The use of sensitive chemical antibodies for diagnosis: detection of low levels of Epcam in breast cancer

EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70–90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues.

Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non- specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy.

Peptide-fluorescent bacteria complex as luminescent reagents for cancer diagnosis

Currently in clinic, people use hematoxylin and eosin stain (H&E stain) and immunohistochemistry methods to identify the generation and genre of cancers for human pathological samples. Since these methods are inaccurate and time consuming, developing a rapid and accurate method to detect cancer is urgently demanded. In our study, binding peptides for lung cancer cell line A549 were identified using bacteria surface display method. With those binding peptides for A549 cells on the surface, the fluorescent bacteria (Escherichia coli with stably expressed green fluorescent protein) were served as specific detecting reagents for the diagnosis of cancers. The binding activity of peptide-fluorescent bacteria complex was confirmed by detached cancer cells, attached cancer cells and mice tumor xenograft samples. A unique fixation method was developed for peptide-bacteria complex in order to make this complex more feasible for the clinic use. This peptide-fluorescent bacteria complex has great potential to become a new diagnostic tool for clinical application.

Clinical features and risk factors of oedematous Mycobacterium ulcerans lesions in an Australian population: beware cellulitis in an endemic area

Introduction
Oedematous lesions are a less common but more severe form of Mycobacterium ulcerans disease. Misdiagnosis as bacterial cellulitis can lead to delays in treatment. We report the first comprehensive descriptions of the clinical features and risk factors of patients with oedematous disease from the Bellarine Peninsula of south-eastern Victoria, Australia.

Methods
Data on all confirmed Mycobacterium ulcerans cases managed at Barwon Health, Victoria, were collected from 1/1/1998–31/12/2012. A multivariate logistic regression model was used to assess associations with oedematous forms of Mycobacterium ulcerans disease.

Results
Seventeen of 238 (7%) patients had oedematous Mycobacterium ulcerans lesions. Their median age was 70 years (IQR 17–82 years) and 71% were male. Twenty-one percent of lesions were WHO category one, 35% category two and 41% category three. 16 (94%) patients were initially diagnosed with cellulitis and received a median 14 days (IQR 9–17 days) of antibiotics and 65% required hospitalization prior to Mycobacterium ulcerans diagnosis. Fever was present in 50% and pain in 87% of patients. The WCC, neutrophil count and CRP were elevated in 54%, 62% and 75% of cases respectively. The median duration of antibiotic treatment was 84 days (IQR 67–96) and 94% of cases required surgical intervention. On multivariable analysis, there was an increased likelihood of a lesion being oedematous if on the hand (OR 85.62, 95% CI 13.69–535.70; P<0.001), elbow (OR 7.83, 95% CI 1.39–43.96; p<0.001) or ankle (OR 7.92, 95% CI 1.28–49.16; p<0.001), or if the patient had diabetes mellitus (OR 9.42, 95% CI 1.62–54.74; p = 0.02).

Conclusions
In an Australian population, oedematous Mycobacterium ulcerans lesions present with similar symptoms, signs and investigation results to, and are commonly mistakenly diagnosed for, bacterial limb cellulitis. There is an increased likelihood of oedematous lesions affecting the hand, elbow or ankle, and in patients with diabetes.

Gratitude : a basis for positive psychology interventions with a clinical population

This thesis includes a literature review that summarises the types of psychological research that have been conducted into gratitude, including the research conceptualising and developing assessments around it and exploring its associations with wellbeing, personality, social interaction, and health. The review focuses specifically on the research examining the relationship of gratitude to anxiety, depression and sleep, providing an outline of current theories about the relationship of positive affect to wellbeing, and a summary of the evidence to date. It is noted that there is comparatively little research on the impact of gratitude on anxiety and sleep but promising findings about the role of gratitude in the treatment of depression. Taken together, it is argued, the current research supported the need for trials of gratitude interventions specifically with clinical populations. Finally, the review looks at the literature of experimental interventions using gratitude. Particular emphasis is given to what has been learnt through these trials that might guide the focus and design of future research.

