Population-based register study of children born in Sweden from 1997 to 2014 showed an increase in rickets during infancy

Abstract Aim This population-based study assessed the incidence of rickets in infants up to age of one born in Sweden from 1997-2014. We also examined maternal and perinatal factors and co-morbidity. Methods We used Swedish National Board of Health and Welfare registers and data from Statistics Sweden. The outcome measure was an International Classification of Diseases, Tenth Revision, code for rickets. Results There were 273 cases of rickets, with an incidence of 14.7 per 100,000 and a 10-fold incidence increase between 1997-2014. The majority (78.4%) were born preterm, half were small-for-gestational age (SGA) (birthweightPeer reviewe

The geometry of nutrient space–based life-history trade-offs: Sex-specific effects of macronutrient intake on the trade-off between encapsulation ability and reproductive effort in decorated crickets

This is the final version of the article. Available from University of Chicago Press via the DOI in this record.Life-history theory assumes that traits compete for limited resources, resulting in trade-offs. The most commonly manipulated resource in empirical studies is the quantity or quality of diet. Recent studies using the geometric framework for nutrition, however, suggest that trade-offs are often regulated by the intake of specific nutrients, but a formal approach to identify and quantify the strength of such trade-offs is lacking. We posit that trade-offs occur whenever life-history traits are maximized in different regions of nutrient space, as evidenced by nonoverlapping 95% confidence regions of the global maximum for each trait and large angles (θ) between linear nutritional vectors and Euclidean distances (d) between global maxima. We then examined the effects of protein and carbohydrate intake on the trade-off between reproduction and aspects of immune function in male and female Gryllodes sigillatus. Female encapsulation ability and egg production increased with the intake of both nutrients, whereas male encapsulation ability increased with protein intake but calling effort increased with carbohydrate intake. The trade-offs between traits was therefore larger in males than in females, as demonstrated by significant negative correlations between the traits in males, nonoverlapping 95% confidence regions, and larger estimates of θ and d. Under dietary choice, the sexes had similar regulated intakes, but neither optimally regulated nutrient intake for maximal trait expression. We highlight the fact that greater consideration of specific nutrient intake is needed when examining nutrient space–based trade-offs.S.K.S. was funded by the National Science Foundation (NSF; IOS-1118160 and IOS-1654028). C.M.H. was funded by a Leverhulme Early Career Fellowship. J.H. was funded by a Royal Society Fellowship (UF120087) and Equipment Grant (RG090854) and by the Natural Environment Research Council (NERC; NE/G00949X/1). J.R. was funded by a NERC studentship (awarded to J.H.). E.D.C. was partially funded by NSF grant CMII 1634878

Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO 3- and NO2- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 μM N2O (range 1.4-157.9 μM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention. © 2014 Kolpen et al

Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice

MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing and maintaining neuronal network function. Previous studies in adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) and demonstrated that silencing microRNA-134 using antisense oligonucleotides, termed antagomirs, has potent and long-lasting seizure-suppressive effects. Here we investigated whether targeting microRNA-134 can reduce or delay acute seizures in the immature brain. Status epilepticus was induced in 21 day-old (P21) male mice by systemic injection of 5 mg/kg kainic acid. This triggered prolonged electrographic seizures and select bilateral neuronal death within the CA3 subfield of the hippocampus. Expression of microRNA-134 and functional loading to Argonaute-2 was not significantly changed in the hippocampus after seizures in the model. Nevertheless, when levels of microRNA-134 were reduced by prior intracerebroventricular injection of an antagomir, kainic acid-induced seizures were delayed and less severe and mice displayed reduced neuronal death in the hippocampus. These studies demonstrate targeting microRNA-134 may have therapeutic applications for the treatment of seizures in children

Patients with fibromyalgia display less functional connectivity in the brain’s pain inhibitory network

Background: There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC). We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus. Results: FM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0–100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients. Conclusion: Patients with FM displayed less connectivity within the brain’s pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation

Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells

Alpha-1-adrenergic receptors (α1-ARs) regulate coronary arterial blood flow by binding catecholamines, norepinephrine (NE), and epinephrine (EPI), causing vasoconstriction when the endothelium is disrupted. Among the three α1-AR subtypes (α1A, α1B, and α1D), the α1D subtype predominates in human epicardial coronary arteries and is functional in human coronary smooth muscle cells (SMCs). However, the presence or function of α1-ARs on human coronary endothelial cells (ECs) is unknown. Here we tested the hypothesis that human epicardial coronary ECs express functional α1-ARs. Cultured human epicardial coronary artery ECs were studied using quantitative real-time reverse transcription polymerase chain reaction, radioligand binding, immunoblot, and 3H-thymidine incorporation. The α1B-subtype messenger ribonucleic acid (mRNA) was predominant in cultured human epicardial coronary ECs (90–95% of total α1-AR mRNA), and total α1-AR binding density in ECs was twice that in coronary SMCs. Functionally, NE and EPI through the α1B subtype activated extracellular signal-regulated kinase (ERK) in ECs, stimulated phosphorylation of EC endothelial nitric oxide synthase (eNOS), and increased deoxyribonucleic acid (DNA) synthesis. These results are the first to demonstrate α1-ARs on human coronary ECs and indicate that the α1B subtype is predominant. Our findings provide another potential mechanism for adverse cardiac effects of drug antagonists that nonselectively inhibit all three α1-AR subtypes

