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1.  Fidelity of implementation of an evidence-based HIV prevention program among Bahamian sixth-grade students 
The Bahamian Ministry of Education has elected to implement at a national level in all Bahamian government grade six classes an evidence-based HIV prevention intervention [Focus on Youth in the Caribbean (FOYC)]. This study explores fidelity of implementation of the intervention, factors that may influence implementation fidelity, and the impact of variations in implementation fidelity on student outcomes. Data were collected in the first wave of national implementation in 2011, involving 35 government primary schools and 110 teachers and 2811 students. Structural equation modeling was performed to examine the relationships among factors which facilitated or impeded teachers’ implementation of FOYC. Results indicate that teachers taught 16.3 out of 30 core activities, 24.9 out of 46 total activities and 4.4 out of 8 sessions on average. The strongest predictor of implementation fidelity was teacher comfort level with the FOYC curriculum. Teachers who did not perceive the FOYC intervention to be important for their students or who had attended only part of a FOYC training workshop were more likely to change the curriculum. Increased duration of experience as a teacher (>10 years) was negatively associated with fidelity of implementation. Teacher’s perception of the importance of the FOYC intervention and implementation fidelity had direct positive effects on students’ HIV/AIDS knowledge, reproductive health skills, protective intentions and self-efficacy. Youth did not appear to benefit from FOYC if two or fewer sessions were delivered. We concluded that an evidence-based HIV prevention intervention can be implemented at a national level. Prior training of teachers in the intervention curriculum, teacher perception of the importance of the intervention, and fewer years as a teacher are associated with implementation fidelity. Implementation fidelity is associated with improved student outcomes.
PMCID: PMC4199933  PMID: 24736950
Implementation research; HIV prevention; fidelity; adolescents; Bahamas
2.  A quarter century of HIV prevention intervention efforts among children and adolescents across the globe 
In 1988 a group of pediatricians, developmental, clinical, child and social psychologists, anthropologists and health educators began researching in Baltimore, Maryland on an HIV prevention intervention, Focus on Youth. Over the next 25 years the questions being addressed by Focus on Youth, reflected those of the global HIV research experience.
During the first phase, the questions being addressed by the broader research community included: Can HIV risk behaviors be purposefully impacted by behavioral interventions? If so, how do successful interventions differ from those that are not effective? Are theory-based interventions more likely to be effective than information-only based interventions? Can theories be translated into culturally and developmentally appropriate interventions including those that are appropriate for children and adolescents? Should parents be involved--and if so, how?
During its next phase, the Focus on Youth team increasingly became concerned with a disturbing reality. A large number of interventions had been developed and some had been shown to have evidence of impact. But virtually all of these interventions had been conducted in the USA or Europe. The questions facing researchers included: With the global burden of HIV disproportionately impacting Low and Middle Income Countries (LMIC), especially those in southern Africa, the Caribbean and parts of Asia, what is known about the effectiveness of western-based interventions in these culturally, racially and economically disparate settings?
With the exciting proliferation of interventions, federal agencies in the USA and international agencies including UNAIDS realized the importance of assessing the research portfolio and developing metrics of effectiveness. The questions during this phase included: What is an “effective” intervention? How are effective interventions implemented in a new setting? This phase merged with the next phase as researchers and public health workers realized that the dissemination to a new community of an intervention developed and found to be effective in one community requires change. The central questions during this time included: What changes or kinds of changes can be made to an intervention without undermining its effectiveness? What aspects of an intervention cannot be changed without potentially undermining its effectiveness? What constitutes a “change”? Who should be involved in this decision-making?
These efforts culminated in our current phase, one focused on implementation. We must learn more about the factors that allow an intervention to survive and thrive and selectively target these critical factors. The main objective of this paper is to review our experiences and lessons learned in developing, implementing, and evaluating Focus on Youth in a wide range of socio-cultural settings over the past a quarter of century.
PMCID: PMC4020185  PMID: 24839584
3.  The impact of parent involvement in an effective adolescent risk reduction intervention on sexual risk communication and adolescent outcomes 
Parent involvement in prevention efforts targeting adolescents increases the impact of such programs. However, the majority of risk-reduction intervention programs that are implemented through schools do not include parents, in part because most existing parental interventions require significant time commitment by parents. We designed a brief parent-adolescent sexual risk communication intervention to be delivered with an effective HIV prevention intervention as part of a randomized, controlled trial among 2564 grade 10 students and their parents in The Bahamas. Mixed effects modeling analysis was conducted to evaluate the effect of the brief parent-adolescent communication intervention using four waves of longitudinal data. Results indicate that a brief parent-adolescent communication intervention is effective in improving parent-adolescent communication on sex-related issues and perceived parental monitoring as well as the youth's condom use skills and self-efficacy. There is a marginal effect on consistent condom use. In addition, there is an apparent dose effect of the brief parent intervention on perceived parent-adolescent sexual risk communication and adolescent outcomes. These findings suggest that adolescent risk reduction interventions should include a brief parent-adolescent communication intervention which should be reinforced by periodic boosters in order to enhance the impact of adolescent HIV prevention programs.
