Hand osteoarthritis phenotypes based on a biopsychosocial approach, and their associations with cross-sectional and longitudinal pain.

OBJECTIVE: Hand osteoarthritis (OA) pain is characterized as heterogeneous and multifactorial. Differences in pain may be explained by underlying phenotypes, which have not been previously explored DESIGN: Latent class analysis determined classes of participants with hand OA from the Nor-Hand study baseline examination (2016-17) based on a biopsychosocial framework. Outcomes were hand and overall bodily pain intensity (Numeric Rating Scale, 0-10) at baseline and follow-up (2019-21), The relations of the classes to pain outcomes at baseline, follow-up, and change over time were analysed in separate models by linear regression, using the overall healthiest class as reference. RESULTS: Five classes differing in radiographic hand OA burden and OA burden in the lower extremities by ultrasound, demographic factors, psychosocial burden and pain sensitization was identified. Persons with the least severe OA but higher burden of biopsychosocial factors reported the most hand pain (beta 3.65, 95% CI 2.53, 4.75). Pain was less pronounced in persons with the most severe hand OA but low burden of biopsychosocial factors (beta 1.03, 95% CI 0.41, 1.65). Results were similar for overall bodily pain and at follow-up. Changes in pain were small, but the association between a separate class defined by higher levels of biopsychosocial burden and pain changes was significant. CONCLUSION: The five hand OA phenotypes were associated with pain at baseline and 3.5 years later. The phenotype with the least OA severity, but higher burden of biopsychosocial factors reported more pain than the phenotype with the most severe OA, reflecting the symptom-structure discordance of the hand OA pain experience.

Third dose mRNA vaccination against SARS-CoV-2 reduces medical complaints seen in primary care: a matched cohort study.

BACKGROUND: SARS-CoV-2 mRNA vaccination has been associated with both side effects and a reduction in COVID-related complaints due to the decrease in COVID-19 incidence. We aimed to investigate if individuals who received three doses of SARS-CoV-2 mRNA vaccines had a lower incidence of (a) medical complaints and (b) COVID-19-related medical complaints, both as seen in primary care, when compared to individuals who received two doses. METHODS: We conducted a daily longitudinal exact one-to-one matching study based on a set of covariates. We obtained a matched sample of 315,650 individuals aged 18-70 years who received the 3rd dose at 20-30 weeks after the 2nd dose and an equally large control group who did not. Outcome variables were diagnostic codes as reported by general practitioners or emergency wards, both alone and in combination with diagnostic codes of confirmed COVID-19. For each outcome, we estimated cumulative incidence functions with hospitalization and death as competing events. RESULTS: We found that the number of medical complaints was lower in individuals aged 18-44 years who received three doses compared to those who received two doses. The differences in estimates per 100,000 vaccinated were as follows: fatigue 458 less (95% confidence interval: 355-539), musculoskeletal pain 171 less (48-292), cough 118 less (65-173), heart palpitations 57 less (22-98), shortness of breath 118 less (81-149), and brain fog 31 less (8-55). We also found a lower number of COVID-19-related medical complaints: per 100,000 individuals aged 18-44 years vaccinated with three doses, there were 102 (76-125) fewer individuals with fatigue, 32 (18-45) fewer with musculoskeletal pain, 30 (14-45) fewer with cough, and 36 (22-48) fewer with shortness of breath. There were no or fewer differences in heart palpitations (8 (1-16)) or brain fog (0 (- 1-8)). We observed similar results, though more uncertain, for individuals aged 45-70 years, both for medical complaints and for medical complaints that were COVID-19 related. CONCLUSIONS: Our findings suggest that a 3rd dose of SARS-CoV-2 mRNA vaccine administered 20-30 weeks after the 2nd dose may reduce the incidence of medical complaints. It may also reduce the COVID-19-related burden on primary healthcare services.

