Predictors of the post-COVID condition following mild SARS-CoV-2 infection.

Whereas the nature of the post-COVID condition following mild acute COVID-19 is increasingly well described in the literature, knowledge of its risk factors, and whether it can be predicted, remains limited. This study, conducted in Norway, uses individual-level register data from 214,667 SARS-CoV-2 infected individuals covering a range of demographic, socioeconomic factors, as well as cause-specific healthcare utilization in the years prior to infection to assess the risk of post-COVID complaints ≥3 months after testing positive. We find that the risk of post-COVID was higher among individuals who prior to infection had been diagnosed with psychological (OR = 2.12, 95% CI 1.84-2.44), respiratory (OR = 2.03, 95% CI 1.78-2.32), or general and unspecified health problems (OR = 1.78, 95% CI 1.52-2.09). To assess the predictability of post-COVID after mild initial disease, we use machine learning methods and find that pre-infection characteristics, combined with information on the SARS-CoV-2 virus type and vaccine status, to a considerable extent (AUC = 0.79, 95% CI 0.75-0.81) could predict the occurrence of post-COVID complaints in our sample.

Changes to consultations and diagnosis of osteoarthritis in primary care during the COVID-19 pandemic.

OBJECTIVE: General practitioners (GP) are often the first medical professionals to treat musculoskeletal complaints. Yet the impact of COVID-19 on primary care utilisation for musculoskeletal complaints is largely unknown. This study quantifies the impact of the pandemic on primary care utilisation for musculoskeletal complaints and specifically osteoarthritis (OA) in the Netherlands. DESIGN: We extracted data on GP consultations in 2015-2020 from 118,756 patients over 45 years of age and estimated reductions in consultations in 2020 as compared to 5-year average. Outcomes were GP consultations for: any musculoskeletal complaints, knee and hip OA, knee and hip complaints, and newly diagnosed knee and hip OA/complaints. RESULTS: The relative reductions in consultations ranged from 46.7% (95% confidence intervals (CI): 43.9-49.3%) (all musculoskeletal consultations) to 61.6% (95% CI: 44.7-73.3%) (hip complaints) at the peak of the first wave, and from 9.3% (95% CI: 5.7-12.7%) (all musculoskeletal consultations) to 26.6% (95% CI: 11.5-39.1%) (knee OA) at the peak of the second wave. The reductions for new diagnoses were 87.0% (95% CI: 71.5-94.1%) for knee OA/complaints, and 70.5% (95% CI: 37.7-86.0%) for hip OA/complaints at the peak of the first wave, and not statistically significant at the peak of the second wave. CONCLUSION: We observed 47% reduction in GP consultations for musculoskeletal disorders during the first wave and 9% during the second wave. For hip and knee OA/complaints, the reductions were over 50% during the first, and 10% during the second wave. This disruption may lead to accumulation of patients with severe OA symptoms and more requests for arthroplasty surgery.

The genetic contribution to hand osteoarthritis.

OBJECTIVE: To estimate the genetic contribution to doctor-diagnosed hand osteoarthritis (OA). METHODS: Using data from the Swedish Twin Registry and National Patient Register, we conducted a 20-year population-based longitudinal cohort study including 59,970 twins aged 35 years or older. We studied inpatient and outpatient doctor-diagnosed hand OA using ICD-10 codes from 1997 until 2016, including both the distal/proximal interphalangeal (DIP/PIP) joints and/or the first carpometacarpal (CMC-1) joints. We calculated intra-pair correlation, estimated the heritability (i.e., the percentage variation in hand OA that can be explained by genetic factors) as well as a genetic risk. RESULTS: Among 59,970 included persons, 936 had a hand OA diagnosis registered during the study period. The heritabilities of hand OA (any joint), CMC-1 OA and DIP/PIP OA were ∼87%, 86% and 48%, respectively, yet the two latter should be interpreted with care due to low numbers. Hand OA in any joint in both twins in a pair occurred more frequently in identical twins (54/554 = 9.7%, intra-pair correlation = 0.54, 95% CI = 0.44-0.63) than in fraternal twins (18/1,246 = 1.4%, intra-pair correlation = 0.10, 95% CI = -0.01-0.22). Identical twins who were diagnosed with hand OA in any joint had a far higher risk than fraternal twins with hand OA to also have their co-twin diagnosed with hand OA in any joint (Hazard Ratio = 6.98, 95% CI = 3.08-15.45). CONCLUSION: The genetic contribution to hand OA is high and likely varying between 48% and 87%. Potential differential heritability by hand OA phenotypes should be further explored.

