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AIM: To estimate the disease specific prevalence of undiagnosed rheumatic and musculoskeletal diseases (RMDs) in Portugal and determine if people with undiagnosed RMDs have worse quality of life, physical function and higher health resources consumption, than people without RMDs. METHODS: A subgroup analysis of EpiReumaPt was made that included all participants≥18 years evaluated by a rheumatologist. Participants were stratified into three groups: undiagnosed RMDs; previously diagnosed RMDs; non-RMDs. A descriptive analysis of the three groups was performed. To estimate the prevalence of undiagnosed RMDs, weighted proportion were computed considering the sample design. The three groups were compared (Undiagnosed RMDs vs non-RMDs; Previously diagnosed RMDs vs non-RMDs) for health related quality of life (HRQoL) (EQ5D), physical function (HAQ), mental health (HADS) and health resources consumption. The effect of being undiagnosed for these outcomes was assessed in multivariable models adjusted for age, gender, geographical region and years of education (reference: non-RMD). RESULTS: A total of 3877 participants were included. The prevalence of undiagnosed RMDs was 29%. Compared to participants without RMDs, undiagnosed participants had lower HRQoL (EQ-5D: β (95% CI)=-0.07 (-0.103,-0.043)) and physical function (HAQ: β (95% CI)=0.10 (0.05, 0.15)), more anxiety (OR (95% CI)=2.3 (1.4, 3.7)) and depression symptoms (OR (95% CI)=1.4 (0.8, 2.4)). Undiagnosed RMDs participants were more likely to visit an orthopedist (OR (95% CI)=2.0 (1.1, 3.5)) and had a higher number of orthopedic appointments (IRR (95% CI)=2.5 (1.3, 4.9)) than participants without RMDs. CONCLUSION: Patients with undiagnosed RMDs are frequent in Portugal, have worse HRQoL, physical function and mental health than people without RMDs. Undiagnosed patients are nonetheless consumers of health resources and tend to seek help from specialties other than rheumatology. Increasing the awareness of RMDs might promote their early identification and treatment leading to both personal and societal benefits. publishersversion epub_ahead_of_print

Funding Information: This study received funding from an independent research grant (ID 64165707) by Pfizer, and Daniela Costa received a grant from Fundação Ciência e Tecnologia, IP under the PhD grant SFRH/BD/148420/2019 and national support through CHRC (UIDP/04923/2020). The funders were not involved in the study design; the collection, analysis, or interpretation of the data; the writing of this article; or the decision to submit it for publication. Hip and knee osteoarthritis (HKOA) is a chronic disease characterized by joint pain that leads to reduced physical function and health-related quality of life (HRQoL). At present, no cure is available. Clinical trials indicate that people with HKOA benefit from physical activity in several health-related outcomes. However, few studies have evaluated the long-term positive effect of regular physical activity. This study analyzed participants with HKOA from a nationwide population-based cohort (EpiDoC Cohort) to assess the impact of physical activity on patients’ physical function and HRQoL over a long-term follow-up. The regular weekly frequency of intentional physical activity was self-reported as non-frequent (0 times/week), frequent (1–2 times/week), or very frequent (≥ 3 times/week). This study followed 1086 participants over a mean period of 4.7 ± 3.4 years, during which 6.3% and 14.9% of participants reported frequent and very frequent physical activity, respectively. Using linear mixed models, we found that frequent (β = − 0.101 [− 0.187, − 0.016]; β = 0.039 [− 0.002, 0.080]) and very frequent physical activity (β = − 0.061 [− 0.118, − 0.004]; β = 0.057 [0.029, 0.084]) were associated with improved physical function and HRQoL over time, respectively, when compared with non-frequent exercise, adjusting for years to baseline, sex, age, years of education, body mass index, multimorbidity, hospitalizations, clinical severity, and unmanageable pain levels. These findings raise awareness of the importance of maintaining exercise/physical activity long term to optimize HRQoL and physical function. Further studies must address barriers and facilitators to improve the adoption of regular physical activity among citizens with HKOA. publishersversion published

