494 resultados para Aetiology
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Background: Cerebro-meningeal pathology is common in human immunodeficiency virus (HIV) infection and the aetiology is often difficult to ascertain with certainty. Objective: To describe the major suspected and identified causes of meningeal or encephalitic syndromes in HIV infection in Libreville, Gabon. Methods: A descriptive study using clinical records of patients hospitalised in the Department of Medicine in the Military Hospital of Libreville (Gabon) between January 2006 and May 2010. Clinical features were evaluated using multivariable logistic regression to evaluate association with the outcome of a clinical improvement or death. Results: The most frequent neurological symptoms were reduced level of consciousness (54.3%), headache (55.2%), motor deficit (38.7%), and convulsions (36.2%). Cerebral toxoplasmosis represented 64.7% of diagnoses, followed by cryptococcal neuromeningitis in 12.9% of cases. Tuberculoma was diagnosed in 4 cases and lymphoma in 2 cases. In 9.5% of cases, no aetiology was determined. Toxoplasmosis treatment led to clinical improvement in 69.3% of cases with suspected cerebral toxoplasmosis. Overall mortality was 39.7%. Conclusion: The diagnosis of neurological conditions in HIV positive patients is difficult, particularly in a low-resource setting. A trial of treatment for toxoplasmosis should be initiated first line with all signs of neurological pathology in a patient infected with HIV.
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The aetiology of autoimmunes disease is multifactorial and involves interactions among environmental, hormonal and genetic factors. Many different genes may contribute to autoimmunes disease susceptibility. The major histocompatibility complex (MHC) genes have been extensively studied, however many non-polymorphic MHC genes have also been reported to contribute to autoimmune diseases susceptibility. The aim of the present study was to evaluate the influence of SLC11A1 gene in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Ninety-six patients with SLE, 37 with RA and 202 controls enrolled in this case-control study, were evaluated with regard to demographic, genetic, laboratorial and clinical data. SLE mainly affects females in the ratio of 18 women for each man, 88,3% of the patients aged from 15 to 45 years old and it occurs with similar frequency in whites and mulattos. The rate of RA between women and men was 11:1, with 77,1% of the cases occurring from 31 to 60 years. The genetic analysis of the point mutation -236 of the SLC11A1 gene by SSCP did not show significant differences between alleles/genotypes in patients with SLE or RA when compared to controls. The most frequent clinical manifestations in patients with SLE were cutaneous (87%) and joint (84.9%). In patients with RA, the most frequent out-joint clinical manifestation were rheumatoid nodules (13,5%). Antinuclear antibodies were present in 100% of the patients with SLE. There was no significant relation between activity of disease and presence of rheumatoid factor in patients with RA, however 55,6% of patients with active disease presented positive rheumatoid factor. Significant association between alleles/genotypes of point mutation -236 and clinical manifestations was not found
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Background: Malnutrition in surgical patients is associated with delayed recovery, higher rates of morbidity and mortality, prolonged hospital stay, increased healthcare costs and a higher early re-admission rate. Methods: Data synthesis after review of pertinent literature. Results: The aetiology of malnutrition is multifactorial. In cancer patients, there is an abnormal peripheral glucose disposal, gluconeogenesis, and whole-body glucose turnover. Malnourished cancer patients undergoing major operations are at significant risk from perioperative complications such as infectious complications. Surgical aggression generates an inflammatory response which worsens intermediary metabolism. Conclusions: Nutritional evaluation and nutritional support must be performed in all surgical patients, in order to minimize infectious complications. Enteral nutrition early in the postoperative period is effective and well tolerated reducing infectious complications, improving wound healing and reducing length of hospital stay. Pharmaconutrition is indicated in those patients, who benefit from enteral administration of arginine, omega 3 and RNA, as well as parenteral glutamine supplementation. When proximal sutures are used, tubes allowing early jejunal feeding should be used.
