A complex case of young child with ADHD, developmental delay who developed seronegative autoimmune encephalitis exacerbated by stimulants.

Autoimmune encephalitis (AE) is a group of disorders characterized by a wide clinical spectrum ranging from the typical limbic encephalitis to more complex neuropsychiatric symptoms including abnormal movements, psychosis, deficits in memory and cognition, dysautonomia, seizures, or coma. Psychiatric symptoms can occur early in the disease progress or manifest during its course. These symptoms are challenging and often slow down the diagnosis of AE. This is a crucial aspect considering that early diagnosis and management of AE are critical for a good outcome. However, there is a lack in studies outlining the exact symptomatology and specific appropriate care that would allow clinicians to achieve an early diagnosis and management. Additionally, AE in children mostly presents with neuropsychiatric symptoms and diagnosis is especially challenging in kids because of their limited capacity in describing their symptoms, the normal childhood behavioral changes and the possibility of a comorbid psychiatric diagnosis. We present a complex case of seronegative AE with comorbid ADHD (Attention Deficit Hyperactivity Disorder) and anxiety in a young six-year-old girl.

Dynamic ventral disc contraction is necessary for Giardia attachment and host pathology.

Giardia lamblia is a common parasitic protist that infects the small intestine and causes giardiasis, resulting in diarrhea, vomiting, weight loss, and malabsorption. Giardiasis leads to cellular damage, including loss of microvilli, disruption of tight junctions, impaired barrier function, enzyme inhibition, malabsorption, and apoptosis. In the host, motile Giardia trophozoites attach to the duodenal microvilli using a unique microtubule organelle called the ventral disc. Despite early observations of disc-shaped depressions in microvilli after parasite detachment, little is known about disc-mediated attachment mechanisms and there little direct evidence showing that parasite attachment causes cellular damage. However, advancements in in vitro organoid models of infection and genetic tools have opened new possibilities for studying molecular mechanisms of attachment and the impact of attachment on the host. Through high-resolution live imaging and a novel disc mutant, we provide direct evidence for disc contraction during attachment, resolving the long-standing controversy of its existence. Specifically, we identify three types of disc movements that characterize contraction, which in combination result in a decrease in disc diameter and volume. Additionally, we investigate the consequences of attachment and disc contractility using an attachment mutant that has abnormal disc architecture. In a human organoid model, we demonstrate that this mutant has a limited ability to break down the epithelial barrier as compared to wild type. Based on this direct evidence, we propose a model of attachment that incorporates disc contraction to generates the forces required for the observed "grasping" of trophozoites on the host epithelium. Overall, this work highlights the importance of disc contractility in establishing and maintaining parasite attachment, leading to intestinal barrier breakdown.

Development and external validation of a prediction model for patient-relevant outcomes in patients with chronic widespread pain and fibromyalgia.

BACKGROUND: The objective of this study was to develop prediction models and explore the external validity of the models in a large sample of patients with chronic widespread pain (CWP) and fibromyalgia (FM). METHODS: Patients with CWP and FM referred to rehabilitation services in Norway (n = 986) self-reported data on potential predictors prior to entering rehabilitation, and self-reported outcomes at one-year follow-up. Logistic regression models of improvement, worsening and work status, and a linear regression model of health-related quality of life (HRQoL), were developed using lasso regression. Externally validated estimates of model performance were obtained from the validation set. RESULTS: The number of participants in the development and the validation sets was 771 and 215 respectively; only participants with outcome data (n = 519-532 and 185, respectively) were included in the analyses. On average, HRQoL and work status changed little over one year. The prediction models included 10-11 predictors. Discrimination (AUC statistic) for prediction of outcome at follow-up was 0.71 for improvement, 0.67 for worsening, and 0.87 for working. The median absolute error of predictions of HRQoL was 0.36 (0.22-0.51). Reasonably good predictions of working at follow-up and HRQoL could be obtained using only the baseline scores as predictors. CONCLUSIONS: Moderately complex prediction models (10-11 predictors) generated poor to excellent predictions of patient-relevant outcomes. Simple prediction models of working and HRQoL at follow-up may be nearly as accurate and more practical. SIGNIFICANCE: Prediction modelling of outcome in rehabilitation has been sparsely explored. Such models may guide clinical decision-making. This study developed and externally validated prediction models for outcomes of people with chronic widespread pain and fibromyalgia in a rehabilitation setting. Multivariable prediction models generated poor to excellent predictions of patient-relevant outcomes, but the complexity of these models may reduce their clinical utility. Simple univariable prediction models were nearly as accurate and may have more potential for use in clinical practice.