Impact of the COVID-19 pandemic on sick leave among healthcare workers: a register-based observational study.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on sick leave among healthcare workers (HCWs) in primary and specialist care and examine its causes. METHODS: Using individual-level register data, we studied monthly proportions of sick leave (all-cause and not related to SARS-CoV-2 infection) from 2017 to February 2022 for all HCWs in primary (N=60 973) and specialist care (N=34 978) in Norway. First, we estimated the impact of the pandemic on sick leave, by comparing the sick leave rates during the pandemic to sick leave rates in 2017-2019. We then examined the impact of COVID-19-related workload on sick leave, by comparing HCWs working in healthcare facilities with different levels of COVID-19 patient loads. RESULTS: HCWs had elevated monthly rates of all-cause sick leave during the COVID-19 pandemic of 2.8 (95% CI 2.67 to 2.9) and 2.2 (95% CI 2.07 to 2.35) percentage points in primary and specialist care. The corresponding increases for sick leave not related to SARS-CoV-2 infection were 1.2 (95% CI 1.29 to 1.05) and 0.7 (95% CI 0.52 to 0.78) percentage points. All-cause sick leave was higher in areas with high versus low COVID-19 workloads. However, after removing sick leave episodes due to SARS-CoV-2 infections, there was no difference. CONCLUSIONS: There was a substantial increase in sick leave among HCWs during the pandemic. Our results suggest that the increase was due to HCWs becoming infected with SARS-CoV-2 and/or sector-wide effects, such as strict infection control measures. More differentiated countermeasures should, therefore, be evaluated to limit capacity constraints in healthcare provision.

Occupational risk of COVID-19 by country of birth. A register-based study.

BACKGROUND: Occupational exposure has been suggested to contribute to a disproportionate burden of COVID-19 among immigrants. We aim to assess this hypothesis in Norway. METHODS: In 2729 627 adults born in Norway, Somalia, Pakistan, Iraq, Afghanistan and Turkey, we examined whether persons employed as taxi drivers, bus and tram drivers, child care workers, nurses, personal care workers in health, food service counter attendants, waiters/bartenders, cleaners and shop sale persons had a higher risk of COVID-19, from 1 April 2020 to 2 December 2020, compared with (i) Norwegian-born in the same occupational group and (ii) all others with the same birth country and aged 20-70 years, using logistic regressions. RESULTS: Within each occupational group, immigrants had a greatly increased odds of COVID-19 when compared with Norwegian-born (odds ratio [OR] ~ 1.66-12.72). However, immigrants working in the selected occupations had the same odds of COVID-19 as person with same birth country not having the same occupation (OR ~ 1). Exceptions were Somalian, Afghani and Iraqi personal care workers in health services who had an increased odds of COVID-19 compared with others from the same country. CONCLUSION: Occupation is not an important driver of the high rates of COVID-19 among immigrants from Somalia, Pakistan, Iraq, Afghanistan and Turkey.

Health care use after severe respiratory tract infections in children aged 0 to 5 years.

AIM: To explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared with children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs). METHODS: In 34,214 children aged 1 month to 5 years who were registered as having one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 (N = 128), RSV infection (N = 4,009), or other RTIs (N = 34,458) from 2017 to 2021, we used a difference-in-differences study design to investigate individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified by infants (1 to 11 months) and children (1 to 5 years). RESULTS: We found a slight increase in primary health care use in the first 4 weeks after the hospital visit for infants with COVID-19 when compared with infants with RSV infection (6 per 10,000; 95% CI [2, 13], a 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared with infants with RSV infection, which lasted for 12 weeks. CONCLUSIONS: Our findings imply a slightly increased health care use among infants after a hospital visit for COVID-19 than among infants with other RTIs, the potential etiological mechanisms of which deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services.

Does lower educational attainment increase the risk of osteoarthritis surgery? a Swedish twin study.

BACKGROUND: Previous studies have reported an inverse association between educational attainment and different osteoarthritis (OA) outcomes. However, none of the previous studies have accounted for potential confounding by early-life environment and genetics. Thus, we aimed to examine the association between educational attainment and knee and hip OA surgery using twin data. METHODS: From the Swedish Twin Registry (STR), we identified dizygotic (DZ) and monozygotic (MZ) twins. All twins in the STR aged 35 to 64 years were followed from January the 1st 1987 or the date they turned 35 years until OA surgery, relocation outside Sweden, death or the end of 2016 (18,784 DZ and 8,657 MZ complete twin pairs). Associations between educational attainment and knee and hip OA surgery were estimated in models matched on twin pairs, using Weibull within-between (WB) shared frailty model. RESULTS: For knee OA surgery, the analysis matched on MZ twins yielded a within-estimate hazard ratio (HR) per 3 years of education, of 1.06 (95% CI: 0.81, 1.32), suggesting no association between the outcome and the individual´s education. Rather, there seemed to be a so called familial effect of education, with a between-pair estimate of HR = 0.71 (95% CI: 0.41, 1.01). For hip OA surgery, the within- and between-pair estimates for MZ twins were 0.92 (95% CI: 0.69, 1.14) and 1.15 (95% CI: 0.87, 1.42), respectively. CONCLUSIONS: Our results suggest that the inverse associations between education and knee/hip OA surgery observed in cohort studies are potentially confounded by unobserved familial factors like genetics and/or early life exposures.

