Hypothetical 22-Year Intervention With the Dietary Approaches to Stop Hypertension and Risk of Heart Failure in a General Population.

We used design principles of target trial methodology to emulate the effect of sustained adherence to the Dietary Approaches to Stop Hypertension (DASH) diet on the 22-year risk of heart failure. Women and men aged 45-83 years without previous heart failure, who answered questionnaires in 1997 from the Swedish Mammography Cohort and the Cohort of Swedish Men, were eligible. Follow-up questionnaires were sent in 2008-2009. Incidence of heart failure was ascertained using the Swedish Patient Register, updated until December 31, 2019. The parametric g-formula was used to estimate the 22-year risk of heart failure under sustained adherence to a population-adapted DASH diet compared with no intervention. Intakes before 1997 for before-baseline adjustment was available only for women. In total, 31,238 women and 34,939 men were eligible. The 22-year risk of heart failure was 14.5% with long-term adherence to the DASH diet compared with 15.2% with no intervention (risk difference = -0.7%, 95% confidence interval: 1.6, 0.0%) in women and correspondingly in men 15.3% vs. 16.2% (risk difference = -0.9%, 95% confidence interval: -1.6, -0.2%). Our hypothetical intervention suggests that sustained adherence to the population-adapted DASH diet may reduce risk of heart failure in middle-aged and elderly Swedish women and men.

Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Period effects in the risk of labour market marginalization among refugees in Sweden: a register-based cohort study.

BACKGROUND: Changes in Swedish national insurance policies over time and/or migration-related health inequalities may influence the risk for labour market marginalization (LMM) in refugees as compared to the Swedish-born host population. This study aimed to investigate potential period effects in the association between refugee status and the risk of LMM and explore any differences by country of birth, age and duration of residence. METHODS: Using national registers, three cohorts including all Swedish residents during 1999, 2004 and 2009 were followed for 4 years (cohort 2000, 2005 and 2010). Cox regression models were used to examine associations between refugee status and LMM defined as long-term unemployment (>180 days annually) and disability pension. The analyses were adjusted for socio-demographic factors, morbidities and labour market-related factors. Stratified analyses were run for age, country of birth and duration of residence. RESULTS: Across the cohorts, hazard ratios (HRs) were higher for long-term unemployment [2000: HR = 1.98; 95% confidence interval (CI): 1.96-2.01; 2005: HR = 2.30; 95% CI: 2.27-2.33; 2010: HR = 2.78; 95% CI: 2.75-2.81] for refugees compared to Swedish-born but not for disability pension. HRs for long-term unemployment were highest among refugees aged 25-34 and 35-44 years, from Somalia, Afghanistan and Iraq and refugees with a shorter duration of residence. CONCLUSIONS: The risk of long-term unemployment appears to have increased for refugees over time. Particularly some refugee subgroups experienced more difficulties. These findings highlight ongoing disparities for refugees and implicate on a broader scale that changes in policies such as stricter regulations in the insurance or healthcare system might adversely affect them.

Risk for Acute Myocardial Infarction After Ophthalmologic Procedures.

BACKGROUND: Preoperative cardiovascular evaluations are frequently done before ambulatory ophthalmologic procedures. However, whether these procedures can trigger an acute myocardial infarction (AMI) is unknown. OBJECTIVE: To assess the short-term risk for AMI associated with ophthalmologic procedures. DESIGN: Case-crossover design. SETTING: Population-based nationwide study from Norway and Sweden. PARTICIPANTS: First-time patients with AMI, aged 40 years and older, identified via inpatient registries and linked to outpatient surgical procedures in Norway (2008 to 2014) and Sweden (2001 to 2014), respectively. MEASUREMENTS: Using self-matching, for each participant, exposure to ophthalmologic procedures in the 0 to 7 days before AMI diagnosis (hazard period) was compared with an 8-day period 30 days earlier, that is, days 29 to 36 before AMI (control period) to estimate the relative risk for an AMI the week after an ophthalmologic procedure. The odds ratios (ORs) with 95% CIs were calculated, using conditional logistic regression. Only patients who had a procedure of interest during either the hazard or control period were included. RESULTS: For the 806 patients with AMI included in this study, there was a lower likelihood of AMI in the week after an ophthalmologic procedure than during the control week (OR, 0.83; 95% CI, 0.75 to 0.91). Furthermore, there was no evidence of increased risk for AMI when analyses were stratified by surgery subtype, anesthesia (local or general), duration, invasiveness (low, intermediate, or high), patient's age (<65 years or ≥65 years), or comorbidity (none vs. any). LIMITATION: Potential bias from time-varying confounders between the hazard and the control periods. CONCLUSION: Ophthalmologic procedures done in an outpatient setting did not seem to be associated with an increased risk for AMI. PRIMARY FUNDING SOURCE: Central Norway Regional Health Authority and the Swedish Research Council.