PMCID: PMC4261929  PMID: 25490732
adolescent; condom use skills; self-efficacy; parent-adolescent communication; brief parental intervention; risk behaviors; The Bahamas
4.  A Drosophila XPD model links cell cycle coordination with neuro-development and suggests links to cancer 
Disease Models & Mechanisms  2014;8(1):81-91.
XPD functions in transcription, DNA repair and in cell cycle control. Mutations in human XPD (also known as ERCC2) mainly cause three clinical phenotypes: xeroderma pigmentosum (XP), Cockayne syndrome (XP/CS) and trichothiodystrophy (TTD), and only XP patients have a high predisposition to developing cancer. Hence, we developed a fly model to obtain novel insights into the defects caused by individual hypomorphic alleles identified in human XP-D patients. This model revealed that the mutations that displayed the greatest in vivo UV sensitivity in Drosophila did not correlate with those that led to tumor formation in humans. Immunoprecipitations followed by targeted quantitative MS/MS analysis showed how different xpd mutations affected the formation or stability of different transcription factor IIH (TFIIH) subcomplexes. The XP mutants most clearly linked to high cancer risk, Xpd R683W and R601L, showed a reduced interaction with the core TFIIH and also an abnormal interaction with the Cdk-activating kinase (CAK) complex. Interestingly, these two XP alleles additionally displayed high levels of chromatin loss and free centrosomes during the rapid nuclear division phase of the Drosophila embryo. Finally, the xpd mutations showing defects in the coordination of cell cycle timing during the Drosophila embryonic divisions correlated with those human mutations that cause the neurodevelopmental abnormalities and developmental growth defects observed in XP/CS and TTD patients.
PMCID: PMC4283652  PMID: 25431422
Xeroderma pigmentosum; Cell cycle synchronization; Xpd; Mitotic defect
5.  Delineating Interpersonal Communication Networks: A Study of the Diffusion of an Intervention Among Female Entertainment Workers in Shanghai, China 
AIDS and behavior  2012;16(7):2004-2014.
Diffusion of innovation (DOI) is widely cited in the HIV behavior change literature; however there is a dearth of research on the application of DOI in interventions for sex workers. Following a randomized-controlled trial of HIV risk reduction among female entertainment workers (FEWs) in Shanghai, China, we used qualitative approaches to delineate potential interpersonal communication networks and contributing factors that promote diffusion of information in entertainment venues. Results showed that top-down communication networks from the venue owners to the FEWs were efficient for diffusion of information. Mammies/madams, who act as intermediaries between FEWs and clients form an essential part of FEWs’ social networks but do not function as information disseminators due to a conflict of interest between safer sex and maximizing profits. Diffusion of information in large venues tended to rely more on aspects of the physical environment to create intimacy and on pressure from managers to stimulate communication. In small venues, communication and conversations occurred more spontaneously among FEWs. Information about safer sex appeared to be more easily disseminated when the message and the approach used to convey information could be tailored to people working at different levels in the venues. Results suggest that safer sex messages should be provided consistently following an intervention to further promote intervention diffusion, and health-related employer liability systems in entertainment venues should be established, in which employers are responsible for the health of their employees. Our study suggests that existing personal networks can be used to disseminate information in entertainment venues and one should be mindful about the context-specific interactions between FEWs and others in their social networks to better achieve diffusion of interventions.
PMCID: PMC4273942  PMID: 22638867
Diffusion of innovation; HIV behavior intervention; Female entertainment workers; Social networks; China
6.  Alcohol and Sexual Risk: An Event-Level Analysis in Commercial Sex Setting 
Addictive behaviors  2013;38(12):10.1016/j.addbeh.2013.08.019.
To assess the episodic relationship between alcohol and sexual risk in multiple-client occasions among female sex workers (FSWs).
