The effect of menthol rinsing before intermittent exercise on physiological, physical, and thermo-behavioral responses of male football referees in hot and humid environment.

Introduction: In the current experiment, we aimed to evaluate whether eliciting pre-exercise non-thermal cooling sensations would alter perceptual measures, and physical and physiological responses in football referees. Methods: Nine highly trained male football referees undertook two 45-minute intermittent exercise protocols in hot and humid conditions (34.2 ± 0.6°C, 62.5 ± 1.0% relative humidity). In a randomized counterbalanced crossover design, 1 of 2 beverages were given before the warm-up: a 0.01% menthol solution or a placebo noncaloric solution. Physical performance was quantified as total distance covered in each of the three 15-minute exercise blocks. Core temperature, heart rate, thermal sensation and thermal comfort were measured at rest and after each exercise block. Results: No changes were observed between trials and over time for distance covered. No main effect of mouth rinse was observed for core temperature and heart rate, but both increased over time in all conditions (P < 0.001). Thermal sensation and thermal comfort were significantly improved with menthol after mouth-rinsing (P < 0.05), but with no differences at any other time-point. Discussion: These results indicate that non-thermal cooling oral stimuli provide immediate behavioral changes but may not influence physiological or physical responses in football referees, during intermittent exercise in hot and humid environments. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT05632692.

Menthol mouth rinsing and performance in elite football referees in the heat: A study protocol for a randomized crossover trial.

Background: Within professional European competitions, matches can be played in extreme environmental temperatures, ranging from -5 °C to +30 °C in different countries. Furthermore, the World Cups are usually played in the summer months, when temperatures can exceed 35 °C, increasing physiological stress. Practical and cost-effective cooling strategies may be implemented to help players and referees to cope with exercising in the heat. No study has evaluated the effect of non-thermal internal cooling techniques regarding performance responses on elite football referees, so far. This study aims to analyse the effects of a menthol mouth rinse regarding physical, physiological, and perceptual performance in elite male football referees, during a 90-min football protocol in the heat. Methods: At least thirteen male football referees will be recruited to perform two intermittent football protocols, separated by no less than 7 days. After passing the eligibility criteria, the participants will be randomly assigned to 1 of 2 beverages: (1) intervention - menthol solution 0.01% and (2) placebo - noncaloric berry-flavored solution, both at room temperature. The beverages will be given before warm-up (pre-cooling) and at the half-time (per-cooling). The trials will follow a randomized counterbalanced crossover design, single blinded, and will take place in indoor facilities, with Wet Bulb Globe Temperature (WBGT) > 30 °C, at the same time of the day to control for circadian variations. Impact of the project: The results of this study are expected to determine whether mouth rinsing a menthol solution before and during a football exercise protocol performed in the heat will alter perceptual measures and help ease physiological strain and attenuate performance decrements in elite male football referees, comparing to a non-cooling strategy. Thus, we can be closer to defining nutritional strategies of internal cooling that may be an advantage for the performance of the football referees in the heat. Trial registration: www.ClinicalTrials.gov NCT05632692 registered on 20 November 2022.

Performance effects of internal pre- and per-cooling across different exercise and environmental conditions: A systematic review.

Exercise in a hot and humid environment may endanger athlete's health and affect physical performance. This systematic review aimed to examine whether internal administration of ice, cold beverages or menthol solutions may be beneficial for physical performance when exercising in different environmental conditions and sports backgrounds. A systematic search was performed in PubMed, Web of Science, Scopus and SPORTDiscus databases, from inception to April 2022, to identify studies meeting the following inclusion criteria: healthy male and female physically active individuals or athletes (aged ≥18 years); an intervention consisting in the internal administration (i.e., ingestion or mouth rinse) of ice slush, ice slurry or crushed ice and/or cold beverages and/or menthol solutions before and/or during exercise; a randomized crossover design with a control or placebo condition; the report of at least one physical performance outcome; and to be written in English. Our search retrieved 2,714 articles in total; after selection, 43 studies were considered, including 472 participants, 408 men and 64 women, aged 18-42 years, with a VO2max ranging from 46.2 to 67.2 mL⋅kg-1⋅min-1. Average ambient temperature and relative humidity during the exercise tasks were 32.4 ± 3.5°C (ranging from 22°C to 38°C) and 50.8 ± 13.4% (varying from 20.0% to 80.0%), respectively. Across the 43 studies, 7 exclusively included a menthol solution mouth rinse, 30 exclusively involved ice slurry/ice slush/crushed ice/cold beverages intake, and 6 examined both the effect of thermal and non-thermal internal techniques in the same protocol. Rinsing a menthol solution (0.01%) improved physical performance during continuous endurance exercise in the heat. Conversely, the ingestion of ice or cold beverages did not seem to consistently increase performance, being more likely to improve performance in continuous endurance trials, especially when consumed during exercises. Co-administration of menthol with or within ice beverages seems to exert a synergistic effect by improving physical performance. Even in environmental conditions that are not extreme, internal cooling strategies may have an ergogenic effect. Further studies exploring both intermittent and outdoor exercise protocols, involving elite male and female athletes and performed under not extreme environmental conditions are warranted. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268197], identifier [CRD42021268197].