Nitro-oxidative response to internalized multi-walled carbon nanotubes in Brassica napus and Solanum lycopersicum.

In addition to their beneficial effects on plant physiology, multi-walled carbon nanotubes (MWCNTs) are harmful to plants in elevated concentrations. This study compared the effects of two doses of MWCNT (10 and 80 mg/L) in Brassica napus and Solanum lycopersicum seedlings focusing on nitro-oxidative processes. The presence of MWCNTs was detectable in the root and hypocotyl of both species. Additionally, transmission electron microscopy analysis revealed that MWCNTs are heavily transformed within the root cells forming large aggregates. The uptake of MWCNTs negatively affected root viability and root cell proliferation of both species, but more intense toxicity was observed in S. lycopersicum compared to B. napus. The presence of MWCNT triggered more intense protein carbonylation in the relative sensitive S. lycopersicum, where increased hydrogen peroxide levels were observed. Moreover, MWCNT exposure increased the level of physiological protein tyrosine nitration which was more intense in S. lycopersicum where notable peroxynitrite accumulation occurred. These suggest for the first time that MWCNT triggers secondary nitro-oxidative stress which contributes to its toxicity. Moreover, the results indicate that the extent of the nitro-oxidative processes is associated with the extent of MWCNT toxicity.

Predicting the duration of sickness absence due to knee osteoarthritis: a prognostic model developed in a population-based cohort in Sweden.

BACKGROUND: Predicting the duration of sickness absence (SA) among sickness absent patients is a task many sickness certifying physicians as well as social insurance officers struggle with. Our aim was to develop a prediction model for prognosticating the duration of SA due to knee osteoarthritis. METHODS: A population-based prospective study of SA spells was conducted using comprehensive microdata linked from five Swedish nationwide registers. All 12,098 new SA spells > 14 days due to knee osteoarthritis in 1/1 2010 through 30/6 2012 were included for individuals 18-64 years. The data was split into a development dataset (70 %, nspells =8468) and a validation data set (nspells =3690) for internal validation. Piecewise-constant hazards regression was performed to prognosticate the duration of SA (overall duration and duration > 90, >180, or > 365 days). Possible predictors were selected based on the log-likelihood loss when excluding them from the model. RESULTS: Of all SA spells, 53 % were > 90 days and 3 % >365 days. Factors included in the final model were age, sex, geographical region, extent of sickness absence, previous sickness absence, history of specialized outpatient healthcare and/or inpatient healthcare, employment status, and educational level. The model was well calibrated. Overall, discrimination was poor (c = 0.53, 95 % confidence interval (CI) 0.52-0.54). For predicting SA > 90 days, discrimination as measured by AUC was 0.63 (95 % CI 0.61-0.65), for > 180 days, 0.69 (95 % CI 0.65-0.71), and for SA > 365 days, AUC was 0.75 (95 % CI 0.72-0.78). CONCLUSION: It was possible to predict patients at risk of long-term SA (> 180 days) with acceptable precision. However, the prediction of duration of SA spells due to knee osteoarthritis has room for improvement.

Burden and prevalence of prognostic factors for severe COVID-19 in Sweden.

