| 81. |
- Pereira, Maria J., et al.
(author)
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Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors
- 2016
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In: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:12, s. 1768-1780
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Journal article (peer-reviewed)abstract
- Background Elevated levels of circulating non-esterified fatty acids (NEFA) mediate many adverse metabolic effects. In this work we aim to determine the impact of type 2 diabetes (T2D), glycemic control and obesity on lipolysis regulation. Design and Participants 20 control and 20 metformin-treated T2D subjects were matched for sex (10 M/10 F), age (58 ± 11 vs 58 ± 9 y) and BMI (30.8 ± 4.6 vs 30.7 ± 4.9 kg/m2). In vivo lipolysis was assessed during a 3 h-OGTT with plasma glycerol and NEFA levels. Subcutaneous adipose tissue (SAT) biopsies were obtained to measure mRNA and metabolite levels of factors related to lipolysis and lipid storage and to assess in vitro lipolysis in isolated subcutaneous adipocytes. Results Plasma NEFA AUC during the OGTT where higher 30% (P = 0.005) in T2D than in control subjects, but plasma glycerol AUC and subcutaneous adipocyte lipolysis in vitro were similar, suggesting that adipose tissue lipolysis is not altered. Expression in SAT of genes involved in lipid storage (FABP4, DGAT1, FASN) were reduced in T2D subjects compared with controls, but no differences were seen for genes involved in lipolysis. T2D subjects had elevated markers of beta-oxidation, α-hydroxybutyrate (1.4-fold, P < 0.01) and β-hydroxybutyrate (1.7-fold, P < 0.05) in plasma. In multivariate analysis, HbA1c, visceral adipose tissue volume and sex (male) were significantly associated with NEFA AUC in T2D subjects. Conclusions In T2D subjects, NEFA turnover is impaired, but not due to defects in lipolysis or lipid beta-oxidation. Impaired adipose NEFA re-esterification or de novo lipogenesis is likely to contribute to higher NEFA plasma levels in T2D. The data suggest that hyperglycemia and adiposity are important contributing factors for the regulation of plasma NEFA concentrations. © 2016 Elsevier Inc.
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| 82. |
- Rubino, Domenica, et al.
(author)
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Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial
- 2021
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 325:14, s. 1414-1425
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Journal article (peer-reviewed)abstract
- IMPORTANCE The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. OBJECTIVE To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or 7 , -27 with >1 weight-related comorbidity) and without diabetes. INTERVENTIONS A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. MAIN OUTCOMES AND MEASURES The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). RESULTS Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741(92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3,3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
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| 83. |
- Smeds, Helena, 1972-
(author)
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Blindness and Second Language Acquisition : Studies of Cognitive Advantages in Blind L1 and L2 speakers
- 2015
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Doctoral thesis (other academic/artistic)abstract
- The aim of this study is to investigate whether blind individuals display cognitive advantages over sighted individuals with regard to second language acquisition. Previous studies from neuropsychology have indicated that this is the case. It has been found that blind L1 speakers can compensate for loss of vision by developing better perceptual and cognitive skills compared to sighted individuals, skills that are highly relevant to language acquisition. These studies do not, however, investigate blind L2 speakers, for whom it is not clear whether these advantages are also found. In all, 80 adults participated in the study: 40 L2 speakers of Swedish (11 early blind, 9 late blind, 20 sighted, AO<18) and a matching group and subgroups of L1 speakers. These speakers underwent tests on speech perception in noise, accentedness in an L2 and memory functions. The results revealed that L2 speakers are at a great disadvantage perceiving speech in noise compared to L1 speakers, and that there was no advantage associated with blindness. In the L1 speakers group, however, the results revealed that the early blind had advantages compared to the late blind and sighted in white noise, but that both blind groups were more negatively affected by babble noise than the sighted. The results in relation to accentedness in an L2 revealed that there were no advantages associated with blindness. The results further revealed there were no advantages associated with blindness on the episodic memory test. The results did, however, reveal that the early blind performed significantly better than the late blind and sighted on all phonological short-term memory tests and that both the early and late blind were significantly better than the sighted on recognition memory for new words, irrespective of language background. The conclusion is that blindness is associated with advantages in, for example, ability to learn new words and syntax, acquisition rate, ultimate L2 attainment, and language aptitude.