Effects of Acute and Chronic Exercise in Hypoxia on Cardiovascular and Glycemic Parameters in Patients with Type 2 Diabetes: A Systematic Review.

Kindlovits, Raquel, Alberto Mello da Silva Pereira, Ana Catarina Sousa, João Luís Viana,and Vitor Hugo Teixeira. Effects of acute and chronic exercise in hypoxia on cardiovascular and glycemic parameters in patients with type 2 diabetes: a systematic review. High Alt Med Biol. 23:301-312, 2022. Background: Exercise in hypoxia (EH, decreased oxygen availability) has been proposed as a potential therapeutic intervention to promote angiogenesis and improve glucose metabolism to a greater extent than exercise under normoxia (normal ambient air) in patients with type 2 diabetes (T2D). Currently, there are no studies that systematize the existent evidence. This study aims to systematically review the literature and qualitatively evaluate the effects of acute and chronic EH on cardiovascular and glycemic parameters in T2D patients. Methods: A structured search was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines until March 2021, in the MEDLINE/PubMed, Scopus, and Web of Science databases. The inclusion criteria were as follows: (1) randomized and nonrandomized trials, (2) in complication-free patients with T2D, (3) in which EH was compared with exercise in normoxia or with baseline data, and (4) published in English. Results: Six articles (64 subjects) met the inclusion criteria and were reviewed to data extraction. Four articles investigated the acute effect of EH (33 subjects), and two articles investigated the chronic effect of EH (31 subjects), ranging from 6 to 8 weeks. All studies used a cycle ergometer as exercise. Acute EH benefits insulin sensitivity, blood glucose, vascular endothelial growth factor, and metalloproteinase-9, while chronic EH benefits nitric oxide synthase in erythrocytes, but not brachial artery flow-mediated dilation. Conclusion: Acute EH improves glucose homeostasis in T2D patients, which was not seen with chronic EH. Both acute EH and chronic EH improve angiogenesis regulators, but not vascular function. Despite the putative benefits of EH in patients with T2D, the evidence is still scarce and further research is needed before recommendations can be provided.

Dietary supplements usage by elite female football players: an exploration of current practices.

The present study aimed to investigate the prevalence of dietary supplements usage (types, reasons for usage, sources of information, purchase venues) among elite female football players, using a self-administered questionnaire. The study participants (n = 103) were recruited through team physicians during an official international tournament. Overall, 82% reported using dietary supplements at least once during the last 12 months. The most common dietary supplements were vitamin D (52%), omega-3 fatty acids (49%), and protein (45%). Primary reasons for dietary supplement use were to stay healthy (66%), to accelerate recovery (58%), and to increase energy/reduce fatigue (54%). Supplement advice came mainly from medical doctors (46%), dietitians/nutritionists (43%), and coaches/fitness coaches (41%). Most dietary supplements were acquired from supplement stores (30%), a sponsor (26%), or drugstores/pharmacies (22%). Elite female football players are frequent dietary supplement users. Further research needs to explore the frequency, dose, and timing of these supplements.

Prevalence of dietary supplement use by gym members in Portugal and associated factors.

