Diabetic eye screening in multi ethnic population of Malaysia: epidemiological risk factors for development of diabetic retinopathy

Background:The objective of this study is to evaluate epidemiological risk factors for development of diabetic retinopathy.Methods:The cases of type-2 diabetes mellitus attending Melaka Manipal medical college, Malaysia were retrospectively reviewed. The epidemiological characteristics of diabetic retinopathy were estimated. The cases were graded according to degree of retinopathy in to: non-diabetic retinopathy group and diabetic retinopathy. Clinical and biochemical studies were used for studying the risk factors associated with development of retinopathy.Results:The prevalence of diabetic retinopathy in the population was 21% in known diabetic subjects and was significantly higher in men than in women (21.3% vs. 14.6%) with increasing age and duration of diabetes. Ethnicity is a complex, independent risk factor for diabetic retinopathy. Sight threatening diabetic retinopathy, and clinically significant macular edema was higher in people of Malaysia (20%) when compared with Chinese (16%) and Indonesians (12%). In all, 55 percent of patients with known diabetes mellitus had never undergone an eye examination. Among patients who had undergone eye examinations, 32.8 percent had the last examination within the last one year, 49.8 percent within the last one to two years, and 17.4 percent more than two years ago.Conclusion:Diabetic retinopathy is highly prevalent in the patients with type-2 diabetes mellitus in Malaysia. Besides blood glucose, many factors are associated with the present and development of diabetic retinopathy.

Comparison of Flow field in the proximity of A Single Planar & Wrap-around Fin

Abstract This paper analyses the results of the computational analysis between a single planar and a wrap-around fin mounted on a semi-cylindrical body. A free-stream Computational Fluid Dynamics (CFD) model was simulated for both cases in the Mach 0.4-3.0M range at 0°Angle of attack, in which, the behavior of flow around the fin was investigated using a turbulence model of higher order discretization. The post-processing shows all the possible views of the flow dynamics around the fins, as well as the missile body. The aerodynamic drag and the rolling moment characteristics of the planar and the wrap-around fin have been compared and adequate validation has been performed for the current missile model. This work forms a preliminary step in turbulence modelling and comparing the flow aerodynamics around both fin geometries

Use of Semi-Structured Interviews to Explore Competing Demands in a Prostate Cancer Prevention Intervention Clinical Trial (PCPICT)

In this paper we report on findings from the first known study using qualitative methods to explore factors influencing physicians’ participation in an ongoing federally-funded prostate cancer chemoprevention clinical trial. We sought to identify ways to improve collaboration between researchers and physicians and enhance the success of future projects and employed purposive sampling to recruit physician/investigators who were involved or invited to participate in the trial. Using the data from open-ended semi-structured interviews, we examined patterns in their languaging and created themes. We found that individual and structural factors served as barriers and facilitators to participation. Willingness and desire to participate in the trial (individual factors) were not always enough to result in actual participation due to practice environment (structural) constraints. Our research provides a better understanding of the complex intersection of factors in this setting and through our findings we extend the theory of competing demands into the arena of prostate cancer prevention clinical trials, moving the science towards solutions to current challenges in recruitment to this type of trial

Determination of putative virulence factors among clinical isolates of enterococci isolated from a military hospital in the eastern province of Saudi Arabia

Background: The pathogenic potential of enterococci to produce life-threatening infections is well-documented. The scientific community has, of late, evinced a renewed interest in the putative virulence factors of enterococci. Objective of the study was to determine the putative virulence factors of clinically isolated Enterococcus species from a military hospital and to describe the association between virulence factors and vancomycin susceptibility.Methods: A total of 245 enterococci were isolated from clinical samples collected from KFMMC, a leading military hospital in the eastern province of Saudi Arabia. Following species identification and antimicrobial susceptibility testing using the Vitek 2 system; the isolates were tested for the production of caseinase, gelatinase, biofilm, and presence of haemolysin.Results: Among the enterococcal isolates, 36.7% produced caseinase, 38% produced gelatinase, 24.1% exhibited biofilm formation, and 30.6% were positive for haemolytic activity. A significant association between vancomycin susceptibility patterns and the virulence factors, gelatinase and haemolytic activity, were noted. No significant associations were observed between vancomycin susceptibility patterns and the presence of caseinase or the formation of biofilms.Conclusions: Virulence factors are invariably produced by several clinical isolates of enterococci in our hospital, and some virulence factors are associated with vancomycin susceptibility

Cancer Cachexia: Traditional Therapies and Novel Molecular Mechanism-Based Approaches to Treatment

The complex syndrome of cancer cachexia (CC) that occurs in 50% to 80% cancer patients has been identified as an independent predictor of shorter survival and increased risk of treatment failure and toxicity, contributing to the mortality and morbidity in this population. CC is a pathological state including a symptom cluster of loss of muscle (skeletal and visceral) and fat, manifested in the cardinal feature of emaciation, weakness affecting functional status, impaired immune system, and metabolic dysfunction. The most prominent feature of CC is its non-responsiveness to traditional treatment approaches; randomized clinical trials with appetite stimulants, 5-HT3 antagonists, nutrient supplementation, and Cox-2 inhibitors all have failed to demonstrate success in reversing the metabolic abnormalities seen in CC. Interventions based on a clear understanding of the mechanism of CC, using validated markers relevant to the underlying metabolic abnormalities implicated in CC are much needed. Although the etiopathogenesis of CC is poorly understood, studies have proposed that NFkB is upregulated in CC, modulating immune and inflammatory responses induce the cellular breakdown of muscle, resulting in sarcopenia. Several recent laboratory studies have shown that n-3 fatty acid may attenuate protein degradation, potentially by preventing NFkB accumulation in the nucleus, preventing the degradation of muscle proteins. However, clinical trials to date have produced mixed results potentially attributed to timing of interventions (end stage) and utilizing outcome markers such as weight which is confounded by hydration, cytotoxic therapies, and serum cytokines. We propose that selective targeting of proteasome activity with a standardized dose of omega-3-acid ethyl esters, administered to cancer patients diagnosed with early stage CC, in addition to a standard intervention with nutritionally adequate diet and appetite stimulants, will alter metabolic abnormalities by downregulating NFkB, preventing the breakdown of myofibrillar proteins and resulting in increasing serum protein markers, lean body mass, and functional status

Proceedings of the I ndo‐ U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo‐U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo‐U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo‐U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, the proceedings of the Indo‐U.S. collaborative Workshop represent one of the most contemporary issues in Cancer Medicine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96353/1/cam442.pd

Proceedings of the I ndo‐ U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo‐U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo‐U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo‐U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, the proceedings of the Indo‐U.S. collaborative Workshop represent one of the most contemporary issues in Cancer Medicine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96353/1/cam442.pd

Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study

African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p < 0.0001. Gene ontology terms prevalent in African American prostate tumor/normal ratios relative to Caucasian American prostate tumor/normal ratios included interleukins, progesterone signaling, Chromatin-mediated maintenance and myeloid dendritic cell proliferation. Functional in vitro assays are underway to determine roles that selected genes in these onotologies play in contributing to prostate cancer development and health disparity

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer