Implementing Phytosterols Into Medical Practice as a Cholesterol-Lowering Strategy: Overview of Efficacy,Effectiveness, and Safety

More than 200 clinical trial reports and several meta-analyses have demonstrated that phytosterols (PSs), natural components of plants, induce clinically relevant reductions in blood low-density lipoprotein cholesterol levels. Here we review data regarding the biochemical effects and potential cardiovascular benefit of PSs as part of the dietary management of dyslipidemia. In addition to discussing the efficacy, effectiveness, and safety of PSs as hypocholesterolemic agents, this review provides an overview of PSs as an adjunctive therapy to cholesterol-lowering pharmaceuticals. Given this lack of evidence regarding the benefits of PSs for reducing cardiovascular end points, this review also discusses the present knowledge that exists about the ability for therapeutic dosages of PSs to confer protection from cardiovascular-related mortality and morbidity. Finally, this review summarizes the factors that affect PS efficacy and the Canadian regulations that govern the use of PSs as cholesterol-lowering agents in foods and supplements.     

Impact of climate change on wetland ecosystems: A critical review of experimental wetlands

Climate change is identified as a major threat to wetlands. Altered hydrology and rising temperature can change the biogeochemistry and function of a wetland to the degree that some important services might be turned into disservices. This means that they will, for example, no longer provide a water purification service and adversely they may start to decompose and release nutrients to the surface water. Moreover, a higher rate of decomposition than primary production (photosynthesis) may lead to a shift of their function from being a sink of carbon to a source. This review paper assesses the potential response of natural wetlands (peatlands) and constructed wetlands to climate change in terms of gas emission and nutrients release. In addition, the impact of key climatic factors such as temperature and water availability on wetlands has been reviewed. The authors identified the methodological gaps and weaknesses in the literature and then introduced a new framework for conducting a comprehensive mesocosm experiment to address the existing gaps in literature to support future climate change research on wetland ecosystems. In the future, higher temperatures resulting in drought might shift the role of both constructed wetland and peatland from a sink to a source of carbon. However, higher temperatures accompanied by more precipitation can promote photosynthesis to a degree that might exceed the respiration and maintain the carbon sink role of the wetland. There might be a critical water level at which the wetland can preserve most of its services. In order to find that level, a study of the key factors of climate change and their interactions using an appropriate experimental method is necessary. Some contradictory results of past experiments can be associated with different methodologies, designs, time periods, climates, and natural variability. Hence a long-term simulation of climate change for wetlands according to the proposed framework is recommended. This framework provides relatively more accurate and realistic simulations, valid comparative results, comprehensive understanding and supports coordination between researchers. This can help to find a sustainable management strategy for wetlands to be resilient to climate change.     

A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo

The central role of Src in the development of several malignancies, including breast cancer, and the accumulating evidence of its interaction with receptor tyrosine kinases, integrins, and steroid receptors have identified it as an attractive therapeutic target. In the current study, we have evaluated the effect of a Src/Abl kinase inhibitor, SKI-606, on breast cancer growth, migration, invasion, and metastasis. Treatment of human breast cancer cells MDA-MB-231 with SKI-606 caused a marked inhibition of cell proliferation, invasion, and migration by inhibiting mitogen-activated protein kinase and Akt phosphorylation. For in vivo studies, MDA-MB-231 cells transfected with the plasmid encoding green fluorescent protein (GFP; MDA-MB-231-GFP) were inoculated into the mammary fat pads of female BALB/c nu/nu mice. Once tumor volume reached 30 to 50 mm(3), animals were randomized and treated with vehicle alone or 150 mg/kg SKI-606 by daily oral gavage. Experimental animals receiving SKI-606 developed tumors of significantly smaller volume (45-54%) compared with control animals receiving vehicle alone. Analysis of lungs, liver, and spleen of these animals showed a significant decrease in GFP-positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated. Western blot analysis and immunohistochemical analysis of primary tumors showed that these effects were due to the ability of SKI-606 to block tumor cell proliferation, angiogenesis, growth factor expression, and inhibition of Src-mediated signaling pathways in vivo. Together, the results from these studies provide compelling evidence for the role of Src inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.     