The heritability of doctor-diagnosed traumatic and degenerative meniscus tears.

OBJECTIVE: To estimate the genetic contribution to traumatic and degenerative meniscus tears for men and women across the lifespan. METHODS: We linked the Swedish Twin Register with individual-level national healthcare data to form a 30-year, population-wide, longitudinal twin cohort. To study genetic contribution to meniscus tears, we estimated the heritability and familial risk using incident traumatic and degenerative tear diagnostic codes in a cohort of 88,414 monozygotic and dizygotic twin-pairs, aged ≥17 years. RESULTS: During follow-up, 3,372 (3.8%) of 88,414 twins were diagnosed with a traumatic or degenerative meniscus tear. The heritability was 0.39 (95% CI = 0.32-0.47) for men and 0.43 (95% CI = 0.36-0.50) for women, and did not vary by age. Environmental factors that were unique to each twin in a pair explained a greater proportion of the variance than genetic factors, both for men (0.61, 95% CI = 0.53-0.68) and women (0.57, 95% CI = 0.50-0.64). Separate analyses of traumatic vs degenerative meniscus tears yielded similar results. CONCLUSION: For the first time, we have estimated the genetic contribution to doctor-diagnosed meniscus tears using a twin study design. We found a relatively low to modest heritability for meniscus tears (∼40%). The heritability was also fairly stable over the lifespan, and equal in both men and women. Our findings suggest that environmental risk factors are a more important contributor to both traumatic and degenerative doctor-diagnosed meniscus tears than genetic factors.

Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study.

OBJECTIVE: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women. DESIGN: We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70 years at baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting. RESULTS: The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57-0.65). CONCLUSION: We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability.

Nature vs nurture in knee osteoarthritis - the importance of age, sex and body mass index.

OBJECTIVE: (1) To estimate the life-time genetic contribution for knee osteoarthritis (OA) surgery and (2) to explore any differences in the genetic contribution across age, sex and body mass index (BMI). METHODS: We studied the sex-specific genetic contribution to knee OA surgery in a prospective cohort study of 62,490 twins aged 35 years or older with a follow-up period of up to 47 years (10,092 identical and 21,153 non-identical twin pairs, 54% women). To study interactions with age, we graphed the heritabilities over the lifespan for men and women. We also studied the sex-specific heritability across strata of the median BMI to explore any interactions with BMI. RESULTS: The overall heritability of knee OA surgery was 0.53 (95% confidence intervals [CI] = 0.31-0.75), with higher heritability among women (H2 = 0.80 (95% CI = 0.73-0.87)) than men (H2 = 0.39 (95% CI = 0.10-0.69)). For men, the heritability started to rise after age 68. The genetic contribution was particularly low in men above median BMI (H2≥23.7 kg/m2 = 0.08, 95% CI = -0.32-0.48). For women, the heritability was consistently high from age 50 to death, independently of BMI (H2≥22.5 kg/m2 = 0.77, 95% CI = 0.66-0.87). CONCLUSION: There is a higher and more consistent genetic contribution for knee OA surgery in women than men. In men the genetic contribution was relatively low and varied with age and BMI.

A naturally aging knee, or development of early knee osteoarthritis?