BACKGROUND: Although there seems to be an increasing interest in the use of dietary supplements in those who exercise recreationally and want to improve body composition, there is little published data regarding gym users and dietary supplement use. METHODS: This cross-sectional study describes the prevalence and type of supplements used by gyms members, the reasons for using them and the information source using a self-administered online questionnaire. RESULTS: Of the 459 participants (301 females) who answered the survey, 43.8% reported using dietary supplements. Users were more likely men (62.7% vs. 33.9%, p < 0.05), younger (32 ± 9 vs. 34 ± 11 years, p < 0.05) and trained more hours per week (6 ± 3 vs 4 ± 3 h, p < 0.05) than non-users. The most consumed supplements were proteins (80.1%), multivitamins and/or minerals (38.3%), sport bars (37.3%), branched-chain amino acids (BCAA's) (36.8%) and n-3 fatty acids (35.5%). Men consumed more arginine, BCAA's, creatine, glutamine, ß-hydroxy-ß-methylbutyrate (HMB), proteins, ß-alanine, taurine, multivitamin/minerals, and carbohydrate supplements (p < 0.05). The most commonly cited reasons for the use of supplements were gaining muscle (55.7%), accelerating recovery (52.7%) and improving performance (47.3%). Men have more often referred increase strength, increase resistance, gain muscle mass, accelerate recovery and improve performance as reasons to use supplements than women (p < 0.05). Those who mentioned muscle gain as a reason were younger than those who did not (30.4 years vs. 33.7 years, p < 0.05). The sources of information most mentioned were registered dietitians (23.1%), internet (22.2%) and him/herself (16.6%). The majority (> 70%) of participants declared being well or very well informed about supplements, while only a minority (4%) felt very poorly or poorly informed. Most individuals purchased dietary supplements from the internet (56.2%) and supplement/health food stores (43.4%). CONCLUSION: This study concluded that gyms users are large consumers of dietary supplements, and are more likely to be men, young, use protein powders, aiming to increase muscle mass, obtain information from registered dietitians, consider themselves well informed and buy supplements online.

Does diet strictness level during weekends and holiday periods influence 1-year follow-up weight loss maintenance? Evidence from the Portuguese Weight Control Registry.

There is not much evidence about how diet strictness during weekends and holidays influence long-term weight loss maintenance. Our aim was to examine how dieting more or less strictly during weekends and holidays (vs. weekdays and non-holiday periods) influence weight loss maintenance.Participants (n = 108) from the Portuguese Weight Control Registry indicated whether they had a more or less strict diet regimen during weekends compared to weekdays. A similar question about holiday and non-holiday period' diet regimen was answered. Weight and height were measured at baseline and 1y follow-up. A 3% maximum weight variation defined participants as "non-regainers".General level on dieting strictness on weekends vs. weekdays (r = - 0.28, p < 0.01) and holidays vs. non-holidays (r = - 0.33, p < 0.001) predicted 1y weight change.Participants who reported being less strict on weekends (OR = 0.34, 95% CI: 0.15-0.81) were more likely to be non-regainers when compared with the ones who reported being more strict on weekends. Non-significant results were found during holidays (OR = 0.47, 95% CI: 0.20-1.09).Adopting a less strict diet regimen during weekends, when compared to weekdays, was a behavioral strategy associated with long-term weight management in our sample.

Body Mass Index Categories and Attained Height in Portuguese Adults.

OBJECTIVE: To analyze the associations between height and BMI categories in a Portuguese representative sample. METHODS: This is a cross-sectional study with a representative sample of 32,644 Portuguese adults (52.4% females). Sociodemographic and lifestyle characteristics were obtained along with self-reported height and weight. We performed generalized linear models to assess the differences in attained height across BMI categories; analyses were adjusted for age, gender, education, family income per month, proxy reporting information, dietary patterns, and smoking. RESULTS: BMI categories included underweight and normal weight (46.4%), overweight (37.6%), obese class I and II (15.2%), and obese class III (0.8%). Adults with normal weight had a significantly higher height (females +7 cm and males +5 cm) when compared to obese class III. As BMI categories increased, height decreased. In females and males, after adjusting for confounders, estimates of attained height decreased when compared to the unadjusted model (ß = -0.049, 95% CI = -0.050; -0.049 and ß = -0.030, 95% CI = -0.031; -0.029, respectively), although they remained still significant. CONCLUSION: Our results suggest a significant difference in attained height between BMI categories. Future intervention programs aiming at preventing overweight and obesity should monitor sociodemographic, health and environmental conditions that affect attained height potential.

