| 1. |
- Osman, Ayman
(författare)
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Autophagy in Peripheral Neuropathy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor.Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of patients with chronic idiopathic axonal polyneuropathy (CIAP) and inflammatory neuropathy than in controls. The density of these structures increases with the severity of the neuropathy.In animal model, using Goto-Kakizaki (GK) rats with diabetes resembling human type 2 diabetes, activation of autophagy by local administration of rapamycin incorporated in collagen conduits that were used for reconnection of the transected sciatic nerve led to an increase in autophagy proteins LC3 and a decrease in p62 suggesting that the autophagic flux was activated. In addition, immunoreactivity of neurofilaments, which are parts of the cytoskeleton of axons, was increased indicating increased axonal regeneration. I also show that many proteins involved in axonal regeneration and cell survival were up-regulated by rapamycin in the injured sciatic nerve of GK rats four weeks after injury.Taken together, these findings provide new knowledge about the involvement of autophagy in neuropathy and after peripheral nerve injury and reconstruction using collagen conduits.
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| 2. |
- Bourke, Grainne, 1970-
(författare)
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Magnetic resonance imaging and diffusion tensor imaging after brachial plexus injury and repair : Experimental and clinical study
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brachial plexus injuries (BPI) cause permanent upper limb paralysis and serious disability in adults and children. Timely identification of the severity of nerve injury and early appreciation of the inane potential for recovery would revolutionise management. Radiology supports clinical assessment but is not an independent marker of disease severity. Surgical evaluation in severe closed nerve injuries defines the reconstructive potential. This thesis explores aspects of BPI assessment and treatment that remain unsolved. Conventional magnetic resonance imaging (MRI) and novel diffusion tensor imaging (DTI) are evaluated in adults to gain a better understanding of their current diagnostic accuracy in BPI and future value in assessing nerve health. In neonates, this thesis evaluates the preganglionic effects related to timing of injury and repair and socioeconomic factors that influence the incidence and presentation of neonates to specialist centres. These currently controversial factors are important prerequisites to designing and evaluating the optimal objective imaging modality in this age group. Data from 29 high energy trauma BPI patients were analysed. The diagnostic accuracy of 1.5T MRI for BP root avulsion was 79% (Index test MRI, Reference standard Surgery). The negative predictive value was 81% meaning there was one occult avulsion in every 5 cases. DTI data sets from 12 patients with unilateral BPI and seven matched adult controls were acquired. The test was considered positive for root avulsion when there was a visible lack of continuity between tracts in the spinal cord and the brachial plexus. The mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated from a region of interest (ROI) - five 2.5mm2 pixels in the axial plane covering the lateral recess of the vertebral foramen. The overall diagnostic accuracy of DTI for determining root avulsion was 71% (95%CI 54, 85). The fractional anisotropy (FA) of avulsed roots was 10% lower than normal roots (95% [CI 7%,13%] p<0.001). The mean diffusivity (MD) of avulsed roots was 0.32x10-3mm2/s higher than normal intact roots (95%CI 0.11, 0.53; p><0.001). The T1 tracts were not clearly visualised in most BPI cases. The time course comparing survival of motoneurons in a neonatal rat BPI model, was evaluated at 2- 28 days after injury and repair. At day 10, the injury group survival of motoneurons was 22% and at 28 days only 9%of motoneurons remained. In the repair group the surviving neurons were 51% at 10 days and 20% at 28 days. The repair group had significantly reduced reactivity of macrophages and microglial cells in the C5/C6 ventral horn. In analysis (Index of Multiple Deprivation, IMD) of a 13 year, retrospective cohort series of 321 children with Obstetric Brachial Plexus injury (England), 109 (39%) were from the most deprived quintile. In Yorkshire and Humber 44% were from the most deprived quintile. No relationship was identified between severity of condition and IMD. These laboratory and clinical studies in adults, children and neonatal animals align with the real-time clinical conundrum in evaluating the injured nerve’s ability to recover to functional significance. ><0.001). The mean diffusivity (MD) of avulsed roots was 0.32x10-3mm2/s higher than normal intact roots (95%CI 0.11, 0.53;p<0.001). The T1 tracts were not clearly visualised in most BPI cases. The time course comparing survival ofmotoneurons in a neonatal rat BPI model, was evaluated at 2- 28 days after injury and repair. At day 10, the injury group survival of motoneurons was 22% and at 28 days only 9%of motoneurons remained. In the repair group the surviving neurons were 51% at 10 days and 20% at 28 days. The repair group had significantly reduced reactivity of macrophages and microglial cells in the C5/C6 ventral horn. In analysis (Index of Multiple Deprivation, IMD) of a 13 year, retrospective cohort series of 321 children with Obstetric Brachial Plexus injury (England), 109 (39%) were from the most deprived quintile. In Yorkshire and Humber 44% were from the most deprived quintile. No relationship was identified between severity of condition and IMD. These laboratory and clinical studies in adults, children and neonatal animals align with the real-time clinical conundrum in evaluating the injured nerve’s ability to recover to functional significance.