The study aimed to quantify two main phenolic acids (p-coumaric and ferulic acids) and ɣ-oryzanol (rice specific compound) in 21 varieties, grouped in 5 commercial types of rice: Long A, Long B, Medium grain, Short grain and Basmati. ɣ-Oryzanol is the mainly compound followed by ferulic acid. The phenolic compounds ferulic acid, and p-coumaric acid in brown rice are mostly found in bound form. Rice characterization of ɣ-oryzanol, ferulic acid, and p-coumaric acid, combined with genomic studies, is crucial for the selection and breeding of rice varieties with higher health benefits.

Additional file 2. Sensitivity Analysis of participants with hip OA and with knee OA. Table S.2 a). Sociodemographic, lifestyle, and health-related variables for people with Hip OA. Table S.2 b) Sociodemographic, lifestyle, and health-related variables for people with Knee OA. Table S.3- Univariable models factors associated with UPL in people with Knee OA or Hip OA. Table S.4- Multivariable models factors associated with UPL in people with Knee OA or Hip OA. Table S.5. HOOS/KOOS ADL and QoL subscale scores and anxiety and depression symptoms in people with Hip OA and UPL or MPL and people with Knee OA and UPL or MPL.

Rice is a staple food and one of the world’s major grain crops, serving as the staple food for 2/3 of the world population. Rice is rich in bioactive compounds such as γ-Oryzanol (GO), remarkably predominant in the bran fraction (Pereira et al, 2021). Previous studies have explored the physiological effects of GO, including as antioxidant, antidiabetic, anti-carcinogenic, neuroprotective, and hypocholesteremic effects (Rungratanawanich et al., 2020). GO is a mixture of ferulic acid (FA) esters of triterpene alcohols and plant sterols present in cereals such as rice. The GO composition is characterized by several isomers that determine its final concentration and profile in the rice grain. About ten GO molecular species have been reported to date (Miller & Engel, 2006; Kim et al., 2013). The major components of rice GO are cycloartenyl ferulate (CAF), 24-methylenecycloartanyl ferulate (24MCAF), campesteryl ferulate (CampF), and β-sitosteryl ferulate (SF) that account for more than 80% of GO in rice bran. The aim of this work was to identify the major components of GO in whole flour and bran of 5 different rice varieties (Arelate, Ariete, Caravela, Carnaroli and Giza 177) approached in the TRACE-RICE project, as well as other minor components including 7-campestenyl ferulate, campestanyl ferulate (CampF), cycloartanyl ferulate, stigmasteryl ferulate (SF), sitostenyl ferulate and sitostanyl ferulate, using Liquid chromatography associated to different mass spectrometry-based approaches, namely the high-resolution mass spectrometer Orbitrap and QTRAP LC-MS/MS. The QTRAP mass spectrometer enabled to identify the four major and six minor GO components. However, because some of these minor components share the same precursor to product ion transitions as some of the major components, resolution is hindered. For example, the resolution of the major component CampF is affected by the presence of the minor components 7-campestenyl ferulate and campestanyl ferulate and the same for SF and sitostanyl ferulate. Using the orbitrap mass analyzer the four major GO components were identified in rice samples and only one minor component (cycloartanyl ferulate).