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Vibrio pathogens are causative agents of mid-culture outbreaks, and early mortality syndrome and secondary aetiology of most dreadful viral outbreaks in shrimp aquaculture. Among the pathogenic vibrios group, Vibrio alginolyticus and V. harveyi are considered as the most significant ones in the grow-out ponds of giant black tiger shrimp Penaeus monodon in India. Use of antibiotics was banned in many countries due to the emergence of antibiotic-resistant strains and accumulation of residual antibiotics in harvested shrimp. There is an urgent need to consider the use of alternative antibiotics for the control of vibriosis in shrimp aquaculture. Biofilm formation is a pathogenic and/or establishment mechanism of Vibrio spp. This study aims to develop novel safe antibiofilm and/ or antiadhesive process using PHB to contain vibrios outbreaks in shrimp aquaculture.
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Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas
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The determination of aetiological factors in sports injuries is challenging. Recently, investigators have devoted significant attention to this topic. A reasonable amount of studies provides information on the occurrence, aetiology, and severity of golf-related injuries. However, gaps of evidence still limit the understanding of the injury problem in golf and the comparability of epidemiological findings. Observational studies using surveys and medical records were reviewed. Surveys are suited to find precise occurrence patterns of golf-related injuries, but fail to adequately ascertain the levels of exposure and aetiological factors. Due to the proximity to the injury event, medical records are able to clearly identify the aetiology and severity of golf-related injuries. While reviewing observational studies using surveys a comment was provided on the methodological quality and risk of bias. Overall, these studies seem to be disturbed on their ability to produce generalizations and comparison of study findings. With the information obtained from reviewing observational studies and the collaboration of a panel of internationally recognised experts on golf science and sports injury research, a web-based bilingual questionnaire was developed and tested for one of the provided languages. The bilingual nature of the questionnaire is also expected to facilitate the acceptance of the scientific community and enable the translation to different languages. A standardised questionnaire applied in different cultural contexts is expected to help and further improve the comparability of epidemiological findings. The questionnaire was proficient in capturing information on golf-related injuries and participation habits of golfers. While using a wider outcome definition focusing on any type of physical complaints, episodes of injury could be recognized despite onset and level of severity. Questions on the need for medical attention, time loss, and impact on performance also enabled additional categorisation of severity.
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This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/
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Advances in healthcare over the last 100 years has resulted in an ever increasing elderly population. This presents greater challenges for adequate systemic and oral healthcare delivery. With increasing age there is a natural decline in oral health, leading to the loss of teeth and ultimately for some having to wear denture prosthesis. It is currently estimated that approximately one fifth of the UK and US populations have some form of removable prosthesis. The microbiology of denture induced mucosal inflammation is a pivotal factor to consider in denture care management, similar to many other oral diseases of microbial influence, such as caries, gingivitis and periodontitis. Dentures support the growth of microbial biofilms, structures commonly known as denture plaque. Microbiologically, denture stomatitis (DS) is a disease primarily considered to be of yeast aetiology, with the literature disproportionately focussed on Candida spp. However, the denture surface is capable of carrying up to 1011 microbes per milligram, the majority of which are bacteria. Thus it is apparent that denture plaque is more diverse than we assume. There is a fundamental gap in our understanding of the bacterial composition of denture plaque and the role that they may play in denture related disease such as DS. This is categorised as inflammation of the oral mucosa, a disease affecting around half of all denture wearers. It has been proposed that bacteria and fungi interact on the denture surface and that these polymicrobial interactions lead to synergism and increased DS pathogenesis. Therefore, understanding the denture microbiome composition is the key step to beginning to understand disease pathogenesis, and ultimately help improve treatments and identify novel targets for therapeutic and preventative strategies. A group of 131 patients were included within this study in which they provided samples from their dentures, palatal mucosa, saliva and dental plaque. Microbes residing on the denture surface were quantified using standard Miles and Misra culture