AIM: To study the development of early knee osteoarthritis (OA) in subjects with and without risk factors for knee OA. METHODS: We studied 340 subjects from the Osteoarthritis Initiative (OAI), aged 45-55 years (51% women), free of radiographic knee OA at baseline (n = 294 with and n = 46 without knee pain and other OA risk factors). At baseline, 24, 48, 72 and 96 months we compared the two groups for prevalence and overlap of knee OA as defined by magnetic resonance imaging (MRI-based OA), x-rays (Kellgren-Lawrence grade [KLG] ≥ 1), and pain, using a logistic mixed model. We studied the group differences (%) over time by subtracting the OA prevalence of those without risk factors from the group with risk factors. RESULTS: The group with OA risk factors had higher proportions of MRI-based OA than the group without OA risk factors at all visits, but the difference diminished at 72 months (72 months difference = 11.9%, 95% confidence intervals [CI] = -2.3-26.1). Further, at 72 months, the presence of KLG ≥ 1 were similar in the two groups (-3.5%, 95% CI = -15.2-8.2). The proportion fulfilling all three OA definitions was 1.7% at 24 months and 4.8% at 72 months of those with OA risk factors and 0% and 2.2%, respectively, in those without. CONCLUSION: Structural changes of the knee are common irrespective of the presence of pain or other OA risk factors. Such structural changes in absence of knee symptoms should probably be considered as risk factors for early OA rather than disease.

Prediction of midlife hand osteoarthritis in young men.

OBJECTIVES: Improved prediction modeling in osteoarthritis (OA) may encourage risk reduction through calculation of individual and population lifetime risks. There are currently no prediction models for hand OA. Thus, we aimed to 1) develop a prediction model for hand OA in men and 2) to contrast its discriminative performance to a prediction model for lung cancer and chronic obstructive pulmonary disease (COPD). METHODS: We included 40,118 men aged 18 years undergoing mandatory conscription in Sweden 1969-70. Incident hand OA and lung cancer/COPD were obtained from diagnostic codes in the Swedish National Patient Register 1987-2010, i.e., until subjects were 59 years of age. We studied the strongest candidate predictors from five domains; socioeconomic, local biomechanical, systemic, lifestyle-related and general health factors, using logistic regression with backward elimination of candidate predictors with P > 0.2 to determine final models. To avoid overfitting we used bootstrapping. RESULTS: The strongest predictors for hand OA were body mass index (BMI), elbow flexor strength, systolic blood pressure, lower education and sleep problems. We observed excellent agreement between observed and predicted values, yet the discrimination was moderate (Area Under the Curve [AUC] = 0.62, 95% CI = 0.58-0.64). The discrimination in the prediction model for lung cancer/COPD was good (AUC = 0.74, 95% CI = 0.72-0.76). CONCLUSION: This prediction model for hand OA was capable of discriminating between persons with and without hand OA to a similar extent that has been previously reported for knee OA. Still, prediction of OA is more challenging than for chronic pulmonary disease.

Smoking and alcohol use are associated with structural and inflammatory hand osteoarthritis features.

OBJECTIVES: To explore whether smoking and alcohol use are associated with hand osteoarthritis (OA) features in two different OA cohorts. METHOD: We studied 530 people with radiographic hand OA from the Musculoskeletal pain in Ullensaker STudy (MUST) and 187 people from the Oslo hand OA cohort [mean (sd) age 65 (8.0) and 62 (5.7) years, 71% and 91% women, respectively]. Smoking, alcohol use and hand pain were self-reported. Participants underwent conventional hand radiographs and ultrasound examination of 30 hand joints. The Kellgren-Lawrence sum score for radiographic OA severity (0-120 scale) and the proportion of participants having at least one joint with grey-scale synovitis (grade ≥1) were calculated. We studied whether smoking and alcohol use were cross-sectionally associated with radiographic OA, synovitis, and pain using adjusted linear and logistic regression analyses. RESULTS: Smoking was associated with less radiographic OA in both cohorts [ß = -4.71, 95% confidence interval (CI) -8.36 to -1.06 for current smoking in MUST and ß = -0.15, 95% CI -0.29 to -0.02 for smoking pack-years in the Oslo hand OA cohort]. Stratified analyses indicated that the association was present in men only. Being a monthly drinker (examined in MUST only) was significantly associated with present synovitis compared to never drinkers (odds ratio = 2.35, 95% CI 1.27 to 4.34) (no gender differences). Neither smoking nor alcohol was associated with hand pain. CONCLUSIONS: Smoking was associated with less radiographic hand OA whereas alcohol consumption was associated with present joint inflammation in hand OA. Future longitudinal studies are needed to explore the causal associations and explanatory mechanisms behind gender differences.