Knowledge of Jordanian mothers with regards to emergency management of dental trauma

Abstract –  Studies in Jordan indicated that delay in seeking emergency management of dental trauma leads to unfavorable outcome of even mild forms of trauma. The purpose of this cross-sectional study was to assess, by means of a structured questionnaire, the level of general knowledge of mothers in Jordan with regards to the immediate emergency management of dental trauma, and its relation to socioeconomic variables. The questionnaire surveyed mothers' demographic data, basic knowledge of immediate management of tooth fracture, avulsion, and loss of consciousness. It also investigated the participants self assessed knowledge, attitude to public education, and knowledge of availability and priority of emergency services for trauma in Jordan. The sample consisted of 2215 mothers who attended mother and child care centers in the capital Amman, and in Irbid (the second largest city in Jordan) over a period of 3 months (July to September, 2003). Overall the participants' basic knowledge with regards to the emergency management of the trauma cases presented in the questionnaire was deficient regardless of age, level of education, socioeconomic class, or number of previous encounters with dental trauma. Generally, the attitude to public education on the topic was positive and chi-square test indicated that the level of education of mothers positively affected their knowledge of 'during working hour' emergency services and the importance of immediate management of dental trauma. Educational programs that can be added to the mother and child care advice protocols may help improve the knowledge and awareness of mothers and therefore improve the outcomes of dental trauma.     

Defining the role of prolactin as an invasion suppressor hormone in breast cancer cells

Prolactin hormone (PRL) is well characterized as a terminal differentiation factor for mammary epithelial cells and as an autocrine growth/survival factor in breast cancer cells. However, this function of PRL may not fully signify its role in breast tumorigenesis. Cancer is a complex multistep progressive disease resulting not only from defects in cell growth but also in cell differentiation. Indeed, dedifferentiation of tumor cells is now recognized as a crucial event in invasion and metastasis. PRL plays a critical role in inducing/maintaining differentiation of mammary epithelial cells, suggesting that PRL signaling could serve to inhibit tumor progression. We show here that in breast cancer cells, PRL and Janus-activated kinase 2, a major kinase involved in PRL signaling, play a critical role in regulating epithelial-mesenchymal transformation (EMT), an essential process associated with tumor metastasis. Activation of the PRL receptor (PRLR), achieved by restoring PRL/JAK2 signaling in mesenchymal-like breast cancer cells, MDA-MB-231, suppressed their mesenchymal properties and reduced their invasive behavior. While blocking PRL autocrine function in epithelial-like breast cancer cells, T47D, using pharmacologic and genetic approaches induced mesenchymal-like phenotypic changes and enhanced their invasive propensity. Moreover, our results indicate that blocking PRL signaling led to activation of mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) and transforming growth factor-beta/Smad signaling pathways, two major prometastatic pathways. Furthermore, our results indicate that following PRL/JAK2 inhibition, ERK1/2 activation precedes and is required for Smad2 activation and EMT induction in breast cancer cells. Together, these results highlight PRL as a critical regulator of epithelial plasticity and implicate PRL as an invasion suppressor hormone in breast cancer.     

Association between mass media and body weight concern among Jordanian adolescents’ residents of Amman: the role of gender and obesity

Objectives

Body image in the mass media promotes an unrealistic picture of body shape that leads to body dissatisfaction among adolescentsQuery. Therefore, the study presented in this paper aimed to assess the association between mass media and adolescents’ weight concerns and perceptions of body weight and shape.

Methods

A cross-sectional survey was conducted on school adolescents aged between 15 and 18 years during the academic year 2013–2014. Multistage stratified sampling method was used. The number of participants in the study was 795 students: 400 boys and 395 girls.

Results

All participants have a common behavior in rarely reading magazines, but they spend more than 2 h in watching television or less than 3 h using the internet. However, most of obese/non-obese adolescents, boys or girls, have shown high influence (p < 0.05) of reading magazines on the subject of dieting to lose weight.

Conclusion

While obese students read more magazines on dieting to lose weight, other mass media did not show the same results on weight concerns and body shape among Jordanian adolescents.