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| 3. |
- Nyman, Erika, 1976-
(författare)
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Guided Regeneration of the Human Skin : in vitro and in vivo studies
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every day and in all parts of the world, humans experience different grades of wounding and tissue loss of the skin, thus initiating one of the most complex biological processes. Acute and chronic wounds, as well as the additional problem of skin scarring, involve not only great suffering for the patient but also extensive health care costs for the society. Although the wound-healing process is a wellstudied field much knowledge must be gained to unlock the door to regenerative pathways in humans.Epidermis heals by complete regeneration, but dermal and full thickness injuries heal with fibrosis and scar formation. In Papers I and II, we studied whether dermal scarring could be turned into regeneration by using two different types of threedimensional dermal scaffolds. In Paper I, we studied a solid scaffold made of poly(urethane urea), initially in vitro then followed by in vivo studies. In Paper II, we intradermally injected a liquid three-dimensional scaffold consisting of porous gelatin spheres in human healthy volunteers. Both materials showed ingrowth of functional fibroblasts and blood vessels and appeared to stimulate regeneration while slowly degrading. This finding could be of significant clinical importance, for example in burn wound care or after cancer surgery.In Papers III and IV, we wanted to study the effects of amniotic fluid and hyaluronic acid on adult wound healing, because early fetal wounds re-epithelialize rapidly and naturally heal dermis by regeneration without the need of a dermal scaffold. Amniotic fluid, naturally rich in hyaluronic acid, induced an accelerated reepithelialization of adult human wounds in vitro, and hyaluronic acid seemed to be important for this effect. Stimulation with exogenous hyaluronic acid in vivo induced accelerated re-epithelialization and an altered protein expression in healthy human volunteers. The inflammatory phase of wound healing, as measured by tissue viability imaging, was not affected by hyaluronic acid. Elucidating the effects of amniotic fluid and hyaluronic acid on the wound-healing process may allow improved treatment of wounds with impaired healing.Studies on finding new dermal scaffolds and studies on the positive effect of amniotic fluid or hyaluronic acid on the wound-healing process are two different ways of gaining insight that may lead to regeneration and improved wound healing for the patient.
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| 4. |
- Pettersson, Jonas, 1979-
(författare)
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Biosynthetic conduits and cell transplantation for neural repair
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spinal cord injury results in complete failure of the central neurons to regenerate and is associated with cyst formation and enlargement of the trauma zone. In contrast to the spinal cord, axons in the injured peripheral nerve have the capacity to undergo some spontaneous regeneration. However, significant post-traumatic loss of nervous tissue causing long nerve gap is one of the main reasons for the poor restoration of function following microsurgical repair of injured nerves. The present thesis investigates the effects of biodegradable conduits prepared from fibrin glue and poly-beta-hydroxybutyrate (PHB) in combination with cultured Schwann cells, mesenchymal stem cells and extracellular matrix molecules on regeneration after spinal cord and peripheral nerve injury in adult rats. At 4-8 weeks after transplantation into the injured spinal cord, the PHB conduit was well integrated into the cavity but regenerating axons were found mainly outside the PHB. When suspension of BrdU-labeled Schwann cells was added to the PHB, regenerating axons filled the conduit and became associated with the implanted cells. Modification of the PHB surface with extracellular matrix molecules significantly increased Schwann cell attachment and proliferation but did not alter axonal regeneration. To improve the labeling technique of the transplanted cells, the efficacy of fluorescent cell tracers Fast Blue, PKH26, Vibrant DiO and Cell Tracker™ Green CMFDA was evaluated. All tested dyes produced very efficient initial labeling of olfactory ensheathing glial cells in culture. The number of Fast Blue-labeled cells remained largely unchanged during the first 4 weeks whereas the number of cells labeled with other tracers was significantly reduced after 2 weeks. After transplantation into the spinal cord, Fast Blue-labeled glial cells survived for 8 weeks but demonstrated very limited migration from the injection sites. Additional immunostaining with glial and neuronal markers demonstrated transfer of the dye from the transplanted cells to the host tissue. In a sciatic nerve injury model, the extent of axonal regeneration through a 10mm gap bridged with tubular PHB conduit was compared with a fibrin glue conduit. At 2 weeks after injury, the fibrin conduit supported similar axonal regeneration and migration of the host Schwann cells compared with the PHB conduit augmented with a diluted fibrin matrix and GFP-labeled Schwann cells or mesenchymal stem cells. The long-term regenerative response was evaluated using retrograde neuronal