Creatine or vitamin D supplementation in individuals with a spinal cord injury undergoing resistance training: A double-blinded, randomized pilot trial.

PURPOSE: Determine whether creatine or vitamin D supplementation improves muscle strength in individuals with spinal cord injury undergoing resistance training. METHODS: Thirteen male and one female with spinal cord injury, from two Portuguese rehabilitation centers, were randomized to creatine (3g daily), vitamin D (25000 IU each two weeks) or placebo group in a double-blind design. All participants performed progressive resistance training during eight weeks. The outcome measures, obtained at baseline and after intervention, included: Sum of four skinfolds; Corrected arm muscle area; Seated medicine ball throw; Handgrip strength with dynamometer; Manual wheelchair slalom test and one repetition maximum for Chest press, Triceps, Pec deck and Lat pulldown. Vitamin D levels were obtained in all participants before and after intervention. RESULTS: 71.4% of participants had deficit values of vitamin D. The corrected arm muscle area improved significantly (p<0.05) in creatine group relatively to the control group. There was a significant correlation (p<0.05) between the one repetition maximum Pec deck and levels of vitamin D. CONCLUSIONS: Supplementation with creatine may improve muscle strength parameters in individuals with spinal cord injury. Vitamin D deficiency is highly prevalent in this population. It is recommended an initial screening of vitamin D levels at the beginning of the physical rehabilitation process.

Exercise induced dehydration status and skinfold compressibility in athletes: an intervention study.

BACKGROUND AND OBJECTIVES: Skinfold thickness assessment is a widely recognized technique for the estimation of body adiposity and fat free mass. This method assumes that skinfolds' compressibility is constant but there are some factors that could influence its compressibility. This study aims to evaluate whether the skinfolds' compressibility is influenced by hydration status. METHODS AND STUDY DESIGN: An intervention study was conducted in a sample of 22 adult male amateur soccer players, who took part in a 90min simulated soccer match. Before and after the intervention skinfolds thicknesses were measured in eight anatomical sites. An electronic caliper, Lipotool, was used to collect and record 120 values during 2s of evaluation. To analyze skinfolds' compressibility, two methods were used: identification of lowest skinfold thickness measurement (SL) and SH = 110% x SL, and the parameter TAU (τ) determination. Baseline hydration status was evaluated by total body water (TBW) through multifrequency bioimpedance analysis. Dehydration was assessed by the difference of body weight before and after the intervention. RESULTS: The intervention resulted in a loss of 2.11% of participants' baseline weight. The skinfolds thicknesses, assessed by SL and SH, were significantly higher after exercise for all skinfolds except for skinfolds at iliac crest and abdominal. This intervention did not affect skinfolds' compressibility when assessed by τ. However, an association between dehydration and medial-calf skinfold' compressibility was found (r=0.48, p=0.042). CONCLUSIONS: Although an increase in the skinfolds thickness after the intervention was found, skinfolds' compressibility did not change.

Nutritional supplements use in high-performance athletes is related with lower nutritional inadequacy from food.

BACKGROUND: The use of nutritional supplements (NS) among athletes is widespread. However, little is known about the relationship between nutritional adequacy and NS usage. The aims of this study were to evaluate the NS usage and to compare the nutritional intake from food and prevalence of micronutrient inadequacy (PMI) between NS users and non-users. METHODS: Portuguese athletes from 13 sports completed an NS usage questionnaire and a semi-quantitative food-frequency questionnaire assessing information over the previous 12 months. The estimated average requirement cut-point method was used to calculate PMI. General linear models were used to compare nutritional intake and NS usage. Chi-squared tests and logistic regression were performed to study, respectively, relationships and associations between PMI and NS usage. RESULTS: From the 244 athletes (66% males, 13-37 years), 64% reported NS usage. After adjustment, NS users showed a higher intake from food (p < 0.05), for at least 1 gender, for energy, and for 7 of the 17 studied nutrients. The highest PMI were seen for vitamins D and E, calcium, folate, and magnesium. After adjustment, NS users, irrespective of gender, reported lower PMI for calcium (OR = 0.28, 95%CI: 0.12-0.65), and female users for magnesium (OR = 0.06, 95%CI: 0.00-0.98). CONCLUSION: Athletes using NS reported a higher nutritional intake from food, and a lower PMI for several nutrients. Perhaps, those who were taking NS were probably the ones who would least benefit from it.