There follows the report of a randomized wait-list controlled pre-post trial of a gratitude diary intended to extend the research into the efficacy of gratitude diaries in the treatment of clinical populations with depression, anxiety and sleep difficulties. It was hypothesised that after completing a brief gratitude diary for three weeks, participants would have lower scores on measures of depression, anxiety, and perceived sleep difficulties, and higher scores on a measure of life satisfaction. These results were also expected to be evident at three-week follow-up. In a randomised waitlist-controlled trial with repeated measures pre-, post- and follow-up design, participants (N=109, from Australia) aged 18-64 years with a current self-reported diagnosis of an anxiety disorder and/or depression, took part in a self-help study via the internet. After completing the diary participants had lower scores on measures of depression, anxiety and perceived sleep difficulties and higher scores on a measure of subjective wellbeing than immediately pre-intervention. In addition, they had improved scores on a measure of stress. At three-week follow-up scores on depression and perceived sleep difficulties were no longer significantly different from pre-intervention, however improvements for subjective wellbeing and stress at post-intervention were maintained. At follow-up scores for anxiety had not only been maintained but had improved significantly beyond post-intervention results. This trial provides support for the use of gratitude diaries as a short-term intervention with a clinical population. Different patterns of anxiety and depression scores raise the possibility that gratitude interventions work differently to address depression and anxiety symptoms and provide support for the idea that gratitude interventions may have sustainable effects on anxiety symptoms.

Are material safety data sheets (MSDS) useful in the diagnosis and management of occupational contact dermatitis?

This study assesses both the success of medical practitioners in accessing hazardous substances' information from product manufacturers and the accuracy and clinical usefulness of Material Safety Data Sheets (MSDS) presented by workers with suspected occupational contact dermatitis (OCD). 00 consecutively presented MSDS were collected from 42 workers attending an occupational dermatology clinic. Product manufacturers were contacted to verify ingredients. MSDS were evaluated for compliance with the Australian criteria for listing of OCD relevant information (sensitizers present at a concentration > or =1%, irritants present at a concentration > or =20%), and for clinical usefulness. All sensitizers were checked for clinical relevance to the worker's dermatitis. Manufacturers supplied product constituents for 77/100 MSDS. 58 MSDS satisfied the Australian standard. 57/58 MSDS were deemed clinically useful. Irritants were listed for 19/23 MSDS and sensitizers were listed for 30/68 MSDS (P = 0.001). 3 MSDS contained sensitizers, which were clinically relevant to the presenting worker's dermatitis, 1 appropriately listed, 1 present at > or =1% but not listed, and 1 present at <1% in the product and therefore, not required to be listed. Sensitizers are frequently omitted from MSDS and clinicians are often unsuccessful in obtaining crucial information from manufacturers. MSDS are inadequate for the protection and diagnosis of workers with suspected OCD.

Validation and development of a clinical prediction rule in clinically suspected community-acquired pneumonia

To develop a mathematical model to predict the probability of having community-acquired pneumonia and to evaluate an already developed prediction rule that has not been validated in a clinical scenario.

Validation of DNA methylation biomarkers for diagnosis of acute lymphoblastic leukemia

DNA methylation biomarkers capable of diagnosis and subtyping have been found for many cancers. Fifteen such markers have previously been identified for pediatric acute lymphoblastic leukemia (ALL). Validation of these markers is necessary to assess their clinical utility for molecular diagnostics. Substantial efficiencies could be achieved with these DNA methylation markers for disease tracking with potential to replace patient-specific genetic testing.

Association between surgical indications, operative risk, and clinical outcome in infective endocarditis: a prospective study from the International Collaboration on Endocarditis.

Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined.

Diagnosis and management of oral leishmaniasis--case series and literature review

The worldwide prevalence of leishmaniasis is increasing because of ecologic changes and increased medical profession awareness. Furthermore, solitary cases have been recently reported in Western countries. The authors describe the epidemiology, mode of transmission, and diagnosis of leishmaniasis and present 4 oral cases treated with systemic, localized, or combined therapy. The authors suggest that clinicians should maintain a high index of suspicion for atypical, resistant, oral and perioral lesions in individuals with a history of traveling in certain geographic regions. After diagnosis, treatment should be determined jointly by experts from the fields of oral and maxillofacial surgery, oral medicine, and dermatology based on leishmaniasis species and clinical presentation.

Restorative care for palliative patients: a retrospective clinical audit of outcomes for patients admitted to an inpatient palliative care unit