     

Risk factors for nutritional rickets among children in Kuwait

AIM: To assess the risk factors for nutritional rickets among children in Kuwait. METHODS: One hundred and three children with rickets and 102 control children matched for age and socioethnic characteristics were recruited over a 2 year period (January 1995 to January 1997) in Al-Adan Hospital in Kuwait. Diagnosis was made on clinical, radiologic and biochemical parameters. A specially designed questionnaire was administered by one of the investigators to both mothers of patients and mothers of control subjects to assess the role of social, nutritional and other related factors in the pathogenesis of nutritional rickets. Biochemical investigations included estimation of hemoglobin, serum calcium, serum phosphorus, serum alkaline phosphatase and serum 25-hydroxy vitamin D. RESULTS: The mean birthweights of rickets patients and control subjects were 3.20 +/- 0.46 and 3.19 +/- 0.45 kg, respectively. At the time of diagnosis, bodyweights of the patients and controls were 9.36 +/- 1.50 and 10.15 +/- 2.10 kg, respectively. Heights at the time of diagnosis were 73.58 and 77.24 cm for the patients and the controls, respectively. Mean hemoglobin, serum calcium and serum phosphate were significantly lower in the patients compared with the controls. Alkaline phosphatase was higher among the patients (P < 0.0001). The mean serum 25-hydroxy vitamin D level of the patients was 26.5 nmol/L, compared with 83.5 nmol/L in the controls. The mean age of starting semisolid feeds for the patients was 8.12 months, compared with 5.7 months in the controls. The nutritional quality of semisolid feeds was adequate among 71.6% of the controls as opposed to 13.6% of the patients. CONCLUSION: Nutritional rickets is a multifactorial condition. However, several factors seem to make important contributions. Among these, lack of exposure to sunlight, prolonged breast feeding without supplementation and inadequate weaning practices are important. Maternal education is important as it can influence all of the above factors.     

Cyclin D1 cooperates with p21 to regulate TGFβ-mediated breast cancer cell migration and tumor local invasion

Introduction

Deregulation of the cell cycle machinery is often found in human cancers. Modulations in the cell cycle regulator function and expression result not only in proliferative advantages, but also lead to tumor progression and invasiveness of the cancer. In particular, cyclin D1 and p21 are often over-expressed in human cancers, correlating with high tumor grade, poor prognosis and increased metastasis. This prompted us to investigate the role of the cyclin D1/p21 signaling axis downstream of transforming growth factor beta (TGFβ) in breast cancer progression.

Methods

Cyclins mRNA and protein expressions were assessed by quantitative real-time PCR and Western blot in triple negative breast cancer cell lines. Co-localization and interaction between cyclin D1 and p21 were performed by immunocytochemistry and co-immunoprecipitation, respectively. Cell migration was assessed by wound healing and quantitative time-lapse imaging assays. In addition, the effects of cyclin D1 on cellular structure and actin organization were examined by staining with F-actin marker phalloidin and mesenchymal intermediate filament vimentin. Finally, a mammary fat pad xenograft mouse model was used to assess mammary tumor growth and local invasion.

Results

We found TGFβ to specifically up-regulate the expression of cyclin D1 in triple negative breast cancer cells. Induction of cyclin D1 is also required for TGFβ-mediated cell migration. Suppression of cyclin D1 expression not only resulted in a rounded and epithelial-like phenotype, but also prevented TGFβ-induced vimentin and F-actin co-localization at the cell edge as well as invadopodia formation. Furthermore, TGFβ promoted the nuclear co-localization and physical interaction between cyclin D1 and p21. The co-expression of cyclin D1 and p21 proteins are required for the initial steps of tumor development, as double knockdown of these two molecules prevented primary tumor formation in a Xenograft mouse model. Moreover, the in vivo studies indicated that locally advanced features of the invasive tumors, including skeletal muscle, mammary fat pad and lymphovascular invasion, as well as ulcerated skin, were attenuated in the absence of cyclin D1 and p21.

Conclusions

Thus, our findings highlight the cyclin D1/p21 signaling axis as a critical regulator of TGFβ-mediated tumor growth initiation and local tumor cell invasion, both in vitro and in vivo.     

Cross-cultural comparison of mental illness stigma and help-seeking attitudes: a multinational population-based study from 16 Arab countries and 10,036 individuals

Social Psychiatry and Psychiatric Epidemiology - There is evidence that culture deeply affects beliefs about mental illnesses' causes, treatment, and help-seeking. We aimed to explore and...