Associations between joint pathologies and central sensitization in persons with hand osteoarthritis: results from the Nor-Hand study.

OBJECTIVE: Pain sensitization is associated with pain severity in persons with hand OA. What contributes to pain sensitization is unclear. This study explores whether hand OA pathologies and symptom duration are related to central sensitization. METHOD: Participants with hand OA in the Nor-Hand study underwent bilateral hand radiography and US examination. Central sensitization was assessed with pressure pain thresholds (PPT) at remote sites (wrist, trapezius and tibialis anterior muscles) and temporal summation. We examined whether hand OA pathologies, independent of each other, including structural severity (Kellgren-Lawrence sum score, presence of erosive hand OA), inflammatory severity (greyscale synovitis and power Doppler activity sum scores) and symptom duration, were related to central sensitization, adjusting for age, sex, BMI, comorbidities and OA-severity of knee/hip. RESULTS: In 291 participants (88% women, median age 61 years, interquartile range 57-66 years) Kellgren-Lawrence, greyscale synovitis and power Doppler activity sum scores were not associated with lower PPTs at remote sites. Persons with erosive hand OA had lower PPTs at the wrist (adjusted beta -0.75, 95% CI -1.32, -0.19) and tibialis anterior (adjusted beta -0.82, 95% CI -1.54, -0.09) and had greater temporal summation (adjusted beta 0.56, 95% CI 0.12, 1.01) compared with persons with non-erosive disease. No associations were found for symptom duration. CONCLUSIONS: A person's overall amount of structural or inflammatory hand OA pathologies was not associated with central sensitization. Although persons with erosive hand OA showed greater signs of central sensitization, the small differences suggest that central sensitization is mainly explained by factors other than joint pathologies.

COVID-19 infection among bartenders and waiters before and after pub lockdown.

OBJECTIVE: To assess how different bans on serving alcohol in Norwegian bars and restaurants were related to the detection of SARS-CoV-2 in bartenders and waiters and in persons in any occupation. METHODS: In 25 392 bartenders and waiters and 1 496 328 persons with other occupations (mean (SD) age 42.0 (12.9) years and 51.8% men), we examined the weekly rates of workers tested and detected with SARS-CoV-2, 1-10 weeks before and 1-5 weeks after implementation of different degrees of bans on serving alcohol in pubs and restaurants, across 102 Norwegian municipalities with: (1) full blanket ban, (2) partial ban with hourly restrictions (eg, from 22:00 hours) or (3) no ban, adjusted for age, sex, testing behaviour and population size. RESULTS: By 4 weeks after the implementation of ban, COVID-19 infection among bartenders and waiters had been reduced by 60% (from 2.8 (95% CI 2.0 to 3.6) to 1.1 (95% CI 0.5 to 1.6) per 1000) in municipalities introducing full ban, and by almost 50% (from 2.5 (95% CI 1.5 to 3.5) to 1.3 (95% CI 0.4 to 2.2) per 1000) in municipalities introducing partial ban. A similar reduction within 4 weeks was also observed for workers in all occupations, both in municipalities with full (from 1.3 (95% CI 1.3 to 1.4) to 0.9 (95% CI 0.9 to 1.0)) and partial bans (from 1.2 (95% CI 1.1 to 1.3) to 0.5 (95% CI 0.5 to 0.6)). CONCLUSION: Partial bans on serving alcohol in bars and restaurants may be similarly associated with declines in confirmed COVID-19 infection as full bans.

Physiotherapy use is increased for up to nine months after receiving respiratory support for COVID-19.