Genetic factors contribute more to hip than knee surgery due to osteoarthritis - a population-based twin registry study of joint arthroplasty.

OBJECTIVE: To explore and quantify the relative strengths of the genetic contribution vs the contribution of modifiable environmental factors to severe osteoarthritis (OA) having progressed to total joint arthroplasty. DESIGN: Incident data from the Norwegian Arthroplasty Registry were linked with the Norwegian Twin Registry on the National ID-number in 2014 in a population-based prospective cohort study of same-sex twins born 1915-60 (53.4% females). Education level and height/weight were self-reported and Body Mass Index (BMI) calculated. The total follow-up time was 27 years for hip arthroplasty (1987-2014, 424,914 person-years) and 20 years for knee arthroplasty (1994-2014, 306,207 person-years). We estimated concordances and the genetic contribution to arthroplasty due to OA in separate analyses for the hip and knee joint. RESULTS: The population comprised N = 9058 twin pairs (N = 3803 monozygotic (MZ), N = 5226 dizygotic (DZ)). In total, 73% (95% confidence intervals (CI) = 66-78%) and 45% (95% CI = 30-58%) of the respective variation in hip and knee arthroplasty could be explained by genetic factors. Zygosity (as a proxy for genetic factors) was associated with hip arthroplasty concordance over time when adjusted for sex, age, education and BMI (HR = 2.98, 95% CI = 1.90-4.67 for MZ compared to DZ twins). Knee arthroplasty was to a greater extent dependent on BMI when adjusted for zygosity and the other covariates (HR = 1.15, 95% CI = 1.02-1.29). CONCLUSION: Hip arthroplasty was strongly influenced by genetic factors whereas knee arthroplasty to a greater extent depended on a high BMI. The study may imply there is a greater potential for preventing progression of knee OA to arthroplasty in comparison with hip OA.

Individual and joint effects of risk factors for onset widespread pain and obesity - a population-based prospective cohort study.

BACKGROUND: Widespread musculoskeletal pain (WSP) and obesity frequently co-occur and may have shared risk factors. We aimed to investigate whether four dichotomized risk factors individually or jointly increase the risk for the onset of WSP and onset of obesity. METHODS: Persons aged 34-76 years in 2004 living in Ullensaker municipality, Norway, responded to questionnaires in 2004 and 2010 (n = 1553). Using causal interaction analyses, we examined whether baseline obesity and WSP, poor sleep quality, mental distress and poor physical fitness jointly increased the risk of new onset WSP (≥3 pain sites leading to disability the last year) and new onset obesity (self-reported BMI ≥30 kg/m(2) ) in persons without WSP (n = 1270) or without obesity (n = 1300) at baseline respectively. RESULTS: The mean (SD) age was 51 (12.1) years and 56% were female. The incidence of WSP and obesity were 9.1% and 5.4%. Mental distress and poor sleep quality individually and jointly with poor physical fitness increased WSP onset risk (relative excess risk due to interaction [RERI] = 1.90, 95% CI, 0.39-3.42 and RERI = 1.43, 95% CI, 0.10-2.76). Poor physical fitness individually increased the risk for new onset obesity, and baseline WSP and poor sleep quality jointly (RERI = 1.87, 95% CI, 0.49-3.24). The presence of more risk factors was dose-dependently associated with onset WSP and to a lesser extent with onset obesity. CONCLUSION: The onset of WSP and the onset of obesity were results of joint effects of exposures. Poor physical fitness was a key covariate in increasing the risk for both conditions. WHAT DOES THIS STUDY ADD?: In a general population, the new onset of widespread pain and new onset of obesity were results of joint effects of risk factors and particularly poor physical fitness. The study may aid in the identification of patients at risk of future disability.