The World Health Organization and European Centre for Disease Prevention and Control suggest that individuals over the age of 70 years or with underlying cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, or diabetes are at increased risk of severe COVID-19. However, the prevalence of these prognostic factors is unknown in many countries. We aimed to describe the burden and prevalence of prognostic factors of severe COVID-19 at national and county level in Sweden. We calculated the burden and prevalence of prognostic factors for severe COVID-19 based on records from the Swedish national health care and population registers for 3 years before 1st January 2016. 9,624,428 individuals were included in the study population. 22.1% had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). We show that one in five individuals in Sweden is at increased risk of severe COVID-19. When compared with the critical care capacity at a local and national level, these results can aid authorities in optimally planning healthcare resources during the current pandemic. Findings can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning.

Predicting the duration of sickness absence spells due to back pain: a population-based study from Sweden.

OBJECTIVES: We aimed to develop and validate a prediction model for the duration of sickness absence (SA) spells due to back pain (International Statistical Classification of Diseases and Related Health Problems 10th Revision: M54), using Swedish nationwide register microdata. METHODS: Information on all new SA spells >14 days from 1 January 2010 to 30 June 2012 and on possible predictors were obtained. The duration of SA was predicted by using piecewise constant hazard models. Nine predictors were selected for the final model based on a priori decision and log-likelihood loss. The final model was estimated in a random sample of 70% of the SA spells and later validated in the remaining 30%. RESULTS: Overall, 64 048 SA spells due to back pain were identified during the 2.5 years; 74% lasted ≤90 days, and 9% >365 days. The predictors included in the final model were age, sex, geographical region, employment status, multimorbidity, SA extent at the start of the spell, initiation of SA spell in primary healthcare and number of SA days and specialised outpatient healthcare visits from the preceding year. The overall c-statistic (0.547, 95% CI 0.542 to 0.552) suggested a low discriminatory capacity at the individual level. The c-statistic was 0.643 (95% CI 0.634 to 0.652) to predict >90 days spells, 0.686 (95% CI 0.676 to 0.697) to predict >180 spells and 0.753 (95% CI 0.740 to 0.766) to predict >365 days spells. CONCLUSIONS: The model discriminates SA spells >365 days from shorter SA spells with good discriminatory accuracy.

An NADPH-Oxidase/Polyamine Oxidase Feedback Loop Controls Oxidative Burst Under Salinity.

The apoplastic polyamine oxidase (PAO) catalyzes the oxidation of the higher polyamines spermidine and spermine, contributing to hydrogen peroxide (H2O2) accumulation. However, it is yet unclear whether apoplastic PAO is part of a network that coordinates the accumulation of reactive oxygen species (ROS) under salinity or if it acts independently. Here, we unravel that NADPH oxidase and apoplastic PAO cooperate to control the accumulation of H2O2 and superoxides (O2·-) in tobacco (Nicotiana tabacum). To examine to what extent apoplastic PAO constitutes part of a ROS-generating network, we examined ROS accumulation in guard cells of plants overexpressing or down-regulating apoplastic PAO (lines S2.2 and A2, respectively) or down-regulating NADPH oxidase (line AS-NtRbohD/F). The H2O2-specific probe benzene sulfonyl-H2O2 showed that, under salinity, H2O2 increased in S2.2 and decreased in A2 compared with the wild type. Surprisingly, the O2·--specific probe benzene sulfonyl-So showed that O2·- levels correlated positively with that of apoplastic PAO (i.e. showed high and low levels in S2.2 and A2, respectively). By using AS-NtRbohD/F lines and a pharmacological approach, we could show that H2O2 and O2·- accumulation at the onset of salinity stress was dependent on NADPH oxidase, indicating that NADPH oxidase is upstream of apoplastic PAO. Our results suggest that NADPH oxidase and the apoplastic PAO form a feed-forward ROS amplification loop, which impinges on oxidative state and culminates in the execution of programmed cell death. We propose that the PAO/NADPH oxidase loop is a central hub in the plethora of responses controlling salt stress tolerance, with potential functions extending beyond stress tolerance.

Membrane Assays to Characterize Interaction of Drugs with ABCB1.

