Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

Review of refugee mental health assessment: Best practices and recommendations

This article focuses on mental health assessment of refugees in clinical, educational and administrative-legal settings in order to synthesise research and practice designed to enhance and promote further development of culturally appropriate clinical assessment services during the refugee resettlement process. It specifically surveys research published over the last 25 years into the development, reliability measurement and validity testing of assessment instruments, which have been used with children, adolescents and adults from refugee backgrounds, prior to or following their arrival in a resettlement country, to determine whether the instruments meet established crosscultural standards of conceptual, functional, linguistic, technical and normative equivalence. The findings suggest that, although attempts have been made to develop internally reliable, appropriately normed tests for use with refugees from diverse cultural and linguistic backgrounds, matters of conceptual and linguistic equivalence and test–retest reliability are often overlooked. Implications of these oversights for underreporting refugees' mental health needs are considered. Efforts should also be directed towards development of culturally comparable, valid and reliable measures of refugee children's mental health and of refugee children's and adults' psychoeducational, neuropsychological and applied memory capabilities.

Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis

Summary This systematic review demonstrates that vitamin D supplementation does not have a significant effect on muscle strength in vitamin D replete adults. However, a limited number of studies demonstrate an increase in proximal muscle strength in adults with vitamin D deficiency. Introduction The purpose of this study is to systematically review the evidence on the effect of vitamin D supplementation on muscle strength in adults. Methods A comprehensive systematic database search was performed. Inclusion criteria included randomised controlled trials (RCTs) involving adult human participants. All forms and doses of vitamin D supplementation with or without calcium supplementation were included compared with placebo or standard care. Outcome measures included evaluation of strength. Outcomes were compared by calculating standardised mean difference (SMD) and 95% confidence intervals. Results Of 52 identified studies, 17 RCTs involving 5,072 participants met the inclusion criteria. Meta-analysis showed no significant effect of vitamin D supplementation on grip strength (SMD −0.02, 95%CI −0.15,0.11) or proximal lower limb strength (SMD 0.1, 95%CI −0.01,0.22) in adults with 25(OH)D levels >25 nmol/L. Pooled data from two studies in vitamin D deficient participants (25(OH)D <25 nmol/L) demonstrated a large effect of vitamin D supplementation on hip muscle strength (SMD 3.52, 95%CI 2.18, 4.85). Conclusion Based on studies included in this systematic review, vitamin D supplementation does not have a significant effect on muscle strength in adults with baseline 25(OH)D >25 nmol/L. However, a limited number of studies demonstrate an increase in proximal muscle strength in adults with vitamin D deficiency. Keywords Muscle – Muscle fibre – Strength – Vitamin D

Laser doppler imaging in a paediatric burns population

Objective Laser Doppler imaging (LDI) was compared to wound outcomes in children's burns, to determine if the technology could be used to predict these outcomes. Methods Forty-eight patients with a total of 85 burns were included in the study. Patient median age was 4 years 10 months and scans were taken 0–186 h post-burn using the fast, low-resolution setting on the Moor LDI2 laser Doppler imager. Wounds were managed by standard practice, without taking into account the scan results. Time until complete re-epithelialisation and whether or not grafting and scar management were required were recorded for each wound. If wounds were treated with Silvazine™ or Acticoat™ prior to the scan, this was also recorded. Results The predominant colour of the scan was found to be significantly related to the re-epithelialisation, grafting and scar management outcomes and could be used to predict those outcomes. The prior use of Acticoat™ did not affect the scan relationship to outcomes, however, the use of Silvazine™ did complicate the relationship for light blue and green scanned partial thickness wounds. Scans taken within the 24-h window after-burn also appeared to be accurate predictors of wound outcome. Conclusion Laser Doppler imaging is accurate and effective in a paediatric population with a low-resolution fast-scan.

Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia

A novel antioxidant for the potential treatment of ischaemia was designed by incorporating an isoindoline nitroxide into the framework of the free radical scavenger edaravone. 5-(3-Methyl-pyrazol-5-ol-1-yl)-1,1,3,3-tetramethylisoindolin-2-yloxyl 7 was prepared by N-arylation of 3-methyl-5-pyrazolone with 5-iodo-1,1,3,3-tetramethylisoindoline-2-yloxyl 8 in the presence of catalytic copper(I)iodide. Evaluation of 7, its methoxyamine derivative 10 and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) against edaravone 1 in ischaemic rat atrial cardiomyocytes revealed significant decreases in cell death after prolonged ischaemia for each agent; however the protective effect of the novel antioxidant 7 (showing greater than 85% reduction in cell death at 100 μM) was significantly enhanced over that of edaravone 1 alone. Furthermore, the activity for 7 was found to be equal to or greater than the potent cardioprotective agent N6-cyclopentyladenosine (CPA). The methoxyamine adduct 10 and edaravone 1 showed no difference between the extent of reduction in cell death whilst CTMIO had only a modest protective effect.