AIM: To explore whether physiotherapy use is increased after hospitalization with COVID-19 with or without respiratory support vs. other respiratory tract infections (RTI). METHODS: In all Norwegian residents aged 18-80 years who were hospitalized with COVID-19 (N = 5,344) or other RTI (N = 82,235) between July 1st 2017 and August 1st 2021, we used a pre-post study design to explore the weekly individual average physiotherapy use in community care from 12 weeks prior to hospital admission, to 36 weeks (9 months) after hospital discharge for individuals who received and who did not receive respiratory support. RESULTS: Prior to the hospital stay, COVID-19 patients and patients with other RTI had ~ 40-60 physiotherapist consultations per 1000 inpatients per week. COVID-19 patients on respiratory support had a higher increase in physiotherapy use after discharge than persons with other RTI on respiratory support (an additional 27.3 (95% confidence interval = 10.2 to 44.4) consultations per 1000 for men, and 41.8 (13.7 to 69.9) per 1000 for women)). The increase in physiotherapy use lasted for 6 months for men, and 9 months for women. COVID-19 inpatients without respiratory support had a similar up-to-9-months-change post-discharge physiotherapy use as inpatients with other RTI without respiratory support (-0.2 (-0.7 to 0.2) for men, and 0.09 (-6.4 to 6.6) for women). CONCLUSION: The need for physiotherapy was increased for up to 9 months after having COVID-19 requiring respiratory support vs. other RTI requiring respiratory support. No difference between diseases was seen for individuals who were hospitalized but not on respiratory support.

Utilization of health care services before and after media attention about fatal side effects of the AstraZeneca vaccine: a nation-wide register-based event study.

BACKGROUND: Survey studies have found that vaccinated persons tend to report more side effects after being given information about side effects rather than benefits. However, the impact of high media attention about vaccine-related side effects on the utilization of health care is unknown. We aimed to assess whether utilization of health care services for newly vaccinated health care workers changed after media attention about fatal side effects of the AstraZeneca vaccine on March 11th, 2021, and whether changes differed by age, sex, or occupation. METHODS: We utilized individual-level data on health care use, vaccination, employment, and demographics available in the Norwegian emergency preparedness register Beredt C19. In all 99,899 health care workers in Norway who were vaccinated with AstraZeneca between February 11th and March 11th, we used an event-study design with a matched comparison group to compare the change in primary and inpatient specialist care use from 14 days before to 14 days after the information shock on March 11th, 2021. RESULTS: Primary health care use increased with 8.2 daily consultations per 1000 health care workers (95% CI 7.51 to 8.89) the week following March 11th for those vaccinated with AstraZeneca (n = 99,899), compared with no increase for the unvaccinated comparison group (n = 186,885). Utilization of inpatient care also increased with 0.8 daily hospitalizations per 1000 health care workers (95% CI 0.37 to 1.23) in week two after March 11th. The sharpest increase in daily primary health care use in the first week after March 11th was found for women aged 18-44 (10.6 consultations per 1000, 95% CI 9.52 to 11.68) and for cleaners working in the health care sector (9.8 consultations per 1000, 95% CI 3.41 to 16.19). CONCLUSIONS: Health care use was higher after the media reports of a few cases of fatal or severe side effects of the AstraZeneca vaccine. Our results suggest that the reports did not only lead vaccinated individuals to contact primary health care more, but also that physicians referred and treated more cases to specialist care after the new information.

Occupational risk of COVID-19 in the first versus second epidemic wave in Norway, 2020.

BackgroundThe occupational risk of COVID-19 may be different in the first versus second epidemic wave.AimTo study whether employees in occupations that typically entail close contact with others were at higher risk of SARS-CoV-2 infection and COVID-19-related hospitalisation during the first and second epidemic wave before and after 18 July 2020, in Norway.MethodsWe included individuals in occupations working with patients, children, students, or customers using Standard Classification of Occupations (ISCO-08) codes. We compared residents (3,559,694 on 1 January 2020) in such occupations aged 20-70 years (mean: 44.1; standard deviation: 14.3 years; 51% men) to age-matched individuals in other professions using logistic regression adjusted for age, sex, birth country and marital status.ResultsNurses, physicians, dentists and physiotherapists had 2-3.5 times the odds of COVID-19 during the first wave when compared with others of working age. In the second wave, bartenders, waiters, food counter attendants, transport conductors, travel stewards, childcare workers, preschool and primary school teachers had ca 1.25-2 times the odds of infection. Bus, tram and taxi drivers had an increased odds of infection in both waves (odds ratio: 1.2-2.1). Occupation was of limited relevance for the odds of severe infection, here studied as hospitalisation with the disease.ConclusionOur findings from the entire Norwegian population may be of relevance to national and regional authorities in handling the epidemic. Also, we provide a knowledge foundation for more targeted future studies of lockdowns and disease control measures.

Impact of the COVID-19 pandemic on emergency and elective hip surgeries in Norway.