technique which investigated the presence of Candida, aerobes and anaerobes. These clinical samples also underwent next generation sequencing using the Miseq Illumina platform to give a more global representation of the microbes present at each of these sites in the oral cavity of these denture wearers. This data was then used to compare the composition and diversity of denture, mucosal and dental plaque between one another, as well as between healthy and diseased individuals. Additional comparisons included denture type and the presence or absence of natural teeth. Furthermore, microbiome data was used to assess differences between patients with varying levels of oral hygiene. The host response to the denture microbiome was investigated by screening the patients saliva for the presence and quantification of a range of antimicrobial peptides that are associated with the oral cavity. Based on the microbiome data an in vitro biofilm model was developed that reflected the composition of denture plaque. These biofilms were then used to assess quantitative and compositional changes over time and in response to denture cleansing treatments. Finally, the systemic implications of denture plaque were assessed by screening denture plaque samples for the presence of nine well known respiratory pathogens using quantitative PCR. The results from this study have shown that the bacterial microbiome composition of denture wearers is not consistent throughout the mouth and varies depending on sample site. Moreover, the presence of natural dentition has a significant impact on the microbiome composition. As for healthy and diseased patients the data suggests that compositional changes responsible for disease progression are occurring at the mucosa, and that dentures may in fact be a reservoir for these microbes. In terms of denture hygiene practices, sleeping with a denture in situ was found to be a common occurrence. Furthermore, significant shifts in denture microbiome composition were found in these individuals when compared to the denture microbiome of those that removed their denture at night. As for the host response, some antimicrobial peptides were found to be significantly reduced in the absence of natural dentition, indicating that the oral immune response is gradually impaired with the loss of teeth. This study also identified potentially serious systemic implications in terms of respiratory infection, as 64.6% of patients carried respiratory pathogens on their denture. In conclusion, this is the first study to provide a detailed understanding of the oral microbiome of denture wearers, and has provided evidence that DS development is more complex than simply a candidal infection. Both fungal and bacterial kingdoms clearly play a role in defining the progression of DS. The biofilm model created in this study demonstrated its potential as a platform to test novel actives. Future use of this model will aid in greater understanding of host: biofilm interactions. Such findings are applicable to oral health and beyond, and may help to identify novel therapeutic targets for the treatment of DS and other biofilm associated diseases.
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Hypertension is the major risk factor for coronary disease worldwide. Primary hypertension is idiopathic in origin but is thought to arise from multiple risk factors including genetic, lifestyle and environmental influences. Secondary hypertension has a more definite aetiology; its major single cause is primary aldosteronism (PA), the greatest proportion of which is caused by aldosteroneproducing adenoma (APA), where aldosterone is synthesized at high levels by an adenoma of the adrenal gland. There is strong evidence to show that high aldosterone levels cause adverse effects on cardiovascular, cerebrovascular, renal and other systems. Extensive studies have been conducted to analyse the role that regulation of CYP11B2, the gene encoding the aldosterone synthase enzyme plays in determining aldosterone production and the development of hypertension. One significant regulatory factor that has only recently emerged is microRNA (miRNA). miRNAs are small non-coding RNAs, synthesized by a series of enzymatic processes, that negatively regulate gene expression at the posttranscriptional level. Detection and manipulation of miRNA is now known to be a viable method in the treatment, prevention and prognosis of certain diseases. The aim of the present study was to identify miRNAs likely to have a role in the regulation of corticosteroid biosynthesis. To achieve this, the miRNA profile of APA and normal human adrenal tissue was compared, as was the H295R adrenocortical cell line model of adrenocortical function, under both basal conditions and following stimulation of aldosterone production. Key differentially-expressed miRNAs were then identified and bioinformatic tools used to identify likely mRNA targets and pathways for these miRNAs, several of which were investigated and validated using in vitro methods. The background to this study is set out in Chapter 1 of this thesis, followed by a description of the major technical methods employed in Chapter 2. Chapter 3 presents the first of the study results, analysing differences in miRNA profile between APA and normal human adrenal tissue. Microarray was