 out of 10 was found to be an independent predictor of a less optimal outcome in multiple logistic regression., Conclusions: Sleep interference appears to be an independent risk factor for unsuccessful SCS therapy., (© 2015 International Neuromodulation Society.)

Symmetry is an important feature of protein tertiary and quaternary structures that has been associated with protein folding, function, evolution, and stability. Its emergence and ensuing prevalence has been attributed to gene duplications, fusion events, and subsequent evolutionary drift in sequence. This process maintains structural similarity and is further supported by this study. To further investigate the question of how internal symmetry evolved, how symmetry and function are related, and the overall frequency of internal symmetry, we developed an algorithm, CE-Symm, to detect pseudo-symmetry within the tertiary structure of protein chains. Using a large manually curated benchmark of 1007 protein domains, we show that CE-Symm performs significantly better than previous approaches. We use CE-Symm to build a census of symmetry among domain superfamilies in SCOP and note that 18% of all superfamilies are pseudo-symmetric. Our results indicate that more domains are pseudo-symmetric than previously estimated. We establish a number of recurring types of symmetry-function relationships and describe several characteristic cases in detail. With the use of the Enzyme Commission classification, symmetry was found to be enriched in some enzyme classes but depleted in others. CE-Symm thus provides a methodology for a more complete and detailed study of the role of symmetry in tertiary protein structure [availability: CE-Symm can be run from the Web at http://source.rcsb.org/jfatcatserver/symmetry.jsp. Source code and software binaries are also available under the GNU Lesser General Public License (version 2.1) at https://github.com/rcsb/symmetry. An interactive census of domains identified as symmetric by CE-Symm is available from http://source.rcsb.org/jfatcatserver/scopResults.jsp]., (Copyright © 2014. Published by Elsevier Ltd.)

Problem or Background: There is little information available describing how women who are overweight or obese in pregnancy perceive their bodies, and in particular the effect of body image dissatisfaction on gestational weight gain., Question: To describe how women who are overweight or obese in pregnancy perceive their body, and the effect of body image on gestational weight gain., Methods: This prospective nested cohort study evaluated self estimation of body weight, preferred body shape, dieting behavior, satisfaction with body weight and shape, and gestational weight gain in pregnant women who were overweight or obese, through self-completed questionnaire in early pregnancy in South Australia from October 2010 to February 2012., Findings: Of the 442 women who completed the questionnaire, 25.8% correctly identified their BMI, with 70.1% under-estimating and 4.1% over-estimating their BMI. Women who were obese were significantly less likely to correctly identify their BMI, as were younger women. Women who incorrectly identified their BMI were significantly more likely to have higher gestational weight gain (P<0.001). Approximately 45% of women indicated dissatisfaction with their weight or body shape, with this being more common in women of higher parity and higher BMI. Dissatisfaction was significantly related to gestational weight gain., Conclusion: Women who report increasing dissatisfaction with their body size and shape are more likely to gain excessive weight during pregnancy. Further research should explore insights about maternal body image and diet related behaviors., (Copyright © 2013 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Induction of labour often begins with the application of a priming agent to soften the cervix, generally requiring women to stay in hospital overnight (inpatient priming). An alternative is outpatient priming by a midwife, where women are allowed to go home following priming. This approach has the potential to impact, either positively or negatively, on the midwives involved., Question: To what extent did the introduction of outpatient priming influence midwives' work demands, work autonomy, stress and job satisfaction., Methods: A before-after study (with two separate cross-sectional samples) was conducted alongside a randomized controlled trial of outpatient versus inpatient priming, conducted at two metropolitan teaching hospitals in Australia. Midwives completed a questionnaire before the introduction of outpatient priming and again approximately two years later., Findings: 208 midwives participated (response rates-time 1:81% (87/108); time 2:78% (121/156)). A mixed model analysis test of pre-post intervention differences found no changes in work demand, work autonomy and satisfaction. At time 2, over 80% of midwives reported that the introduction of the practice had reduced or made no difference to their work stress and workload, and 93% reported that outpatient priming had increased or had no impact on their job satisfaction. Furthermore, 97% of respondents were of the opinion that the option of outpatient priming should continue to be offered., Conclusion: Results suggest that outpatient priming for induction of labour is viable from a midwifery practice perspective, although more research is needed., (Copyright © 2013. Published by Elsevier Ltd.)