MR Imaging Features of Middle Cranial Fossa Encephaloceles and Their Associations with Epilepsy.

BACKGROUND AND PURPOSE: Middle cranial fossa encephaloceles are an increasingly recognized cause of epilepsy; however, they are also often encountered on neuroimaging in patients with no history of seizure. We characterized the MR imaging features of middle cranial fossa encephaloceles in seizure and nonseizure groups with the hope of uncovering features predictive of epileptogenicity. MATERIALS AND METHODS: Seventy-seven patients with middle cranial fossa encephaloceles were prospectively identified during routine clinical practice of neuroradiology at a tertiary care hospital during an 18-month period. Thirty-five of 77 (45%) had a history of seizure, 20/77 (26%) had temporal lobe epilepsy, and 42/77 (55%) had no history of seizures. Middle cranial fossa encephalocele features on MR imaging were characterized, including depth, area, number, location, presence of adjacent encephalomalacia, and degree of associated parenchymal morphologic distortion. MR imaging features were compared between the seizure and nonseizure groups. RESULTS: No significant difference in MR imaging features of middle cranial fossa encephaloceles was seen when comparing the seizure and nonseizure groups. Comparison of just those patients with temporal lobe epilepsy (n = 20) with those with no history of seizure (n = 42) also found no significant difference in MR imaging features. CONCLUSIONS: Anatomic MR imaging features of middle cranial fossa encephaloceles such as size, number, adjacent encephalomalacia, and the degree of adjacent parenchymal morphologic distortion may not be useful in predicting likelihood of epileptogenicity.

Review: Comparative methane production in mammalian herbivores.

Methane (CH4) production is a ubiquitous, apparently unavoidable side effect of fermentative fibre digestion by symbiotic microbiota in mammalian herbivores. Here, a data compilation is presented of in vivo CH4 measurements in individuals of 37 mammalian herbivore species fed forage-only diets, from the literature and from hitherto unpublished measurements. In contrast to previous claims, absolute CH4 emissions scaled linearly to DM intake, and CH4 yields (per DM or gross energy intake) did not vary significantly with body mass. CH4 physiology hence cannot be construed to represent an intrinsic ruminant or herbivore body size limitation. The dataset does not support traditional dichotomies of CH4 emission intensity between ruminants and nonruminants, or between foregut and hindgut fermenters. Several rodent hindgut fermenters and nonruminant foregut fermenters emit CH4 of a magnitude as high as ruminants of similar size, intake level, digesta retention or gut capacity. By contrast, equids, macropods (kangaroos) and rabbits produce few CH4 and have low CH4 : CO2 ratios for their size, intake level, digesta retention or gut capacity, ruling out these factors as explanation for interspecific variation. These findings lead to the conclusion that still unidentified host-specific factors other than digesta retention characteristics, or the presence of rumination or a foregut, influence CH4 production. Measurements of CH4 yield per digested fibre indicate that the amount of CH4 produced during fibre digestion varies not only across but also within species, possibly pointing towards variation in microbiota functionality. Recent findings on the genetic control of microbiome composition, including methanogens, raise the question about the benefits methanogens provide for many (but apparently not to the same extent for all) species, which possibly prevented the evolution of the hosting of low-methanogenic microbiota across mammals.

Extremely low levels of chloroplast genome sequence variability in Astelia pumila (Asteliaceae, Asparagales).