implemented to detect the expression of miRNAs in these two tissue types and several miRNAs were found to vary significantly and consistently between them. Furthermore, members of several miRNA clusters exhibited similar changes in expression pattern between the two tissues e.g. members of cluster miR-29b-1 (miR-29a-3p and miR-29b-3p) and of cluster miR-29b-2 (miR-29b-3p and miR-29c- 3p) are downregulated in APA, while members of cluster let-7a-1 (let-7a-5p and let-7d-5p), cluster let-7a-3 (let-7a-5p and let-7b-5p) and cluster miR-134 (miR- 134 and miR-382) are upregulated. Further bioinformatic analysis explored the possible biological function of these miRNAs using Ingenuity® Systems Pathway Analysis software. This led to the identification of validated mRNAs already known to be targeted by these miRNAs, as well as the prediction of other mRNAs that are likely targets and which are involved in processes relevant to APA pathology including cholesterol synthesis (HMGCR) and corticosteroidogenesis (CYP11B2). It was therefore hypothesised that increases in miR-125a-5p or miR- 335-5p would reduce HMGCR and CYP11B2 expression. Chapter 4 describes the characterisation of H295R cells of different strains and sources (H295R Strain 1, 2, 3 and HAC 15). Expression of CYP11B2 was assessed following application of 3 different stimulants: Angio II, dbcAMP and KCl. The most responsive strain to stimulation was Strain 1 at lower passage numbers. Furthermore, H295R proliferation increased following Angio II stimulation. In Chapter 5, the hypothesis that increases in miR-125a-5p or miR-335-5p reduces HMGCR and CYP11B2 expression was tested using realtime quantitative RT-PCR and transfection of miRNA mimics and inhibitors into the H295R cell line model of adrenocortical function. In this way, miR-125a-5p and miR-335-5p were shown to downregulate CYP11B2 and HMGCR expression, thereby validating certain of the bioinformatic predictions generated in Chapter 3. The study of miRNA profile in the H295R cell lines was conducted in Chapter 6, analysing how it changes under conditions that increase aldosterone secretion, including stimulation Angiotensin II, potassium chloride or dibutyryl cAMP (as a substitute for adrenocorticotropic hormone). miRNA profiling identified 7 miRNAs that are consistently downregulated by all three stimuli relative to basal cells: miR-106a-5p, miR-154-3p, miR-17-5p, miR-196b-5p, miR-19a-3p, miR-20b- 5p and miR-766-3p. These miRNAs include those derived from cluster miR-106a- 5p/miR-20b-5p and cluster miR-17-5p/miR-19a-3p, each producing a single polycistronic transcript. IPA bioinformatic analysis was again applied to identify experimentally validated and predicted mRNA targets of these miRNAs and the key biological pathways likely to be affected. This predicted several interactions between miRNAs derived from cluster miR-17-5p/miR-19a-3p and important mRNAs involved in cholesterol biosynthesis: LDLR and ABCA1. These predictions were investigated by in vitro experiment. miR-17-5p/miR-106a-p and miR-20b-5p were found to be consistently downregulated by stimulation of aldosterone biosynthesis. Moreover, miR-766-3p was upregulation throughout. Furthermore, I was able to validate the downregulation of LDLR by miR-17 transfection, as predicted by IPA. In summary, this study identified key miRNAs that are differentially-expressed in vivo in cases of APA or in vitro following stimulation of aldosterone biosynthesis. The many possible biological actions these miRNAs could have were filtered by bioinformatic analysis and selected interactions validated in vitro. While direct actions of these miRNAs on steroidogenic enzymes were identified, cholesterol handling also emerged as an important target and may represent a useful point of intervention in future therapies designed to modulate aldosterone biosynthesis and reduce its harmful effects.
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In contrast to the definition of metabolic syndrome (MetS) in adults, there is no standard definition of MetS in pediatric populations. We aimed to assess the differences in the prevalence of MetS in children and adolescents aged 9–17 years in the city of Bogota (Colombia) using four different operational definitions for these age groups and to examine the associated variables. A total of 673 children and 1,247 adolescents attending public schools in Bogota (54.4% girls; age range 9–17.9 years) were included. The prevalence of MetS was determined by the definitions provided by the International Diabetes Federation (IDF) and three published studies by Cook et al., de Ferranti et al., and Ford et al. The prevalence of MetS was 0.3%, 6.3%, 7.8%, and 11.0% according to the IDF, Cook et al., Ford et al., and de Ferranti et al. definitions, respectively. The most prevalent components were low high-density lipoprotein cholesterol and high triglyceride levels, whereas the least prevalent components were abdominal obesity and hyperglycemia. Overall, the prevalence of MetS was higher in obese than in non-obese schoolchildren. In conclusion, MetS diagnoses in schoolchildren strongly depend on the definition chosen. These findings may be relevant to health promotion efforts for Colombian youth to develop prospective studies and to define which cut-offs are the best indicators of future morbidity.