Synovitis and radiographic progression in non-erosive and erosive hand osteoarthritis: is erosive hand osteoarthritis a separate inflammatory phenotype?

OBJECTIVE: To compare the prevalence of synovitis, pain and radiographic progression in non-erosive and erosive hand osteoarthritis (HOA), and to explore whether the different rate of disease progression is explained by different levels of synovitis and structural damage. DESIGN: We included 31 and 34 participants with non-erosive and erosive HOA at baseline, respectively. Using Generalized Estimating Equations, we explored whether participants with erosive HOA had more synovitis (by MRI, ultrasound and clinical examination) independent of the degree of structural damage. Similarly, we explored whether pain at baseline and radiographic progression after 5 years were higher in erosive HOA, independent of the levels of synovitis and structural damage. All analyses were adjusted for age and sex. RESULTS: Power Doppler activity was found mainly in erosive HOA. Participants with erosive HOA demonstrated more moderate-to-severe synovitis, assessed by MRI (OR = 1.73, 95% CI 1.11-2.70), grey-scale ultrasound (OR = 2.02, 95% CI 1.25-3.26) and clinical examination (OR = 1.80, 95% CI 1.44-2.25). The associations became non-significant when adjusting for more structural damage. The higher frequency of joint tenderness in erosive HOA was at least partly explained more structural damage and inflammation. Radiographic progression (OR = 2.53, 95% CI 1.73-3.69) was more common in erosive HOA independent of radiographic HOA severity and synovitis (here: adjusted for grey-scale synovitis by ultrasound). CONCLUSION: Erosive HOA is characterized by higher frequency and more severe synovitis, pain and radiographic progression compared to non-erosive HOA. The higher rate of disease progression was independent of baseline synovitis and structural damage.

Relationships between diet-related changes in the gut microbiome and cognitive flexibility.

Western diets are high in fat and sucrose and can influence behavior and gut microbiota. There is growing evidence that altering the microbiome can influence the brain and behavior. This study was designed to determine whether diet-induced changes in the gut microbiota could contribute to alterations in anxiety, memory or cognitive flexibility. Two-month-old, male C57BL/6 mice were randomly assigned high-fat (42% fat, 43% carbohydrate (CHO), high-sucrose (12% fat, 70% CHO (primarily sucrose) or normal chow (13% kcal fat, 62% CHO) diets. Fecal microbiome analysis, step-down latency, novel object and novel location tasks were performed prior to and 2weeks after diet change. Water maze testing for long- and short-term memory and cognitive flexibility was conducted during weeks 5-6 post-diet change. Some similarities in alterations in the microbiome were seen in both the high-fat and high-sucrose diets (e.g., increased Clostridiales), as compared to the normal diet, but the percentage decreases in Bacteroidales were greater in the high-sucrose diet mice. Lactobacillales was only significantly increased in the high-sucrose diet group and Erysipelotrichales was only significantly affected by the high-fat diet. The high-sucrose diet group was significantly impaired in early development of a spatial bias for long-term memory, short-term memory and reversal training, compared to mice on normal diet. An increased focus on the former platform position was seen in both high-sucrose and high-fat groups during the reversal probe trials. There was no significant effect of diet on step-down, exploration or novel recognitions. Higher percentages of Clostridiales and lower expression of Bacteroidales in high-energy diets were related to the poorer cognitive flexibility in the reversal trials. These results suggest that changes in the microbiome may contribute to cognitive changes associated with eating a Western diet.

Body mass index and progressive hand osteoarthritis: data from the Oslo hand osteoarthritis cohort.

