One of the characteristics of hypertrophic scarring is its raised appearance. Its maturation often results in increased thickness. Therapists usually rely on subjective observation and palpation to ...document scar thickness. The result of these subjective assessments may reflect only the superficial scar thickness but is unable to measure the whole scar volume and thickness under the skin surface. Measurement of scar thickness using ultrasound imaging has been previously reported, but has not been commonly used in clinics due to its complex operation method and high cost. In this study, we have adopted a newly developed and user-friendly Tissue ultrasound palpation system (TUPS) for the assessment of scar thickness. It consists of a finger size palpation probe, connected to an ultrasound transducer and an in-series load cell to measure the thickness of the soft tissue over the human body. The method of operation is easy and it can be used to measure skin thickness on various parts of the body, thus reflecting the skin thickness. The reliability of the TUPS in clinical application was tested on 30 subjects with a hypertrophic scar at a local hospital. Three raters implemented two assessments on each subject to study its test-retest and inter-rater reliabilities. It was then used to assess 100 subjects with various severity of hypertrophic scar caused by trauma, scald, burn or surgery. They were assessed using TUPS as well as the Vancouver Scar Scale (VSS) for rating scar thickness, pliability, pigmentation and vascularity. Two-way mixed intra-class correlation showed a high test-retest reliability with Intraclass Correlation Coefficient (ICC)
=
0.98 and inter-rater reliability ICC
=
0.84. Fair positive correlations with VSS thickness score and VSS total score
r
=
0.34 (
p
<
0.05) and 0.42 (
p
<
0.05), respectively. A significant difference between two scar type groups (50 burn scald scars and 50 surgical scars) was demonstrated (d.f.
=
52.94,
t
=
3.99,
p
<
0.01). TUPS was proved to have high inter-rater, test-retest reliability and it had a moderate correlation with the VSS that clinicians used for assessment of the scar. This system is recommended for clinical assessment of scar thickness.
Abstract
Background: We have previously demonstrated promising activity of sunitinib, a multi-targeted tyrosine kinase inhibitor (TKI) against vascular endothelial growth factor (VEGF) receptor, ...platelet-derived growth factor receptor (PDGFR), c-kit and RET, in preclinical models of NPC (Invest New Drugs 2011:1123-31). However, the significant host related toxicity encountered in a phase 2 clinical trial of NPC patients has limited its clinical efficacy (Ann Oncol 2011:1280-7). Axitinib is a highly selective TKI of VEGF receptor 1, 2 and 3. Selectively targeting a single growth factor receptor pathway provides the potential to rationally adjust dosages and combine drugs directed at specific parts of the pathway to minimize toxicity and achieve the optimum therapeutic benefit. Methods: In vitro cytotoxicity of axitinib was evaluated by MTT assay in five NPC cell lines (C666-1, CNE-2, HK1-LMP1, HNE-1, HONE-1-EBV). In vivo activity was tested in two representative NPC xenograft models (CNE-2 and HK1-LMP1). We also studied treatment induced changes in tumor histology, microvessel density (MVD) and murine serum biomarkers. Results: All NPC cell lines tested except C666-1 were sensitive to axitinib with IC50 of 0.8-7 µM and maximum growth inhibition of 45-87%. In vivo, axitinib demonstrated significant tumor growth inhibition (fractional tumor volume reduction of 32-63% for axitinib treated mice versus 0-10% for vehicle control), reduced MVD and induced extensive tumor necrosis with no significant host toxicity in mice. There were significant increases in serum murine-derived VEGF and SDF-1α and decrease of sVEGFR-2 in axitinib treated tumor bearing mice as compared to vehicle treated controls. Conclusion: Axitinib demonstrated potent in vitro and in vivo activity in NPC preclinical models. Host derived serum proteins may serve as potential biomarkers of drug activity. A phase 2 clinical trial of axitinib in NPC is on-going (NCT01249547) to validate these findings in patients. Acknowledgement: supported by a direct grant (2041496) from CUHK. Axitinib was provided by Pfizer Inc.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1373. doi:1538-7445.AM2012-1373
Abstract
TIGAR (TP53-induced glycolysis and apoptosis regulator) is a novel dual regulator of glycolysis and apoptosis regulated by p53. TIGAR was first found to protect normal cells from oxidative ...stress by inducing cellular production of NADPH, a powerful reducing agent in the cell, via the pentose phosphate shunt.
Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer prevalent in Southeast Asia. Our previous studies demonstrated that overexpression of TIGAR rescued NPC cells from growth inhibition induced by c-Met kinase inhibitors and an RNA anti-metabolite (ECyd), suggesting an anti-apoptotic function of TIGAR in NPC. Here, we demonstrated by Western blotting and immunohistochemistry that TIGAR was expressed in primary tumor biopsies of NPC. Moreover, NPC cell lines from various differentiation status also expressed TIGAR. Using an Epstein-Barr virus-associated NPC cell line, HONE-1-LMP1 cells, we showed that specific knockdown of TIGAR by siRNA inhibited cell proliferation (∼45%) at 48 hrs. Moreover, TIGAR overexpression markedly increased NPC cell proliferation (>300%), which was accompanied by significant induction of cellular NADPH production (>200%). This indicates that TIGAR-induced generation of NADPH, which is an important building block for major cellular metabolites for proliferation (including DNA, RNA and fatty acids, etc), may be involved in NPC carcinogenesis. Furthermore, TIGAR overexpression induced the expression of a pro-survival protein, Mcl-1 in NPC cells, which supports an anti-apoptotic function of TIGAR in NPC. Our results implicate that TIGAR may confer survival benefits to NPC cells via metabolic alteration.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1006. doi:10.1158/1538-7445.AM2011-1006
Abstract
Undifferentiated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and ubiquitously associated with Epstein-Barr virus (EBV) infection. AKT is frequently activated in NPC and PIK3CA ...amplification can be found in 40% of NPC tissues. BEZ235 is a dual inhibitor of PI3K and mTOR, which results in inhibition of downstream effectors AKT, S6 ribosomal protein and 4EBP1. The preclinical activity of BEZ235 was evaluated in 6 NPC cell lines (Table 1). Western Blot analysis showed all 6 NPC cell lines showed basal activation of AKT and mTOR. The effect of BEZ235 on cell growth was evaluated by exposing NPC cell lines to increasing concentrations of BEZ235 (0.1nM, 0.5nM, 1nM, 10nM, 100nM, 1µM& 10µM) for up to 72 hrs followed by MTT assay. Over 80% of growth inhibition was achieved in all NPC cell lines except C666-1 (∼70% inhibition), with the respective IC50 concentrations in the nanomolar range (Table 1). Two representative cell lines (HONE1-LMP-1 and CNE-2 cells) were selected for assessing the effect of BEZ235 on AKT-mTOR signaling, apoptosis, cell cycle and synergism with chemotherapy. Treatment of HONE1-LMP-1 and CNE-2 cells with BEZ235 at 5nM and 50nM for 24-48 hours, resulted in cell cycle arrest at G1 phase, apoptosis (indicated by the induction of PARP cleavage), and moderate reduction of cyclin D1 expression. After BEZ235 treatment, the expression level of phosphorylated (p-)AKT, pS6K, p4EBP-1 and p-mTOR were reduced, but the level of p-p44/42 MAPK was increased in both HONE1-LMP-1 and CNE-2 cells. No synergistic effect on growth inhibition was observed when HONE1-LMP-1 and CNE-2 cells were treated with concomitant BEZ235 and chemotherapy (cisplatin, or paclitaxel). Our preliminary result suggests that BEZ235 has promising activity in most NPC cells, while the increase in p-p44/42 MAPK observed in some cell lines suggest the presence of compensatory MAPK activation that have been previously described with mTORC1 inhibitors in other cancer types. Further investigations are warranted.Table 1: IC50 (growth)% growth inhibition by BEZ235% cells at G1 arrest after BEZ235 (5nM) treatment for 24hrsEBV-associated NPC cell linesHK1-LMP14.1nM∼85%-HONE-1-LMP14.9nM∼75%62%C666-19.5nM∼70%-Poorly-differentiated NPC cell linesHONE-16.4nM∼85%-CNE-25.7nM∼90%58%Well-differentiated NPC cell lineHK14.7nM∼90%-
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1638.
To determine the effectiveness of a simple, self-administrable moxibustion-cum-massage intervention for relieving chronic pain and improving psychological well-being for older adults in the ...community.
A randomized controlled trial.
Seventy-eight participants with chronic pain were randomly assigned to the intervention and waitlist control groups.
Participants received two moxa sticks a day to use the moxibustion-cum-massage procedure with the help of trained volunteers or caregivers for five consecutive days.
Participates’ pain level, sleep quality, depression and subjective well-being were measured before the intervention (T0), immediately after the intervention (T1), and one week after the intervention (T2).
Repeated measures ANOVA revealed a significant group × time interaction effect in subjective well-being with a medium effect size. Regarding within-group effects in the intervention group at post-intervention (T1), the subjective pain level was significantly reduced with a small effect size, while sleep quality and depression significantly improved with large effect sizes. The control group showed no significant within-group effects in these variables. Maintenance effects at follow-up (T2) were not significant.
Despite the short intervention timeframe of five days, the study revealed preliminary evidence that the moxibustion-cum-massage intervention can be an effective, self-administrable pain relief regime for older adults. A longer period of intervention time is suggested for future studies.