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The objectives of this study are to investigate the association between cardiorespiratory fitness and cardiovascular risk factors in schoolchildren and to evaluate the degree of association between overall and abdominal adiposity and cardiorespiratory fitness. A total of 1,875 children and adolescents attending public schools in Bogota, Colombia (56.2% girls; age range of 9–17.9 years). A cardiovascular risk score (Z-score) was calculated and participants were divided into tertiles according to low and high levels of overall (sum of the skinfold thicknesses) and abdominal adiposity. Schoolchildren with a high level of overall adiposity demonstrated significant differences in seven of the 10 variables analyzed (i.e. systolic and diastolic blood pressure, triglycerides, triglycerides/HDL-c ratio, total cholesterol, glucose and cardiovascular risk score). Schoolchildren with high levels of both overall and abdominal adiposity and low cardiorespiratory fitness had the least favorable cardiovascular risk factors score. These findings may be relevant to health promotion in Colombian youth.
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Background: Indices predictive of central obesity include waist circumference (WC) and waist-to-height ratio (WHtR). The aims of this study were 1) to establish a Colombian youth smoothed centile charts and LMS tables for WC and WHtR and 2) to evaluate the utility of these parameters as predictors of overweight and obesity. Method: A cross-sectional study whose sample population comprised 7954 healthy Colombian schoolchildren [boys n=3460 and girls n=4494, mean (standard deviation) age 12.8 (2.3) years old]. Weight, height, body mass index (BMI), WC and WHtR and its percentiles were calculated. Appropriate cut-offs point of WC and WHtR for overweight and obesity, as defined by the International Obesity Task Force (IOTF) definitions, were selected using receiver operating characteristic (ROC) analysis. The discriminating power of WC and WHtR was expressed as area under the curve (AUC). Results: Reference values for WC and WHtR are presented. Mean WC increased and WHtR decreased with age for both genders. We found a moderate positive correlation between WC and BMI (r= 0.756, P < 0.01) and WHtR and BMI (r= 0.604, P < 0.01). The ROC analysis showed a high discrimination power in the identification of overweight and obesity for both measures in our sample population. Overall, WHtR was slightly a better predictor for overweight/obesity (AUC 95% CI 0.868-0.916) than the WC (AUC 95% CI 0.862-0.904). Conclusion: This paper presents the first sex- and age-specific WC and WHtR percentiles for both measures among Colombian children and adolescents aged 9–17.9 years. By providing LMS tables for Latin-American people based on Colombian reference data, we hope to provide quantitative tools for the study of obesity and its comorbidities.
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OBJECTIVES: The aims of this study were to establish a Colombian smoothed centile charts and LMS tables for tríceps, subscapular and sum tríceps+subscapular skinfolds; appropriate cut-offs were selected using receiver operating characteristic analysis based in a populationbased sample of schoolchildren in Bogota, Colombia and to compare them with international studies. METHODS: A total of 9 618 children and adolescents attending public schools in Bogota, Colombia (55.7% girls; age range of 9–17.9 years). Height, weight, body mass index (BMI), waist circumference, triceps and subscapular skinfold measurements were obtained using standardized methods. We have calculated tríceps+subscapular skinfold (T+SS) sum. Smoothed percentile curves for triceps and subscapular skinfold thickness were derived by the LMS method. Receiver operating characteristics curve (ROC) analyses were used to evaluate the optimal cut-off point of tríceps, subscapular and sum tríceps+subscapular skinfolds for overweight and obesity based on the International Obesity Task Force (IOTF) definitions. Data were compared with international studies. RESULTS: Subscapular, triceps skinfolds and T+SS were significantly higher in girls than in boys (P <0.001). The median values for triceps, subscapular as well as T+SS skinfold thickness increased in a sex-specific pattern with age. The ROC analysis showed that subscapular, triceps skinfolds and T+SS have a high discrimination power in the identification of overweight and obesity in the sample population in this study. Based on the raw non-adjusted data, we found that Colombian boys and girls had high triceps and subscapular skinfolds values than their counterparts from Spain, UK, German and US. CONCLUSIONS: Our results provide sex- and age-specific normative reference standards for the triceps and subscapular skinfold thickness values in a large, population-based sample of 3 schoolchildren and adolescents from an Latin-American population. By providing LMS tables for Latin-American people based on Colombian reference data, we hope to provide quantitative tools for the study of obesity and its complications.