Astelia pumila (G.Forst.) Gaudich. (Asteliaceae, Asparagales) is a major element of West Patagonian cushion peat bog vegetation. With the aim to identify appropriate chloroplast markers for the use in a phylogeographic study, the complete chloroplast genomes of five A. pumila accessions from almost the entire geographical range of the species were assembled and screened for variable positions. The chloroplast genome sequence was obtained via a mapping approach, using Eustrephus latifolius (Asparagaceae) as a reference. The chloroplast genome of A. pumila varies in length from 158,215 bp to 158,221 bp, containing a large single copy region of 85,981-85,983 bp, a small single copy region of 18,182-18,186 bp and two inverted repeats of 27,026 bp. Genome annotation predicted a total of 113 genes, including 30 tRNA and four rRNA genes. Sequence comparisons revealed a very low degree of intraspecific genetic variability, as only 37 variable sites (18 indels, 18 single nucleotide polymorphisms, one 3-bp mutation)-most of them autapomorphies-were found among the five assembled chloroplast genomes. A Maximum Likelihood analysis, based on whole chloroplast genome sequences of several Asparagales accessions representing six of the currently recognized 14 families (sensu APG IV), confirmed the phylogenetic position of A. pumila. The chloroplast genome of A. pumila is the first to be reported for a member of the astelioid clade (14 genera with c. 215 species), a basally branching group within Asparagales.

RBC alloantibody prevalence and specificity in a Western Norwegian tertiary hospital.

BACKGROUND AND OBJECTIVE: Although several studies focus on red blood cell (RBC) alloantibody distribution in selected patient populations, few address the specificity and frequency in all relevant groups. This study reports alloantibody frequency, distribution and the relationship to age and gender in blood donors, pregnant women and potential recipients of blood products. METHODS: This historical cohort study included 55 462 consecutive antibody screening tests from a tertiary Western Norwegian Hospital. Descriptive statistics were performed, and the results were compared with the literature. RESULTS: The detection and immunisation frequency for the whole cohort were 0·39 and 0·51%, respectively, whereas the RBC alloantibody prevalence was 0·73%. The most frequent RBC alloantibodies were anti-E (20·1%), anti-M (18·7%), anti-K (9·8%), anti-D (8·9%) and anti-Fy(a) (7·0%). In pregnant women, the most frequent RBC alloantibodies were anti-M, anti-D and anti-Le(a) (20·8, 18·9 and 18·9%, respectively), whereas there was no anti-K detected. Anti-E and anti-M were the dominating RBC alloantibodies in the pre-transfusion testing of in-hospital patients (24·1 and 17·1%, respectively). Eighteen (9·2%) persons in the total cohort had two RBC alloantibodies, six persons had three alloantibodies, and two persons had four alloantibodies. Rh and K typing to prevent future immunisations was only performed in 21·0% of the individuals who presented with a new alloantibody; despite that, 50·5% of the detected alloantibodies had such specificities. CONCLUSIONS: The immunisation frequency and the level of anti-K are low compared to national and international studies. Rh and K phenotype-matched blood transfusions might be a feasible future strategy to further decrease RBC alloantibodies.

Robust and stable transcriptional repression in Giardia using CRISPRi.

Giardia lamblia is a binucleate protistan parasite causing significant diarrheal disease worldwide. An inability to target Cas9 to both nuclei, combined with the lack of nonhomologous end joining and markers for positive selection, has stalled the adaptation of CRISPR/Cas9-mediated genetic tools for this widespread parasite. CRISPR interference (CRISPRi) is a modification of the CRISPR/Cas9 system that directs catalytically inactive Cas9 (dCas9) to target loci for stable transcriptional repression. Using a Giardia nuclear localization signal to target dCas9 to both nuclei, we developed efficient and stable CRISPRi-mediated transcriptional repression of exogenous and endogenous genes in Giardia. Specifically, CRISPRi knockdown of kinesin-2a and kinesin-13 causes severe flagellar length defects that mirror defects with morpholino knockdown. Knockdown of the ventral disk MBP protein also causes severe structural defects that are highly prevalent and persist in the population more than 5 d longer than defects associated with transient morpholino-based knockdown. By expressing two guide RNAs in tandem to simultaneously knock down kinesin-13 and MBP, we created a stable dual knockdown strain with both flagellar length and disk defects. The efficiency and simplicity of CRISPRi in polyploid Giardia allows rapid evaluation of knockdown phenotypes and highlights the utility of CRISPRi for emerging model systems.

The relationship between obstructive sleep apnea and insomnia: a population-based cross-sectional polysomnographic study.

