Neurobiological and psychological evidence of chronic stress in prostate cancer patients.

To measure the prevalence and severity of Generalised Anxiety Disorder (GAD), hypo- and hypercortisolaemia, and their association in a sample of prostate cancer (PCa) patients, 97 Australian PCa patients completed a background questionnaire and the GAD-7, and provided a sample of saliva collected 30-45 min after waking. The mean GAD7 score was 9.67 (SD = 3.09), and prevalence rates for current anxiety were higher than those reported for non-PCa males of a similar age. Mean salivary cortisol concentrations (30.78 nmol/L, SD = 13.97 nmol/L) were also higher than for age-comparative non-PCa men. There was a significant inverse correlation between GAD and cortisol (r = -. 209, p < .05), and four subgroups of GAD-cortisol patients were able to be identified, with evidence of both hyper- and hypocortisolaemia. These findings provide initial neurobiological evidence of the chronic and profound nature of stress experienced by PCa patients, and also suggest a possible measure that might be used to identify most at-risk PCa patients.

Measuring depression in prostate cancer patients: does the scale used make a difference?

This study investigated differences in the scores, relative severity and major depressive disorder (MDD) and subsyndromal depression status from three standardised self-report scales for depression in prostate cancer (PCa) patients. The Hospital Anxiety and Depression Scale Depression subscale (HADS-D), the Self-rating Depression Scale (SDS) and the Patient Health Questionnaire (PHQ-9) for depression were administered to a sample of 138 PCa patients via mail-out self-reports in Queensland, Australia during May 2014. Despite significant correlations between the total scores from the three scales, severity classification differed across the three scales and there was evidence of considerable underestimation of depression by the HADS-D compared to the PHQ-9, and a similar tendency for the SDS. When patients were classified as fulfilling the criteria for Subsyndromal Depression on the PHQ-9, there were statistically significant differences in the proportion of patients who met those criteria using the HADS-D and the SDS, with large underestimation also present for these two scales. Scale construction and depression items included can produce different results across scales, making inter-study comparisons difficult. Implications for research and clinical practice are described.

Total depression and subtypes in prostate cancer survivors 10 years after treatment.

To describe the prevalence, severity and nature of depression in a sample of prostate cancer (PCa) survivors 10 years after diagnosis and treatment, 146 Australian patients from the RADAR trial who received their diagnosis 10 years previously completed the Zung Self-rating Depression Scale and a background questionnaire. Prevalence rates for clinically significant depression and severe depression were higher than those reported for the non-PCa men of the same age in Australia. The most common subtype of depression was Anhedonia, followed by Cognitive depression. Change in eating habits was the most powerful depression symptom predicting Anhedonia. By providing the first detailed documentation of major depression prevalence in PCa survivors, plus describing the nature of that depression, these data suggest that there is an ongoing need to provide treatments for these men and that those treatments should be focussed upon loss of previously available sources of enjoyment.

The Hot Flush Beliefs and Behaviour Scale for Men (HFBBS-Men) undergoing treatment for prostate cancer.

OBJECTIVE: Hot flushes and night sweats (HFNS) are commonly experienced by men receiving treatment for prostate cancer. Cognitive behavioural therapy (CBT) has been found to be an effective treatment for HFNS in women, but cognitions and behavioural reactions to HFNS in men are under-researched. This study describes the development of the HFNS beliefs and behaviour scale for men. METHODS: HFNS beliefs and behaviour items were generated from a qualitative study, from pilot interviews with men with prostate cancer and HFNS, and from scales used for women. 118 men with prostate cancer, aged above 18, English-speaking, who had minimum of seven HFNS weekly for at least 1 month, completed the initial measure, and measures of HFNS frequency, problem rating, anxiety and depression (HADS). Principal components analyses with orthogonal rotation determined the most coherent solution. RESULTS: Exploratory factor analysis culminated in a 17-item HFNS beliefs and behaviour scale for men (HFBBS-Men) with three subscales: (1) HFNS social context and sleep, (2) Calm/Acceptance, (3) Humour/Openness. The subscales had reasonable internal consistency (Cronbach alpha 0.56-0.83). Validity was supported, by correlations between subscale 1, HFNS frequency, problem-rating and mood; men with locally advanced cancer more likely to adopt Calm/Acceptance and those with metastatic cancer Humour/Openness. CONCLUSIONS: Preliminary analysis of the HFBBS-Men suggests that it is a psychometrically sound instrument, grounded in men's experiences. As a measure of cognitive and behavioural reactions to HF/NS, the HFBBS-Men should increase understanding of the mediators of outcomes of psychological interventions, such as CBT.