ATP-binding cassette sub-family B member 1 (ABCB1) [P-glycoprotein (P-gp), multidrug resistance protein 1 (MDR1)] can affect the pharmacokinetics, safety, and efficacy of drugs making it important to identify compounds that interact with ABCB1. The ATPase assay and vesicular transport (VT) assay are membrane based assays that can be used to measure the interaction of compounds with ABCB1 at a lower cost and higher throughput compared to cellular-based assays and therefore can be used earlier in the drug development process. To that end, we tested compounds previously identified as ABCB1 substrates and inhibitors for interaction with ABCB1 using the ATPase and VT assays. All compounds tested interacted with ABCB1 in both the ATPase and VT assays. All compounds previously identified as ABCB1 substrates activated ABCB1-mediated ATPase activity in the ATPase assay. All compounds previously identified as ABCB1 inhibitors inhibited the ABCB1-mediated transport in the VT assay. Interestingly, six of the ten compounds previously identified as ABCB1 inhibitors activated the basal ATPase activity in activation assays suggesting that the compounds are substrates of ABCB1 but can inhibit ABCB1 in inhibition assays. Importantly, for ATPase activators the EC50 of activation correlated with the IC50 values from the VT assay showing that interactions of compounds with ABCB1 can be measured with similar levels of potency in either assay. For ATPase nonactivators the IC50 values from the ATPase inhibition and VT inhibition assay showed correlation. These results demonstrate the utility of membrane assays as tools to detect and rank order drug-transporter interactions.

Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.

Importance: Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients. Objective: To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD. Design, Setting, and Participants: This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023. Exposure: Use of specific ADHD medications. Main Outcomes and Measures: The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models. Results: A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92). Conclusions and Relevance: In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.

Nitric oxide contributes to copper tolerance by influencing ROS metabolism in Arabidopsis.

KEY MESSAGE: Nitric oxide improves copper tolerance via modulation of superoxide and hydrogen peroxide levels. This reflects the necessity of a well-coordinated interplay between NO and ROS during stress tolerance. Copper (Cu) excess causes toxicity and one probable consequence of this is the disturbance of cell redox state maintenance, inter alia, by reactive oxygen- (ROS) and nitrogen species (RNS). The objective of this paper was to examine the role of nitric oxide (NO) in Cu stress tolerance and its relationship with ROS in Arabidopsis. In agar-grown seedlings, concentration-dependent Cu accumulation was observed. The 5 µM Cu resulted in reduced cell viability in the NO overproducing nox1 and gsnor1-3 root tips compared to the wild-type (WT). In contrast, 25 and 50 µM Cu caused higher viability in these mutants, while in the NO-lacking nia1nia2 lower viability was detected than in the WT. The exogenous NO donor enhanced cell viability and scavenging endogenous NO decreased it in Cu-exposed WT seedlings. Besides, SNP in nia1nia2 roots led to the improvement of viability. The ascorbic acid-deficient mutants (vtc2-1, vtc2-3) possessing slightly elevated ROS levels proved to be Cu sensitive, while miox4 showing decreased ROS production was more tolerant to Cu than the WT. In nox1 and gsnor1-3, Cu did not induce superoxide formation, and H2O2 accumulation occurred only in the case of NO deficiency. Based on these, under mild stress NO intensifies cell injury, while in the case of severe Cu excess it contributes to better viability. ROS were found to be responsible for aggravation of Cu-induced damage. NO alleviates acute Cu stress via modulation of O2(·-) and H2O2 levels reflecting the necessity of a well-coordinated interplay between NO and ROS during stress tolerance.

Physiological and morphological responses of the root system of Indian mustard (Brassica juncea L. Czern.) and rapeseed (Brassica napus L.) to copper stress.

Copper (Cu) is an essential microelement for growth and development, but in excess it can cause toxicity in plants. In this comparative study, the uptake and accumulation of Cu as well as the morphological and physiological responses of Indian mustard (Brassica juncea L. Czern.) and rapeseed (Brassica napus L.) roots to Cu treatment were investigated. The possible involvement of redox active molecules (reactive oxygen species and nitric oxide) and modification in cell wall structure associated with Cu-induced morphological responses were also studied. In short- and long-term treatments, B. juncea suffered more pronounced growth inhibition as compared with B. napus. In addition to the shortening of primary and lateral roots, the number and the density of the laterals were also decreased by Cu. Exposure to copper induced nitric oxide generation in the root tips and this event proved to be dependent on the duration of the exposure and on the plant species. In short- and long-term treatments, Indian mustard showed more significant activation of superoxide dismutase (SOD), inhibition of ascorbate peroxidase (APX) and oxidation of ascorbate (AsA) than B. napus. Moreover, H2O2-dependent lignification was also observed in the Cu-exposed plants. In longer term, significant AsA accumulation and callose deposition were observed, reflecting serious oxidative stress in B. juncea. Based on the morphological and physiological results, we conclude that rapeseed tolerates Cu excess better than Indian mustard.