2,3-Dimethoxy-10-oxostrychnidinium 2-(2,4,6-trinitroanilino)benzoate monohydrate : a 1:1 proton-transfer salt of brucine with o-picraminobenzoic acid

In the structure of the 1:1 proton-transfer compound of brucine with 2-(2,4,6-trinitroanilino)benzoic acid C23H27N2O4+ . C13H7N4O8- . H~2~O, the brucinium cations form the classic undulating ribbon substructures through overlapping head-to-tail interactions while the anions and the three related partial water molecules of solvation (having occupancies of 0.73, 0.17 and 0.10) occupy the interstitial regions of the structure. The cations are linked to the anions directly through N-H...O(carboxyl) hydrogen bonds and indirectly by the three water molecules which form similar conjoint cyclic bridging units [graph set R2/4(8)] through O-H...O(carbonyl) and O(carboxyl) hydrogen bonds, giving a two-dimensional layered structure. Within the anion, intramolecular N-H...O(carboxyl) and N H...O(nitro) hydrogen bonds result in the benzoate and picrate rings being rotated slightly out of coplanarity inter-ring dihedral angle 32.50(14)\%]. This work provides another example of the molecular selectivity of brucine in forming stable crystal structures and also represents the first reported structure of any form of the guest compound 2-(2,4,6-trinitroanilino)benzoic acid.

Model selection and error estimation

We study model selection strategies based on penalized empirical loss minimization. We point out a tight relationship between error estimation and data-based complexity penalization: any good error estimate may be converted into a data-based penalty function and the performance of the estimate is governed by the quality of the error estimate. We consider several penalty functions, involving error estimates on independent test data, empirical VC dimension, empirical VC entropy, and margin-based quantities. We also consider the maximal difference between the error on the first half of the training data and the second half, and the expected maximal discrepancy, a closely related capacity estimate that can be calculated by Monte Carlo integration. Maximal discrepancy penalty functions are appealing for pattern classification problems, since their computation is equivalent to empirical risk minimization over the training data with some labels flipped.

Measurement and correlates of caregiver self-efficacy amongst family caregivers of persons with dementia living in Shanghai, China

Background: Caring for family members with dementia can be a long-term, burdensome task resulting in physical and emotional distress and impairment. Research has demonstrated significantly lower levels of selfefficacy among family caregivers of people with dementia (CGs) than caregivers of relatives with non-dementia diseases. Intervention studies have also suggested that the mental and physical health of dementia CGs could be improved through the enhancement of their self-efficacy. However, studies are limited in terms of the influences of caregiver self-efficacy on caregiver behaviour, subjective burden and health-related quality of life. Of particular note is that there are no studies on the applicability of caregiver self-efficacy in the social context of China. Objective: The purpose of this thesis was to undertake theoretical exploration using Bandura’s (1997) self-efficacy theory to 1) revise the Revised Caregiving Self-Efficacy Scale (C-RCSES) (Steffen, McKibbin, Zeiss, Gallagher-Thompson, & Bandura, 2002), and 2) explore determinants of caregiver self-efficacy and the role of caregiver self-efficacy and other conceptual constructs (including CGs’ socio-demographic characteristics, CRs’ impairment and CGs’ social support) in explaining and predicting caregiver behaviour, subjective burden and health-related quality of life among CGs in China. Methodology: Two studies were undertaken: a qualitative elicitation study with 10 CGs; and a cross-sectional survey with 196 CGs. In the first study, semi-structured interviews were conducted to explore caregiver behaviours and corresponding challenges for their performance. The findings of the study assisted in the development of the initial items and domains of the Chinese version of the Revised Caregiving Self-Efficacy Scale (C-RCSES). Following changes to items in the scale, the second study, a cross-sectional survey with 196 CGs was conducted to evaluate the psychometric properties of C-RCSES and to test a hypothesised self-efficacy model of family caregiving adapted from Bandura’s theory (1997). Results: 35 items were generated from the qualitative data. The content validity of the C-RCSES was assessed and ensured in Study One before being used for the cross-sectional survey. Eight items were removed and five subscales (caregiver self-efficacy for gathering information about treatment, symptoms and health care; obtaining support; responding to problematic behaviours; management of household, personal and medical care; and controlling upsetting thoughts about caregiving) were identified after principal component factor analysis on the cross-sectional survey data. The reliability of the scale is acceptable: the Cronbach’s alpha coefficients for the whole scale and for each subscale were all over .80; and the fourweek test-retest reliabilities for the whole scale and for each subscale ranged from .64 to .85. The concurrent, convergent and divergent validity were also acceptable. CGs reported moderate levels of caregiver self-efficacy. Furthermore, the level of self-efficacy for management of household, personal and medical care was relatively high in comparison to those of the other four domains of caregiver self-efficacy. Caregiver self-efficacy was also significantly influenced by CGs’ socio-demographic characteristics and the caregiving external factors (CR impairment and social support that CGs obtained). The level of caregiver behaviour that CGs reported was higher than that reported in other Chinese research. CGs’ socio-demographics significantly influenced caregiver behaviour, whereas caregiver self-efficacy did not influence caregiver behaviour. Regarding the two external factors, CGs who cared for highly impaired relatives reported high levels of caregiver behaviour, but social support did not influence caregiver behaviour. Regarding caregiver subjective burden and health-related quality of life, CGs reported moderate levels of subjective burden, and their level of healthrelated quality of life was significantly lower than that of the general population in China. The findings also indicated that CGs’ subjective burden and health-related quality of life were influenced by all major factors in the hypothesised model, including CGs’ socio-demographics, CRs’ impairment, social support that CGs obtained, caregiver self-efficacy and caregiver behaviour. Of these factors, caregiver self-efficacy and social support significantly improved their subjective burden and health-related quality of life; whereas caregiver behaviour and CRs’ impairment were detrimental to CGs, such as increasing subjective burden and worsening health-related quality of life. Conclusion: While requiring further exploration, the qualitative study was the first qualitative research conducted in China to provide an in-depth understanding of CGs’ caregiving experience, including their major caregiver behaviours and the corresponding challenges. Meanwhile, although the C-RCSES needs further psychometric testing, it is a useful tool for assessing caregiver self-efficacy in Chinese populations. Results of the qualitative and quantitative study provide useful information for future studies regarding the explanatory power of caregiver self-efficacy to caregiver behaviour, subjective burden and health-related quality of life. Additionally, integrated with Bandura’s theory, the findings from the quantitative study also suggested a further study exploring the role of outcome expectations in caregiver behaviour, subjective burden and healthrelated quality of life.

