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Multifactorial Nature (multifactorial + nature)
Selected AbstractsGene therapy and enhancement for diabetes (and other diseases): the multiplicity of considerationsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2010Marta Bertolaso Abstract Gene therapy has reached the forefront of studies and research over the last 30 years because of its potential for curing, treating, and preventing diseases associated with DNA mutations. Type 1 and type 2 diabetes are two examples of very common polygenic and multifactorial diseases. The huge amount of scientific literature on this topic reflects a growing general interest in the possibilities of altering our genetic heritage and thus controlling the onset of diseases associated with mutations and relative risk factors. We have focussed on the new treatment opportunities and possibility of enhancing an individual's health, physical well-being, and even an individual's behaviour through technologies specially designed for therapeutic purposes, which have been presented in literature. This historical perspective shows how this type of research, however, was immediately subjected to an ethical evaluation, especially regarding the decoding of the human genome and the questions raised by the alteration of our genetic heritage through new biotechnologies. Moreover, understanding the limitations of gene therapy protocol experiments and the multifactorial nature of many diseases, which have a genetic base, also contributes to these considerations. Copyright © 2010 John Wiley & Sons, Ltd. [source] Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathyDIABETIC MEDICINE, Issue 12 2007Y-H. Yang Abstract Aims Microalbuminuria is the earliest clinical sign of diabetic nephropathy (DN). However, the multifactorial nature of DN supports the application of combined markers as a diagnostic tool. Thus, another screening approach, such as protein profiling, is required for accurate diagnosis. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a novel method for biomarker discovery. We aimed to use SELDI and bioinformatics to define and validate a DN-specific protein pattern in serum. Methods SELDI was used to obtain protein or polypeptide patterns from serum samples of 65 patients with DN and 65 non-DN subjects. From signatures of protein/polypeptide mass, a decision tree model was established for diagnosing the presence of DN. We estimated the proportion of correct classifications from the model by applying it to a masked group of 22 patients with DN and 28 non-DN subjects. The weak cationic exchange (CM10) ProteinChip arrays were performed on a ProteinChip PBS IIC reader. Results The intensities of 22 detected peaks appeared up-regulated, whereas 24 peaks were down-regulated more than twofold (P < 0.01) in the DN group compared with the non-DN groups. The algorithm identified a diagnostic DN pattern of six protein/polypeptide masses. On masked assessment, prediction models based on these protein/polypeptides achieved a sensitivity of 90.9% and specificity of 89.3%. Conclusion These observations suggest that DN patients have a unique cluster of molecular components in serum, which are present in their SELDI profile. Identification and characterization of these molecular components will help in the understanding of the pathogenesis of DN. The serum protein signature, combined with a tree analysis pattern, may provide a novel clinical diagnostic approach for DN. [source] Interaction of the G182C polymorphism in the APOA5 gene and fasting plasma glucose on plasma triglycerides in Type 2 diabetic subjectsDIABETIC MEDICINE, Issue 12 2005Y.-D. Jiang Abstract Aim Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population. Methods This study enrolled two cohorts: non-diabetic subjects (112 males and 89 females) aged 50.3 ± 11.0 years (mean ± sd) and diabetic subjects (106 males and 96 females) aged 62.1 ± 10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained. Results The G182C polymorphism was a determinant of plasma triglycerides in both non-diabetic (P = 0.022) and diabetic (P = 0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P = 0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol. Conclusions In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non-diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes. Diabet. Med. (2005) [source] Orthodontic treatment of anterior open biteINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 2 2008CHUI SHAN TERESA NG Objective. To review the currently available treatment options of anterior open bite. Methods. Search all major dental journals and literature on treatment and management of anterior open bite. Medline search (1960,2006). Literature and data on treatment and management of anterior open bite with keywords ,open bite', ,anterior open bite', ,orthodontic treatment', ,long face', ,vertical dentoalveolar problem' and ,vertical skeletal problem'. Results. Over 50 articles were found and relevant information and data were reviewed by the authors. It was found that the multifactorial nature of anterior open bite makes its management difficult and various treatment modalities are being used. Clinicians must be able to diagnose the problem and choose the best treatment. Conclusion. Successful treatment of anterior open bite greatly relies on both diagnosis and therapeutics. Although there are many different treatment modalities available, stability after treatment is still a critical issue as evidence on long term stability of various treatment options is lacking. Thus, clinicians should pay more attention during retention phase and long-term studies on post-treatment changes and stability should be encouraged. [source] Evaluating the Cost-Effectiveness of Fall Prevention Programs that Reduce Fall-Related Hip Fractures in Older AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2010Kevin D. Frick PhD OBJECTIVES: To model the incremental cost-utility of seven interventions reported as effective for preventing falls in older adults. DESIGN: Mathematical epidemiological model populated by data based on direct clinical experience and a critical review of the literature. SETTING: Model represents population