Objective: To compare the personal preferences of pregnant women, midwives and obstetricians regarding a range of physical, psychosocial and pharmacological methods of pain relief for childbirth., Method: Self-completed questionnaires were posted to a consecutive sample of 400 pregnant women booked-in to a large tertiary referral centre for maternity care in South Australia. A similar questionnaire was distributed to a national sample of 500 obstetricians as well as 425 midwives at: (1) the same hospital as the pregnant women, (2) an outer-metropolitan teaching hospital and (3) a district hospital. Eligible response rates were: pregnant women 31% (n=123), obstetricians 50% (n=242) and midwives 49% (n=210)., Findings: Overall, midwives had a greater personal preference for most of the physical pain relief methods and obstetricians a greater personal preference for pharmacological methods than the other groups. Pregnant women's preferences were generally located between the two care provider groups, though somewhat closer to the midwives. All groups had the greatest preference for having a support person for labour with more than 90% of all participants wanting such support. The least preferred method for pregnant women was pethidine/morphine (14%)., Conclusion: There are differences in the personal preferences of pregnant women, midwives and obstetricians regarding pain relief for childbirth. It is important that the pain relief methods available in maternity care settings reflect the informed preferences of pregnant women., (Copyright © 2011 Australian College of Midwives. All rights reserved.)

A qualitative study was conducted in Australia to explore women's preferences for inpatient or outpatient settings for cervical priming for induction of labour. The concept of therapeutic landscapes was used to explore the different aspects of the home and hospital that make them therapeutic to women. The therapeutic value of the home and hospital landscapes was defined by their ability to provide women with 'comfort' and 'safety', and women were found to draw on a range of contextual factors to negotiate between the comfort of home and the perceived safety of the hospital. The study provides important information for health professionals to enable them to enhance women's wellbeing should they be offered the choice of inpatient or outpatient priming., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: In 2008, the National Patient Safety Agency (NPSA) published a report after 42 incidents and two deaths where glucose-containing flush solutions were attached to the arterial line. The molar concentration of 5% glucose is 277 mmol litre(-1). Only a tiny amount of sample contamination will lead to an artificially high glucose. As the NPSA sought a solution, a bench model was constructed to compare the performance of three open and three closed arterial line systems in limiting sample contamination., Methods: All arterial line systems were set up in a standard manner and pressurized to 300 mm Hg with 5% glucose used as the flush solution. This was connected to the 'radial artery' using an 18 G needle representing the radial cannula. The radial artery was simulated using a wide-bore extension set with 'blood' flow at 60 ml min(-1). Blood was simulated by the addition of red dye to Hartmann's solution. Increasing multiples of arterial line dead space were aspirated and discarded. Blood samples were then obtained and glucose concentration was measured., Results: Significant glucose contamination (3 mmol litre(-1) +/-3.4) was detected in all open arterial line systems up to an aspiration volume of five times the dead space. No samples from the closed systems recorded glucose concentration >1 mmol litre(-1)., Conclusions: Recommended minimal discard volumes are inadequate in the presence of glucose as the flush solution and can lead to high blood glucose readings, inappropriate insulin use, and iatrogenic neuroglycopaenia. Our study demonstrates that the closed-loop arterial sampling system could be the universal solution sought by the NPSA.

Background: Novel laryngoscopes may demonstrate advantages over the traditional Macintosh laryngoscope for difficult airways. Our study compared Glidescope laryngoscope, Bonfils fibrescope, and CTrach intubating laryngeal mask airway with the Macintosh laryngoscope in a simulated normal and difficult airway, considering the additional effect of previous intubation experience., Methods: Twenty-two non-anaesthetists, 21 trainees, and 20 consultant anaesthetists attempted tracheal intubation of a Laerdal SimMan manikin, comparing a normal with a difficult airway scenario for each intubation device. The time taken to view the vocal cords and time to intubate were recorded. Also success rate and ease of use for each device were scored, alongside scope preference for each scenario., Results: Time to intubate was significantly shorter with the Macintosh compared with all three novel devices. All the devices had a high first-attempt success rate, but the Glidescope had a 100% first time successful intubation for all participants in both a normal and a difficult airway. Non-anaesthetists took significantly longer time to intubate compared with consultant anaesthetists, but there was no difference between trainee and consultant anaesthetists. Higher proportions of participants found the Glidescope easy to use, compared with other devices. For the normal airway, the Macintosh was the preferred device, but for the difficult airway, the Glidescope was favoured., Conclusions: In this study, the Macintosh laryngoscope outperformed the other devices. However, the Glidescope was considered easy to use regardless of previous experience and was the preferred device for the simulated difficult airway.

