Mitrochondrial target discovery in diabetic skeletal muscle

This study identified the protein PARL (Presenilin-associated rhomboid like) as a potential mediator of the mitochondrial abnormalities that are observed in diabetic skeletal muscle. This was demonstrated by analysing PARL expression in an animal model of type 2 diabetes and by investigating the biological effects of genetic variation in the human PARL gene.

Regulation of skeletal muscle oxidative capacity and insulin signaling by the Mitochondrial Rhomboid Protease PARL

Type 2 diabetes mellitus (T2DM) and aging are characterized by insulin resistance and impaired mitochondrial energetics. In lower organisms, remodeling by the protease pcp1 (PARL ortholog) maintains the function and lifecycle of mitochondria. We examined whether variation in PARL protein content is associated with mitochondrial abnormalities and insulin resistance. PARL mRNA and mitochondrial mass were both reduced in elderly subjects and in subjects with T2DM. Muscle knockdown of PARL in mice resulted in malformed mitochondrial cristae, lower mitochondrial content, decreased PGC1α protein levels, and impaired insulin signaling. Suppression of PARL protein in healthy myotubes lowered mitochondrial mass and insulin-stimulated glycogen synthesis and increased reactive oxygen species production. We propose that lower PARL expression may contribute to the mitochondrial abnormalities seen in aging and T2DM.

Respiratory muscle dysfunction and training in chronic heart failure

A characteristic feature of chronic heart failure (CHF) is reduced exercise tolerance. Several factors contributing to this have been identified, including alterations in central haemodynamics, skeletal muscle oxygen utilisation and respiratory muscle dysfunction. This review focuses on abnormalities identified in respiratory muscle structure and function in CHF and recent evidence for the benefit of selective inspiratory muscle training in CHF. Included in this review are findings from original investigations, with a specific focus on recent published data.

Automated detection of lung nodules in computed tomography images: a review

Lung nodules refer to a range of lung abnormalities the detection of which can facilitate early treatment for lung patients. Lung nodules can be detected by radiologists through examining lung images. Automated detection systems that locate nodules of various sizes within lung images can assist radiologists in their decision making. This paper presents a study of the existing methods on automated lung nodule detection. It introduces a generic structure for lung nodule detection that can be used to represent and describe the existing methods. The structure consists of a number of components including: acquisition, pre-processing, lung segmentation, nodule detection, and false positives reduction. The paper describes the algorithms used to realise each component in different systems. It also provides a comparison of the performance of the existing approaches.

Oxidative pathways as a drug target for the treatment of autism

Importance of the field: Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed.

Areas covered in this review: Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews.

What the reader will gain: This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder.

Take home message: Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.

Association between sexual behavior and cervical cancer screening

Background: Not much is known about whether women who follow Pap testing recommendations report the same pattern of sexual behavior as women who do not.
Methods: Data come from part of a larger population-based computer-assisted telephone survey of 8656 Australians aged 16–64 years resident in Australian households with a fixed telephone line (Australian Longitudinal Study of Health and Relationships [ALSHR]). The main outcome measure in the current study was having had a Pap test in the past 2 years.
Results: Data on a weighted sample of 4052 women who reported sexual experience (ever had vaginal intercourse) were analyzed. Overall, 73% of women in the sample reported having a Pap test in the past 2 years. Variables individually associated with Pap testing behavior included age, education, occupation, cohabitation status, residential location, tobacco and alcohol use, body mass index (BMI), lifetime and recent number of opposite sex partners, sexually transmitted infection (STI) history, and condom reliance for contraception. In adjusted analyses, women in their 30s, those who lived with their partner, and nonsmokers were more likely to have had a recent Pap test. Those who drank alcohol at least weekly were more likely to have had a recent test than irregular drinkers or nondrinkers. Women with no sexual partners in the last year were less likely to have had a Pap test, and women who reported a previous STI diagnosis were more likely to have had a Pap test in the past 2 years.
Conclusions: There are differences in Pap testing behavior among Australian women related to factors that may affect their risk of developing cervical abnormalities. Younger women and regular smokers were less likely to report a recent test. Screening programs should consider the need to focus recruitment strategies for these women.

