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- Rönnblom, Anders, et al.
(author)
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Appearance of hepatobiliary diseases in a population-based cohort with inflammatory bowel diseases (Inflammatory Bowel Disease Cohort of the Uppsala Region)
- 2015
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In: Journal of Gastroenterology and Hepatology. - : Wiley. - 0815-9319 .- 1440-1746. ; 30:8, s. 1288-1292
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Journal article (peer-reviewed)abstract
- Background and AimTo prospectively follow the evolution of hepatobiliary diseases in a population-based cohort of patients with inflammatory bowel diseases. MethodsBetween 2005 and 2009, 790 incident cases of ulcerative colitis and Crohn's disease were registered in the Uppsala Health Region, corresponding to an average incidence of 20.0 and 9.9 new cases/100000 inhabitants/year, respectively. Liver function tests were analyzed in 97.1% and the results of ensuing investigations were summarized. ResultsSeventeen patients with primary sclerosing cholangitis were diagnosed corresponding to an overall prevalence of 2.2% (ulcerative colitis 1.7% and Crohn's disease 3.0%, respectively). The median age at diagnosis was 25 years (interquartile range: 17.0-34.0). Among the 92 patients below 17 years of age, three had autoimmune hepatitis and three primary sclerosing cholangitis, summing up to a prevalence of 6.5% immune-mediated hepatobiliary diseases among the pediatric patients. Three patients have undergone liver transplantation and one died of colonic carcinoma. Ten patients have demonstrated persistent elevation of alkaline phosphatases but had a normal magnetic resonance cholangiopancreatography (two patients) or refused further investigation (one patient). ConclusionIn this first large prospective population-based cohort of 526 patients with ulcerative colitis (UC) and 264 with Crohn's disease, 17 cases of primary sclerosing cholangitis were found, among whom three (17%) so far have been liver transplanted and one has died of colon carcinoma. The average age of those affected by primary sclerosing cholangitis is considerably lower than usually reported. Ten patients had or have had elevated alkaline phosphatase without confirmed liver or biliary disease.
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- Serenius, Fredrik, et al.
(author)
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Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden
- 2013
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In: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 68:12, s. 781-783
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Journal article (other academic/artistic)abstract
- A proactive approach to the care of extremely preterm infants has increased survival and lowered the gestational age of viability, but these improvements may be associated with later neurodevelopmental disability. EXPRESS is a national population-based prospective study of all infants born alive or stillborn at less than 27 weeks’ gestation between 2004 and 2007 in Sweden. This prospective follow-up study was undertaken to assess neurologic and developmental outcome of the EXPRESS cohort at 2.5 years corrected age compared with a matched control group born at term.Of 707 live-born infants, 497 (70%) survived to corrected age 2.5 years; the final cohort included 491 children. Each preterm child was matched with 2 control subjects at 2.5 years chronological age. Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development (Bayley III). Cerebral palsy (CP), visual and hearing disability, and a composite outcome of overall disabilities were assessed. The overall outcome was characterized as no, mild, moderate, and severe disability.Of 415 infants assessed with clinical examinations, 399, 393, and 382, respectively, completed the Bayley III cognitive, language, and motor scales; 366 control children were assessed with Bayley III. The mean composite cognitive, language, and motor scores for children in the preterm and control groups were 94 ± 12 and 104 ± 11, respectively (P < 0.001), 98 ± 17 and 109 ± 12 (P < 0.001), respectively, and 94 ± 16 and 107 ± 14 (P < 0.001), respectively. Normal cognitive development or mild cognitive disability was found in 354 preterm children (88.8%) and 364 control children (99.5%). Moderate or severe cognitive disability was present in 20 preterm children (5.0%) and 1 control child (0.3%) (P < 0.001) and in 25 (6.3%) and 1 (0.3%), respectively (P < 0.001). Normal language development or mild language disability was found in 330 children (83.9%) in the preterm group and with 351 (97.5%) in the control group (all group comparisons, P < 0.001). Normal motor development or mild motor disability occurred in 324 (84.8%) and 348 (98.6%) of children in the preterm and control groups, respectively. Moderate or severe mental developmental delay was seen in 88 and 10 children (20% and 2.8%), respectively (P < 0.001).In the preterm group, Bayley III cognitive, language, and motor scores increased with advancing gestational age at birth by 2.5 points (99% confidence interval [CI], 1.0–4.0) per week (P < 0.001), by 3.6 points (99% CI, 1.6–5.6) per week (P < 0.001), and by 2.5 points (99% CI, 0.5–4.5) per week scores (P = 0.001), respectively. Cerebral palsy was present in 32 preterm children (7.0%; 99% CI, 3.9–10.1%). Of 456 preterm children, 42.1% were classified as normal, 30.7% as having mild disabilities, and 27.2% as having moderate or severe disabilities (vs 78.1%, 18.6%, 3.3% of control subjects, respectively; P < 0.001 for all comparisons). The proportion of children with mild or no disabilities increased from 40% at 22 weeks to 83% at 26 weeks (P < 0.001 for trend). Moderate or severe disabilities decreased from 60% at 22 weeks to 17% at 26 weeks (P < 0.001 for trend).The impact of prematurity on neurodevelopmental outcome indicates that further improvements in neonatal care are necessary. Although preterm children had poorer neurodevelopmental outcomes than those born at term, 73% had no or mild disability, and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling couples facing extremely preterm birth of their infant
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- Sharma, Rajhans, 1990, et al.
(author)
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Real-time compaction of nanoconfined DNA by an intrinsically disordered macromolecular counterion
- 2020
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 533:1, s. 175-180
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Journal article (peer-reviewed)abstract
- We demonstrate how a recently developed nanofluidic device can be used to study protein-induced compaction of genome-length DNA freely suspended in solution. The protein we use in this study is the hepatitis C virus core protein (HCVcp), which is a positively charged, intrinsically disordered protein. Using nanofluidic devices in combination with fluorescence microscopy, we observe that protein-induced compaction preferentially begins at the ends of linear DNA. This observation would be difficult to make with many other single-molecule techniques, which generally require the DNA ends to be anchored to a substrate. We also demonstrate that this protein-induced compaction is reversible and can be dynamically modulated by exposing the confined DNA molecules to solutions containing either HCVcp (to promote compaction) or Proteinase K (to disassemble the compact nucleo-protein complex). Although the natural binding partner for HCVcp is genomic viral RNA, the general biophysical principles governing protein-induced compaction of DNA are likely relevant for a broad range of nucleic acid-binding proteins and their targets.
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- Tiklova, Katarina, et al.
(author)
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Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development
- 2019
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because their degeneration causes major symptoms in Parkinson's disease. Understanding the diversity of mDA neurons - previously well characterized anatomically - requires a systematic molecular classification at the genome-wide gene expression level. Here, we use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3, a marker for mDA neurons. Analyses include cells isolated during development up until adulthood and the results are validated by histological characterization of newly identified markers. This identifies seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons. Five of them express dopaminergic markers, while two express glutamatergic and GABAergic markers, respectively. Analysis also indicate evolutionary conservation of diversity in humans. This comprehensive molecular characterization will provide a valuable resource for elucidating mDA neuron subgroup development and function in the mammalian brain.
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