The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

Unique residues involved in activation of the multitasking protease/chaperone HtrA from Chlamydia trachomatis

DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly.

Helping understand nutritional gaps in the elderly (HUNGER) : a prospective study of patient factors associated with inadequate nutritional intake in older medical inpatients

BACKGROUND: Malnutrition, and poor intake during hospitalisation, are common in older medical patients. Better understanding of patient-specific factors associated with poor intake may inform nutritional interventions. AIMS: To measure the proportion of older medical patients with inadequate nutritional intake, and identify patient-related factors associated with this outcome. METHODS: Prospective cohort study enrolling consecutive consenting medical inpatients aged 65 years or older. Primary outcome was energy intake less than resting energy expenditure estimated using weight-based equations. Energy intake was calculated for a single day using direct observation of plate waste. Explanatory variables included age, gender, number of co-morbidities, number of medications, diagnosis, usual residence, nutritional status, functional and cognitive impairment, depressive symptoms, poor appetite, poor dentition, and dysphagia. RESULTS: Of 134 participants (mean age 80 years, 51% female), only 41% met estimated resting energy requirements. Mean energy intake was 1220 kcal/day (SD 440), or 18.1 kcal/kg/day. Factors associated with inadequate energy intake in multivariate analysis were poor appetite, higher BMI, diagnosis of infection or cancer, delirium and need for assistance with feeding. CONCLUSIONS: Inadequate nutritional intake is common, and patient factors contributing to poor intake need to be considered in nutritional interventions.

Everyone's problem but nobody's job : staff perceptions and explanations for poor nutritional intake in older medical patients

Aim: Up to 60% of older medical patients are malnourished with further decline during hospital stay. There is limited evidence for effective nutrition intervention. Staff focus groups were conducted to improve understanding of potential contextual and cultural barriers to feeding older adults in hospital. Methods: Three focus groups involved 22 staff working on the acute medical wards of a large tertiary teaching hospital. Staff disciplines were nursing, dietetics, speech pathology, occupational therapy, physiotherapy, pharmacy. A semistructured topic guide was used by the same facilitator to prompt discussions on hospital nutrition care including barriers. Focus groups were tape-recorded, transcribed and analysed thematically. Results: All staff recognised malnutrition to be an important problem in older patients during hospital stay and identified patient-level barriers to nutrition care such as non-compliance to feeding plans and hospital-level barriers including nursing staff shortages. Differences between disciplines revealed a lack of a coordinated approach, including poor knowledge of nutrition care processes, poor interdisciplinary communication, and a lack of a sense of shared responsibility/coordinated approach to nutrition care. All staff talked about competing activities at meal times and felt disempowered to prioritise nutrition in the acute medical setting. Staff agreed education and ‘extra hands’ would address most barriers but did not consider organisational change. Conclusions: Redesigning the model of care to reprioritise meal-time activities and redefine multidisciplinary roles and responsibilities would support coordinated nutrition care. However, effectiveness may also depend on hospitalwide leadership and support to empower staff and increase accountability within a team-led approach.

Malnutrition screening tools : comparison against two validated nutrition assessment methods in older medical inpatients

Objective Although several validated nutritional screening tools have been developed to “triage” inpatients for malnutrition diagnosis and intervention, there continues to be debate in the literature as to which tool/tools clinicians should use in practice. This study compared the accuracy of seven validated screening tools in older medical inpatients against two validated nutritional assessment methods. Methods This was a prospective cohort study of medical inpatients at least 65 y old. Malnutrition screening was conducted using seven tools recommended in evidence-based guidelines. Nutritional status was assessed by an accredited practicing dietitian using the Subjective Global Assessment (SGA) and the Mini-Nutritional Assessment (MNA). Energy intake was observed on a single day during first week of hospitalization. Results In this sample of 134 participants (80 ± 8 y old, 50% women), there was fair agreement between the SGA and MNA (κ = 0.53), with MNA identifying more “at-risk” patients and the SGA better identifying existing malnutrition. Most tools were accurate in identifying patients with malnutrition as determined by the SGA, in particular the Malnutrition Screening Tool and the Nutritional Risk Screening 2002. The MNA Short Form was most accurate at identifying nutritional risk according to the MNA. No tool accurately predicted patients with inadequate energy intake in the hospital. Conclusion Because all tools generally performed well, clinicians should consider choosing a screening tool that best aligns with their chosen nutritional assessment and is easiest to implement in practice. This study confirmed the importance of rescreening and monitoring food intake to allow the early identification and prevention of nutritional decline in patients with a poor intake during hospitalization.

A review of medical image watermarking requirements for teleradiology

Teleradiology allows medical images to be transmitted over electronic networks for clinical interpretation, and for improved healthcare access, delivery and standards. Although, such remote transmission of the images is raising various new and complex legal and ethical issues, including image retention and fraud, privacy, malpractice liability, etc., considerations of the security measures used in teleradiology remain unchanged. Addressing this problem naturally warrants investigations on the security measures for their relative functional limitations and for the scope of considering them further. In this paper, starting with various security and privacy standards, the security requirements of medical images as well as expected threats in teleradiology are reviewed. This will make it possible to determine the limitations of the conventional measures used against the expected threats. Further, we thoroughly study the utilization of digital watermarking for teleradiology. Following the key attributes and roles of various watermarking parameters, justification for watermarking over conventional security measures is made in terms of their various objectives, properties, and requirements. We also outline the main objectives of medical image watermarking for teleradiology, and provide recommendations on suitable watermarking techniques and their characterization. Finally, concluding remarks and directions for future research are presented.