BACKGROUND: Restorative care in palliative care is a subset of rehabilitation that aims to improve quality of life through restoration or maintenance of physical functions. Outcomes for restorative care programmes delivered by palliative care units have not adequately been assessed. OBJECTIVES: The objectives are to examine the outcomes of a restorative care programme in an inpatient palliative care unit, including discharge destination, performance status changes and length of stay. METHODS: Retrospective clinical audit of consecutive patients admitted to Calvary Health Care Bethlehem in Melbourne, Australia, principally for restorative care from July 2010 to December 2011. RESULTS: 79 admissions met inclusion criteria. Mean age was 76.5 years (SD=11.14) and 43 (54%) were men. 75 (95%) patients had a malignant diagnosis; of these, the majority had lung cancer (24%). 16 patients (20%) were discharged home, 51 (65%) died and 12 (15%) were transferred. Of the patients discharged home, only 6 (38% of those discharged home) improved their performance status. Those discharged home had a significantly shorter length of stay (17 days compared to 39 days; p<0.05). Patients discharged home also had significantly better Australia-modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups-Activities of Daily Living (RUG-ADL) scores on admission than others (both p<0.05). CONCLUSIONS: The majority of patients referred for restorative care died during admission, with only a minority discharged home. Patients discharged most commonly experienced maintenance and not improvement in performance status. A successful discharge home following restorative care was associated with a shorter length of stay. Implications and recommendations for successful restorative care will be discussed.

Retrospective clinical audit of outcomes for patients admitted to an inpatient palliative care unit for restorative care

Background Restorative care in palliative care is a subset of rehabilitation that aims to improve quality of life through restoration or maintenance of physical functions. Outcomes for restorative care programmes delivered by palliative care units have not adequately been assessed.

Objectives The objectives are to examine the outcomes of a restorative care programme in an inpatient palliative care unit, including discharge destination, performance status changes and length of stay.

Methods Retrospective clinical audit of consecutive patients admitted to Calvary Health Care Bethlehem in Melbourne, Australia, principally for restorative care from July 2010 to December 2011.

Results 79 admissions met inclusion criteria. Mean age was 76.5 years (SD=11.14) and 43 (54%) were men. 75 (95%) patients had a malignant diagnosis; of these, the majority had lung cancer (24%). 16 patients (20%) were discharged home, 51 (65%) died and 12 (15%) were transferred. Of the patients discharged home, only 6 (38% of those discharged home) improved their performance status. Those discharged home had a significantly shorter length of stay (17 days compared to 39 days; p<0.05). Patients discharged home also had significantly better Australia-modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups-Activities of Daily Living (RUG-ADL) scores on admission than others (both p<0.05).

Conclusions The majority of patients referred for restorative care died during admission, with only a minority discharged home. Patients discharged most commonly experienced maintenance and not improvement in performance status. A successful discharge home following restorative care was associated with a shorter length of stay. Implications and recommendations for successful restorative care will be discussed.

The relationship between suicide and violence in schizophrenia: analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset

Background

Suicide and violence often co-occur in the general population as well as in mentally ill individuals. Few studies, however, have assessed whether these suicidal behaviors are predictive of violence risk in mental illness.

Aims

The aim of this study is to investigate whether suicidal behaviors, including suicidal ideation, threats, and attempts, are significantly associated with increased violence risk in individuals with schizophrenia.

Method

Data for these analyses were obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, a randomized controlled trial of antipsychotic medication in 1460 adults with schizophrenia. Univariate Cox regression analyses were used to calculate hazard ratios (HRs) for suicidal ideation, threats, and attempts. Multivariate analyses were conducted to adjust for common confounding factors, including: age, alcohol or drug misuse, major depression, antisocial personality disorder, depression, hostility, positive symptom, and poor impulse control scores. Tests of discrimination, calibration, and reclassification assessed the incremental predictive validity of suicidal behaviors for the prediction of violence risk.

Results

Suicidal threats and attempts were significantly associated with violence in both males and females with schizophrenia with little change following adjustment for common confounders. Only suicidal threats, however, were associated with a significant increase in incremental validity beyond age, diagnosis with a comorbid substance use disorder, and recent violent behavior.

Conclusions

Suicidal threats are independently associated with violence risk in both males and females with schizophrenia, and may improve violence risk prediction.

Mass spectrometry-based proteomic data for cancer diagnosis using interval type-2 fuzzy system

An interval type-2 fuzzy logic system is introduced for cancer diagnosis using mass spectrometry-based proteomic data. The fuzzy system is incorporated with a feature extraction procedure that combines wavelet transform and Wilcoxon ranking test. The proposed feature extraction generates feature sets that serve as inputs to the type-2 fuzzy classifier. Uncertainty, noise and outliers that are common in the proteomic data motivate the use of type-2 fuzzy system. Tabu search is applied for structure learning of the fuzzy classifier. Experiments are performed using two benchmark proteomic datasets for the prediction of ovarian and pancreatic cancer. The dominance of the suggested feature extraction as well as type-2 fuzzy classifier against their competing methods is showcased through experimental results. The proposed approach therefore is helpful to clinicians and practitioners as it can be implemented as a medical decision support system in practice.