•Traditional Chinese Medicine (TCM) use in elder Chinese population is rising.•A self-administrable moxibustion-cum-massage intervention can relieve chronic pain.•Sleep quality, depression and well-being can be improved while pain release.
The emphasis of risk has been recognized as a crucial component to effective and successful policy compliance amidst a crisis. Yet, during the COVID-19 pandemic, when the impact of risk may fluctuate ...with the severity of the prolonged pandemic, and that the public consider not only public health factors when they choose but also whether to follow a COVID-19-related policy, perceived risk may not always lead to policy compliance. Two cross-sectional online surveys (during almost zero case period in late April to May, 2020 (Wave 2) and during the biggest outbreak in July, 2020 (Wave 3)) with convenient sampling were conducted to examine the dichotomous role of perceived severity and perceived susceptibility in influencing policy compliance in Hong Kong. A total of 1816 responses from local adults were collected (Wave 2: N = 564; Female % = 69.7%; Mean age = 39.4; Wave 3: N = 1252; Female %=68.8%; Mean age = 40.2). Although policy compliance is found to increase with the scale of the outbreak, results from path analyses showed that perceived susceptibility and perceived severity have an indirect role in policy complying behaviour when the objective risk is low. Risk variables, including attitude, knowledge, benefit and trust, have directly shaped policy compliance. More importantly, perceived severity boosts policy compliance but perceived susceptibility was associated with disobedience to public health policies. Meanwhile, Hong Kong citizens have a selective and conscious preference regarding the stringency of public health policy: They welcome more law and order, with increasing magnitude of penalty, but reject lockdown measures such as a curfew. Regression results implied that demography had a mild contribution to the acceptance of public health policies, with only the female gender being statistically related to higher policy acceptance. The findings of this study imply that boosting attitude, knowledge, benefit and trust would come more directly helpful in promoting public health policy compliance than emphasizing on risks alone. This study calls for further reflection on the traditional role of risk, especially perceived susceptibility, in mobilizing policy compliance to COVID-19-related measures.
At the beginning of the pandemic, the world has likened COVID-19 to SARS which devastated Hong Kong in 2003. Based on the results of a survey conducted between March and April 2020 with 761 Hong Kong ...adult residents, we summarised three lessons on the coping of Hong Kong people: (i) Establish adequate personal vigilance, (ii) Brace for a mental health crisis and (iii) Find strengths in social and community support. Social workers' roles in health education, identifying service gaps, resource mapping and orchestrating community actions are vital for empowering flexible and adaptive community responses.
Generativity has recently received increasing attention as a key contributor to healthy aging. Personal resources and social expectations are shown to influence the desire to be generative and that ...generativity affects later-life health. However, whether generativity has a mediating role in linking its driving factors and health, and how gender may affect these pathways, is underexplored. Cross-sectional online data from 1085 Hong Kong residents aged 45+ were collected between November and December 2020. Latent variable path analysis was used to examine the mediating effect of generativity between human, social, and financial capital, and physical and mental well-being. Gendered pathways were investigated using multi-group analysis. Results showed that human, social, and financial capital contributed to better health through generativity, and gendered pathways were observed. Human capital had a stronger effect on generativity for men, but for women, social capital was vital for increased generativity and consequently improved health. Findings suggested that health benefits of generativity depend on different capital drivers and differ by gender. Implications for program development that aim to facilitate health should include generativity components that maximize physical and psychosocial engagement so that individuals can reap the health benefits through contributions to others.
Studies have shown individuals with chronic illnesses tend to experience poorer mental health compared to their counterparts without a chronic illness under the COVID-19 pandemic. The pervasive ...disruption on daily lifestyles due to social distancing could be a contributing factor. In this study, we collaborated with local patient support groups to explore the psychological adjustment among a group of community-dwelling individuals with chronic illnesses under the COVID-19 pandemic in Hong Kong. We collected responses from 408 adults with one or more chronic illnesses using an online survey. Results show that about one in four participants experienced moderate to high levels of depression (26.0%), anxiety (26.2%) and stress (20.1%) symptoms measured by the Depression, Anxiety and Stress Scale and the World Health Organisation-Five Well-Being Index. While 62.3% (gatherings) to 91.9% (contact with others) of participants reported changes in their daily lifestyles, these changes—both an increase and a decrease—were related to poorer mental health. The relationship was mediated by psychological resilience, measured by the Connor–Davidson Resilience Scale, with an estimate of indirect effect of −0.28 (95% confidence interval −0.44 to −0.10). In light of our findings, we urge social and healthcare professionals to support chronic illness patients to continue their daily lifestyles such as exercises and social contacts as much as possible by educating the public on feasible and practical preventive measures and enhance the psychological resilience of community-dwelling patients with scalable and efficacious psychological interventions.
Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes ...from the 1000 Genomes Project, we report a GWAS meta-analysis of ~185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
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