Background: Midwifery Group Practice (MGP) is a continuity of midwifery care model for women in all risk groups (Low, Moderate and High) available at a tertiary metropolitan hospital in Australia. This demonstration study aimed to compare the clinical effectiveness of MGP with other models of care at the hospital., Methods: Comparisons of clinical outcomes were made between women who received care under MGP (n=618) and those receiving 'Other' modes of care at the hospital (n=3548) between three risk categories over a 15-month period., Results: There were more Low (MGP n=218, 35.3%, 'Other' n=773, 21.8%) and fewer High Risk (MGP n=46, 7.4%, 'Other' n=564, 15.9%) women in MGP, with similar proportions of Moderate Risk women (MGP n=354, 57.3%, 'Other' n=2211, 62.3%). Significant differences include: fewer assisted deliveries for Moderate Risk women in MGP (27.7% MGP, 46.1% 'Other'); fewer labour inductions (Low Risk: 12.8% MGP, 25.1% 'Other'; Moderate Risk: 21.8% MGP, 29.5% 'Other'; High Risk: 19.6% MGP, 34.9% 'Other'); less epidural analgesia (Low Risk: 22.5% MGP, 49.0% 'Other'; Moderate Risk: 20.3% MGP, 38.4% 'Other'; High Risk: 17.4% MGP, 32.6% 'Other'); and differences in the overall pattern of perineal trauma. No significant differences were found in the incidence of post-partum haemorrhage, antenatal hospital admissions, or neonatal admission to Special or Intensive Care., Conclusions: MGP is clinically effective when practiced in a routine setting.

Background: Midwifery Group Practice (MGP) is a continuity of midwifery care model for women of all levels of pregnancy risk available at a tertiary metropolitan hospital in Australia. This paper presents Part II of the demonstration study exploring the effectiveness of MGP, and reports on women's satisfaction with the model of care., Methods: A Maternal Satisfaction Questionnaire was developed and sent to all women (n=120) enrolled in MGP over a three-month period. The questionnaire comprised two open-ended questions asking women to list up to three things they liked and did not like about MGP, and a structured section exploring levels of satisfaction through a five-point Likert response format. The open-ended questions were analysed using qualitative content analysis, and analysis of the structured part of the questionnaire was undertaken by comparing mean scores of satisfaction ranging from -2 (very negative attitudes) to +2 (very positive attitudes)., Results: Of the 120 women who were sent a Maternal Satisfaction Questionnaire, 84 returned their questionnaire (70% response rate). Three overarching themes were identified in the content analysis of open-ended questions, namely: Continuity of care; Accessibility; and Personal and professional attributes of the midwife. Analysis of the structured part of the questionnaire showed that women were satisfied with the care they received in MGP, as indicated by positive scores on all questions., Conclusions: Women being cared for in MGP are satisfied with their care.

Background: Inadvertent perioperative hypothermia (IPH) occurs in many patients because warming techniques are insufficient to counteract thermal redistribution resulting from the ablation of thermoregulatory vasoconstriction associated with anaesthesia. We tested the efficiency of a preoperative forced-air warming (FAW) device (Bair Paws) in preventing IPH., Methods: Sixty-eight adult patients undergoing spinal surgery under general anaesthesia were randomized to receive either normal care or prewarming for 60 min, at 38 degrees C, using the Bair Paws system. All patients received routine FAW intraoperatively., Results: Thirty-one patients were prewarmed and 37 patients were in the control group. There was a 0.3 degrees C smaller decrease in mean core temperature in the prewarmed group at 40, 60, and 80 min post-induction (P< or =0.05). Temperature was maintained above the hypothermic threshold of 36 degrees C in 21 (68%) patients in the prewarmed group, compared with 16 (43%) patients in the control group (P<0.05)., Conclusions: Preoperative warming using the Bair Paws system results in smaller decreases in core temperature intraoperatively and less IPH in patients undergoing spinal surgery under general anaesthesia.