OBJECTIVES: Few longitudinal studies have studied the association between body mass index (BMI) and hand osteoarthritis (OA). We aimed to explore the association between BMI and progressive hand OA in a longitudinal study of the Oslo hand OA cohort. METHOD: Participants with existing hand OA had hand radiographs and BMI data taken at baseline and 7-year follow-up (n = 103). The radiographs were read according to the Kellgren-Lawrence (KL) scale. First, we examined the association between baseline BMI and incident OA (KL grade ≥ 2) in joints without OA at baseline (adjusted for age and sex) using generalized estimating equation (GEE) analyses. Second, we examined whether changes in BMI from baseline to follow-up were associated with increasing KL sum score from baseline to follow-up using linear regression. We repeated the analyses using changes in number of joints with symptomatic OA and patient-reported pain and physical function as the outcome. RESULTS: The mean (SD) age at baseline was 61.6 (5.6) years and 91 (94%) of the cohort were women. The mean (SD) BMI was 25.7 (4.0) kg/m(2) at baseline and the mean (SD) BMI change was 1.1 (2.0) kg/m(2). There was no relationship between baseline BMI and development of more joints with OA during follow-up. Similarly, there was no association between change in BMI and hand OA progression, increasing hand pain or disability. CONCLUSIONS: In the Oslo hand OA cohort, higher BMI was not related to hand OA progression.

Boar spermatozoa successfully predict mitochondrial modes of toxicity: implications for drug toxicity testing and the 3R principles.

Replacement of animal testing by in vitro methods (3-R principles) requires validation of suitable cell models, preferably obtained non-invasively, defying traditional use of explants. Ejaculated spermatozoa are highly dependent on mitochondrial production and consumption of ATP for their metabolism, including motility display, thus becoming a suitable model for capturing multiple modes of action of drugs and other chemicals acting via mitochondrial disturbance. In this study, a hypothesis was tested that the boar spermatozoon is a suitable cell type for toxicity assessment, providing a protocol for 3R-replacement of animals for research and drug-testing. Boar sperm kinetics was challenged with a wide variety of known frank mito-toxic chemicals with previously shown mitochondrial effects, using a semi-automated motility analyser allied with real-time fluorescent probing of mitochondrial potential (MitoTracker & JC-1). Output of this sperm assay (obtained after 30 min) was compared to cell viability (ATP-content, data obtained after 24-48 h) of a hepatome-cell line (HepG2). Results of compound effects significantly correlated (P<0.01) for all sperm variables and for most variables in (HepG2). Dose-dependent decreases of relative ATP content in HepG2 cells correlated to sperm speed (r=0.559) and proportions of motile (r=0.55) or progressively motile (r=0.53) spermatozoa. The significance of the study relies on the objectivity of computerized testing of sperm motility inhibition which is comparable albeit of faster output than somatic cell culture models. Sperm suspensions, easily and painlessly obtained from breeding boars, are confirmed as suitable biosensors for preclinical toxicology screening and ranking of lead compounds in the drug development processes.

No strong relationship between body mass index and clinical hand osteoarthritis: results from a population-based case-control study.

OBJECTIVES: The aim of this population-based case-control study was to investigate whether a high body mass index (BMI) is a risk factor for clinical hand osteoarthritis (OA). METHOD: Persons living in Ullensaker municipality in Norway who were aged 20-52 years in 1990 reported height and weight in 1990, 1994, 2004, and 2010 (n = 1276). Cases (clinical hand OA in 2010, n = 59) were compared to controls (participants without self-reported OA or hand pain in 2010, n = 805) with regard to the prospectively measured BMI by means of a generalized estimating equation (GEE) analysis adjusted for age, sex, time, and education. RESULTS: The mean age of hand OA cases was 64 (SD = 7.5) years in 2010 and 78% were women. There was no association between total average BMI over the entire period and later clinical hand OA (p = 0.320). Cases had a higher mean BMI in 1990 [unstandardized B = 0.93, 95% confidence interval (CI) 0.07-1.79] and in 1994 (B = 0.75, 95% CI 0.22-1.28) but there were no differences between the groups in 2004 or 2010. CONCLUSIONS: The study lend support to the hypothesis that having a higher BMI when young or middle-aged might be associated with later hand OA.