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| 84. |
- Stölten, Katrin, et al.
(author)
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Effects of age and speaking rate on voice onset time: The production of voiceless stops by near-native L2 speakers
- 2015
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In: Studies in Second Language Acquisition. - 0272-2631 .- 1470-1545. ; 37:1, s. 71-100
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Journal article (peer-reviewed)abstract
- As part of a research project on the investigation of second language (L2) ultimate attainment in 41 Spanish early and late near-native speakers of L2 Swedish, the present study reports on voice onset time (VOT) analyses of the production of Swedish word-initial voiceless stops, /p t k/. VOT is analyzed in milliseconds as well as in percentages of word duration, thereby accounting for speaking rate effects. The results revealed an overall age effect on VOT production; however, this age effect became salient and statistically significant for all three stops only when speaking rate was taken into consideration. Similarly, when speaking rate was accounted for, only a small minority of the late learners exhibited actual nativelike L2 behavior, and most (but far from all) early learners performed within native-speaker range. The results are taken as an indication for relative VOT, as opposed to absolute VOT, constituting a reliable measure of nativelike L2 stop production, which has important implications for future research on age effects and maturational constraints in L2 acquisition.
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| 85. |
- Stölten, Katrin, et al.
(author)
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Effects of age of learning on voice onset time: Categorical perception of Swedish stops by near-native L2 speakers
- 2014
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In: Language and Speech. - : SAGE Publications. - 0023-8309 .- 1756-6053. ; 57:4, s. 425-450
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Journal article (peer-reviewed)abstract
- This study examined the effects of age of onset (AO) of L2 acquisition on the categorical perception of the voicing contrast in Swedish word-initial stops varying in Voice Onset Time (VOT). Three voicing continua created on the basis of natural Swedish word pairs with /p–b/, /t–d/, /k–ɡ/ in initial position were presented to 41 Spanish early (AO < 12) and late (AO > 12) near-native speakers of L2 Swedish. 15 native speakers of Swedish served as controls. Categorizations were influenced by AO and listener status as L1/L2 speaker, in that the late learners deviated the most from native-speaker perception. In addition, only a small minority of the late learners perceived the voicing contrast in a way comparable to native-speaker categorization, while most early L2 learners demonstrated nativelike categorization patterns. However, when the results were combined with the L2 learners’ production of Swedish voiceless stops (Stölten, 2005; Stölten, Abrahamsson & Hyltenstam, in press), nativelike production and perception was never found among the late learners, while a majority of the early learners still exhibited nativelike production and perception. It is concluded that, despite their being perceived as mother-tongue speakers of Swedish by native listeners, the late learners do not, after detailed phonetic scrutiny, exhibit a fully nativelike command of Swedish VOT. Consequently, being near-native rather than nativelike speakers of their second language, these individuals do not constitute the evidence necessary to reject the hypothesis of one or several critical (or sensitive) periods for language acquisition.
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| 86. |
- Stölten, Katrin, 1977-
(author)
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The Effects of Age of Onset on VOT in L2 Aquisition and L1 Attrition : A Study of the Speech Production and Perception of Advanced Spanish-Swedish Bilinguals
- 2013
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Doctoral thesis (other academic/artistic)abstract
- This thesis explores the role of age in second language (L2) acquisition and first language (L1) attrition. The focus is on Voice Onset Time (VOT) in the production and categorical perception of word-initial L1 and L2 stops in highly advanced L1 Spanish learners of L2 Swedish. Using as the point of departure a maturational constraints perspective and the Critical Period Hypothesis (CPH), Study I examines the impact of age of onset (AO) of L2 acquisition on the production of L2 Swedish voiceless stops. The results show that there are AO effects even in the speech of highly advanced L2 learners and that the incidence of nativelike L2 learners is considerably lower than earlier assumed. However, conclusions like these are only possible when speaking rate is accounted for, thereby highlighting the importance of speaking rate effects on VOT as a measure of nativelikeness. Like Study I, Study II reveals age effects on the same L2 learners’ categorical perceptions of L2 Swedish stops. Moreover, after combining the results with the data from Study I, the incidence of nativelike behavior drops remarkably with no late L2 learner performing within the range of native-speaker production and perception. The results suggest that L2 acquisition of phonetic/phonological aspects is especially sensitive to AO effects. It is concluded that theories on maturational constraints, including the CPH, cannot be refuted on the basis of the present data. Study III concerns the same participants’ production and perception of L1 Spanish stops. Age of reduced contact (ARC) is identified as an important predictor for L1 attrition and retention of voiceless stop production, although not of stop perception. This discrepancy is related to different activation thresholds as proposed by the Activation Threshold Hypothesis (ATH). It is further suggested that early bilinguals are more dependent on high-frequency L1 use than late bilinguals when compensating for age effects, but only in production.
