| 1. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Briem, Birgir, et al.
(author)
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Acute epiglottitis in Iceland 1983-2005
- 2009
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In: Auris, nasus, larynx. - : Elsevier BV. - 0385-8146 .- 1879-1476. ; 36:1, s. 46-52
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Journal article (peer-reviewed)abstract
- Objective: To describe the changes in the epidemiology of epiglottitis in Iceland from 1983 to 2005. Methods: All patients with the discharge diagnosis of epiglottitis during the study years were identified and diagnosis confirmed by chart review. Main outcome measures were age, gender, month/year of diagnosis, microbiology, airway management, ICU admissions, choice of antibiotics, length of hospital stay and major complications/mortality. Results: Fifty-seven patients were identified (annual incidence 0.93/100.000). The mean age was 33.3 years (1-82). Childhood epiglottitis disappeared after introduction of Haemophilus influenzae type b (Hib) vaccination in 1989 but adult disease showed non-significant increase. In the pre-vaccination era Hib was the most common organism cultured but it has not been diagnosed in Iceland since 1991 and Streptococci are now the leading cause of epiglottitis. The mean hospital stay was 5.05 nights with 51% of patients admitted to ICU. All children under 10 years and a total 30% of patients received airway intervention. Ninety percent of adults were observed without airway intervention. Major complications were rare and mortality was 0% in our series. Conclusion: There have been major changes in the epidemiology of epiglottitis in Iceland during the study period. Previously a childhood disease, epiglottitis has disappeared in children and is now almost exclusively found in adults. This can be attributed to widespread Hib vaccination, eliminating the major causative agent in children. The treatment of this life-threatening disease remains a challenge. Our series suggest that it is safe to observe patients with mild/moderate symptoms without airway intervention.
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| 3. |
- Einarsson, Einar Jón, et al.
(author)
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Decreased postural control in adult survivors of childhood cancer treated with chemotherapy
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- The objective of cancer treatment is to secure survival. However, as chemotherapeutic agents can affect the central and peripheral nervous systems, patients must undergo a process of central compensation. We explored the effectiveness of this compensation process by measuring postural behaviour in adult survivors of childhood cancer treated with chemotherapy (CTS). We recruited sixteen adults treated with chemotherapy in childhood for malignant solid (non-CNS) tumours and 25 healthy age-matched controls. Subjects performed posturography with eyes open and closed during quiet and perturbed standing. Repeated balance perturbations through calf vibrations were used to study postural adaptation. Subjects were stratified into two groups (treatment before or from 12 years of age) to determine age at treatment effects. Both quiet (p = 0.040) and perturbed standing (p ≤ 0.009) were significantly poorer in CTS compared to controls, particularly with eyes open and among those treated younger. Moreover, CTS had reduced levels of adaptation compared to controls, both with eyes closed and open. Hence, adults treated with chemotherapy for childhood cancer may suffer late effects of poorer postural control manifested as reduced contribution of vision and as reduced adaptation skills. These findings advocate development of chemotherapeutic agents that cause fewer long-term side effects when used for treating children.
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| 4. |
- Einarsson, Einar Jón, et al.
(author)
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Elevated visual dependency in young adults after chemotherapy in childhood
- 2018
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:2
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Journal article (peer-reviewed)abstract
- Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20 from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood.
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| 5. |
- Einarsson, Einar-Jon, et al.
(author)
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Hearing impairment after platinum-based chemotherapy in childhood.
- 2011
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 56:4, s. 631-637
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Journal article (peer-reviewed)abstract
- Chemotherapy is used in the treatment of children and adolescents with malignant diseases. Some of the chemotherapeutic agents are highly toxic and may cause a number of side effects. The primary objective of this study was to evaluate the long-term effects on hearing in cancer survivors who had received platinum-based chemotherapy in childhood or adolescence.
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| 6. |
- Einarsson, Einar-Jon, et al.
(author)
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Long term hearing degeneration after platinum-based chemotherapy in childhood.
- 2010
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In: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 49:10, s. 765-771
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate long-term development of hearing in subjects who had received platinum-based chemotherapy in childhood or adolescence. Another aim was to assess the self-reported hearing loss handicap and compare it to audiometric measurements. Medical records from individuals diagnosed with childhood cancer and treated with platinum-based chemotherapy between 1985 and 2000 at the University Hospital in Lund Sweden were reviewed retrospectively. Fifteen subjects, who fulfilled the eligibility criteria set for the study, underwent a thorough audiometric evaluation. The results show that the hearing loss, in subjects with ototoxicity had increased after the end of treatment, to include also the lower frequencies. The largest deterioration in hearing thresholds, up to 55 dB HL, was found at frequencies above 2 kHz. The findings also reveal that the subjects have a considerably greater hearing loss handicap and disability than would be expected from the results of the audiometric evaluations. The conclusion of this study is that children and adolescence treated with platinum-based chemotherapy should have regular audiometric follow-up examinations, also many years after the end of treatment. Furthermore, assessments of self-reported hearing disability should be made during and after chemotherapy.