Objective: An exploratory study to determine the proportion of people aged 50-76 years who have Internet access, the location of this access, predictive characteristics of such access, and preparedness to receive unsolicited health information through this medium., Methods: A random sample of 1,000 South Australians was identified from the Australian Electoral Commission roll and contacted by telephone in 2006. They were invited to answer questions about their access to the Internet and attitude towards receiving unsolicited health information via the Internet., Results: Of those contacted, 41% provided information. Of this group, 59% indicated that they had Internet access, mostly at home. Men were more likely than women to have home access (p<0.05). Higher educational achievement, higher economic status and younger age were all significantly associated with access. Of those who had access, 65% would be willing to receive health information through the Internet., Conclusions: More than half the population older than 50 years has access to the Internet at some location, and there is a general acceptance of the possibility of receiving health-promoting material via this medium. However, delivery via the Internet alone would disadvantage those who are less educated, less financially well off and older., Implications: It is likely that a generational change in the entire nature of public communication will influence the efficiency and effectiveness of preventive health promotion delivery via the Internet. In order to facilitate improved health outcomes, issues of disparity of access must be addressed.

Background: The diagnosis of abdominal compartment syndrome depends upon the demonstration of an elevated intra-abdominal pressure (IAP). Direct measures of IAP are impractical in the critical care unit; intravesical pressure (IVP) and intragastric pressure (IGP) should represent acceptable surrogate measures. IVP is the preferred measure of IAP in critical care. We considered that IGP represents a practical alternative. The objective of this preliminary study was to observe the relationship between IGP and IAP., Methods: After Institutional Ethics Board approval, 29 patients having elective laparoscopic surgery were recruited. IAP was measured directly via the abdominal trochar. This was compared with IGP measured via a commercial balloon catheter placed into the stomach., Results: Measured IGP was always more positive than IAP; both showed linear correlation (r2>0.9). When IGP was calibrated against IAP, an estimated difference between the IGP and IAP of+/-2.5 mm Hg for 95% of the measurements was seen., Conclusions: The study demonstrates the strength of the relationship between IGP and IAP in normal individuals. Application of IGP measurement in the critical care patient is necessary to demonstrate its suitability for continuous IAP assessment.

Mitochondria are ubiquitous organelles that are intimately involved in many cellular processes, but whose principal task is to provide the energy necessary for normal cell functioning and maintenance. Disruption of this energy supply can have devastating consequences for the cell, organ, and individual. Over the last two decades, mutations in both mitochondrial DNA (mtDNA) and nuclear DNA have been identified as causative in a number of well-characterized clinical syndromes, although for mtDNA mutations in particular, this relationship between genotype and phenotype is often not straightforward. Despite this, a number of epidemiological studies have been undertaken to assess the prevalence of mtDNA mutations and these have highlighted the impact that mtDNA disease has on both the community and individual families. Although there has been considerable improvement in the diagnosis of mitochondrial disorders, disappointingly this has not been matched by developments toward effective treatment. Nevertheless, our understanding of mitochondrial biology is gathering pace and progress in this area will be crucial to devising future treatment strategies. In addition to mitochondrial disease, evidence for a central role of mitochondria in other processes, such as aging and neurodegeneration, is slowly accumulating, although their role in cancer remains controversial. In this chapter, we discuss these issues and offer our own views based on our cumulative experience of investigating and managing these diseases over the last 20 years., (2007, Elsevier Inc.)

Introduction: Heat and moisture exchangers in combination with a bacterial and viral filter (HMEF) are widely used during general anaesthesia. Excess patient secretions occluding the HMEF have been responsible for previous case reports of airway obstruction. A previous study suggested that differences in HMEF design might contribute to filter obstruction under wet conditions., Methods: We tested 14 types of HMEF under wet conditions to establish which design features contributed to HMEF obstruction. Incremental amounts of saline were added to each filter. The pressure across the filter was measured with an air flow of 60 litre min(-1)., Results: We observed that saline added to the filter was often not easily visible to the casual observer. This concealment volume varied between filters. Ceramic hydrophobic pleated-membrane filters did not absorb saline and their resistance did not change. The composite filter where the moisture exchange component was either polyurethane foam or cellulose absorbed saline and contributed to a rise in resistance of 70-480% with the higher value more typical of the cellulose-paper-based HMEF., Conclusion: The ideal HMEF for use during general anaesthesia should prevent the passage of viral, bacterial and prion material, should provide this filtration performance even under wet conditions, should supplement humidification of the inspired air and anaesthetic gases and should not increase respiratory work. We have identified large variations in HMEF performance under wet conditions. Users should be aware of performance variation in HMEFs and use a filter suited to the intended application.