level interventions. PARTICIPANTS: No human subjects were involved in the study. MEASUREMENS: The last Cochrane database review and meta-analyses of randomized controlled trials categorized effective fall-prevention interventions into seven groups: medical management (withdrawal) of psychotropics, group tai chi, vitamin D supplementation, muscle and balance exercises, home modifications, multifactorial individualized programs for all elderly people, and multifactorial individualized treatments for high-risk frail elderly people. Fall-related hip fracture incidence was obtained from the literature. Salary figures for health professionals were based on Bureau of Labor Statistics data. Using an integrated healthcare system perspective, healthcare costs were estimated based on practice and studies on falls in older adults. Base case incremental cost utility ratios were calculated, and probabilistic sensitivity analyses were conducted. RESULTS: Medical management of psychotropics and group tai chi were the least-costly, most-effective options, but they were also the least studied. Excluding these interventions, the least-expensive, most-effective options are vitamin D supplementation and home modifications. Vitamin D supplementation costs less than home modifications, but home modifications cost only $14,794/quality-adjusted life year (QALY) gained more than vitamin D. In probabilistic sensitivity analyses excluding management of psychotropics and tai chi, home modification is most likely to have the highest economic benefit when QALYs are valued at $50,000 or $100,000. CONCLUSION: Of single interventions studied, management of psychotropics and tai chi reduces costs the most. Of more-studied interventions, home modifications provide the best value. These results must be interpreted in the context of the multifactorial nature of falls. [source] Effectiveness of Falls Clinics: An Evaluation of Outcomes and Client Adherence to Recommended InterventionsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2008Keith D. Hill PhD OBJECTIVES: To evaluate outcomes associated with falls clinic programs. DESIGN: Longitudinal. SETTING: Thirteen outpatient falls clinics in Victoria, Australia. PARTICIPANTS: Four hundred fifty-four people referred for clinic assessment (mean age±standard deviation 77.9±8.8; 73% female). INTERVENTION: After assessment, multifactorial interventions were organized to address identified risk factors. MEASUREMENTS: A Minimum Data Set was developed and used across all clinics to derive common data on falls, falls injuries, and secondary measures associated with falls risk, including balance, falls efficacy, gait, leg strength, function, and activity. All measures were repeated 6 months later. RESULTS: Clients had a high risk of falls, with 78% having had falls in the preceding 6 months (63% multiple fallers, 10% experiencing fractures from the falls). An average of 7.6±2.8 falls risk factors were identified per client. The clinic team organized an average of 5.7±2.3 new or additional interventions per client. Sixty-one percent of eligible clients returned for the 6-month assessment. At this time, there was more than a 50% reduction in falls, multiple falls, and fall injuries (P,.004) and small but significant improvements evident on secondary measures of balance, leg strength, gait speed, and confidence outcomes (P<.006). Average adherence to recommendations was 74.3%. Factors associated with higher adherence included being male, younger than 65, living with others, and having a caregiver (P<.05). CONCLUSION: This large multicenter study identified high falls risk of older people referred to falls clinics, the multifactorial nature of their presenting problems and provides preliminary evidence of positive outcomes after falls clinic management. [source] PPAR: a therapeutic target in Parkinson's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Rajnish K. Chaturvedi Abstract Parkinson's disease (PD) is a progressive and chronic neurodegenerative disorder, characterized by progressive loss of dopaminergic neurons in substantia nigra. The etiology and pathogenesis of PD is still elusive, however, a large body of evidence suggests a prominent role of oxidative stress, inflammation, apoptosis, mitochondrial dysfunction and proteosomal dysfunction in the pathogenesis of PD. Due to multifactorial nature of the disease, currently available drug therapy cannot halt / slow down the disease progression, and only provides symptomatic relief. Peroxisome proliferator-activated receptor (PPAR), a member of nuclear receptor superfamily, regulates development, tissue differentiation, inflammation, mitochondrial function, wound healing, lipid metabolism and glucose metabolism. Recently, several PPAR agonists were shown to exert neuroprotective activity against oxidative damage, inflammation and apoptosis in several neurodegenerative disorders including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis and multiple sclerosis. Similarly, regular intake of PPAR activating non-steroidal anti-inflammatory drugs such as indomethacin and ibuprofen was associated with reduced incidence and progression of neurodegenerative disorders in several epidemiological studies. In this article, we review studies relating to the neuroprotective effect of PPAR agonists in in vitro and in vivo models of PD. Similarly, the pharmacological mechanism in neuroprotective actions of PPAR agonists is also reviewed. In conclusion, PPAR agonists exert neuroprotective actions by regulating the expression of a set of genes involved in cell survival processes, and could be a therapeutic target in debilitating neurodegenerative illnesses such as PD. [source] Taxonomy of pain. (Lehigh Valley Hospital, Center for Pain Management, Allentown, PA) Clin J Pain 2000;16:S114,S117.PAIN PRACTICE, Issue 2 2001Bruce Nicholson: This article discussed the way that research on the pathophysiology of chronic pain has started to challenge the traditional diagnostic and treatment paradigms for the patient with neuropathic pain. It stated that the heterogeneous nature of neuropathic pain indicated that more than one anatomic lesion is most likely responsible for the clinical presentation of a