Data on alcohol use and sexual episodes with clients from the past two days were collected among FSWs in Guangxi, China (n=336 for yesterday, and n=299 for the day before yesterday). Logistic regression using generalized estimating equations with robust variance estimation was used to assess the alcohol-sexual risk relationship, controlling for contextual variables salient in the setting of commercial sex. Results: alcohol use among FSWs was associated with a higher likelihood of unprotected sex with clients during both days. This relationship was modified by the number of clients received within a day. Additionally, having a larger number of drinks was associated with higher odds of unprotected sex, but the association was not consistent across the two days.
Findings from the study support an association between alcohol use and sexual risk among FSWs. The design of alcohol and sexual risk reduction intervention among FSWs in China may take advantage of the interaction between contextual factors and alcohol use on sexual risk.
PMCID: PMC3816608  PMID: 24045031
7.  Clinical Study of the Hypothesis of Endogenous Collateral Wind on Acute Coronary Syndrome: A Review 
Acute Coronary Syndrome (ACS), is a serious threat to people's health, and life, and in recent years, the incidence has increased yearly. This study was to propose the hypothesis of “endogenous collateral wind” based on the patho-mechanism of thrombogenesis complicated by ruptured plaque on ACS, and the theory of traditional Chinese medicine.
Materials and Methods
Through successful coronary angiography (CAG), and intravascular ultrasound (IVUS), patients with coronary artery disease were made the differential diagnosis such as blood stasis, blood stasis due to phlegm obstruction, and endogenous collateral wind. The levels of plasma inflammatory marker were measured to study on the characteristics of “endogenous collateral wind”. Luo heng dripping pills with promoting blood circulation to expel wind-evil, and remove wetness were made based on the hypothesis of “endogenous collateral wind” on ACS. Patients with unstable angina were randomly divided into 3, groups based on therapeutic methods: conventional therapy group, Luo Heng dripping pills group and Tongxinluo caps. Differences among groups were compared.
There were great changes in number and degree of coronary arteriostenosis confirmed by CAG, the types of ACC/AHA lesion and Levin lesion confirmed by CAG, remodeling index, positive or negative remodeling percentage measured by IVUS, the plasma levels of plasma inflammatory marker measured by ELLSA in the patients with endogenous collateral wind, compared with patients with blood stasis and blood stasis due to phlegm obstruction. The total effective rate of improved angina in Luo Heng dripping pills group was significantly higher than those in other two groups. The levels of plasma inflammatory marker were significantly lower in Luo Heng dripping pills group.
There were some pathological basis which were found about the hypothesis of “endogenous collateral wind” on acute coronary syndrome. It provided evidences for patients with coronary artery disease treated by medicines with expelling evil-wind, and removing wetness.
PMCID: PMC3957252  PMID: 24653564
The hypothesis of “endogenous collateral wind”; acute coronary syndrome; Luoheng dripping pills; coronary artery disease
8.  The influence of parental monitoring and parent-adolescent communication on Bahamian adolescent risk involvement: A three-year longitudinal examination 
The literature suggests that parental monitoring can best be conceptualized and measured through the domains of parental knowledge, youth disclosure, parental solicitation, and parental control. Using longitudinal data on 913 grade-six Bahamian students followed over a period of three years, we examined the unique and independent roles of these domains of parental monitoring and parent–adolescent communication in relation to adolescent involvement in delinquency, substance use, and sexual risk behaviors. The results obtained with mixed-effects models indicate that parental knowledge, youth disclosure, and parental control are negatively associated with both delinquency and substance use. Open parent—adolescent communication was associated with decreased sexual risk behavior, whereas problematic parent–adolescent communication was associated with increased sexual risk behavior. The results obtained with path models indicate that youth disclosure is a significant longitudinal predictor of reduced adolescent delinquency and that parental control during early adolescence predicted reduced substance use in middle adolescence. The findings suggest that parental knowledge, youth disclosure and parental control differ in their impacts on substance use, delinquency and sexual risk behaviors. Problematic parent–adolescent communication is consistently associated with increases in all three types of adolescent risk behaviors. Future parental monitoring interventions should focus on enhancing parents’ interpersonal communication skills and emphasize the differences in and importance of the unique components of parental monitoring.
PMCID: PMC4049067  PMID: 24161101
adolescent; parental knowledge; youth disclosure; parental solicitation; parental control; parent–adolescent communication; risk behaviors; Bahamas
9.  Adolescent Age at Time of Receipt of One or More Sexual Risk Reduction Interventions 
Age of the target audience at time of intervention is thought to be a critical variable influencing the effectiveness of adolescent sexual risk reduction interventions. Despite this postulated importance, to date studies have not been designed to enable a direct comparison of outcomes according to age at time of intervention delivery.