Background and purpose - Many countries implemented strict lockdown policies to control the COVID-19 pandemic during March 2020. The impacts of lockdown policies on joint surgeries are unknown. Therefore, we assessed the effects of COVID-19 pandemic lockdown restrictions on the number of emergency and elective hip joint surgeries, and explored whether these procedures are more/less affected by lockdown restrictions than other hospital care.Patients and methods - In 1,344,355 persons aged ≥ 35 years in the Norwegian emergency preparedness (BEREDT C19) register, we studied the daily number of persons having (1) emergency surgeries due to hip fractures, and (2) electively planned surgeries due to hip osteoarthritis before and after COVID-19 lockdown restrictions were implemented nationally on March 13, 2020, for different age and sex groups. Incidence rate ratios (IRR) reflect the after-lockdown number of surgeries divided by the before-lockdown number of surgeries.Results - After-lockdown elective hip surgeries comprised one-third the number of before-lockdown (IRR ∼0.3), which is a greater drop than that seen in all-cause elective hospital care (IRR ∼0.6). Men aged 35-69 had half the number of emergency hip fracture surgeries (IRR ∼0.6), whereas women aged ≥ 70 had the same number of emergency hip fracture surgeries after lockdown (IRR ∼1). Only women aged 35-69 and men aged ≥ 70 had emergency hip fracture surgery rates after lockdown comparable to what may be expected based on analyses of all-cause acute care (IRR ∼0.80)Interpretation - It is important to note for future pandemics management that lockdown restrictions may impact more on scheduled joint surgery than other scheduled hospital care. Lockdown may also impact the number of emergency joint surgeries for men aged ≥ 35 but not those for women aged ≥ 70.

High genetic contribution to anterior cruciate ligament rupture: Heritability ~69.

OBJECTIVES: We aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture. METHODS: We used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twins, aged ≥17 years, to determine the familial risk and heritability of ACL rupture. RESULTS: The incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture. CONCLUSION: The genetic contribution to ACL rupture of ~69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.

Risk of knee osteoarthritis after different types of knee injuries in young adults: a population-based cohort study.

OBJECTIVES: To estimate the risk of clinically diagnosed knee osteoarthritis (OA) after different types of knee injuries in young adults. METHODS: In a longitudinal cohort study based on population-based healthcare data from Skåne, Sweden, we included all persons aged 25-34 years in 1998-2007 (n=149 288) with and without diagnoses of knee injuries according to International Classification of Diseases (ICD)-10. We estimated the HR of future diagnosed knee OA in injured and uninjured persons using Cox regression, adjusted for potential confounders. We also explored the impact of type of injury (contusion, fracture, dislocation, meniscal tear, cartilage tear/other injury, collateral ligament tear, cruciate ligament tear and injury to multiple structures) on diagnosed knee OA risk. RESULTS: We identified 5247 persons (mean (SD) age 29.4 (2.9) years, 67% men) with a knee injury and 142 825 persons (mean (SD) age 30.2 (3.0) years, 45% men) without. We found an adjusted HR of 5.7 (95% CI 5.0 to 6.6) for diagnosed knee OA in injured compared with uninjured persons during the first 11 years of follow-up and 3.4 (95% CI 2.9 to 4.0) during the following 8 years. The corresponding risk difference (RD) after 19 years of follow-up was 8.1% (95% CI 6.7% to 9.4%). Cruciate ligament injury, meniscal tear and fracture of the tibia plateau/patella were associated with greatest increase in risk (RD of 19.6% (95% CI 13.2% to 25.9%), 10.5% (95% CI 6.4% to 14.7%) and 6.6% (95% CI 1.1% to 12.2%), respectively). CONCLUSION: In young adults, knee injury increases the risk of future diagnosed knee OA about sixfold with highest risks found after cruciate ligament injury, meniscal tear and intra-articular fracture.

Is the Association Between Obesity and Hip Osteoarthritis Surgery Explained by Familial Confounding?