particular syndrome. Conclude that the current taxonomy often falls short of identifying the multifactorial nature of neuropathic pain syndromes and, therefore, may lead to imprecise management of those conditions. It is suggested that an integrated approach to the diagnosis and treatment of neuropathic pain that considers both etiologic factors and possible mechanisms will lead to more effective taxonomy, treatment paradigms, and outcomes. [source] Head and Neck Cancer: The Importance of Oxygen ,THE LARYNGOSCOPE, Issue 5 2000David J. Terris MD Abstract Objectives To use recently introduced polarographic technology to characterize the distribution of oxygenation in solid tumors, explore the differences between severe hypoxia and true necrosis, and evaluate the ability to predict treatment outcomes based on tumor oxygenation. Study Design Prospective, nonrandomized trial of patients with advanced head and neck cancer, conducted at an academic institution. Methods A total of 63 patients underwent polarographic oxygen measurements of their tumors. Experiment 1 was designed to determine whether a gradient of oxygenation exists within tumors by examining several series of measurements in each tumor. Experiment 2 was an analysis of the difference in data variance incurred when comparing oxygen measurements using oxygen electrodes of two different sizes. Experiment 3 compared the proportion of tumor necrosis to the proportion of very low (,2.5 mm Hg) polarographic oxygen measurements. Experiment 4 was designed to explore the correlation between oxygenation and treatment outcomes after nonsurgical management. Results No gradient of oxygenation was found within cervical lymph node metastases from head and neck squamous cell carcinomas (P > .9). Tumor measurements achieved with larger (17 ,m) electrodes displayed smaller variances than those obtained with smaller (12 ,m) electrodes, although this difference failed to reach statistical significance (P = .60). There was no correlation between tumor necrosis and the proportion of very low (,2.5 mm Hg) oxygen measurements. There was a nonsignificant trend toward poorer locoregional control and overall survival in hypoxic tumors. Conclusions Hypoxia exists within cervical lymph node metastases from head and neck squamous carcinomas, but the hypoxic regions are distributed essentially randomly. As expected, measurements of oxygen achieved with larger electrodes results in lowered variance, but with no change in overall tumor mean oxygen levels. Polarographic oxygen measurements are independent of tumor necrosis. Finally, oxygenation as an independent variable is incapable of predicting prognosis, probably reflecting the multifactorial nature of the biological behavior of head and neck cancers. [source] Epidemiology, clinical presentation and diagnosis of onychomycosisBRITISH JOURNAL OF DERMATOLOGY, Issue 2003J. Faergemann Summary Onychomycosis is a common nail disease, responsible for up to 50% of diseases of the nail. The distribution of different pathogens is not uniform; it depends on various factors such as climate, geography and migration. However, studies have revealed that two dermatophytes, Trichophyton rubrum and Trichophyton mentagrophytes, account for more than 90% of onychomycoses. Onychomycosis can be divided into four major clinical presentations: distal subungal (the most common form of the disease), proximal subungal (the most common form found in patients with human immunodeficiency virus infection), and superficial and total dystrophic onychomycosis. Onychomycosis is a multifactorial disease. Age has a very important effect on the occurrence of onychomycosis, with a correlation between increasing age and infection. Genetics has also been identified as a factor governing the epidemiology of onychomycosis; T. rubrum infection shows a familial pattern of autosomal dominant inheritance. Disease and lifestyle may also play a role in the epidemiology of fungal nail infections. Studies have shown that diabetes, acquired immunodeficiency syndrome and peripheral arterial disease may be independent predictors of onychomycosis. Because of the multifactorial nature of the epidemiology, accurate diagnosis, pertinent treatment and patient education must be paramount when treating the disease. [source] The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research,CANCER, Issue 7 2002Jose Luis Perez-Gracia M.D. Abstract The investigation of genetic alterations that may be related to the prognosis of patients with malignant disease has become a frequently used strategy in recent years. Although some conclusions have been reached in certain studies, the complexity and the multifactorial nature of most neoplastic diseases makes it difficult to identify clinically relevant information, and the results of some studies have been of borderline significance or have been conflicting. In contrast, the identification and the study of patients or families with very characteristic phenotypes have yielded outstanding results in the identification of the genetic characteristics underlying such phenotypes. Although, in most cases, the individuals who are selected for these types of studies are characterized by a negative phenotype (i.e., individuals who are at increased risk for developing a specific disease), a few studies have been directed toward individuals with phenotypes that imply an unusually good prognosis (i.e., individuals who present with a decreased risk for developing specific diseases despite an important exposure to well-known risk factors). Therefore, it seems logical to develop this strategy further as a valid methodology for the study of other diseases, such as cancer. The study of individuals with phenotypes that imply an extremely good prognosis, such as long-term survivors of theoretically incurable malignancies or individuals who seem to be protected against a certain neoplastic disorder despite having a markedly increased risk for its development, may unveil genetic alterations that explain such characteristic phenotypes and may provide potentially useful therapeutic targets against these diseases. Cancer 2002;95:1605,10. © 2002 American Cancer Society. DOI 10.1002/cncr.10877 [source] | ||||||||||