AEHRC & QUT at TREC 2011 Medical Track : a concept-based information retrieval approach

The Australian e-Health Research Centre and Queensland University of Technology recently participated in the TREC 2011 Medical Records Track. This paper reports on our methods, results and experience using a concept-based information retrieval approach. Our concept-based approach is intended to overcome specific challenges we identify in searching medical records. Queries and documents are transformed from their term-based originals into medical concepts as de ned by the SNOMED-CT ontology. Results show our concept-based approach performed above the median in all three performance metrics: bref (+12%), R-prec (+18%) and Prec@10 (+6%).

Three-dimensional medical ultrasound

A number of groups around the world are working in the field of three dimensional(3D) ultrasound (US) in order to obtain higher quality diagnostic information. 3D US, in general, involves collecting a sequence of conventional 2D US images along with information on the position and orientation of each image plane. A transformation matrix is calculated relating image space to real world space. This allows image pixels and region of interest (ROI) points drawn on the image to be displayed in 3D. The 3D data can be used for the production of volume or surface rendered images, or for the direct calculation of ROI volumes.

An evolving perspective on physical activity counselling by medical professionals

Background Physical inactivity is a modifiable risk factor for many chronic conditions and a leading cause of premature mortality. An increasing proportion of adults worldwide are not engaging in a level of physical activity sufficient to prevent or alleviate these adverse effects. Medical professionals have been identified as potentially powerful sources of influence for those who do not meet minimum physical activity guidelines. Health professionals are respected and expected sources of advice and they reach a large and relevant proportion of the population. Despite this potential, health professionals are not routinely practicing physical activity promotion. Discussion Medical professionals experience several known barriers to physical activity promotion including lack of time and lack of perceived efficacy in changing physical activity behaviour in patients. Furthermore, evidence for effective physical activity promotion by medical professionals is inconclusive. To address these problems, new approaches to physical activity promotion are being proposed. These include collaborating with community based physical activity behaviour change interventions, preparing patients for effective brief counselling during a consultation with the medical professional, and use of interactive behaviour change technology. Summary It is important that we recognise the latent risk of physical inactivity among patients presenting in clinical settings. Preparation for improving patient physical activity behaviours should commence before the consultation and may include physical activity screening. Medical professionals should also identify suitable community interventions to which they can refer physically inactive patients. Outsourcing the majority of a comprehensive physical activity intervention to community based interventions will reduce the required clinical consultation time for addressing the issue with each patient. Priorities for future research include investigating ways to promote successful referrals and subsequent engagement in comprehensive community support programs to increase physical activity levels of inactive patients. Additionally, future clinical trials of physical activity interventions should be evaluated in the context of a broader framework of outcomes to inform a systematic consideration of broad strengths and weaknesses regarding not only efficacy but cost-effectiveness and likelihood of successful translation of interventions to clinical contexts.

Integration of medical images to the teaching of systematic pathology : an evaluation of relevance

A sound knowledge of pathological disease processes is required for professional practice within health professions. The project described in this paper reviewed the resources currently available for the delivery of systematic pathology tutorials. Additional complementary resources were developed and the inclusion of these additional learning resources in practical tutorial sessions was evaluated for their impact on student learning. Student evaluation of the learning resources was undertaken across one semester with two different cohorts of health profession students using questionnaires and focus group discussion. Both cohorts reported an enhancement to their understanding of pathological disease processes through the use of the additional resources. Results indicate student perception of the value of the resources correlates with staff perception and is independent of prior experiences.

Educational technology in medical imaging education

Purpose The emergence of digital technologies has created enthusiasm for their application to student learning. An evolving issue in medical imaging is how these technologies might be implemented within programs. Method A review of the literature was performed to explore applications and issues of educational technology in medical imaging Results There are a range of applications for educational technology within medical imaging education however limitations do exist. Learners must be supported by the development of skills to utilize education technologies. The digital picture archival and communication environment presents an ideal opportunity to enhance student learning through interaction and engagement with images. Implementation of education technologies to support student placement activities is an area for future development provided equity of access is addressed. Conclusion Education technologies have specific application to medical imaging education as part of a blended curriculum.

Vaccination of healthy and diseased koalas (Phascolarctos cinereus) with a Chlamydia pecorum multi-subunit vaccine : evaluation of immunity and pathology

Chlamydial infections represent a major threat to the long-term survival of the koala and a successful vaccine would provide a valuable management tool. Vaccination however has the potential to enhance inflammatory disease in animals exposed to a natural infection prior to vaccination, a finding in early human and primate trials of whole cell vaccines to prevent trachoma. In the present study, we vaccinated both healthy koalas as well as clinically diseased koalas with a multi-subunit vaccine consisting of Chlamydia pecorum MOMP and NrdB mixed with immune stimulating complex as adjuvant. Following vaccination, there was no increase in inflammatory pathological changes in animals previously infected with Chlamydia. Strong antibody (including neutralizing antibodies) and lymphocyte proliferation responses were recorded in all vaccinated koalas, both healthy and clinically diseased. Vaccine induced antibodies specific for both vaccine antigens were observed not only in plasma but also in ocular secretions. Our data shows that an experimental chlamydial vaccine is safe to use in previously infected koalas, in that it does not worsen infection-associated lesions. Furthermore, the prototype vaccine is effective, as demonstrated by strong levels of neutralizing antibody and lymphocyte proliferation responses in both healthy and clinically diseased koalas. Collectively, this work illustrates the feasibility of developing a safe and effective Chlamydia vaccine as a tool for management of disease in wild koalas.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women's Health

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.