Rice is a staple food and one of the world’s major grain crops, serving as the staple food for 2/3 of the world population. Rice is rich in bioactive compounds such as γ-Oryzanol (GO), remarkably predominant in the bran fraction (Pereira et al, 2021). Previous studies have explored the physiological effects of GO, including as antioxidant, antidiabetic, anti-carcinogenic, neuroprotective, and hypocholesteremic effects (Rungratanawanich et al., 2020). GO is a mixture of ferulic acid (FA) esters of triterpene alcohols and plant sterols present in cereals such as rice. The GO composition is characterized by several isomers that determine its final concentration and profile in the rice grain. About ten GO molecular species have been reported to date (Miller & Engel, 2006; Kim et al., 2013). The major components of rice GO are cycloartenyl ferulate (CAF), 24-methylenecycloartanyl ferulate (24MCAF), campesteryl ferulate (CampF), and β-sitosteryl ferulate (SF) that account for more than 80% of GO in rice bran. The aim of this work was to identify the major components of GO in whole flour and bran of 5 different rice varieties (Arelate, Ariete, Caravela, Carnaroli and Giza 177) approached in the TRACE-RICE project, as well as other minor components including 7-campestenyl ferulate, campestanyl ferulate (CampF), cycloartanyl ferulate, stigmasteryl ferulate (SF), sitostenyl ferulate and sitostanyl ferulate, using Liquid chromatography associated to different mass spectrometry-based approaches, namely the high-resolution mass spectrometer Orbitrap and QTRAP LC-MS/MS. The QTRAP mass spectrometer enabled to identify the four major and six minor GO components. However, because some of these minor components share the same precursor to product ion transitions as some of the major components, resolution is hindered. For example, the resolution of the major component CampF is affected by the presence of the minor components 7-campestenyl ferulate and campestanyl ferulate and the same for SF and sitostanyl ferulate. Using the orbitrap mass analyzer the four major GO components were identified in rice samples and only one minor component (cycloartanyl ferulate).

Brown rice grain is a rich source of bioactive compounds, mainly in the rice bran, with several health benefits, namely high antioxidant properties [1]. The health promoting phytochemicals of whole rice grain include antioxidant compounds such as γ-oryzanol, and phenolic compounds including ferulic acid and p-coumaric acid. In addition, previous studies have shown that these compounds are bioaccessible and bioavailable after ingestion [2,3]. The present study aimed to characterize the phytochemical profile of 22 varieties of brown rice, namely the quantification of phenolic compounds p-coumaric acid and ferulic acid, and γ-oryzanol. The 22 varieties of brown rice included 6 different types of rice: long A, long B, short grain, medium grain, European aromatic and basmati rice. γ-Oryzanol was the main compound present in brown rice varieties, ranging from 31.31- 45.72 mg/100g, and was positively correlated with the amount of ferulic acid in free/conjugated and bound phenolic fractions. The short grain, European aromatic and long A rice types presented higher amounts of γ-oryzanol and free/conjugated and bound ferulic acid. In turn, long B rice showed a lower amount of these compounds. Ferulic acid in free and free/conjugated phenolic fractions, varying between 0.12 and 1.82 mg/100g, was much higher in the bound phenolic fraction of brown rice samples, which ranged between 12.15 to 16.57 mg/100g. The p-coumaric acid was the minor component, present mainly in the bound phenolic fraction of aromatic and basmati rice types and ranged between 3.88- 5.90 mg/100g. The characterization of phenolic and antioxidant compounds in rice is crucial for the selection and breeding of rice varieties with a higher content of bioactive compounds associated with health benefits.

Rice is an important staple food for more than half of the world population and is mainly consumed as cooked white rice. White rice is known to contain the highest carbohydrate content [1] thus being considered a highly glycemic food. To improve the nutritional value of rice different strategies have been suggested, namely the selection of rice varieties with higher nutritional value [2], and the consumption of brown rice, which is receiving increasing attention due to its beneficial health effects [3]. The bran of brown rice is also an important source of fiber, minerals, proteins, vitamins, and health promoting compounds with antioxidant activity, including γ-oryzanol, γ-aminobutyric acid (GABA), phytic acid, ferulic acid and p-coumaric acid [4,5]. In this study, the content of these antioxidant compounds in brown rice and in the bran of the rice variety Ariete was determined. The extraction protocol was optimized for each compound, including quantification by high performance liquid chromatography (HPLC) coupled to a diode array (DAD) or refractive index (RI) detector. All compounds were present in higher amounts in the bran with phytic acid being the major compound with 7.59 and 0.85 g/100 g in the bran and brown rice. The minor compound was p-coumaric acid with 74.04 mg/100 g in the bran and 3.18 mg/100 g in the brown rice. The quantification of these antioxidant compounds is of great importance for the selection the appropriate rice processing method and for development of a database of antioxidant composition of rice varieties.