BACKGROUND: The relationship between insomnia and objectively measured obstructive sleep apnea (OSA) severity has not previously been investigated in both genders in the general population. The main aim of this population-based polysomnography (PSG) study was to evaluate the cross-sectional association between severity of OSA and DSM-V insomnia and insomnia severity. METHODS: A random sample of 1200 participants in the third Nord-Trøndelag Health Study (HUNT3) was invited and 213 (18%) aged between 21 and 82 years underwent an ambulatory PSG, a semi-structured interview, and a sleep-specific questionnaire. A proxy DSM-V insomnia diagnosis as well as an Insomnia Symptom Score (ISS, range 0-12) were calculated from three insomnia questions and one daytime sleepiness symptom question. Participants were then divided into three groups according to their apnea-hypopnea index (AHI): AHI < 5 (without OSA), AHI 5-14.9 (mild OSA), and AHI ≥ 15 (moderate-to-severe OSA). Associations between prevalence of insomnia and OSA groups were assessed by logistic regression models adjusted for age and gender. Associations between ISS and OSA were assessed in a general linear model with contrasts. RESULTS: A total of 25.2% (29.1% women, 12.5% men) had insomnia. Insomnia prevalence did not differ between subjects with and without OSA, but ISS differed significantly between OSA categories (ANCOVA df 2, F = 6.73, p = 0.001). ISS was lower in the moderate-to-severe OSA-group compared to those without OSA (mean difference -2.68; 95% [CI -4.33, -1.04]; p = 0.002). In subjects with moderate-to-severe OSA, ISS correlated negatively with age (Pearson r = -0.66, p = 0.015). CONCLUSION: In this population-based PSG study, no overall statistical association between OSA and insomnia prevalence was found. However, participants with moderate-to-severe OSA reported less insomnia symptoms than subjects without OSA, in particular in older individuals.

Measurement properties for the revised patient-reported OsteoArthritis Quality Indicator questionnaire.

OBJECTIVES: To assess validity, reliability, responsiveness and interpretability of the revised OsteoArthritis Quality Indicator (OA-QI) questionnaire version 2 (v2) assessing patient-reported quality of osteoarthritis care. METHODS: The OA-QI v2 (16 items, score range 0-100 (100 = best score)) was included in a longitudinal cohort study. Attendees of a 4.5 h osteoarthritis patient education programme at Diakonhjemmet Hospital, Norway, completed the OA-QI at four time points: 2 weeks before, immediately before, immediately after, and 3 months after the programme. Test-retest reliability and measurement error over a 2-week time period were assessed in those that had not seen health professionals in the interim. Construct validity and responsiveness were assessed with predefined hypotheses. Floor and ceiling effects, smallest detectable change (SDC95%) and minimal important change (MIC) were assessed to evaluate interpretability. RESULTS: The intraclass correlation coefficient for all 16 items was 0.89. For single items the test-retest kappa estimates ranged 0.38-0.85 and percent agreement 69-92%. Construct validity was acceptable with all six predefined hypotheses confirmed. Responsiveness was acceptable with 33 of 48 and three of four predefined hypotheses confirmed for single items and all items, respectively. There were no floor or ceiling effects. The SDC95% was 29.1 and 3.0 at the individual and group levels, respectively. MIC was 20.4. CONCLUSIONS: The OA-QI v2 had higher reliability estimates compared to v1, showed acceptable validity, and is the recommended version for future use. The results of responsiveness testing further support the use of the OA-QI v2 as an outcome measure in studies aiming to improve osteoarthritis care.

The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT study.

BACKGROUND AND PURPOSE: Headache has been associated with various lifestyle and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal. METHOD: A total of 58 316 participants from the Nord-Trøndelag Health (HUNT) study with information on headache status were genotyped for the rs1051730 C>T single-nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization analysis. The association between rs1051730 T alleles and headache was estimated by odds ratios with 95% confidence intervals. Additionally, the association between the SNP and migraine or non-migrainous headache versus no headache was investigated. All analyses were adjusted for age and sex. RESULTS: There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (odds ratio 0.99, 95% confidence interval 0.95-1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non-migrainous headache versus no headache. CONCLUSION: The findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger Mendelian randomization studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes.

Insomnia and risk of chronic musculoskeletal complaints: longitudinal data from the HUNT study, Norway.