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| 7. |
- Einarsson, Einar-Jon, et al.
(author)
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Oculomotor Deficits after Chemotherapy in Childhood.
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1, s. 1-17
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Journal article (peer-reviewed)abstract
- Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.
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| 8. |
- Einarsson, Einar-Jon, et al.
(author)
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Severe difficulties with word recognition in noise after platinum chemotherapy in childhood, and improvements with open-fitting hearing-aids.
- 2011
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In: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 50, s. 642-651
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Journal article (peer-reviewed)abstract
- To investigate word recognition in noise in subjects treated in childhood with chemotherapy, study benefits of open-fitting hearing-aids for word recognition, and investigate whether self-reported hearing-handicap corresponded to subjects' word recognition ability. Design: Subjects diagnosed with cancer and treated with platinum-based chemotherapy in childhood underwent audiometric evaluations. Study Sample: Fifteen subjects (eight females and seven males) fulfilled the criteria set for the study, and four of those received customized open-fitting hearing-aids. Results: Subjects with cisplatin-induced ototoxicity had severe difficulties recognizing words in noise, and scored as low as 54% below reference scores standardized for age and degree of hearing loss. Hearing-impaired subjects' self-reported hearing-handicap correlated significantly with word recognition in a quiet environment but not in noise. Word recognition in noise improved markedly (up to 46%) with hearing-aids, and the self-reported hearing-handicap and disability score were reduced by more than 50%. Conclusions: This study demonstrates the importance of testing word recognition in noise in subjects treated with platinum-based chemotherapy in childhood, and to use specific custom-made questionnaires to evaluate the experienced hearing-handicap. Open-fitting hearing-aids are a good alternative for subjects suffering from poor word recognition in noise. Sumario Objectivo: Investigar el reconocimiento de palabras en ruido en sujetos tratados en la infancia con quimioterapia, los beneficios en el estudio de la adaptación abierta de auxiliares auditivos para el reconocimiento de palabras e investigar si el impedimento auditivo auto-reportado corresponde a la capacidad de reconocimiento de palabras del sujeto. Diseño: Se evaluó audiométricamente a sujetos que había sido diagnosticados con cáncer y tratados con una quimioterapia basada en platino en la infancia. Muestra del Estudio: Quince sujetos (8 mujeres y 7 hombres) cumplieron los criterios establecidos para el estudio y cuatro de ellos recibieron auxiliares auditivos de adaptación abierta, hecha a la medida. Resultados: Los sujetos con ototoxicidad inducida por cisplatino tuvieron dificultades severas para reconocer palabras en ruido y tuvieron puntuaciones tan bajas como 54% por debajo de las de referencia, estandarizadas por edad y por grado de pérdida auditiva. Los auto-reportes de impedimento auditivo de los sujetos con hipoacusia correlacionaron significativamente con el reconocimiento de palabra en un ambiente silencioso pero no en ruido. El reconocimiento de palabras en ruido mejoró marcadamente (hasta en un 46%) con los auxiliares auditivos, y el impedimento y discapacidad auditiva auto-reportados se redujeron en más del 50%. Conclusiones: Este estudio demuestra la importancia de evaluar el reconocimiento de palabras en ruido en sujetos tratados con quimioterapias basadas en platino en la infancia, y de usar cuestionarios específicos, hechos a la medida, para evaluar la disminución auditiva experimentada. Los auxiliares auditivos de adaptación abierta son una buena alternativa para sujetos que sufren de un pobre reconocimiento de palabras en ruido
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| 9. |
- Erjefält, Jonas, et al.
(author)
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Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways
- 1999
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In: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 160:1, s. 304-312
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Journal article (peer-reviewed)abstract
- Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0. 001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway mucosa. The nature and extent of the ECL and its product (i.e., protein-laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in human allergic airway inflammation in vivo.
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| 10. |
- Korchynska, Solomiia, et al.
(author)
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Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants
- 2020
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In: EMBO Journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 39:1
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Journal article (peer-reviewed)abstract
- Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic β cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.
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