Correlates of Pedometer Use: Results from a Community-based Physical Activity Intervention Trial (10,000 Steps Rockhampton)

Background Pedometers have become common place in physical activity promotion, yet little information exists on who is using them. The multi-strategy, community-based 10,000 Steps Rockhampton physical activity intervention trial provided an opportunity to examine correlates of pedometer use at the population level. Methods Pedometer use was promoted across all intervention strategies including: local media, pedometer loan schemes through general practice, other health professionals and libraries, direct mail posted to dog owners, walking trail signage, and workplace competitions. Data on pedometer use were collected during the 2-year follow-up telephone interviews from random population samples in Rockhampton, Australia, and a matched comparison community (Mackay). Logistic regression analyses were used to determine the independent influence of interpersonal characteristics and program exposure variables on pedometer use. Results Data from 2478 participants indicated that 18.1% of Rockhampton and 5.6% of Mackay participants used a pedometer in the previous 18-months. Rockhampton pedometer users (n = 222) were more likely to be female (OR = 1.59, 95% CI: 1.11, 2.23), aged 45 or older (OR = 1.69, 95% CI: 1.16, 2.46) and to have higher levels of education (university degree OR = 4.23, 95% CI: 1.86, 9.6). Respondents with a BMI > 30 were more likely to report using a pedometer (OR = 1.68, 95% CI: 1.11, 2.54) than those in the healthy weight range. Compared with those in full-time paid work, respondents in 'home duties' were significantly less likely to report pedometer use (OR = 0.18, 95% CI: 0.06, 0.53). Exposure to individual program components, in particular seeing 10,000 Steps street signage and walking trails or visiting the website, was also significantly associated with greater pedometer use. Conclusion Pedometer use varies between population subgroups, and alternate strategies need to be investigated to engage men, people with lower levels of education and those in full-time 'home duties', when using pedometers in community-based physical activity promotion initiatives.

Lessons learned from implementation of a demonstration program to reduce the burden of anemia and hookworm in women in Yen Bai Province, Viet Nam

Background Iron deficiency, anemia and hookworm disease are important public health problems for women of reproductive age living in developing countries and affect the health of newborns and infants. Iron supplementation and deworming treatment are effective in addressing these problems in both pregnant and non-pregnant women. Daily iron supplementation and deworming after the first trimester is recommended for pregnant women although these programs usually do not operate efficiently or effectively. Weekly iron-folic acid supplementation and regular deworming for non-pregnant women may be a viable approach for improving iron status and preventing anemia during the reproductive years. Addressing these diseases at a population level before women become pregnant could significantly improve women's health before and during pregnancy, as well as their infants' growth and development. Methods and Results This paper describes the major processes undertaken in a demonstration intervention of preventive weekly iron-folic acid supplementation with regular deworming for all 52,000 women aged 15–45 years in two districts of Yen Bai province, in northern Viet Nam. The intervention strategy included extensive consultation with community leaders and village, commune, district and provincial health staff, and training for village health workers. Distribution of the drugs was integrated with the existing health service infrastructure and the village health workers were the direct point of contact with women. Iron-folic acid tablets and deworming treatment were provided free of charge from May 2006. An independent Vietnamese NGO was commissioned to evaluate compliance and identify potential problems. The program resulted in effective distribution of iron-folic acid tablets and deworming treatment to all villages in the target districts, with full or partial compliance of 85%. Conclusion Training for health staff, the strong commitment of all partners and the use of appropriate educational materials led to broad support for weekly iron-folic acid supplementation and high participation in the regular deworming days. In March 2008 the program was expanded to all districts in the province, a target population of approximately 250,000 WRA, and management was handed over to provincial authorities.