BACKGROUND: The aim of this study was to investigate the prospective association between insomnia and risk of chronic musculoskeletal complaints (CMSC) and chronic widespread musculoskeletal complaints (CWMSC). A second aim was to evaluate the association between insomnia and number of body regions with CMSC at follow-up. METHODS: We used data from the second (HUNT2, 1995-1997) and third (HUNT3, 2006-2008) wave of the Nord-Trøndelag Health Study (the HUNT Study). The population-at-risk included 13,429 people aged 20-70 years who reported no CMSC at baseline in HUNT2 and who answered the questionnaires on insomnia in HUNT2 and CMSC in HUNT3. Insomnia was defined according to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) with minor modification, whereas CMSC was assessed for nine different body regions. CWMSC was defined according to the 1990 criteria by the American College of Rheumatology. We used Poisson regression to estimate adjusted risk ratios (RRs) for CMSC and CWMSC at 11 years follow-up. Precision of the estimates was assessed by a 95% confidence interval (CIs). RESULTS: Insomnia at baseline was associated with increased risk of any CMSC (RR 1.16, 95% CI 1.03-1.32) and CWMSC (RR 1.58, 95% CI 1.26-1.98) at follow-up. RR for CMSC for specific body regions ranged from 1.34 (95% CI 1.05-1.73) for the knees and 1.34 (1.10-1.63) for the neck to 1.60 (95% CI 1.19-2.14) for the ankles/ft. Further, insomnia was associated with increased risk of CMSC in 3-4 regions (RR 1.36, 95% CI 1.05-1.77), and 5 or more regions (RR 1.93, 95% CI 1.40-2.66), but not 1-2 regions (RR 0.99, 95% CI 0.80-1.24). CONCLUSIONS: Insomnia is associated with increased risk of CMSC, CWMSC, and CMSC located in 3 or more body regions.

Little differences in digestive efficiency for protein and fat in mammals of different trophic guilds and digestive strategies: data constraints or fundamental functional similarity?

Carnivores do not vary markedly in their digestive efficiency for protein and fat, but whether they resemble other trophic guilds (omnivores and herbivores) in this respect has not been evaluated. We collated data on apparent crude protein (CP) and crude fat (ether extracts, EE) digestibility in 157 mammal species, applying the Lucas principle of regressing digestible nutrient content against nutrient content, where the slope of the regression equation represents the true digestibility and the intercept the metabolic losses per unit dry matter intake. The data collection is marked by the evident uneven distribution of dietary nutrient contents across trophic guilds and differences in the nutrient range by which different species have been evaluated, making statistical interpretation difficult. Results indicate a lower true digestibility of CP in herbivores compared to carnivores, most likely due to a lower digestibility of fibre-bound protein in herbivore diets. Metabolic CP losses did not appear to differ between trophic guilds, but herbivores had higher metabolic EE losses, compatible with the hypothesis that a higher proportion of metabolic CP losses were bound in microbes that also contain lipids in herbivores. Among herbivores, no clear pattern was evident that would indicate a difference in metabolic losses associated with microbes between digestive strategies (coprophagy, foregut/hindgut fermentation). Foregut fermenters had a lower true EE digestibility, possibly linked to the hydrogenation of lipids in their forestomach prior to digestion. The results do not demonstrate clear differences in digestive efficiency and metabolic losses for protein and fat between mammalian trophic guilds and digestive strategies, leading to the hypothesis that the process of CP and EE digestion is not physiologically challenging and hence does not lead to a noticeable differentiation between species or species groups.

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.

Rasch analysis of the Norwegian version of the Arthritis Self-Efficacy Scale (ASES).

OBJECTIVES: To apply the Rasch model to the Norwegian version of the Arthritis Self-Efficacy Scale (ASES). METHOD: The ASES was included in a self-administered questionnaire sent to 224 patients attending one of three rehabilitation centres for rheumatic diseases in Norway in 2009. The fit of the ASES to the Rasch model was assessed together with hypothesized associations with the Modified Health Assessment Questionnaire (MHAQ), the 36-item Short Form Health Survey (SF-36), the numerical rating scale (NRS) for pain, and NRS fatigue. RESULTS: A total of 145 (64.7%) patients responded to the questionnaire. The two scales of other symptoms and pain showed good fit to the Rasch model with no evidence for differential item functioning (DIF) according to eight sociodemographic and disease-related variables. The Person Separation Index (PSI), which is equivalent to Cronbach's alpha, ranged from 0.74 to 0.78. Correlations with scores for other instruments were as hypothesized: ASES pain had the highest correlations with SF-36 pain and NRS pain and ASES other symptoms had the highest correlations with other aspects of the SF-36 and NRS fatigue. CONCLUSIONS: The ASES had good fit to the Rasch model and correlations with other instrument scores that followed hypotheses, lending further support to the application of the instrument in patients with rheumatic diseases.