We examined outcomes of 598 youth who were sequentially involved in two randomized controlled trials of sexual risk prevention interventions, the first one delivered in grade 6 [Focus on Youth in the Caribbean (FOYC)] and the second one in grade ten [Bahamian Focus on Older Youth (BFOOY)]. Four groups were examined, including those who received: 1) both treatment conditions, FOYC and BFOOY; 2) FOYC in grade 6 and the control condition in grade 10; 3) the control condition in grade 6 and BFOOY in grade 10; and 4) both control conditions. Intentions, perceptions, condom-use skills as well as HIV-related knowledge were assessed over 60 months.
Data showed that those who received both interventions had the greatest increase in condom-use skills. Youth who received FOYC in grade 6 had greater scores in knowledge and intention.
These results suggest that youth receive the most protection with early and repeated exposure to interventions. These findings suggest that educators should consider implementing HIV prevention and risk reduction programs as a fixed component of education curriculum beginning in the pre-adolescent years and if possible also during the adolescent years.
PMCID: PMC4108619  PMID: 24656447
HIV Prevention Intervention; Adolescence; Condom-use skills; Randomized Controlled Trials; Risk Reduction Behavior
10.  Psychological Fears among Low-Paid Female Sex Workers in Southwest China and Their Implications for HIV Prevention 
PLoS ONE  2014;9(10):e111012.
Commercial sex plays a critical role in rapidly increasing heterosexual transmission of HIV in China. Low-paid female sex workers (FSWs) are especially vulnerable to HIV/AIDS. Because of the illegality and stigma associated with sex work, FSWs may constantly live with fears in their daily life. Based on cross-sectional study of 794 low-paid FSWs in China we described their psychological fears related to commercial sex and examined the associations between fears and HIV-related behaviors. Fear of HIV infection was significantly associated with consistent use of condoms with clients. However, fear of breaching sex worker identity significantly prevented the FSWs from consistently using condoms with clients and taking HIV tests. Fear of being arrested by the police was positively associated with consistent use of condoms but negatively associated with accessing HIV prevention services. Our findings underlined the importance of examining the triadic interaction of behavioral, psychological and environmental factors in HIV prevention interventions among low-paid FSWs.
PMCID: PMC4201579  PMID: 25330242
11.  Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma 
Oncology Letters  2014;8(6):2627-2633.
Delta-like ligand 4 (Dll4)-Notch signaling is important in tumor angiogenesis; however, the prognostic value of D114 detection in patients with clear cell renal cell carcinoma (CCRCC) remains unclear. The present study aimed to determine whether the presence of high Dll4 expression levels was correlated with poor prognosis in CCRCC following curative resection. The D114 expression levels in four paired samples of CCRCC tissues and adjacent normal renal tissues were assayed by western blotting. Surgical specimens comprised 121 CCRCC tissue samples and 65 normal renal tissue samples, obtained from patients with CCRCC. The specimens were immunohistochemically assessed to determine Dll4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression levels. The prognostic significance of Dll4 expression levels was evaluated by the Kaplan-Meier method and Cox regression analysis. The correlation between Dll4 expression levels and VEGFR-2 expression levels, tumor stage, tumor grade and metastasis, was examined by χ2 test and multivariate logistic regression. As determined by the western blotting results, Dll4 protein expression levels were significantly increased in CCRCC tissues compared with those in adjacent non-cancerous tissues. From the analysis of the surgical specimens, 53 (43.8%) CCRCC patients exhibited immunohistochemically high Dll4 expression levels and 68 (56.2%) patients exhibited low Dll4 expression levels. The survival curves revealed that the patients with high Dll4 expression levels had significantly shorter survival times than the patients with low Dll4 expression levels (P<0.001). Multivariate survival analysis demonstrated that the presence of high Dll4 expression levels was independently associated with reduced overall survival and progression-free survival times (P=0.021 and 0.034, respectively). A positive correlation was also identified between Dll4 and VEGFR-2 expression levels (P=0.001). In conclusion, the results show that the presence of high Dll4 expression levels was clearly associated with high VEGFR-2 expression levels, tumor grade, tumor stage and poor prognosis in CCRCC patients. Therefore, inhibition of Dll4 may exert potent growth inhibitory effects on tumors resistant to anti-VEGF therapies for CCRCC.