Genetic control of male fertility in Arabidopsis thaliana : structural analysis of postmeiotic developmental mutants

Seven new male-sterile mutants (ms7–ms13) of Arabidopsis thaliana (L.) Heynh. (ecotype columbia) are described that show a postmeiotic defect of microspore development. In ms9 mutants, microspores recently released from the tetrad appear irregular in shape and are often without exines. The earliest evidence of abnormality in ms12 mutants is degeneration of microspores that lack normal exine sculpturing, suggesting that the MS12 product is important in the formation of pollen exine. Teratomes (abnormally enlarged microsporocytes) are also occasionally present and each has a poorly developed exine. In ms7 mutant plants, the tapetal cytoplasm disintegrates at the late vacuolate microspore stage, apparently causing the degeneration of microspores and pollen grains. With ms8 mutants, the exine of the microspores appears similar to that of the wild type. However, intine development appears impaired and pollen grains rupture prior to maturity. In ms11 mutants, the first detectable abnormality appears at the mid to late vacuolate stage. The absence of fluorescence in the microspores and tapetal cells after staining with 4′,6-diamidino-2-phenylindole (DAPI) and the occasional presence of teratomes indicate degradation of DNA. Viable pollen from ms10 mutant plants is dehisced from anthers but appears to have surface abnormalities affecting interaction with the stigma. Pollen only germinates in high-humidity conditions or during in-vitro germination experiments. Mutant plants also have bright-green stems, suggesting that ms10 belongs to the eceriferum (cer) class of mutants. However, ms10 and cer6 are non-allelic. The ms13 mutant has a similar phenotype to ms10, suggesting is also an eceriferum mutation. Each of these seven mutants had a greater number of flowers than congenic male-fertile plants. The non-allelic nature of these mutants and their different developmental end-points indicate that seven different genes important for the later stages of pollen development have been identified.

Histological alterations in the Antarctic cod, Trematomus bernacchii from Davis Station, East Antarctica

During the summer season 2009/10, a comprehensive environmental impact assessment of the sewage discharge was conducted at Davis Station in the Vestfold Hills region of East Antarctica. As part of this project, a survey of the histology of liver, gill, gonad and muscle tissues in the Antarctic rock cod Trematomus bernacchii from nearshore sites in the receiving environment close to Davis Station in was completed. Fish from 4 sites were examined; 1 site adjacent to the Davis Station sewage outfall (within 500 m of the point of discharge), 2 sites approximately 2 km from the outfall (Anchorage Island and Antennae farm), and 1 site approximately 10 km away from the outfall and adjacent to an Adelie penguin population (Kazak Island). All fish sampled from the sewage outfall site exhibited significant histological alterations in all major tissues. Fish from the other 3 sites showed some alterations in either gill and/or liver tissues. Pathological abnormalities present in all fish collected near the sewage outfall included: extensive multifocal cysts of unknown etiology with necrotic liquification; multifocal granuloma with associated inflammation; coagulative necrosis in the liver; and lamellar hyperplasia with associated proliferation and lamella fusion of the gills. Results of this work form part of a weight of evidence approach alongside ecological monitoring, chemical analysis, ecotoxicological testing and dispersal modelling of the discharge plume which is being used to inform and direct upgrades to the Australian Antarctic Divisions operations and current sewage discharge practises at Davis Station.

Socioeconomic status and bone mineral density in a population-based sample of men

Overall, socioeconomic status (SES) is inversely associated with poorer health outcomes. However, current literature provides conflicting data of the relationship between SES and bone mineral density (BMD) in men. In an age-stratified population-based randomly selected cross-sectional study of men (n = 1467) we assessed the association between SES and lifestyle exposures in relation to BMD. SES was determined by matching the residential address for each subject with Australian Bureau of Statistics 2006 census data for the study region. BMD was measured at the spine and femoral neck by dual energy X-ray absorptiometry. Lifestyle variables were collected by self-report. Regression models were age-stratified into younger and older groups and adjusted for age, weight, dietary calcium, physical activity, and medications known to affect bone. Subjects with spinal abnormalities were excluded from analyses of BMD at the spine. In younger men, BMD was highest at the spine in the mid quintiles of SES, where differences were observed compared to quintile 1 (1–7%, p < 0.05). In older men, the pattern of BMD across SES quintiles was reversed, and subjects from mid quintiles had the lowest BMD, with differences observed compared to quintile 5 (1–7%, p < 0.05). Differences in BMD at the spine across SES quintiles represent a potential 1.5-fold increase in fracture risk for those with the lowest BMD. There were no differences in BMD at the femoral neck. Further research is warranted which examines the mechanisms that may underpin differences in BMD across SES quintiles and to address the current paucity of data in this field of enquiry.

Bone mineral density reference ranges for Australian men : Geelong Osteoporosis Study

Summary : A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations.

Introduction : To provide normative BMD data for Australian men derived from a large population-based random sample.

Methods : An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20–97 years). BMD was quantified at multiple sites using Lunar densitometers.

Results : Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm² per year from age 20. At the hip sites, mean BMD decreased at 0.001–0.006 g/cm² per year from age 20. At the forearm and whole body, BMD peaked at 41–47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain.