Rice is a staple food and one of the world’s major grain crops, serving as the staple food for 2/3 of the world population. Rice is rich in bioactive compounds such as γ-Oryzanol (GO), remarkably predominant in the bran fraction (Pereira et al, 2021). Previous studies have explored the physiological effects of GO, including as antioxidant, antidiabetic, anti-carcinogenic, neuroprotective, and hypocholesteremic effects (Rungratanawanich et al., 2020). GO is a mixture of ferulic acid (FA) esters of triterpene alcohols and plant sterols present in cereals such as rice. The GO composition is characterized by several isomers that determine its final concentration and profile in the rice grain. About ten GO molecular species have been reported to date (Miller & Engel, 2006; Kim et al., 2013). The major components of rice GO are cycloartenyl ferulate (CAF), 24-methylenecycloartanyl ferulate (24MCAF), campesteryl ferulate (CampF), and β-sitosteryl ferulate (SF) that account for more than 80% of GO in rice bran. The aim of this work was to identify the major components of GO in whole flour and bran of 5 different rice varieties (Arelate, Ariete, Caravela, Carnaroli and Giza 177) approached in the TRACE-RICE project, as well as other minor components including 7-campestenyl ferulate, campestanyl ferulate (CampF), cycloartanyl ferulate, stigmasteryl ferulate (SF), sitostenyl ferulate and sitostanyl ferulate, using Liquid chromatography associated to different mass spectrometry-based approaches, namely the high-resolution mass spectrometer Orbitrap and QTRAP LC-MS/MS. The QTRAP mass spectrometer enabled to identify the four major and six minor GO components. However, because some of these minor components share the same precursor to product ion transitions as some of the major components, resolution is hindered. For example, the resolution of the major component CampF is affected by the presence of the minor components 7-campestenyl ferulate and campestanyl ferulate and the same for SF and sitostanyl ferulate. Using the orbitrap mass analyzer the four major GO components were identified in rice samples and only one minor component (cycloartanyl ferulate).

Funding Information: This study is funded by national funds through FCT - Fundação para a Ciência e Tecnologia, I. P. under the PhD grant SFRH/BD/148420/2019 awarded to the first author. This protocol was included in the PhD previously approved project. EpiReumpaPt was supported by unrestricted grants from Direcção-Geral da Saúde, Fundação Calouste Gulbenkian, Fundação Champalimaud, Fundação AstraZeneca, AbbVie, Merck, Sharp & Dohme, Pfizer, Roche, Servier, Bial, D3A Medical Systems, Happybrands, Center de Medicina Laboratorial Germano de Sousa, Clínica Médica da Praia da Vitória, CAL-Clínica, Galp Energia, Açoreana Seguros, and individual rheumatologists. Background: Worldwide, the current management of knee osteoarthritis appears heterogeneous, high-cost and often not based on current best evidence. The absence of epidemiological data regarding the utilisation of healthcare services may conceal the need for improvements in the management of osteoarthritis. The aim of this study is to explore the profiles of healthcare services utilisation by people with knee osteoarthritis, and to analyse their determinants, according to Andersen’s behavioural model. Methods: We analysed a sample of 978 participants diagnosed with knee osteoarthritis from the population-based study EpiReumaPt, in Portugal. Data was collected with a structured interview, and the diagnosis of knee osteoarthritis was validated by a rheumatologist team. With the Two-step Cluster procedure, we primarily identified different profiles of healthcare utilisation according to the services most used by patients with knee osteoarthritis. Secondly, we analysed the determinants of each profile, using multinomial logistic regression, according to the predisposing characteristics, enabling factors and need variables. Results: In our sample, a high proportion of participants are overweight or obese (82,6%, n = 748) and physically inactive (20,6%, n = 201) and a small proportion had physiotherapy management (14,4%, n = 141). We identified three profiles of healthcare utilisation: “HighUsers”; “GPUsers”; “LowUsers”. “HighUsers” represents more than 35% of the sample, and are also the participants with higher utilisation of medical appointments. “GPUsers” represent the participants with higher utilisation of general practitioner appointments. Within these profiles, age and geographic location – indicated as predisposing characteristics; employment status and healthcare insurance - as enabling factors; number of comorbidities, physical function, health-related quality of life, anxiety and physical exercise - as need variables, showed associations (p < 0,05) with the higher utilisation of healthcare services profiles. Conclusions: Healthcare utilisation by people with knee osteoarthritis is not driven only by clinical needs. The predisposing characteristics and enabling factors associated with healthcare utilisation reveal inequities in the access to healthcare and variability in the management of people with knee osteoarthritis. Research and implementation of whole-system strategies to improve equity in the access and quality of care are paramount in order to diminish the impact of osteoarthritis at individual-, societal- and economic-level. publishersversion published