Does resilience 'buffer' against depression in prostate cancer patients? A multi-site replication study.

Although psychological resilience has been shown to 'buffer' against depression following major stressors, no studies have reported on this relationship within the prostate cancer (PCa) population, many of whom are at elevated risk of depression, health problems and suicide. To investigate the effects of resilience upon anxiety and depression in the PCa population, postal surveys of 425 PCa patients were collected from two sites: 189 PCa patients at site 1 and 236 at site 2. Background data plus responses to depression and resilience scales were collected. Results indicated that total resilience score was a significant buffer against depression across both sites. Resilience had different underlying component factor structures across sites, but only one (common) factor significantly (inversely) predicted depression. Within that factor, only some specific items significantly predicted depression scores, suggesting a focused relationship between resilience and depression. It may be concluded that measures of resilience may be used to screen depression at-risk PCa patients. These patients might benefit from resilience training to enhance their ability to cope effectively with the stress of their diagnosis and treatment. A focus upon specific aspects of overall resilience may be of further benefit in both these processes.

The incidence and causes of different subtypes of depression in prostate cancer patients: implications for cancer care.

Although depression occurs in prostate cancer patients at a higher incidence than in age-matched non-cancer peers, little is known about the relative incidence of subtypes of depression among these patients. To examine this issue, 507 prostate cancer patients completed a survey questionnaire of background factors, depression symptoms, and common prostate cancer-related stressors. Five common subtypes of depression were defined from the wider literature, and patients' depressive symptomatology was used to determine their scores on each of the five depression subtypes. Nearly half of the patients had scores which could be classified as clinically significant for at least one of the five depression subtypes, with some patients showing clinically significant scores for multiple depression subtypes. Different depression subtypes were predicted by different prostate-cancer-related stressors. Because each of the five depressive subtypes examined here has different symptomatologies and treatment recommendations, these data suggest that treatment goals for prostate cancer patients might vary according to the type of depression a patient presents.

AF-MSCs fate can be regulated by culture conditions.

Human mesenchymal stem cells (hMSCs) represent a population of multipotent adherent cells able to differentiate into many lineages. In our previous studies, we isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF) and characterized them based on their phenotype, pluripotency and proteomic profile. In the present study, we investigated the plasticity of these cells based on their differentiation, dedifferentiation and transdifferentiation potential in vitro. To this end, adipocyte-like cells (AL cells) derived from AF-MSCs can regain, under certain culture conditions, a more primitive phenotype through the process of dedifferentiation. Dedifferentiated AL cells derived from AF-MSCs (DAF-MSCs), gradually lost the expression of adipogenic markers and obtained similar morphology and differentiation potential to AF-MSCs, together with regaining the pluripotency marker expression. Moreover, a comparative proteomic analysis of AF-MSCs, AL cells and DAF-MSCs revealed 31 differentially expressed proteins among the three cell populations. Proteins, such as vimentin, galectin-1 and prohibitin that have a significant role in stem cell regulatory mechanisms, were expressed in higher levels in AF-MSCs and DAF-MSCs compared with AL cells. We next investigated whether AL cells could transdifferentiate into hepatocyte-like cells (HL cells) directly or through a dedifferentiation step. AL cells were cultured in hepatogenic medium and 4 days later they obtained a phenotype similar to AF-MSCs, and were termed as transdifferentiated AF-MSCs (TRAF-MSCs). This finding, together with the increase in pluripotency marker expression, indicated the adaption of a more primitive phenotype before transdifferentiation. Additionally, we observed that AF-, DAF- and TRAF-MSCs displayed similar clonogenic potential, secretome and proteome profile. Considering the easy access to this fetal cell source, the plasticity of AF-MSCs and their potential to dedifferentiate and transdifferentiate, AF may provide a valuable tool for cell therapy and tissue engineering applications.

Proteomic biomarkers for the early detection of acute kidney injury.

Acute kidney injury (AKI) comprises several syndromes that are associated with a sudden decrease in renal function. AKI is a common condition especially among critically ill patients. It is typically multifactorial and of great prognostic significance. The incidence of AKI has increased while the associated mortality rate has remained unchanged over the last years. Recent definitions of AKI, namely the Risk, Injury, Failure, Loss of renal function and End-stage kidney disease (RIFLE) classifycation or the Acute Kidney Injury Network (AKIN) criteria, incorporate serum creatinine and urine output as the principal markers to define and detect AKI. However, elevated serum creatinine or oliguria were demonstrated to detect AKI at late stages of renal injury when preventive strategies may be less effective. Therefore, there has recently been a great scientific interest in obtainng valuable markers for early AKI detection. In the last 5 years numerous new markers such as neutrophil-gelatinase associated lipo-calin, interleukin-18, cystatin C and kidney injury molecule 1 in the urine and/or serum have been studied and proposed as early detection markers of AKI. Persistently, these markers performed well in initial pilot trials. However, these promising results could often not be confirmed in later, larger multicentre trials and limitation of these biomarkers in the early diagnosis of renal injury were discovered. Furthermore, as AKI is multi-factorial and heterogeneous in origin, it seems likely that not one single marker but a panel of biomarkers will be required to detect all subtypes of AKI early during their evolution. This has initiated proteomic studies to develop panels of biomarkers which may facilitate early detection of AKI. The present review will focus on the most important clinical studies evaluating the ability of single AKI biomarkers and on those in clinical proteomics that attempted to establish panels of biomarkers in urine for early and accurate AKI diagnosis and prognosis.

A comparison between MALDI-MS and CE-MS data for biomarker assessment in chronic kidney diseases.

Non-invasive detection of diseases, based on urinary proteomics, is becoming an increasingly important area of research, especially in the area of chronic kidney disease (CKD). Different platforms have been used in independent studies, mostly capillary-electrophoresis coupled ESI-MS (CE-MS), liquid chromatography coupled mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). We have compared the performance of CE-MS with MALDI-MS in detecting CKD, based on a cohort of 137 urine samples (62 cases and 75 controls). Data cross-talk between the two platforms was established for the comparison of detected biomarkers. The results demonstrate superior performance of the CE-MS approach in terms of peptide resolution and obtained disease prediction accuracy rates. However, the data also demonstrate the ability of the MALDI-MS approach to separate CKD patients from controls, at slightly reduced accuracy, but expected reduced cost and time. As a consequence, a practical approach can be foreseen where MALDI-MS is employed as an inexpensive, fast, and robust screening tool to detect probable CKD. In a second step, high resolution CE-MS could be used in those patients only that scored negative for CKD in the MALDI-MS analysis, reducing costs and time of such a program.

Proteomics approaches in the quest of kidney disease biomarkers.

Proteomics refers to a group of analytical techniques for high throughput protein analysis, providing evidence for protein expression levels, subcellular localization, post-translational modifications and molecular interactions. As such, proteomics has contributed largely to our knowledge regarding molecular mechanisms underlying health and disease and pinpointed potential disease biomarkers. The scope of this review is to briefly introduce the principles of major proteomics techniques employed in biological research, including novel quantitative and molecular imaging mass spectrometry-based platforms. A few examples from the application of these techniques in biomarker discovery for kidney diseases are also provided.

An exploratory analysis of the use of cognitive, adaptive and behavioural indices for cluster analysis of ASD subgroups.

BACKGROUND: Autism spectrum disorder (ASD) includes symptoms that vary in severity and frequency between children. Consequently, multiple psychometric assessment procedures are recommended to detect an ASD, including scales which asses the presence and nature of ASD-related behaviour. However, to date, few studies have examined the relative and specific contribution which such behaviourally oriented scales can make to the diagnosis of individual children with ASD. METHOD: Cluster analysis was used to explore the common characteristics of a group of 53 preschool and elementary school children with an ASD, based upon scores on tests of cognitive ability, adaptive behaviour and behavioural checklists designed to measure the presence of typical ASD. RESULTS: Data confirmed the expected variability in intelligence test scores. In addition, measures of adaptive behaviour and data from a behaviourally based rating scale suggested that children with Asperger's Disorder and autism might be reclassified into subgroups according to the presence of particular ASD-specific behaviours. CONCLUSIONS: As well as confirming that children with ASD vary in their adaptive behaviour and cognitive levels, these data emphasise the limited contribution such assessment procedures make to an understanding of the child's day-to-day behaviour and functioning, thus arguing for the inclusion of behaviourally based rating scales to develop ideographic intervention plans.