Subfunctionalization of Parental Polyamine Oxidase (PAO) Genes in the Allopolyploid Tobacco Nicotiana tabacum (L.).

Polyamines play an important role in developmental and environmental stress responses in plants. Polyamine oxidases (PAOs) are flavin-adenine-dinucleotide-dependent enzymes associated with polyamine catabolism. In this study, 14 genes were identified in the tobacco genome that code for PAO proteins being named based on their sequence homology with Arabidopsis PAOs (AtPAO1-5): NtPAO1A-B; NtPAO2A-C, NtPAO4A-D, and NtPAO5A-E. Sequence analysis confirmed that the PAO gene family of the allopolyploid hybrid Nicotiana tabacum is not an exact combination of the PAO genes of the maternal Nicotiana sylvestris and paternal Nicotiana tomentosiformis ones. The loss of the N. sylvestris homeolog of NtPAO5E and the gain of an extra NtPAO2 copy, likely of Nicotiana othophora origin, was revealed. The latter adds to the few pieces of evidence suggesting that the paternal parent of N. tabacum was an introgressed hybrid of N. tomentosiformis and N. othophora. Gene expression analysis indicated that all 14 PAO genes kept their expression following the formation of the hybrid species. The homeologous gene pairs showed similar or opposite regulation depending on the investigated organ, applied stress, or hormone treatment. The data indicate that the expression pattern of the homeologous genes is diversifying in a process of subfunctionalization.

Predictors of beverage-specific, alcohol consumption trajectories: A Swedish population-based cohort study.

Aim: The aim of the study was to examine whether changes in alcohol consumption over time differ according to beverage types, and to what extent socioeconomic, lifestyle and health-related factors predict beverage-specific trajectories in Sweden. Study design: We included participants from the Stockholm Public Health Cohort who were surveyed repeatedly in 2002, 2010 and 2014. Alcohol consumption trajectories were constructed for 13,152 individuals with valid information on amount and frequency of drinking. Preferred beverage types (i.e., beer, wine or spirits) were defined based on the most consumed beverages. Multinomial logistic regression was used to quantify individual predictors of different trajectories, overall and by beverage type. Results: Overall 56.9% of respondents were women, the mean age was 49.2 years, SD (13.1). Wine was cited as the preferred beverage for 72.4% of participants, and stable moderate drinking was the most common trajectory regardless of beverage type (68.2%, 54.9% and 54.2% in individuals with wine, beer and spirits as preferred beverages, respectively). Associations between drinking trajectories and baseline lifestyle factors did not differ by beverage type. Lower socioeconomic position (SEP) was associated with unstable moderate wine drinking (for unskilled manual SEP: adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.23, 1.93), unstable heavy beer drinking (for skilled manual SEP: aOR 1.99, 95% CI 1.14, 3.52; and unskilled manual SEP: aOR 1.72, 95% CI 1.05, 2.82), and former beer drinking trajectory (for skilled manual SEP: aOR 1.81; 95% CI 1.21, 2.72; and unskilled manual SEP: aOR 1.66; 95% CI 1.17, 2.37). Conclusion: Lower SEP was associated with unstable heavy drinking of beer, former beer drinking, and unstable moderate wine drinking trajectories indicating that targeted alcohol prevention programmes need to focus on these groups.

Absence of Arabidopsis Polyamine Oxidase 5 Influences the Cytokinin-Induced Shoot Meristem Formation from Lateral Root Primordia.

