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- Tranebjærg, Lisbeth, et al.
(författare)
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The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management
- 2018
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 137:2, s. 111-127
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Tidskriftsartikel (refereegranskat)abstract
- Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.
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- Favati, Anna, et al.
(författare)
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The ontogeny of personality traits in the redjunglefowl, Gallus gallus
- 2016
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Ingår i: Behavioral Ecology. - : Oxford University Press. - 1045-2249 .- 1465-7279. ; 27:2, s. 484-493
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Tidskriftsartikel (refereegranskat)abstract
- Consistent behavioral differences among individuals, that is, personality, are described in numerous species. Nevertheless, thedevelopment of behavioral consistency over ontogeny remains unclear, including whether the personality of individuals is consistentthroughout life, and if adult personality can be predicted already at young age. We investigated the ontogeny of personality in thered junglefowl (Gallus gallus) by scoring personality of hatchlings at 5 time points through adulthood, including before and after themajor developmental stages of becoming independent and sexual mature. We use the conceptual framework laid out by Stamps andGroothuis (2010a) to holistically investigate the observed changes in behavioral response over ontogeny. We demonstrate that meanvalues of behavioral responses changed across ontogeny and stabilized after independence. Rank-order consistencies of behavioralresponses were overall low across independence and sexual maturation. Only in 1 case could low rank-order consistencies potentiallybe explained by different phenotypes displaying different amounts of change in behavior; more explorative individuals decreased inexploration after independence, while less explorative individuals remained so. Correlations among behavior varied across ontogenyand weakened after sexual maturation. Our results demonstrate that both absolute values and consistency of behavioral traits maychange across ontogeny and that individual developmental trajectories and adult personality only to some extent can be predictedearly in life. These results have implications for future studies on personality, highlighting that the life stage at which individuals arescored affects the observed consistency of behavioral responses.
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- Broesby-Olsen, Sigurd, et al.
(författare)
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Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
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- Carlsen, Hanne Krage, et al.
(författare)
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Indicators of residential traffic exposure: Modelled NOX, traffic proximity, and self-reported exposure in RHINE III
- 2017
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 167, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have investigated associations between self-reported and modelled exposure to traffic pollution. The objective of this study was to examine correlations between self-reported traffic exposure and modelled (a) NOX and (b) traffic proximity in seven different northern European cities; Aarhus (Denmark), Bergen (Norway), Gothenburg, Umeå, and Uppsala (Sweden), Reykjavik (Iceland), and Tartu (Estonia). We analysed data from the RHINE III (Respiratory Health in Northern Europe, www.rhine.nu) cohorts of the seven study cities. Traffic proximity (distance to the nearest road with >10,000 vehicles per day) was calculated and vehicle exhaust (NOX) was modelled using dispersion models and land-use regression (LUR) data from 2011. Participants were asked a question about self-reported traffic intensity near bedroom window and another about traffic noise exposure at the residence. The data were analysed using rank correlation (Kendall's tau) and inter-rater agreement (Cohen's Kappa) between tertiles of modelled NOX and traffic proximity tertile and traffic proximity categories (0–150 metres (m), 150–200 m, >300 m) in each centre. Data on variables of interest were available for 50–99% of study participants per each cohort. Mean modelled NOX levels were between 6.5 and 16.0 μg/m3; median traffic intensity was between 303 and 10,750 m in each centre. In each centre, 7.7–18.7% of respondents reported exposure to high traffic intensity and 3.6–16.3% of respondents reported high exposure to traffic noise. Self-reported residential traffic exposure had low or no correlation with modelled exposure and traffic proximity in all centres, although results were statistically significant (tau = 0.057–0.305). Self-reported residential traffic noise correlated weakly (tau = 0.090–0.255), with modelled exposure in all centres except Reykjavik. Modelled NOX had the highest correlations between self-reported and modelled traffic exposure in five of seven centres, traffic noise exposure had the highest correlation with traffic proximity in tertiles in three centres. Self-reported exposure to high traffic intensity and traffic noise at each participant's residence had low or weak although statistically significant correlations with modelled vehicle exhaust pollution levels and traffic proximity. © 2017
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- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 9. |
- Holm, Karin, et al.
(författare)
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The role of Fusobacterium necrophorum in pharyngotonsillitis – A review
- 2016
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Ingår i: Anaerobe. - : Elsevier BV. - 1075-9964. ; 42, s. 89-97
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Forskningsöversikt (refereegranskat)abstract
- Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome. In addition, it is also associated with peritonsillar abscess formation and otitis media in small children. Recent research has shown that F. necrophorum may be involved in pharyngotonsillitis especially in adolescent and young adults and that it may be the second most common bacterial cause of pharyngotonsillitis after Streptococcus pyogenes (Group A streptococci). Peritonsillar abscesses and Lemierre's syndrome due to F. necrophorum are also found in this age group, suggesting that they may be complications of F. necrophorum pharyngotonsillitis. In this review we present the present knowledge about the role of F. necrophorum in pharyngotonsillitis with special emphasis on the age distribution. We argue that F. necrophorum is an important pathogen involved in pharyngotonsillitis in the age group of 13–40 years of age and we urge clinical microbiology labs to set up the appropriate techniques to be able to detect F. necrophorum from throat swabs.
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| 10. |
- Jensen, Tina Kold, et al.
(författare)
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Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012)
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 124:7, s. 1107-1113
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported. OBJECTIVE: We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their male infants at 3 months of age (n = 273). METHODS: In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4-30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. RESULTS: Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05). CONCLUSION: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population.
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