The effects of oats on the function of gut microflora in children with coeliac disease.

BACKGROUND: Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. AIM: To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats. METHODS: This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed. RESULTS: The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group. CONCLUSIONS: Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.

No strong temporal relationship between obesity and multisite pain--results from a population-based 20-year follow-up study.

BACKGROUND: Multisite pain and obesity are cross-sectionally related and are common conditions that may influence each other through socio-demographic, lifestyle and/or health-related factors. The aim of the present study was to examine the cross-sectional and prospective associations between overweight/obesity and multisite pain in a general population. METHODS: In a 20-year population-based prospective cohort study, persons aged 20-62 years in 1990 participated in postal surveys in 1990, 1994, 2004 and 2010 (n = 855). Multisite pain was defined as reporting ≥ 2 number of pain sites (NPS) on the Standardized Nordic Questionnaire. Overweight was defined as body mass index (BMI) 25-30 kg/m(2) and obesity as BMI ≥ 30 kg/m(2). To exploit all measurement times, generalized estimating equation analyses adjusting for age, sex, educational and occupational status, smoking, sleep quality, mental distress and physical activity were employed. RESULTS: The mean age was 41 years at baseline and 57% were women. Overweight/obesity and NPS were significantly associated cross-sectionally. Being overweight/obese was associated with reporting future NPS ≥ 2 [overweight: odds ratio (OR), 1.40, 95% confidence interval (CI), 1.12-1.75, obese: OR, 1.54, 95% CI, 1.04-2.28]. Having NPS ≥ 2 was not associated with becoming overweight, but increased the OR for future obesity (OR 1.27, 95% CI, 1.02, 1.59). Smoking was a confounder in this relationship. CONCLUSIONS: Being overweight or obese was associated with future multisite pain, although the magnitude of the association was small and the dose-response relationship observed in cross-sectional analyses disappeared in prospective analyses. There was less evidence that having multisite pain was a predictor of future overweight/obesity.

Memory in aged mice is rescued by enhanced expression of the GluN2B subunit of the NMDA receptor.

The GluN2B subunit of the N-methyl-d-aspartate (NMDA) receptor shows age-related declines in expression across the frontal cortex and hippocampus. This decline is strongly correlated to age-related memory declines. This study was designed to determine if increasing GluN2B subunit expression in the frontal lobe or hippocampus would improve memory in aged mice. Mice were injected bilaterally with either the GluN2B vector, containing cDNA specific for the GluN2B subunit and enhanced green fluorescent protein (eGFP); a control vector or vehicle. Spatial memory, cognitive flexibility, and associative memory were assessed using the Morris water maze. Aged mice, with increased GluN2B subunit expression, exhibited improved long-term spatial memory, comparable to young mice. However, memory was rescued on different days in the Morris water maze; early for hippocampal GluN2B subunit enrichment and later for the frontal lobe. A higher concentration of the GluN2B antagonist, Ro 25-6981, was required to impair long-term spatial memory in aged mice with enhanced GluN2B expression, as compared to aged controls, suggesting there was an increase in the number of GluN2B-containing NMDA receptors. In addition, hippocampal slices from aged mice with increased GluN2B subunit expression exhibited enhanced NMDA receptor-mediated excitatory post-synaptic potentials (EPSP). Treatment with Ro 25-6981 showed that a greater proportion of the NMDA receptor-mediated EPSP was due to the GluN2B subunit in these animals, as compared to aged controls. These results suggest that increasing the production of the GluN2B subunit in aged animals enhances memory and synaptic transmission. Therapies that enhance GluN2B subunit expression within the aged brain may be useful for ameliorating age-related memory declines.