Lateral root primordia (LRPs) of Arabidopsis can be directly converted to shoot meristems (SMs) by the application of exogenous cytokinin. Here, we report that Arabidopsis POLYAMINE OXIDASE 5 (AtPAO5) contributes to this process, since the rate of SM formation from LRPs was significantly lower in the pao5-2 knockout mutant. Furthermore, the presented experiments showed that AtPAO5 influences SM formation via controlling the thermospermine (T-Spm) level. Gene expression analyses supported the view that the pao5-2 mutation as well as exogenous T-Spm downregulate the expression of the class 3 haemoglobin coding genes AtGLB1 and AtGLB2. AtGLB1 and 2 have been reported to augment cytokinin sensitivity, indirectly inhibiting the expression of type-A ARABIDOPSIS RESPONSE REGULATORs (ARRs). In agreement, the same ARR-coding genes were found to be upregulated in the pao5-2 mutant. Although GLB proteins might also control cytokinin-induced nitric oxide (NO) accumulation, we could not find experimental evidence for it. Rather, the negative effect of NO-donor treatment on AtPAO5 gene expression and SM formation was seen. Nevertheless, a hypothetical pathway is set up explaining how AtPAO5 may affect direct shoot meristem formation, controlling cytokinin sensitivity through T-Spm and GLBs.

A prognostic model for predicting the duration of 20,049 sickness absence spells due to shoulder lesions in a population-based cohort in Sweden.

MAIN OBJECTIVE: Sickness absence duration for shoulder lesion patients is difficult to prognosticate, and scientific evidence for the sick-listing practice is lacking. Our objective was to develop a clinically implementable prediction model for the duration of a sickness absence spell due to shoulder lesions. METHODS: All new sickness absence spells due to shoulder lesions (ICD-10-code: M75) issued in the period January 2010-June 2012 that were longer than 14 days were identified through the nationwide sickness absence insurance register. Information on predictors was linked from four other nationwide registers. Piecewise-constant hazards regression models were fitted to predict duration of sickness absence. The model was developed and validated using split sample validation. Variable selection was based on log-likelihood loss ranking when excluding a variable from the model. The model was evaluated using calibration plots and the c-statistic. RESULTS: 20 049 sickness absence spells were identified, of which 34% lasted >90 days. Predictors included in the model were age, sex, geographical region, occupational status, educational level, birth country, specialized healthcare at start of the spell, number of sickness absence days in the last 12 months, and specialized healthcare the last 12 months, before start date of the index sickness absence spell. The model was satisfactorily specified and calibrated. Overall c-statistic was 0.54 (95% CI 0.53-0.55). C-statistic for predicting durations >90, >180, and >365 days was 0.61, 0.66, and 0.74, respectively. SIGNIFICANCE: The model can be used to predict the duration of sickness absence due to shoulder lesions. Covariates had limited predictive power but could discriminate the very long sickness absence spells from the rest.

Working life sequences over the life course among 9269 women and men in Sweden; a prospective cohort study.

OBJECTIVES: To investigate working life courses in women and men and possible associations with socioeconomic, health-, and work-related factors. METHODS: A 15-year prospective cohort study of individuals aged 18-50 in paid work at baseline and answering the Swedish Living Conditions Surveys (2000-2003, N = 9269) and their annual economic activity, using nationwide registers. We used sequence and cluster analyses to identify and group similar working life sequences. Multinomial logistic regression was used to examine associations of sex, socioeconomic, health-, and work-related factors with sequence cluster memberships. RESULTS: We identified 1284 working life sequences, of which 65% represented continuous active (in paid work/studying) states. We then identified five sequence clusters, the largest one with individuals who were continuously active (n = 6034, 65% of the participants; 54% of women and 76% of men) and smaller ones with interruptions of the active state by long-term parental-leave, unemployment, and/or sickness absence/disability pension (SA/DP), or retirement. Women were more likely than men to belong to the "Parental-leave periods" (odds ratio [OR]: 33.2; 95% confidence intervals [CI]: 25.6, 43.1) and the "SA/DP periods" sequence clusters (OR: 1.8; 95% CI: 1.4, 2.1), also after adjustment for covariates. In both sexes, low education and poor health were the strongest predictors of belonging to the sequence cluster "Unemployment & SA/DP periods". Predictors of the "Parental-leave periods" sequence cluster differed between women and men. CONCLUSIONS: In a cohort of individuals in paid work at baseline, the majority of women and men worked most of each year although women were more likely to have some interruptions characterized by long-term parental-leave or SA/DP periods than men, independently of socioeconomic, health-, and work-related factors.