Nutritional intake of elite football referees.

There is a paucity of dietary data in football referees. In this study, 23 elite main and assistant referees (34.4 ± 5.6 years) completed a 7-day dietary record during the competitive season. No nutritional intake differences were observed between main and assistant referees. Referees' mean daily energy intake (DEI) was 2819 ± 279 kcal. The intake of proteins (1.7 ± 0.2 g · kg(-1)), carbohydrates (4.1 ± 0.8 g · kg(-1)) and fats (1.4 ± 0.2 g · kg(-1)) represented, respectively, 18.4 ± 1.5%, 44.4 ± 4.4% and 34.6 ± 4.1% of the DEI. Carbohydrate intakes before, during and after exercise were 66 ± 42, 7 ± 15 and 120 ± 62 g. Daily carbohydrate, fibre, polyunsaturated fat and water intakes were below recommendations, while fat, saturated fat, cholesterol and sodium intakes were above recommended values. The prevalence of inadequate intake was high for vitamin E (96%), folate (74%), vitamin A (61%), vitamin C (39%), magnesium (26%) and calcium (22%). Carbohydrate intake before, during and after exercise were far from achieving the minimum recommended values. Most referees demonstrated a negligent behaviour of hydration during exercise. Referees would benefit from dietary education in order to optimise performance and health.

Nutritional supplements usage by Portuguese athletes.

In this study, we determined the prevalence of nutritional supplements (NS) usage, the type of supplements used, the reasons for usage, and the source of nutritional advice among Portuguese athletes. Two hundred ninety-two athletes (68 % male, 12 - 37 years old) from 13 national sports federations completed a questionnaire that sought information on socio-demographics, sports data, and NS usage. Most athletes (66 %) consumed NS, with a median consumption of 4 supplements per athlete. The most popular supplements included multivitamins/minerals (67 %), sport drinks (62 %), and magnesium (53 %). Significant differences for the type of NS consumed were found between gender and age groups and the number of weekly training hours. Most athletes used NS to accelerate recovery (63 %), improve sports performance (62 %), and have more energy/reduce fatigue (60 %). Athletes sought advice on supplementation mainly from physicians (56 %) and coaches (46 %). Age and gender were found to influence reasons for use and the source of information. Reasons for NS usage were supported scientifically in some cases (e. g., muscle gain upon protein supplementation), but others did not have a scientific basis (e. g., use of glutamine and magnesium). Given the high percentage of NS users, there is an urgent need to provide athletes with education and access to scientific and unbiased information, so that athletes can make assertive and rational choices about the utilization of these products.

ß-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-mesenchymal transition.

Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that ß-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell ß-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness. We demonstrate that transgene-mediated ß-catenin inhibition within keratin 14-expressing basal cells delayed normal airway repair while basal cell-specific ß-catenin activation increased cell proliferation, directed differentiation and promoted elements of early epithelial-mesenchymal transition (EMT), including increased Snail transcription and reduced E-cadherin expression. These observations are recapitulated in normal human bronchial epithelial cells in vitro following both pharmacological ß-catenin activation and E-cadherin inhibition, and mirrored our findings in preinvasive SCCs. Overall, the data show that airway basal cell ß-catenin determines cell fate and its mis-expression is associated with the development of human lung cancer.

Impact of fluid restriction and ad libitum water intake or an 8% carbohydrate-electrolyte beverage on skill performance of elite adolescent basketball players.