PMCID: PMC4214437  PMID: 25364440
delta-like ligand 4; clear cell renal cell carcinoma; survival; prognosis
12.  Impact of Parental HIV/AIDS on Children’s Psychological Well-Being: A Systematic Review of Global Literature 
AIDS and behavior  2013;17(7):2554-2574.
This review examines the global literature regarding the impact of parental HIV/AIDS on children’s psychological well-being. Fifty one articles reporting quantitative data from a total of 30 studies were retrieved and reviewed. Findings were mixed but tended to show that AIDS orphans and vulnerable children had poorer psychological well-being in comparison with children from HIV-free families or children orphaned by other causes. Limited longitudinal studies suggested a negative effect of parental HIV on children’s psychological well-being in an early stage of parental HIV-related illness and such effects persisted through the course of parental illness and after parental death. HIV-related stressful life events, stigma, and poverty were risk factors that might aggravate the negative impact of parental HIV/AIDS on children. Individual coping skills, trusting relationship with caregivers and social support were suggested to protect children against the negative effects of parental HIV/AIDS. This review underlines the vulnerability of children affected by HIV/AIDS. Culturally and developmentally appropriate evidence-based interventions are urgently needed to promote the psychological well-being of children affected by HIV/AIDS.
PMCID: PMC3568204  PMID: 22972606
Parental HIV/AIDS; Children affected by HIV/AIDS; Psychological well-being; Literature review
13.  Perceived Peer Engagement in HIV-related Sexual Risk Behaviors and Self-reported Risk-taking among Female Sex Workers in Guangxi, China 
AIDS care  2013;25(9):10.1080/09540121.2012.750709.
Searching for modifiable perceptions that are associated with sexual risk behaviors among female sex workers (FSWs) is considered a priority in HIV/STD preventions. Perception of peers’ involvement in risk behaviors, a key correlate of individual risk behaviors, has barely been studied among FSWs. A self-administered questionnaire was completed by 1,022 FSWs in Guangxi, China, a country with rapid growth in both HIV epidemic and commercial sex. Multiple imputation using chained equation (MICE) was applied to handle missing values (1-10%) in the dataset. Regression analysis that focused on relationship between perceived peers’ risk involvement and FSWs’ risk-taking was performed on full datasets generated by MICE. FSWs who perceived more peer alcohol use was significantly more likely to have sex under the influence of alcohol. Those who perceived more unprotected sex among peers had a higher likelihood to use condom inconsistently with both stable and casual partners. Perceiving more peers engaging in sex after using alcohol was positively associated with having sex with clients who were intoxicated and/or high on drugs, and with having sex under the influence of alcohol. Perceived peer promiscuity, defined as having sex with any types of clients at any price offered, was positively associated with inconsistent condom use with casual partners, but negatively associated with having sex under the influence of alcohol. These data suggest the potential for intervention programs to address behavioral change among FSWs through modifying perceptions of peer involvement in sexual risk behaviors. Longitudinal studies are needed to confirm these findings and qualitative researches will be essential for the clarification of mechanisms behind associations found in the current study and for the actual design of effective norm-based interventions among FSWs.
PMCID: PMC3860185  PMID: 23316998
Perceived peer behaviors; HIV-related sexual risk behaviors; female sex workers; China
14.  Predictors of responsiveness among early adolescents to a school-based risk reduction intervention over 3 years 
AIDS and behavior  2013;17(3):1096-1104.
This study assesses potential predictive factors for unresponsiveness to the “Focus on Youth in the Caribbean (FOYC)” intervention using longitudinal data from 1360 Bahamian sixth-grade youth. Results from hierarchical logistic regression analyses indicate that the intervention had a greater impact on knowledge, skills, self-efficacy, and condom use intention among low and medium initial scorers. High initial scores in knowledge, skills, self-efficacy, and intention were predictive of relative unresponsiveness to the intervention. Advanced age and male sex were predictive of unresponsiveness to the intervention for HIV/AIDS knowledge. Female gender was predictive of unresponsiveness to the intervention for self-efficacy. High academic self-evaluation was predictive of unresponsiveness to the intervention for condom use intention. The greatest intervention impact was observed at the six-month post-intervention follow-up; these intervention-related gains were sustained over the subsequent follow-up periods. Youth with higher risk attributes (lower knowledge, skills and self-efficacy) were more likely to respond to a risk reduction intervention.
PMCID: PMC4136491  PMID: 22311147
HIV/AIDS knowledge; condom use skills; self-efficacy; condom use intention; intervention; unresponsiveness
15.  Scaffolds Reinforced by Fibers or Tubes for Tissue Repair 
BioMed Research International  2014;2014:501275.