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Fibromyalgia (FM) is a chronic, rheumatic disease characterized by widespread myofascial pain, of unknown aetiology, having a major impact on quality of life (QOL). Available pharmacotherapy for FM is marginally effective. FM is associated with co-morbidities of gastrointestinal (GI) disorders and Irritable Bowel Syndrome (IBS). There is growing evidence that diets low in FODMAPs, “fermentable oligo-, di- or mono-saccharides and polyols” [Low FODMAP Diet (LFD)], are effective in treating IBS. The aim of this pilot study was to examine the effects of LFDs on symptoms of FM, especially with regard to pain, QOL and GI disorders. Methods A longitudinal study using LFD intervention was performed on 38, 51 ± 10 year-old, female patients diagnosed with FM for an average of 10 years, based on ACR (American College of Rheumatology) 2010 criteria. The study was conducted from January through May, 2015, using a four-week, repeated-assessment model, as follows: Moment 0 – introduction of the protocol to participants; Moment 1 – first assessment and delivery of individual LFD dietary plans; Moment 2 – second assessment and reintroduction of FODMAPs; Moment 3 – last assessment and final nutritional counselling. Assessment tools used were the following: RFIQ (Revised Fibromyalgia Impact Questionnaire), FSQ (Fibromyalgia Survey Questionnaire), IBS-SSS (Severity Score System), EQ-5D (Euro-QOL quality of life instrument), and VAS (Visual Analogue Scale). Daily consumption of FODMAPs was quantified based on published food content analyses. Statistical analyses included ANOVA, non-parametric Friedman, t-student and Chi-square tests, using SPSS 22 software. Results The mean scores of the 38 participants at the beginning of the study were: FSQ (severity of FM, 0–31) – 22 ± 4.4; RFIQ (0–100) – 65 ± 17; IBS-SSS (0–500) – 275 ± 101; and EQ-5D (0–100) – 48 ± 19. Mean adherence to dietary regimens was 86%, confirmed by significant difference in FODMAP intakes (25 g/day vs. 2.5 g/day; p < 0.01). Comparisons between the three moments of assessment showed significant (p < 0.01) declines in scores in VAS, FSQ, and RFIQ scores, in all domains measured. An important improvement was observed with a reduction in the severity of GI symptoms, with 50% reduction in IBS scores to 138 ± 117, following LFD therapy. A significant correlation (r = 0.36; p < 0.05) was found between improvements in FM impact (declined scores) and gastrointestinal scores. There was also a significant correlation (r = 0.65; p < 0.01) between “satisfaction with improvement” after introduction of LFDs and “diet adherence”, with satisfaction of the diet achieving 77% among participants. A significant difference was observed between patients who improved as compared to those that did not improve (Chi-square χ2 = 6.16; p < .05), showing that the probability of improvement, depends on the severity of the RFIQ score. Conclusions Implementation of diet therapy involving FODMAP restrictions, in this cohort of FM patients, resulted in a significant reduction in GI disorders and FM symptoms, including pain scores. These results need to be extended in future larger studies on dietary therapy for treatment of FM. Implications According to current scientific knowledge, these are the first relevant results found in an intervention with LFD therapy in FM and must be reproduced looking for a future dietetic approach in FM.