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| 87. |
- Stölten, Katrin, et al.
(author)
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The L1 production and perception of VOT in Spanish-Swedish bilinguals: The role of age and L1 use
-
Other publication (other academic/artistic)abstract
- This study investigates the effects of age of reduced contact (ARC) and L1 use on L1 stop production and perception in Spanish-Swedish bilinguals. Results revealed that ARC had an impact on voice onset time (VOT) in the production of Spanish /p t k/, but not on the categorical perception of Spanish /p–b/, /t–d/, /k–ɡ/. While maturation may explain the ARC effects, it alone does not provide a satisfying explanation for the discrepancy between production and perception. It is proposed that perception may be less prone to change than production due to differences in activation levels, as predicted by the Activation Threshold Hypothesis (ATH). Furthermore, results showed that L1 use influenced stop production, but not perception, especially in early bilinguals. It is concluded that early bilinguals depend on advantageous factors such as high-frequency L1 use in order to compensate for ARC effects, but only in production.
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| 88. |
- Trolle, Carl, et al.
(author)
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Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents
- 2014
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In: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 15, s. 60-
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Journal article (peer-reviewed)abstract
- The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root avulsion for their potential to assist sensory axon regeneration. Grafted cells showed extensive survival and differentiation after transplantation to the avulsed DRTZ. Transplanted cells located outside the spinal cord organized elongated tubes of Sox2/GFAP expressing cells closely associated with regenerating sensory axons or appeared as small clusters on the surface of the spinal cord. Others, migrating into the host spinal cordas single cells, differentiated to spinal cord neurons with different neurotransmitter characteristics, extensive fiber organization, and in some cases surrounded by glutamatergic terminal-like profiles. These findings demonstrate that bNCSCs implanted at the site of dorsal root avulsion injury display remarkable differentiation plasticity inside the spinal cord and in the peripheral compartment where they organize tubes associated with regenerating sensory fibers. These properties offer a basis for exploring the ability of bNCSCs to assist regeneration of sensory axons into the spinal cord and replace lost neurons in the injured spinal cord.
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| 89. |
- Webb, Dominic-Luc, et al.
(author)
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Bariatric surgery - time to replace with GLP-1?
- 2017
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In: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 52:6-7, s. 635-640
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Research review (peer-reviewed)abstract
- Obesity with a body mass index (BMI) over 30kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass. Consistent with outcomes of this surgery, GLP-1 suppresses appetite and reduces food intake. This implies that GLP-1 has the potential to achieve a similar therapeutic outcome as gastric bypass. GLP-1 analogs, which are used for the treatment of type 2 diabetes mellitus, also lead to significant weight loss. Altered hormonal profiles after gastric bypass therefore indicate a logical connection between gut peptide hormone levels, weight loss and glucose homeostasis. Furthermore, combinations of GLP-1 with other gut hormones such as peptide YY (PYY) and cholecystokinin (CCK) may be able to reinforce GLP-1 driven reduction in appetite and food intake. Pharmacological intenvention in obesity by use of GLP-1 analogs (exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, taspoglutide) and inhibitors of dipeptidyl peptidase-IV (DPP-IV) degradation that inactivate GLP-1 (sitagliptin, vildagliptin), leading to reduced appetite and weight with positive effects on metabolic control, are realistically achievable. This may be regarded as a low-risk therapeutic alternative to surgery for reducing obesity-related risk factors in the obese with lower BMIs.
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