PMCID: PMC4151618  PMID: 25210714
16.  Disclosure of parental HIV infection to children and psychosocial impact on children in China: a qualitative study 
This qualitative study aims to investigate parental HIV disclosure and psychological impact from the perspectives of their children. In-depth individual interviews with 47 children who had lost one or both parents to AIDS were conducted in China. All transcripts were coded using the software ATLAS.ti 5. Results showed that few of children knew of parental HIV status before the death of their parents. The main disclosers were the children’s current caregivers. Some children knew about their parent’s HIV infection based on their own observations or through overheard conversation, or their interactions with villagers. Both positive and negative psychological outcomes related to parental HIV disclosure were reported. Psychological counseling is needed for both parents and children to dealing with the parental HIV infection.
PMCID: PMC3992264  PMID: 24761258
Parental HIV disclosure; Psychosocial impact; Orphan; China
17.  Predictive factors associated with gefitinib response in patients with advanced non-small-cell lung cancer (NSCLC) 
A number of different clinical characteristics have been reported to singly correlate with therapeutic activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). This study aimed to identify predictive factors associated with prognostic benefits of gefitinib.
Patients and methods
EGFR gene typing in 33 advanced NSCLC patients received gefitinib (250 mg/day) were analyzed with mutant-enriched PCR assay. Gefitinib response was evaluated with potential predictive factors retrospectively.
The overall objective response rate (ORR) and median progression-free survival (PFS) in the 33 patients treated by gefitinib were 45.5% and 3.0 (2.0-4.0) months. The ORR and median PFS in EGFR gene mutation patients were significantly higher/longer than those in EGFR gene wild-type patients (P<0.01). Similarly, the ORR and median PFS in non-smoker patients were significantly higher/longer than those in smoker patients (P<0.05, P<0.01, respectively). However, no difference for ORR and median PFS occurred between male and female patients. Logistic multivariate analysis showed that only EGFR mutated gene was significantly associated with the ORR (P<0.01). Both EGFR mutated gene and non-smoker were the major factors that contributed to PFS (P<0.05).
EGFR mutated gene and non-smoker status are potential predictors for gefitinib response in NSCLC patients.
PMCID: PMC4153923  PMID: 25232221
Epidermal growth factor receptor inhibitor (EGFR inhibitor); gene mutation; gefitinib; non-small-cell lung cancer (NSCLC); smoking; gender
18.  Accumulation of Extracellular Hyaluronan by Hyaluronan Synthase 3 Promotes Tumor Growth and Modulates the Pancreatic Cancer Microenvironment 
BioMed Research International  2014;2014:817613.
Extensive accumulation of the glycosaminoglycan hyaluronan is found in pancreatic cancer. The role of hyaluronan synthases 2 and 3 (HAS2, 3) was investigated in pancreatic cancer growth and the tumor microenvironment. Overexpression of HAS3 increased hyaluronan synthesis in BxPC-3 pancreatic cancer cells. In vivo, overexpression of HAS3 led to faster growing xenograft tumors with abundant extracellular hyaluronan accumulation. Treatment with pegylated human recombinant hyaluronidase (PEGPH20) removed extracellular hyaluronan and dramatically decreased the growth rate of BxPC-3 HAS3 tumors compared to parental tumors. PEGPH20 had a weaker effect on HAS2-overexpressing tumors which grew more slowly and contained both extracellular and intracellular hyaluronan. Accumulation of hyaluronan was associated with loss of plasma membrane E-cadherin and accumulation of cytoplasmic β-catenin, suggesting disruption of adherens junctions. PEGPH20 decreased the amount of nuclear hypoxia-related proteins and induced translocation of E-cadherin and β-catenin to the plasma membrane. Translocation of E-cadherin was also seen in tumors from a transgenic mouse model of pancreatic cancer and in a human non-small cell lung cancer sample from a patient treated with PEGPH20. In conclusion, hyaluronan accumulation by HAS3 favors pancreatic cancer growth, at least in part by decreasing epithelial cell adhesion, and PEGPH20 inhibits these changes and suppresses tumor growth.