Non-invasive cortical modulation of experimental pain in migraine.

OBJECTIVE: To test the hypothesis that secondary somatosensory cortex (S2) is involved in the migraine pathogenesis, by exploring the effect of navigated repetitive transcranial magnetic stimulation (rTMS) to S2 on thermal perception and pain. METHODS: In this blinded sham-controlled case-control study of 26 interictal migraineurs and 31 controls, we measured thermal detection and pain thresholds on the hand and forehead, and pain ratings to heat stimulation on the forearm and temple, after real and sham 10Hz rTMS. RESULTS: rTMS increased cold and heat pain thresholds in controls as compared to interictal migraineurs (p<0.026). rTMS decreased forehead and arm pain ratings (p<0.005) and increased hand cool detection thresholds (p<0.005) in both interictal migraineurs and controls. CONCLUSIONS: The effects of rTMS to S2 on thermal pain measures differed significantly between migraine and control subjects, although the effects were generally low in magnitude and not present in pain ratings. However, the lack of cold and heat pain threshold increase in migraineurs may reflect a hypofunction of inhibitory pain modulation mechanisms. SIGNIFICANCE: The expected rTMS-induced cold and heat hypoalgesia was not found among migraineurs, possibly a reflection of reduced intracortical inhibition.

Retention of solute and particle markers in the digestive tract of chinchillas (Chinchilla laniger).

The chinchilla (Chinchilla laniger) is a herbivorous hystricomorph South American rodent for which no mean digesta retention times have been reported so far. Six animals (mean body mass ± standard deviation: 513 ± 99 g) on a diet of grass hay and lucerne-based pellets were given a pulse dose of a solute (cobalt-EDTA) and a particle (chromium-mordanted fibre, <2 mm) marker with subsequent frequent faecal collection. Dry matter intake was 45.2 ± 8.0 g/kg(0.75) /day. Mean retention times were 22.2 ± 5.3 h for solutes and 25.4 ± 5.2 h for particles, with the difference being not significant within individuals. This indicates the presence of a 'mucus-trap' colonic separation mechanism, which is in accord with morphological descriptions of the typical colonic furrow in chinchillas. Corresponding to a strategy of colonic digesta separation and caecotroph formation, secondary marker excretion peaks indicated coprophagic events that were spaced approximately 12 h apart. Given that these retention times appear longer than measures reported for rabbits (Oryctolagus cuniculus) or guinea pigs (Cavia procellus), it would be interesting to compare the digestive efficiency of chinchillas on high levels of dietary fibre to other species.

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.

Early menarche and chronic widespread musculoskeletal complaints--Results from the HUNT study.

BACKGROUND: There is a predominance of chronic widespread musculoskeletal complaints (WMSC) among women. Previous studies suggest an association between hormonal factors and pain. However, it is not known whether earlier age at menarche is associated with higher prevalence of chronic WMSC. The aim of this study was to investigate the association between age at menarche and chronic WMSC. METHODS: Data from a cross-sectional study of inhabitants ≥20 years in Nord-Trøndelag County (Helseundersøkelsen i Nord-Trøndelag -HUNT), conducted in 1995-1997 (HUNT 2) were used. The study population comprised 32,673 women with valid information of age at menarche (exposure) and chronic WMSC (outcome data). RESULTS: In total, 8986 (27.5%) women reported WMSC. The overall prevalence of WMSC was 29.7% among those with menarche ≤12 years and 26.7% among those with menarche >12 years. The prevalence of chronic WMSC was consistently higher for those with early age at menarche in all age groups. The crude odds ratio for chronic WMSC, when comparing women with age at menarche ≤12 years to women with age at menarche >12 years, was 1.16 (95% CI: 1.10-1.22). The corresponding odds ratio was 1.26 (95% CI: 1.19-1.34) when adjusted for age, education, body mass index (BMI), smoking, alcohol consumption, depression, systolic blood pressure (SBP) and parity. CONCLUSION: In this cross-sectional study, there was an association between early age at menarche and chronic WMSC later in life, but the difference in absolute risk was low (3%).