935 resultados para Gemstone Team PANACEA: Promoting A Novel Approach to Cellular (gene) Expression Alteration


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Background: Many factors have been associated with the onset and maintenance of depressive symptoms in later life, although this knowledge is yet to be translated into significant health gains for the population. This study gathered information about common modifiable and non-modifiable risk factors for depression with the aim of developing a practical probabilistic model of depression that can be used to guide risk reduction strategies. \Methods: A cross-sectional study was undertaken of 20,677 community-dwelling Australians aged 60 years or over in contact with their general practitioner during the preceding 12 months. Prevalent depression (minor or major) according to the Patient Health Questionnaire (PHQ-9) assessment was the main outcome of interest. Other measured exposures included self-reported age, gender, education, loss of mother or father before age 15 years, physical or sexual abuse before age 15 years, marital status, financial stress, social support, smoking and alcohol use, physical activity, obesity, diabetes, hypertension, and prevalent cardiovascular diseases, chronic respiratory diseases and cancer. Results: The mean age of participants was 71.7 +/- 7.6 years and 57.9% were women. Depression was present in 1665 (8.0%) of our subjects. Multivariate logistic regression showed depression was independently associated with age older than 75 years, childhood adverse experiences, adverse lifestyle practices (smoking, risk alcohol use, physical inactivity), intermediate health hazards (obesity, diabetes and hypertension), comorbid medical conditions (clinical history of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, emphysema or cancers), and social or financial strain. We stratified the exposures to build a matrix that showed that the probability of depression increased progressively with the accumulation of risk factors, from less than 3% for those with no adverse factors to more than 80% for people reporting the maximum number of risk factors. Conclusions: Our probabilistic matrix can be used to estimate depression risk and to guide the introduction of risk reduction strategies. Future studies should now aim to clarify whether interventions designed to mitigate the impact of risk factors can change the prevalence and incidence of depression in later life.

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Neuromodulation is the branch of neurophysiology related to the therapeutic effects of electrical stimulations of the nervous system. There are currently different practical applications of neuromodulation techniques for the treatment of various neurological disorders, such as deep brain stimulation for Parkinson`s disease and repetitive transcranial magnetic stimulation (rTMS) for major depression. An increasing number of studies have been devoted to the analgesic effects of rTMS in chronic pain patients. RTMS has been used either as a therapeutic tool per se, or as a preoperative test in patients undergoing epidural precentral gyrus stimulation. High-frequency rTMS (a parts per thousand yen5 Hz) is considered to be excitatory, while low-frequency stimulation (a parts per thousand currency sign1 Hz) is considered to exert an inhibitory effect over neuronal populations of the primary motor cortex. However, other parameters of stimulation may play a central role on its clinical effects such as the type of coil, its orientation over the scalp, and the total number of rTMS sessions performed. Experimental data from animals, healthy volunteers, and neuropathic pain patients have suggested that stimulation of the primary motor cortex by rTMS is able to activate brain regions implicated in the processing of the different aspects of chronic pain, and influence brain regions involved in the endogenous opioid system. Over twenty prospective randomized sham-controlled trials have studied the analgesic effects of rTMS on chronic pain. Most of the patients included in these trials had central or peripheral neuropathic pain. Although most studies used a single session of stimulation, recent studies have shown that the analgesic effects of rTMS may outlast the stimulation period for many days when repetitive sessions are performed. This opens the possibility to use rTMS as a therapeutic tool of its own in the armamentarium against neuropathic pain.

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Introduction: Glossodynia or burning mouth syndrome (BMS) is a common and poorly understood disorder. Its treatment is uncertain. Otherwise, there is some evidence of the importance of psychological factors in the genesis of this disease. Objectives: Verify the usefulness of group psychotherapy as an adjuvant therapeutic method in the treatment of BMS. Casuistics and Methods: The study group consisted of 64 consecutive patients with a clinical diagnosis of BMS seen at the Stomatology Outpatient Clinic, ENT Department, Sao Paulo University Medical School, between May 2002 and May 2007. All the patients were submitted to physical examination, laboratorial screening tests, psychological assessment (Crown-Crisp Experimental Inventory), and answered a short form of the McGill Pain Questionnaire. Only 44 patients who did not show any abnormality in the protocol exams entered the study. Twenty-four of them underwent group psychotherapy. Twenty patients received placebo. Chi-square test was applied to compare the results of treatment with or without psychotherapy. Results: There were 15 men and 29 women in the study group. Tongue burning was the main complaint of the patients. Improvement of symptoms was reported by 17 (70.8%) of the patients undergoing psychotherapy, while among those who did not eight (40%) had improvement of symptoms (P=.04). Conclusion: Psychological assessment demonstrated a close correlation between symptoms and psychological factors, suggesting that group psychotherapy is an important alternative to conventional treatment methods. (C) 2009 Elsevier Inc. All rights reserved.

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Objective: To develop a new endoscopic approach to the correction of a myelomeningocele-like defect in fetal sheep. Methods: The fetuses of 9 pregnant ewes, with an average gestational age of 115 days, were subjected to a 3.0 x 2.0 cm removal of the skin over the lumbar spine, performed through hysterotomy. The uterus was closed, and three 5-mm endoscopic cannulas, without valve mechanisms, were inserted. In the pilot phase (2 animals), we initially worked exclusively in the amniotic fluid space. In the study phase, we partially withdrew the fetus from the amniotic fluid to completely expose its back. By simply allowing air to enter the amniotic cavity (without gas injection), a working space was created using a uterine lift device. The skin around the defect was dissected, and a biosynthetic cellulose material was applied to cover the area. A continuous suture of the skin was performed to completely hide the material. Results: The combined air/fluid space allowed the skin to be successfully closed in 6 out of 7 cases in the study phase. All fetuses were alive at the end of the procedures. Time to complete the endoscopic part of the procedure fell from 3 to 1 h by the end of this series. Premature birth occurred in 2 of the 4 cases allowed to continue with the pregnancy. Conclusion: A new gasless fetoscopic surgery technique was developed as an alternative to current techniques used for fetal endoscopic surgery. Copyright (C) 2008 S. Karger AG, Basel.

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Background: Deficiency of 11 beta-hydroxylase results in the impairment of the last step of cortisol synthesis. In females, the phenotype of this disorder includes different degrees of genital ambiguity and arterial hypertension. Mutations in the CYP11B1 gene are responsible for this disease. Objective: The objective of the study was to screen the CYP11B1 gene for mutations in two unrelated Brazilian females with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Design: The coding and intron-exon junction regions of CYP11B1 were totally sequenced. A putative splice mutation was further investigated by minigene transcription. Results: We report two novel CYP11B1 mutations in these Brazilian patients. An Arabian Lebanese descendent female was found to be homozygous for a cytosine insertion at the beginning of exon 8, changing the 404 arginine to proline. It alters the open reading frame, creating a putative truncated protein at 421 residue, which eliminates the domain necessary for the association of heme prosthetic group. A severely virilized female was homozygous for the g. 2791G>A transition in the last position of exon 4. This nucleotide is also part of 5` intron 4 donor splice site consensus sequence. Minigene experiments demonstrated that g. 2791G>A activated an alternative splice site within exon 4, leading to a 45-bp deletion in the transcript. The putative translation of such modified mRNA indicates a truncated protein at residue 280. Conclusions: We describe two novel mutations, g. 4671_4672insC and g. 2791G>A, that drastically affects normal protein structure. These mutations abolish normal enzyme activity, leading to a severe phenotype of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. (J Clin Endocrinol Metab 94: 3481-3485, 2009)