Hospital contacts for injuries and musculoskeletal diseases among seamen and fishermen: A population-based cohort study

<p>Abstract</p> <p>Background</p> <p>We studied musculoskeletal diseases (MSD) and injuries among fishermen and seamen with focus on low back disorders, carpal tunnel syndrome (CTS), rotator cuff syndrome and arthrosis.</p> <p>Methods</p> <p>Cohorts of all male Danish seamen (officers and non-officers) and fishermen employed 1994 and 1999 with at least six months employment history were linked to the Occupational Hospitalisation Register. We calculated standardised incidence ratios (SIR) for the two time periods, using rates for the entire Danish workforce as a reference.</p> <p>Results</p> <p>Among fishermen, we found high SIRs for knee arthrosis, thoraco-lumbar disc disorders, injuries and statistically significant SIRs above 200 were seen for both rotator cuff syndrome and CTS. The SIR was augmented for injuries and reduced for hip arthrosis between the two time periods. The SIRs for injuries and CTS were high for non-officers. A sub-analysis revealed that the highest risk for CTS was found among male non-officers working as deck crew, SIR 233 (95% CI: 166–317) based on 40 cases. Among officers, the SIRs for injuries and MSDs were low. The number of employed Danish fishermen declined with 25% 1994–1999 to 3470. Short-term employments were common. None of the SIRs increased with increasing length of employment.</p> <p>Conclusion</p> <p>Both fishermen and non-officers have high SIRs for injuries and fishermen also for MSD. Only the SIR for injuries among fishermen was augmented between 1994 and 1999. Our findings suggest an association between the incidence of rotator cuff syndrome and CTS and work within fishery. Long-term cumulative effects of employment were not shown for any of the disease outcomes. Other conditions may play a role.</p

“My Lung Disease Won’t Go Away, it’s There to Stay”: Profiles of Adaptation to Functional Limitations in Workers with Asthma and COPD

Purpose Earlier research has shown that adaptation (i.e., the way in which employees cope with limitations resulting from their disease) is associated with sick leave. Our aim was to investigate signs of adequate or inadequate adaptation in employees with asthma and COPD. Methods A Q-methodological study was carried out among 34 workers with asthma or COPD. Results Four adaptation profiles were distinguished: the eager, the adjusted, the cautious, and the worried workers. The adaptation profiles provide insight into the different ways in which workers with asthma and COPD cope with their illness at work. Conclusions The adaptation profiles serve as a starting point for the design of appropriate (occupational) care. The eager workers experience little difficulties at work; the cautious workers may need assistance in learning how to accept their disease; the worried workers need reassurance, and may need reactivation; the adjusted workers deserve extra attention, and, when necessary, advice on how to live with their asthma or COPD

The Genotype Specific Competitive Ability Does Not Correlate with Infection in Natural Daphnia magna Populations

Different evolutionary hypotheses predict a correlation between the fitness of a genotype in the absence of infection and the likelihood to become infected. The cost of resistance hypothesis predicts that resistant genotypes pay a cost of being resistant and are less fit in the absence of parasites. The inbreeding-infection hypothesis predicts that the susceptible individuals are less fit due to inbreeding depression.Here we tested if a host's natural infection status was associated with its fitness. First, we experimentally confirmed that cured but formerly infected Daphnia magna are genetically more susceptible to reinfections with Octosporea bayeri than naturally uninfected D. magna. We then collected from each of 22 populations both uninfected and infected D. magna genotypes. All were treated against parasites and kept in their asexual phase. We estimated their relative fitness in an experiment against a tester genotype and in another experiment in direct competition. Consistently, we found no difference in competitive abilities between uninfected and cured but formerly infected genotypes. This was the case both in the presence as well as in the absence of sympatric parasites during the competition trials.Our data do not support the inbreeding-infection hypothesis. They also do not support a cost of resistance, however ignoring other parasite strains or parasite species. We suggest as a possible explanation for our results that resistance genes might segregate largely independently of other fitness associated genes in this system

Knowledge Integration and Diffusion: Measures and Mapping of Diversity and Coherence

I present a framework based on the concepts of diversity and coherence for the analysis of knowledge integration and diffusion. Visualisations that help understand insights gained are also introduced. The key novelty offered by this framework compared to previous approaches is the inclusion of cognitive distance (or proximity) between the categories that characterise the body of knowledge under study. I briefly discuss the different methods to map the cognitive dimension