A factor analytic investigation of the Tripartite model of affect in a clinical sample of young Australians

Background

To investigate and compare the predictors of personal and perceived stigma associated with depression.

Method

Three samples were surveyed to investigate the predictors: a national sample of 1,001 Australian adults; a local community sample of 5,572 residents of the Australian Capital Territory and Queanbeyan aged 18 to 50 years; and a psychologically distressed subset (n = 487) of the latter sample. Personal and Perceived Stigma were measured using the two subscales of the Depression Stigma Scale. Potential predictors included demographic variables (age, gender, education, country of birth, remoteness of residence), psychological distress, awareness of Australia's national depression initiative beyondblue, depression literacy and level of exposure to depression. Not all predictors were used for all samples.

Results

Personal stigma was consistently higher among men, those with less education and those born overseas. It was also associated with greater current psychological distress, lower prior contact with depression, not having heard of a national awareness raising initiative, and lower depression literacy. These findings differed from those for perceived stigma except for psychological distress which was associated with both higher personal and higher perceived stigma. Remoteness of residence was not associated with either type of stigma.

Conclusion

The findings highlight the importance of treating the concepts of personal and perceived stigma separately in designing measures of stigma, in interpreting the pattern of findings in studies of the predictors of stigma, and in designing, interpreting the impact of and disseminating interventions for stigma.     

The β2-adrenoceptor agonist clenbuterol reduces the neuroinflammatory response,neutrophil infiltration and apoptosis following intra-striatal IL-1β administration to rats

Objectives: Clenbuterol is a brain penetrant β₂-adrenoceptor agonist with anti-inflammatory and putative neuroprotective properties. In the present investigation, the effect of clenbuterol was assessed in a rat model of acute brain injury induced by intra-striatal administration of the pro-inflammatory cytokine IL-1β.

Methods: Clenbuterol (0.5?mg/kg; i.p.) was administered one hour prior to stereotactically delivered IL-1β (100?ng) into the striatum. Four hours postinjection, rats were anesthetized, blood samples were collected for circulating cytokine and chemokine analysis, and the ipsilateral striatum and liver tissue were harvested for mRNA expression analysis of target genes.

Results: Intrastriatal IL-1β provoked an inflammatory response with increased expression of IL-1β and the pro-inflammatory cytokine TNF-α. TNF-α expression was also increased in the liver and circulating concentrations of the chemokine cytokine-induced neutrophil chemoattractant 1 (CINC-1) were raised in response to intrastriatal IL-1β administration. The striatal response was accompanied by NFκB activation and 24?hours postinjection, increased immunoreactivity of the neutrophil marker MBS-2, indicative of cell infiltration and increased TUNEL staining, a cell marker of apoptosis. Treatment with clenbuterol attenuated all IL-1β-induced changes in the striatum including MBS-2 immunoreactivity and TUNEL?+?staining. Clenbuterol also attenuated IL-1β-induced expression of TNF-α in the liver and the increase in circulating CINC-1 concentrations.

Conclusions: The results provide evidence that clenbuterol elicits anti-inflammatory effects, suppresses the peripheral acute phase response and reduces the infiltration of neutrophils and apoptotic response to acute IL-1β–induced brain injury. Suppression of both the central and peripheral response following clenbuterol administration may contribute to its protective properties following brain injury.     

Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension

OBJECTIVES: In the European Project on Genes in Hypertension (EPOGH) standardized epidemiological methods were used to determine complex phenotypes consisting of blood pressure (BP) in combination with other traits. In this report, we present the quality control of one of the BP phenotypes. METHODS: In seven European countries eight different research groups recruited random samples of nuclear families. Trained observers measured the BP five times consecutively with the participants in the seated position at each of two separate home visits, 1 to 3 weeks apart, according to the guidelines of the British Hypertension Society. Quality assurance and quality control of this BP phenotype were implemented according to detailed instructions defined in the protocol of the EPOGH study. RESULTS: On 31 August 2001, BP measurements of 2476 subjects were available for analysis. Fewer BP readings than the five planned per visit occurred in one of the eight centres, but only in 0.4% of the home visits. Across centres the relative frequency of identical consecutive readings for systolic or diastolic blood pressure varied from 0 to 6%. The occurrence of odd readings ranged from 0 to 0.1%. Of the 49,488 systolic and diastolic BP readings, 24.0% ended on a zero (expected 20%). In most EPOGH centres there was a progressive decline in the BP from the first to the second home visit. Overall, these decreases averaged 2.36 mmHg [95% confidence interval (CI): 1.98-2.74, P < 0.001] for systolic BP and 1.74 mmHg (95% CI: 1.46-2.02, P < 0.001) for diastolic BP. CONCLUSIONS: Quality assurance and control should be planned at the design stage of a project involving BP measurement and implemented from its very beginnings until the end. The procedures of quality assurance set up in the EPOGH study for the BP measurements resulted in a well-defined BP phenotype, which was consistent across centres.     

Validation protocols for blood pressure measuring devices in the 21st century

Blood pressure (BP) is a vital sign and the essential measurement for the diagnosis of hypertension. Therefore, its accurate measurement is a key element for the evaluation of many medical conditions and for the reliable diagnosis and efficient treatment of hypertension. In the last 3 decades prestigious organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on BP Monitoring, and the International Organization for Standardization (ISO), have developed protocols for clinical validation of BP measuring devices. All these initiatives aim to standardize validation procedures and establish minimum accuracy standards for BP monitors. Unfortunately, only a few of the BP measuring devices available on the market have been subjected to independent validation using one of these protocols. Recently, the AAMI, ESH, and ISO experts agreed to develop a single universally acceptable standard (AAMI/ESH/ISO), which will replace all previous protocols. This major international initiative has been undertaken to best serve the needs of patients with hypertension, a public interested in cardiovascular health, practicing physicians, scientific researchers, regulatory bodies, and manufacturers. There is an urgent need to influence regulatory authorities throughout the world to make it mandatory for all BP measuring devices to have undergone independent validation before approval for marketing. Efforts need to be intensified to improve the accuracy of BP measuring devices, further optimize the validation procedure, and ensure that objective and unbiased validation data become available.     

MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs

Mesenchymal stem or stromal cells (MSCs) have many potential therapeutic applications including therapies for cancers and tissue damages caused by cancers or radical cancer treatments. However, tissue-derived MSCs such as bone marrow MSCs (BM-MSCs) may promote cancer progression and have considerable donor variations and limited expandability. These issues hinder the potential applications of MSCs, especially those in cancer patients. To circumvent these issues, we derived MSCs from transgene-free human induced pluripotent stem cells (iPSCs) efficiently with a modified protocol that eliminated the need of flow cytometric sorting. Our iPSC-derived MSCs were readily expandable, but still underwent senescence after prolonged culture and did not form teratomas. These iPSC-derived MSCs homed to cancers with efficiencies similar to BM-MSCs but were much less prone than BM-MSCs to promote the epithelial–mesenchymal transition, invasion, stemness, and growth of cancer cells. The observations were probably explained by the much lower expression of receptors for interleukin-1 and TGFβ, downstream protumor factors, and hyaluronan and its cofactor TSG6, which all contribute to the protumor effects of BM-MSCs. The data suggest that iPSC-derived MSCs prepared with the modified protocol are a safer and better alternative to BM-MSCs for therapeutic applications in cancer patients. The protocol is scalable and can be used to prepare the large number of cells required for “off-the-shelf” therapies and bioengineering applications.The use of mesenchymal stromal or stem cells (MSCs) in cancer patients or cancer survivors is a promising strategy to improve treatment of advanced cancer (1) and to repair tissues damaged by cancers or by radical cancer therapies (2). Based on the unique homing capability of tissue-derived MSCs to stroma of various primary and metastatic cancers (3–6), MSCs have the potential to treat or even eliminate various cancers by delivering various anticancer agents (7–9). Because of their potential for differentiation (10, 11) and production of immunomodulatory, angiogenic, anti-apoptotic, anti-scarring, and prosurvival factors (12), MSCs have shown promising regeneration potential after radical cancer treatment in animal models, such as soft tissue reconstruction after disfiguring surgeries for head, neck, or breast cancers (13) and salivary gland regeneration for head and neck cancer patients treated with radiotherapy (14, 15). As one example, the combination of osteogenic potential and targeted delivery of anticancer agents make MSCs a promising option to treat tumor-induced osteolysis (16, 17). However, exogenous tissue-derived MSCs, including those from bone marrow, adipose tissues, and umbilical cord, have all shown a tendency to promote rather than inhibit cancers in many circumstances (18–23). Also, endogenous MSCs are a major source of reactive stromal cells that promote growth and metastasis of cancers (4, 24).Moreover, MSCs have a limited proliferation potential and lose some of their important biological functions as they are expanded (25). Therefore, it is difficult to prepare large banks of the cells with uniform biological activities and/or transgene expression required for experiments in large animals and for potential clinical therapies. Another problem is that MSCs are being prepared with a variety of protocols in different laboratories from different donors. As a result, standardization of the cells has been extremely difficult and the data presented in different publications are difficult to compare. Hence large banks of reference cells are needed to advance the MSC research (26).To address the limitations of expandability and standardization, we derived MSCs from induced pluripotent stem cells (iPSCs) with a modified protocol that can be expanded to provide large cell banks from a single cell clone. The protocol produces highly enriched MSC-like cells from iPSCs with high efficiency. The iPSC-derived MSCs (iPSC-MSCs) express the classical surface markers of MSCs, are capable of multilineage mesodermal differentiation and cancer homing, and can be expanded extensively, but do not preserve the pluoripotency of iPSCs. Surprisingly, iPSC-MSCs do not promote epithelial–mesenchymal transition (EMT), invasion, and stemness of cancer cells as is seen with bone marrow-derived MSCs (BM-MSCs). Consistent with these observations, the iPSC-MSCs express much lower levels than BM-MSCs of protumor factors including interleukine-6, prostaglandin E2, SDF1, and hyaluronan before and after exposure to tumor microenvironment. Our data indicated that iPSC-MSCs are a safe alternative to BM-MSCs for cancer therapy and other applications with better expandability and potential for genetic engineering.     

Diagnostic accuracy of magnetic resonance imaging and magnetic resonance arthrography of the hip is dependent on specialist training of the radiologist

Objective

Significant differences between magnetic resonance imaging reports and intraoperative findings at the time of hip arthroscopy were documented in our practice. We sought to examine the accuracy of radiological reporting of hip pathology based on the training level of the reporting radiologist.

Materials and methods

A retrospective review of hip arthroscopies carried out between July 2008 and June 2009 identified 61 cases where original MRI scans had been reported by general community radiologists. These scans were then reviewed by musculoskeletal specialist radiologists who were blinded to both the original report and the surgical findings. Accuracy of both subsets of radiologists was compared to arthroscopic findings with regard to labral, acetabular, femoral and impingement lesions.

Results

Musculoskeletal radiologists performed better than community radiologists in terms of overall accuracy. Accuracy rates for MSK radiologists were 85, 79, 59, and 82% for labral, acetabular chondrosis, and femoral chondrosis and impingement lesions, respectively. Whereas accuracy rates for community radiologists were 70, 28, 52, and 59% (p values?=?0.08, <0.001, 0.59, <0.001). Accuracy was significantly improved for both groups of radiologists when MR arthrograms were reviewed rather than conventional MRIs.

Conclusions

This study establishes the relationship between accuracy of reporting and the training level of the performing radiologists.