Spinal anaesthesia developed in the late 1800s with the work of Wynter, Quincke and Corning. However, it was the German surgeon, Karl August Bier in 1898, who probably gave the first spinal anaesthetic. Bier also gained first-hand experience of the disabling headache related to dural puncture. He correctly surmised that the headache was related to excessive loss of cerebrospinal fluid (CSF). In the last 50 yr, the development of fine-gauge spinal needles and needle tip modification, has enabled a significant reduction in the incidence of post-dural puncture headache. Though it is clear that reducing the size of the dural perforation reduces the loss of CSF, there are many areas regarding the pathogenesis, treatment and prevention of post-dural puncture headache that remain contentious. How does the microscopic pattern of collagen alignment in the spinal dura affect the dimensions of the dural perforation? How do needle design, size and orientation influence leakage of CSF through the dural perforation? Can pharmacological methods reduce the symptoms of post-dural puncture headache? By which mechanism does the epidural blood patch cure headache? Is there a role for the prophylactic epidural blood patch? Do epidural saline, dextran, opioids and tissue glues reduce the rate of CSF loss? This review considers these contentious aspects of post-dural puncture headache.

We studied the accumulation of cytochrome c oxidase (COX)-negative skeletal muscle fibres in six patients with a myopathy due to a mitochondrial DNA (mtDNA) defect. Each patient was biopsied on two or more occasions over a period of 3-15 years. Progressive proximal weakness was associated with an increase in the proportion of COX-negative fibres. These fibres were arranged randomly, indicating that each fibre became COX negative independently of the status of neighbouring fibres. The clinical progression of mtDNA myopathy is therefore a consequence of a biochemical defect that develops independently within individual muscle fibres. It is likely that this is due to the clonal expansion of mutant mtDNA.

The cellular prion protein (PrP(C)), predominantly expressed in the central nervous system, is required for pathogenesis of prion neurodegenerative diseases and its conversion into a pathogenic isoform (PrP(Sc)) is a common feature of disease. While the physiological function of PrP(C) remains unclear, accumulating evidence indicates a role for PrP(C) in oxidative homeostasis in vivo and suggests that PrP(C) may be involved in the cellular response to oxidative stress. Mice in which PrP(C) expression has been ablated are viable and develop normally. Here we show that in an inbred line of mice, in tissues that normally express PrP at moderate to high levels, ablation of PrP(C) results in reduced mitochondrial numbers, unusual mitochondrial morphology, and elevated levels of mitochondrial manganese-dependent superoxide dismutase antioxidant enzyme. These observations may have relevance to the pathogenic mechanism for this group of fatal neurodegenerative conditions., (©2002 Elsevier Science (USA).)

The chronological accumulation of mitochondrial dysfunction has been proposed as a potential mechanism in the physiological processes of aging. Cytochrome c oxidase deficient, succinate dehydrogenase positive muscle fibers containing high copy numbers of a mitochondrial DNA mutation are a pathological hallmark of mitochondrial DNA disorders. We show that there is an age-related increase in cytochrome c oxidase-deficient cells in both hippocampal pyramidal neurons and choroid plexus epithelial cells. We suggest that these cells contribute to the cell death and dysfunction in CNS aging.

To test for potential estrogenic activity of plant stanols and plant stanol esters, two short-term tests were performed. These were the E-screen test, which measures a substance's ability to induce proliferation of estrogen-responsive human breast adenocarcinoma (MCF-7) cells in culture, and an in vivo test, which measures uterotrophic activity in immature female rats fed the test substance. Four samples of vegetable oil-derived stanols (containing 88-99% stanols) were tested in the E-screen test, and one sample of wood-derived and one of vegetable oil-derived stanol fatty acid esters were tested in the in vivo test. In the E-screen test, the positive control substance, 17beta-estradiol, at 100 pM, produced a statistically significant, 11.6-fold increase in cell proliferation, as measured by sulforhodamine B staining. None of the stanol preparations produced any increase in cell proliferation when tested at 1, 10, and 100 microM. The highest dose of each stanol sample was associated with microscopic evidence of cytotoxicity and crystalline precipitation in the culture dishes. In the in vivo test, the positive control compound, diethylstilbestrol, produced a significant, dose-related increase in absolute and relative uterus weight in young female rats (17 days old at the start of treatment) fed the compound at 5, 10, and 20 ppb in the diet for 4 days. Neither of the two stanol ester preparations caused any significant change in absolute or relative uterus weight when fed at a concentration of 8.3% in the diet for 4 days. Thus, under the conditions of testing used, neither the free stanols nor the stanol fatty acid ester preparations showed evidence of estrogenic or uterotrophic activity., (Copyright 1999 Academic Press.)