PMCID: PMC4131462  PMID: 25147816
Adolescents are at particularly high risk to acquire HIV infection; increasing the likelihood of condom use is an effective measure to reduce the risk of such infections. Challenges in assessing actual condom use behavior among early adolescents render the precursor measure, intention to use condoms, an appealing alternative. While analyzing data from a randomized controlled trial to evaluate a theory-based intervention program to promote condom use among early adolescents, we observed a modest effect with regard to condom use intention when the linear analytical approach was used. If intention, as a measure of the readiness to perform a behavior, also contains a nonlinear discrete component, it would be more appropriately modeled using a non-linear approach. In this study, data from a randomized controlled trial (N=1360) were analyzed using the cusp catastrophe method with HIV knowledge and condom skills as the asymmetry variables and condom use self-efficacy as the bifurcation variables. Findings from concurrent and longitudinal modeling analyses indicated a much better fit of the cusp model (R2 = 0.85 and 4+ times smaller AIC and BIC) than the linear (R2 <=0.10 and 4+ times larger AIC and BIC) or the logistic model (R2<0.15, also 4+ times larger AIC and BIC). Receipt of the intervention as an asymmetry variable was significantly predicted condom use intention but did not as a bifurcation variable. In conclusion, adolescent intentions to use a condom contain both a continuous process and a discrete process and can better be modeled with cusp methods. A much greater program effect is likely from the same prevention intervention if additional measures are taken to foster sudden changes in condom intention.
PMCID: PMC4106698  PMID: 23735493
Behavioral Intention; Cusp modeling; HIV/AIDS; Bahamian Youth; Condom use
20.  Accumulation of connective tissue growth factor+ cells during the early phase of rat traumatic brain injury 
Diagnostic Pathology  2014;9:141.
Glial scar formation is a common histopathological feature of traumatic brain injury (TBI). Astrogliosis and expression of transforming growth factor beta (TGF-β) are key components of scar formation and blood-brain barrier modulation. Connective tissue growth factor (CTGF) is considered a cytokine mediating the effects of TGF-β.
Here, we studied the CTGF expression in an open-skull weight-drop-induced TBI, with a focus on the early phase, most amenable to therapy.
In normal rat brains of our study, CTGF+ cells were rarely observed. Significant parenchymal accumulation of CTGF+ non-neuron cells was observed 72 h post-TBI and increased continuously during the investigating time. We also observed that the accumulated CTGF+ non-neuron cells were mainly distributed in the perilesional areas and showed activated astrocyte phenotypes with typical stellate morphologic characteristics.
Our observations demonstrated the time-dependent and lesion-associated accumulation of cellular CTGF expression in TBI, suggesting a pathological role of CTGF in TBI.
Virtual Slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4227000  PMID: 25012526
Connective tissue growth factor; Astrocytes; Weight-drop model; Traumatic brain injury
21.  Production and immunogenicity of chimeric virus-like particles containing the spike glycoprotein of infectious bronchitis virus 
Journal of Veterinary Science  2014;15(2):209-216.
Infectious bronchitis virus (IBV) poses a severe threat to the poultry industry and causes heavy economic losses worldwide. Vaccination is the most effective method of preventing infection and controlling the spread of IBV, but currently available inactivated and attenuated virus vaccines have some disadvantages. We developed a chimeric virus-like particle (VLP)-based candidate vaccine for IBV protection. The chimeric VLP was composed of matrix 1 protein from avian influenza H5N1 virus and a fusion protein neuraminidase (NA)/spike 1 (S1) that was generated by fusing IBV S1 protein to the cytoplasmic and transmembrane domains of NA protein of avian influenza H5N1 virus. The chimeric VLPs elicited significantly higher S1-specific antibody responses in intramuscularly immunized mice and chickens than inactivated IBV viruses. Furthermore, the chimeric VLPs induced significantly higher neutralization antibody levels than inactivated H120 virus in SPF chickens. Finally, the chimeric VLPs induced significantly higher IL-4 production in mice. These results demonstrate that chimeric VLPs have the potential for use in vaccines against IBV infection.
PMCID: PMC4087222  PMID: 24378590
chimeric virus-like particle; immune response; infectious bronchitis virus
22.  Resin Composites Reinforced by Nanoscaled Fibers or Tubes for Dental Regeneration 
BioMed Research International  2014;2014:542958.