Twelve adolescent athletes underwent, in a crossover-design study, 3 separate 90-min training sessions in the following conditions: no fluid ingestion allowed (NF), ad libitum ingestion of water (W), and ad libitum ingestion of a commercial 8% carbohydrate-electrolyte sports beverage (CSB). After each session athletes performed a set of basketball drills (2-point, 3-point, and free-throw shootout, suicide sprints, and defensive zigzags). Body weight (before and after sessions), rating of perceived exertion (RPE), urine color, and beverage acceptability were determined in each session. Athletes also completed a survey about their knowledge and behaviors regarding hydration and fluid replacement. The percentage of weight loss was significantly higher in NF (2.46% ± 0.87%) than in the other 2 conditions (W, 1.08% ± 0.67%, p = .006; CSB, 0.65% ± 0.62%, p = .001) but also higher in W than CSB (p = .012). RPE was higher in NF (16.8 ± 1.96) than in the W (14.2 ± 1.99, p = .004) and CSB (13.3 ± 2.06, p = .002) trials. Athletes' fluid intake was positively correlated with proper self-reported behaviors (r = .75, p = .005) and knowledge (r = .76, p = .004) about fluid and hydration. In conclusion, fluid restriction during exercise was associated with a greater level of dehydration and increased perceived exertion but had no impact on basketball performance compared with ad libitum drinking of water or a CSB. Athletes with more knowledge about hydration and better self-reported hydration behaviors ingested more fluids during training sessions.

Myd88 deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance.

Tracheal epithelial remodelling, excess mucus production, and submucosal gland hyperplasia are features of numerous lung diseases, yet their origins remain poorly understood. Previous studies have suggested that NF-κB signalling may regulate airway epithelial homeostasis. The purpose of this study was to determine whether deletion of the NF-κB signalling pathway protein myeloid differentiation factor 88 (Myd88) influenced tracheal epithelial cell phenotype. We compared wild-type and Myd88-deficient or pharmacologically inhibited adult mouse tracheas and determined that in vivo Myd88 deletion resulted in increased submucosal gland number, secretory cell metaplasia, and excess mucus cell abundance. We also found that Myd88 was required for normal resolution after acute tracheal epithelial injury. Microarray analysis revealed that uninjured Myd88-deficient tracheas contained 103 transcripts that were differentially expressed relative to wild-type and all injured whole tracheal samples. These clustered into several ontologies and networks that are known to functionally influence epithelial cell phenotype. Comparing these transcripts to those expressed in airway progenitor cells revealed only five common genes, suggesting that Myd88 influences tracheal epithelial homeostasis through an extrinsic mechanism. Overall, this study represents the first identification of Myd88 as a regulator of adult tracheal epithelial cell phenotype.

The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and influences its erosive phenotype.

BACKGROUND: Increased expression of type I IFN genes, also referred to as an IFN signature, has been detected in various autoimmune diseases including rheumatoid arthritis (RA). Interferon regulatory factors, such as IRF5, coordinate type I IFN expression. Multiple IRF5 variants were suggested as autoimmunity susceptibility factors. OBJECTIVE: As the linkage proof remains important to establish fully any genetic RA susceptibility factor, the authors took advantage of the largest reported European trio family resource dedicated to RA to test for linkage IRF5 and performed a genotype-phenotype analysis. METHODS: 1140 European Caucasian individuals from 380 RA trio families were genotyped for IRF5 rs3757385, rs2004640 and rs10954213 single nucleotide polymorphisms (SNP). RESULTS: Single marker analysis provided linkage evidence for each IRF5 SNP investigated. IRF5 linked to RA with two haplotypes: the CTA risk haplotype 'R' (transmission (T)=60.6%, p=23.1×10(-5)) and the AGG protective haplotype 'P' (T=39.6%, p=0.0015). Linkage was significantly stronger in non-erosive disease for both IRF5 R and P haplotypes (T=73.9%, p=4.20×10(-5) and T=19.6%, p=3.66×10(-5), respectively). Multivariate logistic regression analysis found IRF5 linked to RA independently of the rheumatoid factor status. IRF5 RR and PP haplotypic genotypes were associated with RA, restricted to the non-erosive phenotype: p=1.68×10(-4), OR 4.80, 95% CI 2.06 to 11.19; p=0.003, OR 0.17, 95% CI 0.05 to 0.57, respectively. CONCLUSION: This study provides the 'association and linkage proof' establishing IRF5 as a RA susceptibility gene and the identification of a genetic factor that seems to contribute to the modulation of the erosive phenotype. Further studies are warranted to clarify the role of IRF5 in RA and its subphenotypes.