In a standard developmental toxicity study, a mixture of vegetable oil-derived stanol fatty acid esters was administered in the diet to groups of 28 mated female HsdCpb:WU Wistar rats at concentrations that provided 0, 1, 2.5, and 5% total stanols (equivalent to 0, 1.75, 4.38, and 8.76% plant stanol esters). Test diets were adjusted with rapeseed oil to maintain an equivalent caloric content of fatty acids at each of the treatment levels. The treatment period extended from day 0 to 21 of gestation. No compound-related toxicity or clinical effects were seen in any of the treated groups. No statistically significant differences were seen in body weights or body weight gain in the low- or mid-dose groups, although slight but statistically significant decreases in mean body weight relative to controls were seen at gestation days 7 and 14 in the high-dose group. The decreases in body weight in the high-dose group may be attributable to the virtual lack of absorption of the dietary stanols. Body weight gains were equivalent to controls throughout the study except for a statistically significant decrease seen only in the 0- to 7-day gestation period in the high-dose group. No significant effects were seen on food consumption in terms of g/rat/day, but a slight, statistically significant increase was seen in the mid-dose group during gestation days 7-14. A significant increase was seen in the high-dose group during the 7- to 21-day period of gestation. Reproductive performance was not affected by the treatment. There were no statistically significant differences in uterine weight, placental weight, fetal weight, number of fetuses, number of implantation sites, number of corpora lutea, and early/late resorptions between the treated and control groups. In addition, there was no biologically meaningful effect on fetal sex ratio. Visceral and skeletal examinations did not show any significant increases in the incidence of malformations, anomalies, or variations that were considered to be treatment related. Dietary plant (8.76% plant stanol esters) stanol esters at concentrations up to 5% total stanols were concluded to have no adverse effects on reproduction or development., (Copyright 1999 Academic Press.)

Plant stanol esters from wood and vegetable oil sources were tested for genotoxicity in bacterial (Salmonella typhimurium) and mammalian cell (L5178Y) gene mutation assays and in a mammalian cell chromosome aberration assay (CHO cells). The two stanol ester formulations were tested separately at doses up to the limit of solubility, with and without the addition of an Aroclor-induced rat liver microsome metabolic activation system (S9 mix). All tests were performed in duplicate and gave negative results for both wood and vegetable oil stanol ester formulations. Thus, plant stanol esters are not genotoxic under the conditions of exposure tested., (Copyright 1999 Academic Press.)

Plant sterols and their saturated derivatives, known as stanols, reduce serum cholesterol when consumed in amounts of approximately 2 g per day. Stanol fatty acid esters have been developed as a highly fat-soluble form that may lower cholesterol more effectively than stanols. Stanol esters occur naturally in human diets, but at levels far below those known to lower cholesterol. The present study was conducted to assess the safety of stanol esters upon subchronic ingestion at levels comparable to or exceeding those recommended for lowering cholesterol. Two stanol fatty acid ester preparations, wood-derived stanol esters and vegetable oil-derived stanol esters, were fed to groups of 20 male and 20 female Wistar rats for 13 weeks, at dietary concentrations of 0, 0.2, 1, and 5% total stanols (equivalent to 0, 0.34, 1.68, and 8.39% wood-derived stanol esters and 0, 0.36, 1.78, and 8.91% vegetable oil-derived stanol esters). Both preparations were well tolerated as evidenced by the absence of clinical changes or major abnormalities in growth, food and water consumption, ophthalmoscopic findings, routine hematological and clinical chemistry values, renal concentrating ability, composition of the urine, appearance of the feces, estrus cycle length, organ weights, gross necropsy findings, and histopathological findings. Plasma cholesterol and phospholipids were slightly decreased in males fed the stanol esters. In both sexes, plasma levels of plant sterols were decreased whereas those of stanols tended to increase. Fecal excretion of sterols, including cholesterol, and stanols was markedly increased in the stanol ester groups. Compared to controls, male rats fed stanol esters showed somewhat lower liver weights and more pronounced glycogen depletion. These hepatic changes were considered to reflect an altered nutritional condition and not a pathological condition. Plasma levels of vitamin E, vitamin K1, and, to a lesser extent, vitamin D were decreased in males and females fed the high-dose diets. Hepatic levels of vitamins E and D showed similar changes (vitamin K1 in the liver was not determined). For both preparations, the mid-dose level (1% total stanols in the diet) was a no-observed-adverse-effect level. This dietary level provided approximately 0.5 g total stanols/kg body wt/day., (Copyright 1999 Academic Press.)