It has been stated clearly that nanofillers could make an enhancement on the mechanical performances of dental composites. In order to address current shortage of traditional dental composites, fillers in forms of nanofibers or nanotubes are broadly regarded as ideal candidates to greatly increase mechanical performances of dental composites with low content of fillers. In this review, the efforts using nanofibers and nanotubes to reinforce mechanical performances of dental composites, including polymeric nanofibers, metallic nanofibers or nanotubes, and inorganic nanofibers or nanotubes, as well as their researches related, are demonstrated in sequence. The first purpose of current paper was to confirm the enhancement of nanofibers or nanotubes' reinforcement on the mechanical performances of dental restorative composite. The second purpose was to make a general description about the reinforcement mechanism of nanofibers and nanotubes, especially, the impact of formation of interphase boundary interaction and nanofibers themselves on the advanced mechanical behaviors of the dental composites. By means of the formation of interface interaction and poststretching nanofibers, reinforced effect of dental composites by sorts of nanofibers/nanotubes has been successfully obtained.
PMCID: PMC4058202  PMID: 24982894
23.  Engineering surface states of carbon dots to achieve controllable luminescence for solid-luminescent composites and sensitive Be2+ detection 
Scientific Reports  2014;4:4976.
Luminescent carbon dots (L-CDs) with high quantum yield value (44.7%) and controllable emission wavelengths were prepared via a facile hydrothermal method. Importantly, the surface states of the materials could be engineered so that their photoluminescence was either excitation-dependent or distinctly independent. This was achieved by changing the density of amino-groups on the L-CD surface. The above materials were successfully used to prepare multicolor L-CDs/polymer composites, which exhibited blue, green, and even white luminescence. In addition, the excellent excitation-independent luminescence of L-CDs prepared at low temperature was tested for detecting various metal ions. As an example, the detection limit of toxic Be2+ ions, tested for the first time, was as low as 23 μM.
PMCID: PMC4021332
24.  Domestic chores workload and depressive symptoms among children affected by HIV/AIDS in China 
AIDS care  2012;25(5):632-639.
Limited data are available regarding the effects of domestic chores workload on psychological problems among children affected by HIV/AIDS in China. The current study aims to examine association between children’s depressive symptoms and the domestic chores workload (i.e., the frequency and the amount of time doing domestic chores). Data were derived from the baseline survey of a longitudinal study which investigated the impact of parental HIV/AIDS on psychological problems of children. A total of 1,449 children in family-based care were included in the analysis: 579 orphaned children who lost one or both parents due to AIDS, 466 vulnerable children living with one or both parents being infected with HIV, and 404 comparison children who did not have HIV/AIDS infected family members in their families. Results showed differences on domestic chores workload between children affected by HIV/AIDS (orphans and vulnerable children) and the comparison children. Children affected by HIV/AIDS worked more frequently and worked longer time on domestic chores than the comparison children. Multivariate linear regression analysis showed that domestic chores workload was positively associated with depressive symptoms. The data suggest that children affected by HIV/AIDS may face increasing burden of domestic chores and it is necessary to reduce the excessive workload of domestic chores among children affected by HIV/AIDS through increasing community-based social support for children in the families affected by HIV/AIDS.
PMCID: PMC3622201  PMID: 22970996
Domestic chores workload; Depressive symptoms; Orphan; HIV/AIDS; China
25.  Alcohol use and client-perpetrated sexual violence against female sex workers in China 
Psychology, health & medicine  2012;18(3):330-342.
The global literature suggests that female sex workers (FSWs) experience high rates of sexual violence perpetrated by their clients, especially when FSWs are under the influence of alcohol. However, such data are limited in China. The current study is aimed to fill in the literature gap by examining the association between alcohol use by FSWs and client-perpetrated sexual violence against FSWs in China.
A total of 1,022 FSWs were recruited through community outreach in Guangxi, China. FSWs completed a self-administered survey on their demographic information, alcohol use, and sexual violence perpetrated by clients. Multivariable regression was employed to assess the relationship between alcohol use and client-perpetrated sexual violence among FSWs while controlling for possible confounders.
Alcohol use was positively associated with the experience of sexual violence in both bivariate and multivariable analyses. Women who were at a higher risk level of alcohol use were more likely to experience sexual violence perpetrated by clients even after controlling confounders (e.g., demographics and alcohol-serving practice).
Given the association between alcohol use and client-perpetrated sexual violence, preventing or reducing alcohol use among FSWs could be an effective strategy to protect these women from sexual violence perpetrated by their clients. Alternatively, psychological counseling and other support should be available to these women so they can reduce their alcohol use as a maladaptive coping strategy. We call for culturally appropriate alcohol use reduction components, incorporated with sexual violence reduction strategies including adaptive coping skills training as well as empowerment, and targeting both FSWs and their clients.
PMCID: PMC3644341  PMID: 22882121
China; Female Sex Workers; Alcohol Use; Sexual Violence; Clients; Prevention

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