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  • Månsson, Kristoffer, et al. (författare)
  • Can Psychological Treatment Slow Down Cellular Aging in Social Anxiety Disorder? : An Intervention Study Evaluating Changes in Telomere Length and Telomerase Activity
  • 2018
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S351-S352
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Mental illness, including anxiety disorders, is linked to accelerated cell aging. This is evidenced by shorter leukocyte telomere length. Cells with critically short telomeres may undergo apoptosis. In dividing cells, telomere shortening is counteracted by the telomeraseenzyme. Telomerase is reportedly low following chronic psychological stress. We hypothesized that a psychological treatment may increase telomerase activity, less telomere attritionand greater symptom improvement.Methods: Forty-six patients (91% SSRI naïve) with social anxiety disorder(SAD; mean age 31, 63% females) underwent a 9-week waiting period, and 9 weeks of Internet-delivered cognitive behavior therapy(CBT). During treatment, symptoms were assessed weekly using the Liebowitz Social Anxiety Scale (LSAS-SR). Fasting blood samples were collected twice before treatment, and at post-treatment. Genomic DNA was extracted using DNeasy® Blood & Tissue Kit (Qiagene) to assess leukocyte telomere length. Telomerase activity was detected by real-time telomeric repeat amplification protocol (RT-TRAP).Results: Patients improved significantly on the LSAS-SR (p<.001; Cohen’s d=1.5). Pre-post changes in telomerase and telomere length correlated positively (Pearson’s r=.31, p=.05). Reduced telomerase activity (<33th percentile) was associated with less improvement and increased activity (>66th percentile) with more improvement on the LSAS-SR (Z=-2.4, p=.02).Conclusions: We demonstrate, to our knowledge for the first time, that altered telomerase activity is associated with clinical response to a psychological treatment in a psychiatric population. The observed CBT effect on telomerase in patients with SAD is consistent with results from animal trials and a small previous study of antidepressants in humans. Thus, telomerase activation may play an important role in clinical recovery.
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  • Serenius, Fredrik, et al. (författare)
  • Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden
  • 2013
  • Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 68:12, s. 781-783
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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  • Hjorth, Martin, et al. (författare)
  • Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
  • 2012
  • Ingår i: European journal of haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:6, s. 485-496
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Objectives:  Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods:  Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results:  After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions:  Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
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