BACKGROUND: Familial confounding is confounding due to genetics or environmental exposures shared by family members. We aimed to study whether familial confounding explains the association between body mass index (BMI) and severe hip osteoarthritis (OA). METHODS: We linked data from the Norwegian Arthroplasty Registry with the Norwegian Twin Registry on the National ID-number in 2014, generating a population-based prospective cohort study of same-sex twins born between 1915 and 1960 (53.4% females). BMI was calculated from self-reported height/weight. The outcome was incident hip arthroplasty due to OA (follow-up time, 1987-2014; 424 914 person-years). We performed sex-specific co-twin control analyses of dizygotic (N = 5,226) and monozygotic (MZ, N = 3,803) twin pairs using Cox regression models and explored reasons for any familial confounding using bivariate twin models. RESULTS: The mean (SD) BMI was 22.6 (2.96), peak lifetime BMI 25.6 (2.61), and N = 614 had hip surgery due to OA. In cohort analyses, BMI was associated with hip OA for women and men (hazard ratio [HR] = 1.09, 95% confidence intervals [CIs] = 1.06 to 1.11 and HR = 1.08, 95% CI = 1.04 to 1.12, respectively). When adjusting for familial confounding within MZ twins, the association got stronger for women (HR = 1.19; 95% CI = 1.05 to 1.36) but weaker for men (HR = 0.93; 95% CI = 0.75 to 1.16). There was no genetic overlap between BMI and hip OA, yet the familial confounding in men provides suggestive evidence that the association could be explained by shared environmental factors. CONCLUSION: The association between BMI and hip OA may be explained by familial confounding for men. For women, there was no evidence for familial confounding, consistent with a causal association. See video abstract at, http://links.lww.com/EDE/B336.

Distribution of osteoarthritis in a Norwegian population-based cohort: associations to risk factor profiles and health-related quality of life.

The objective of the study was to examine the hand-, knee- and hip osteoarthritis (OA) distribution, risk factor profiles and health-related quality of life (HRQoL) in a population-based OA cohort. Persons with self-reported OA responded to questionnaires and attended a clinical examination (N = 606). We analyzed cross-sectional associations to risk factor profiles and HRQoL dimensions (Short Form 36) in four mutually exclusive groups based on fulfillment of The American College of Rheumatology criteria: no OA (NOA), monoarticular upper extremity (hand) OA (MOAupper-ex.), monoarticular lower extremity (hip or knee) OA (MOAlower-ex.) and polyarticular OA (POA). Multivariate regression analyses and correspondence analysis were performed. The distribution of NOA, MOAupper-ex. MOAlower-ex. and POA was 21.1, 25.4, 22.4 and 31.0%, respectively. Compared to NOA, minor differences were found in risk factor profile in MOAupper-ex., whereas POA was significantly associated with sociodemographic, metabolic and mechanical features. The correspondence analysis identified different risk factor profiles between the four OA phenotypes, but the differences were not statistically significant (p = 0.13). Regarding HRQoL, neither OA groups were associated with poorer mental functioning. MOAlower-ex. and POA were associated with, among other things, poorer physical functioning (ß = -6.2, 95% CI -11.2 to -1.2 and ß = -12.5, 95% CI -17.4 to -7.9, respectively) and more pain (ß = -5.4, 95% CI -10.4 to -0.3 and ß = -10.5, 95% CI -15.3 to -5.8, respectively). In this cohort of persons with self-reported OA, POA was the most prevalent phenotype and was associated with an unfortunate risk factor profile and several diminished HRQoL dimensions. POA needs further attention in research and clinical care.

High levels of omega-3 fatty acids in milk from omega-3 fatty acid-supplemented mothers are related to less immunoglobulin E-associated disease in infancy.

AIM: We previously reported a protective effect of maternal omega-3 fatty acid supplements on the development of immunoglobulin E (IgE)-associated disease in infancy. This study assessed omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in maternal milk in relation to omega-3 LCPUFA supplementation and the development of allergic disease in their infants. METHODS: This study randomised 95 pregnant women at risk of having an allergic infant, to daily supplements of 2.6 g omega-3 LCPUFA or a placebo of 2.7 g soya bean oil from gestational week 25 until 3 months of lactation. Breast milk samples were collected as colostrum, at one and 3 months. Milk fatty acids were related to allergic outcome in the infants at 24 months. RESULTS: Omega-3 milk fatty acids were higher in women who received omega-3 supplements than the placebo group (p < 0.01). Higher proportions of milk eicosapentaenoic acid and docosahexaenoic acid and a lower arachidonic/eicosapentaenoic acid ratio were associated with an absence of IgE-associated disease in the infants. None of the children developed IgE-associated atopic eczema above a level of 0.83 mol% eicosapentaenoic acid in colostrum. [Correction added on 7 July 2016, after online publication: In the preceding sentence, the correct word should be "above" instead of "below" and this has been amended in this current version.] CONCLUSION: High omega-3 LCPUFA milk levels in mothers who received omega-3 LCPUFA supplements were related to fewer allergies in their children.

Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte.

Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

Cell type related differences in staining with pentameric thiophene derivatives.

Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease.

OBJECTIVE: The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD. MATERIAL AND METHODS: Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression. RESULTS: The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-γ (IFN-γ) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-γ but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels. CONCLUSION: Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.