Objective: To identify environmental barriers to breastfeeding., Method: Focus groups were conducted with young women, parents-to-be, mothers, fathers and grandmothers in 1996 in northern Adelaide, South Australia (a low socio-economic area)., Results: Seven focus groups (4-8 participants per group) were conducted. Breastfeeding was seen as being embarrassing to do in public, and not possible to combine with paid employment. While fathers were not supportive of their partners breastfeeding in public, health professionals were seen as strong advocates of breastfeeding. Bottle feeding was perceived to be more convenient for the mother, more acceptable in public but not as good as breastfeeding for the baby., Conclusion: An environmental that enables women to breastfeed is far from being achieved in this low socio-economic area, particularly in relation to breastfeeding in public., Implications: Breastfeeding promotion should have a public health focus, concentrating on creating a supportive breastfeeding environment through a multi strategy approach aimed not just at mothers but also at the community.

Mitochondrial DNA (mtDNA) mutations are an important cause of neurological disease. The identification of causative mtDNA mutations may be particularly troublesome in blood where there are often low levels of mutant mtDNA. This is evident from a recent study in which heteroplasmic mtDNA mutations in cytochrome c oxidase genes were incorrectly thought to be linked to Alzheimer's disease. We wished to explore whether analysis of blood mtDNA, prepared by a number of DNA extraction procedures, influenced the diagnosis of mtDNA disease. DNA was extracted by different procedures from 4 patients with heteroplasmic mtDNA mutations, and the level of heteroplasmy investigated by radioactive PCR-RFLP analysis. Whilst there was no consistent decrease in the level of mtDNA heteroplasmy, we observed the coamplification of a novel mtDNA pseudogene from DNA samples extracted by a simple 'boiling' procedure using primers designed to screen for the tRNALeu(UUR) A3243G mutation. This pseudogene was readily amplified from DNA extracted from rho degrees (mtDNA-less) cells, confirming its nuclear location. We believe that mtDNA pseudogenes may therefore present significant difficulties in the accurate identification of pathogenic heteroplasmic mtDNA mutations in blood., (Copyright 1998 Academic Press.)

A basic limitation of the study of development in the mouse is the inaccessibility of the embryos, which are encased in the maternal uterus. We demonstrate the first use of ultrasound backscatter microscopy for guiding injections of cells and other agents into early stage mouse embryos. Cells were injected into the mouse neural tube cavity as early as 9.5 days post coitus (E9.5), and into the developing limb buds as early as E10.5. Furthermore, a cell-line engineered to express the secreted factor Sonic Hedgehog (Shh) was injected into early developing mouse brains or limbs. The Shh-expressing cells were found to induce ectopic expression of the Shh target genes Patched and Hnf3beta in the dorsal brain, and to alter digit patterning in the anterior limb bud. These results show that gene misexpression studies can be performed in mouse embryos using ultrasound-guided injection of transfected cells or retroviruses. In combination with the many available mouse mutants, this method offers a new approach for analyzing genetic interactions through gain-of-function studies performed in mutant mouse backgrounds., (Copyright 1998 Elsevier Science Ireland Ltd. All rights reserved.)

We report a new mutation, a G to A transition at nucleotide position 4298 within the mitochondrial tRNA(Ile) gene in a patient with chronic progressive external ophthalmoplegia and multiple sclerosis. The mutation, which alters an evolutionary conserved nucleotide within the anticodon stem, was heteroplasmic in skeletal muscle but was not present in the patient's blood. Single fibre PCR analysis revealed significantly higher levels of the G4298A mutation in cytochrome c oxidase (COX) negative fibres than in COX-positive fibres. This mutation represents the seventh pathogenic nucleotide substitution to be found in this gene and as such confirms the tRNA(Ile) gene as a susceptible "hot spot" for mitochondrial DNA point mutations. Of particular interest is that this patient has the clinical features of both multiple sclerosis and a mitochondrial DNA disorder.