Funding Information: We thank the EpiDoc Unit and EpiReumaPt team for conceptualising, planning, and implementing the main research project. We would like to acknowledge that the present publication was supported by Fundação Ciência e Tecnologia, IP national support through CHRC (UIDP/04923/2020). Funding Information: This work was supported by an independent research grant from Pfizer. DC received national funding through FCT—Fundação para a Ciência e Tecnologia, I. P. under the Ph.D. grant SFRH/BD/148420/2019 Background: Hip/knee osteoarthritis (HKOA) is a leading cause of disability and imposes a major socioeconomic burden. The aim of this study is to estimate the prevalence of HKOA in Portugal, characterised the clinical severity of HKOA in the population, and identified sociodemographic, lifestyle, and clinical factors associated with higher clinical and radiographic severity. Methods: Participants with a diagnosis of HKOA from the EpiReumaPt study (2011–2013) were included (n = 1,087). Hip/knee osteoarthritis diagnosis was made through a structured evaluation by rheumatologists according to American College of Rheumatology criteria. Clinical severity was classified based on Hip Disability and Osteoarthritis Outcome Scale (HOOS) and Knee Injury and Osteoarthritis Outcome Scale (KOOS) score tertiles. Radiographic severity was classified based on the Kellgren-Lawrence grades as mild, moderate, or severe. Sociodemographic lifestyle and clinical variables, including the presence of anxiety and depression symptoms, were analysed. Factors associated with higher clinical and radiographic severity were identified using ordinal logistic regression models. Results: Hip/knee osteoarthritis diagnosis was present in 14.1% of the Portuguese population [12.4% with knee osteoarthritis (OA) and 2.9% with hip OA]. Clinical severity was similar between people with hip (HOOS = 55.79 ± 20.88) and knee (KOOS = 55.33 ± 20.641) OA. People in the high HOOS/KOOS tertile tended to be older (64.39 ± 0.70 years), female (75.2%), overweight (39.0%) or obese (45.9%), and had multimorbidity (86.1%). Factors significantly associated with higher clinical severity tertile were age [55–64 years: odds ratio (OR) = 3.18; 65–74 years: OR = 3.25; ≥75 years: OR = 4.24], female sex (OR = 1.60), multimorbidity (OR = 1.75), being overweight (OR = 2.01) or obese (OR = 2.82), and having anxiety symptoms (OR = 1.83). Years of education was inversely associated with higher clinical severity. Factors significantly associated with higher radiographic severity were age (65–74 years: OR = 3.59; ≥75 years: OR = 3.05) and being in the high HOOS/KOOS tertile (OR = 4.91). Being a female and live in Lisbon or in the Centre region were inversely associated with the higher radiographic severity. Conclusion: Hip/knee osteoarthritis is present in ~1.1 million of Portuguese people. Age, educational level, and obesity are independently associated with HKOA clinical severity, whereas age, sex, geographic location, and clinical severity are independently associated with radiographic severity. publishersversion published