Conclusions : These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.

The uptake of an early warning system in an Australian emergency department : a pilot study

Objectives: To evaluate the uptake of an emergency department early warning system (ED EWS) for recognition of, and response to, clinical deterioration.

Design, setting and participants: A descriptive exploratory study conducted in an urban district hospital in Melbourne, Australia. Systematic sampling was used to identify every 10th patient for whom the ED EWS was activated from May 2009 to May 2011.

Main outcome measures: Patient characteristics, ED system data and ED EWS activation characteristics.

Results: ED EWS activation occurred in 1.5% of ED patients; 204 patients were included in this pilot study. The median age was 65.1 years (interquartile range [IQR], 47.8-77.5 years), 89.2% of patients were classified as triage category 2 or 3, and 82.4% of patients were seen by medical staff before ED EWS activation. Hypotension (27.7%) and tachycardia (23.7%) were the most common reasons for ED EWS activation. Median duration of clinical instability was 39 minutes (IQR, 5- 129 minutes). Nurses made 93.1% of ED EWS activations. Median time between documenting physiological abnormalities and ED EWS activation was 5 minutes (IQR, 0- 20). Most patients (57.8%) required hospital admission: 4.4% of patients required intensive care unit admission.

Conclusions: The ED EWS resulted in at least two formal reports of clinical deterioration in ED patients per day, indicating reasonable uptake by clinicians. A greater understanding of clinical deterioration in ED patients is warranted to inform an evidence-based approach to recognition of, and response to, clinical deterioration in ED patients.

Associations between smoking status, lifestyle and lipoprotein subclasses

Background: Although the relationship between cigarette smoking and cardiovascular disease (CVD) is well-established, the underlying mechanisms remain unclear. Smokers have a more atherogenic lipid profile but this may be mediated by lifestyle-related factors. Because detailed analysis of lipoprotein subclasses using nuclear magnetic resonance spectroscopy (NMR) may improve characterisation of lipid abnormalities, we applied the technique to investigate the relationships between smoking status, other lifestyle-related risk factors and lipoproteins in a contemporary cohort.

Methods: A total of 612 participants (360 women) aged 40-69 years at baseline (1990-1994) enrolled in the community-based Melbourne Collaborative Cohort Study had plasma lipoproteins measured using NMR. Data were analysed separately for men and women.

Results: After adjusting for other lifestyle-related risk factors, mean total low-density lipoprotein (LDL) particle concentration was higher for female smokers than non-smokers. Both medium and small LDL particle concentrations contributed to this difference. Both total high-density lipoprotein (HDL) and large HDL particle concentrations were lower for female smokers than non-smokers. The proportion at increased risk (according to NMR-determined particle size and number) was higher for female smokers than non-smokers. For men, there were few differences in lipoprotein measures related to smoking.

Conclusions: Female smokers have a more atherogenic lipoprotein profile than non-smokers, and this difference is independent of lifestyle-related risk factors. Lipoprotein profiles did not differ greatly between male smokers and non-smokers. These data reinforce the importance for women of not smoking.

Cervical screening in Australia 2002–2003

The report presents most recent information on participation in cervical screening, rate of early re-screening, low-grade and high-grade abnormalities detected, incidence of cervical cancer and mortality. Analyses of incidence and mortality data by location (major cities, regional and remote) as well as mortality by Indigenous status are also presented. Where possible, data are presented by state and territory stratification.

Cervical screening in Australia 2000–2001 and 1999–2000

This is the third annual report based on key program activity, performance and outcome indicators to monitor the achievements of the National Cervical Screening Program. The report provides a comprehensive national picture of cervical screening in Australia for 2000-2001 and 1999-2000. The report presents most recent information on participation in cervical screening, rate of early rescreening, low-grade and high-grade abnormalities detected, incidence of cervical cancer and mortality. Analysis of incidence and mortality data by location (rural, remote and metropolitan) as well as mortality by Indigenous status are also presented. Where possible, data are presented by state and territory stratification.

Cervical screening in Australia 1999–2000

Cervical Screening in Australia 1999-2000 provides a comprehensive national picture of cervical screening in Australia for the two-year period 1999-2000, based on key program activity, performance and outcome indicators.The report presents the most recent information on participation in cervical screening, the rates of early re-screening, detection of low-grade and high-grade abnormalities, and cervical cancer incidence and mortality. It includes analyses of incidence and mortality by location (rural, remote and metropolitan) as well as mortality by Indigenous status. Where possible, data are presented by State and Territory as well as for Australia as a whole. Cervical Screening in Australia 1999-2000 is the fourth annual report of the National Cervical Screening Program