Risk of myocardial infarction after invasive outpatient procedures.

OBJECTIVE: To assess the short-term risk of acute myocardial infarction (AMI) associated with procedures performed at outpatient specialised hospital clinics. METHODS: In this case-crossover, population-based study, we identified first-time AMI cases aged ≥40 years via patient registries and linked them to their surgical intervention in Norway (2008-2016) and Sweden (2001-2014), respectively. The number of individuals with AMI who underwent procedures 0-7 days (hazard period) prior to the AMI diagnosis was compared with cases who were exposed 29-36 days (control period) before the AMI. A total of 6176 patients with AMI who underwent a procedure either during the defined hazard or control period contributed to the analyses. ORs with 95% CIs were computed using conditional logistic regression. RESULTS: The mean age of the total population was 74.7 years and 64.6% were male. The relative risk was higher following procedures performed under general/regional anaesthesia for gastrointestinal endoscopy (ORsummary, 4.23, 95% CI 1.58 to 11.31), vascular (ORsummary, 3.12, 95% CI 1.10 to 8.90), urological/gynaecological (ORsummary, 2.30, 95% CI 1.50 to 3.53) and orthopaedic (ORsummary,1.78, 95% CI 1.30 to 2.44) procedures, and for ENT (ear, nose and throat) and mouth procedures (ORsummary, 1.53, 95% CI 1.19 to 1.99) performed under local anaesthesia. CONCLUSION: This large population-based register study from two countries suggests that outpatient procedures are generally safe with regard to the postoperative risk of AMI. However, some procedures, such as gastrointestinal endoscopy, vascular procedures and urological/gynaecological procedures may increase the risk of AMI by twofold or threefold within the first 8 days after the procedures. Further studies are warranted to assess whether the effect is modified by cardiovascular medication or other clinical factors.

The role of sociodemographic and clinical factors in the initiation and discontinuation of attention deficit hyperactivity disorder medication among young adults in Sweden.

Introduction: Long-term medication use is a recommended treatment for attention-deficit/hyperactivity disorder (ADHD), however, discontinuation is common. Non-medical factors which might influence initiation and discontinuation are understudied. Therefore, we investigated how different sociodemographic factors and comorbidities were associated with the initiation and discontinuation of ADHD medication use among young adults. Methods and results: We conducted a population-based prospective cohort study using individually linked administrative register data, in which we included all individuals residing in Sweden, between the age of 19 and 29 who were first diagnosed with ADHD between January 2006 and December 2016 (n = 59224). ADHD medication initiation was defined as the first prescription of ADHD medication in the period from 3 months before to 6 months after the cohort entry date. Those who initiated ADHD medication were followed up for medication use until discontinuation, death/emigration, or until 2019. Logistic and Cox regression models were used to investigate the associations between sociodemographics, health-related predictors and initiation, as well as discontinuation. Overall, 48.7% of the 41399 individuals initiated ADHD medication, most often methylphenidate (87%). Among the initiators, 15462 (77%) discontinued medication use during the follow-up (median time: 150 days). After mutually adjusting all other predictors, initiation was positively associated with older age, male sex, higher level of education, and negatively associated with living at home with parents, immigrant status, being unemployed during the year before inclusion, being on disability pension, having autism, substance use, schizophrenia-spectrum disorders, other mental disability/developmental disorders, cardiovascular diseases or previous accidents. Discontinuation was positively associated with being born abroad, living in big cities, being unemployed during the year before inclusion, having cancer, and negatively associated with a higher educational level, having depression, anxiety or stress-related disorder, autism spectrum disorder or diabetes. Conclusion: Besides medical factors, sociodemographics, such as educational attainment and immigrant status might also play a role in the initiation and discontinuation of ADHD medication use among young adults newly diagnosed with ADHD.