labeling. The fibrin glue conduit promoted regeneration of 60% of sensory neurons and 52% of motoneurons when compared with the autologous nerve graft. The total number of myelinated axons in the distal nerve stump in the fibrin conduit group reached 86% of the nerve graft control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89%, respectively. When a fibrin conduit was used to bridge a 20mm sciatic nerve gap, the weight of gastrocnemius muscle reached only 43% of the nerve graft control. The morphology of the muscle showed more chaotic appearance and the mean area and diameter of fast type fibers were significantly worse than those of the corresponding 10mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. In summary, these results show that a PHB conduit promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal growth after transplantation into the injured spinal cord. The data suggest an advantage of the fibrin conduit for the important initial phase of peripheral nerve regeneration and demonstrate potential of the conduit to promote long-term neuronal regeneration and muscle recovery.
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| 5. |
- Vikner, Tomas, et al.
(författare)
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5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions
- 2022
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 92:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Objective: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD.Methods: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64–68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously.Results: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R (Formula presented.) 0.24; p < 0.02 and R (Formula presented.) 0.23; p < 0.03, respectively) and LCS models ((Formula presented.) = 0.28; p = 0.015 and (Formula presented.) = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI.Interpretation: In healthy older adults, indicators of SVD are related in a lead–lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD.
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| 6. |
- Dahlin, Erika, 1981-
(författare)
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Train your brain : updating, transfer, and neural changes
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An initial aim of this thesis was to determine whether training of a specific executive function (updating) produces improvements in performance on trained and transfer tasks, and whether the effects are maintained over time. Neural systems underlying training and transfer effects were also investigated and one question considered is whether transfer depends on general or specific neural overlap between training and transfer tasks. An additional aim was to identify how individual differences in executive functioning are mapped to functional brain changes. In Study I, significant training-related changes in performance on the letter memory criterion task were found in both young and older adults after 5 weeks of updating training. Transfer to a 3-back test of updating was also demonstrated in the young adults. Functional Magnetic Resonance Imaging (fMRI) revealed overlapping activity in letter memory and 3-back tasks in fronto-parietal areas and striatum pre-training, and a joint training-related activity increase for the tasks in a striatal region. No transfer was observed to a task (Stroop) that engaged fronto-parietal areas, but not the striatal region and updating per se. Moreover, age-related striatal changes imposed constraints on transfer. In Study II, additional transfer tasks and a test of long-term maintenance were included. Results revealed that training-related gains in performance were maintained 18 months post-training in both young and older adults, whereas transfer effects were limited to tasks requiring updating and restricted to young participants. In Study III, analyses of brain activity and performance during n-back (1/2/3-back) were executed. This task enables manipulation of executive demand, which permits examination of how individual differences in executive functioning can be mapped to functional brain changes. Relative to a young high- performing group, capacity constraints in executive functioning were apparent between 1–2-back for the elderly participants and between 2–3-back for a young low-performing group. Capacity constraints in neural activity followed this pattern by showing a monotonically increasing response in the parietal cortex and the thalamus for young high performers, whereas activity levelled off at 1-back for elderly performers and at 2-back for young low performers. The response in the dorsal frontal cortex followed a similar pattern. Together, these findings indicate that fronto-parietal as well as sub-cortical areas are important for individual differences in executive functioning, training of updating and transfer effects.
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| 7. |
- Giöstad, Alice, 1994-
(författare)
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Surgery for ulnar nerve compression at the elbow : Focusing on factors influencing outcome
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ulnar nerve compression at the elbow (UNE) is a common peripheral nerve compression disorder in the upper limb. The literature regarding surgical outcome is inconclusive. This thesis aims to highlight various aspects of real-life settings for patients with UNE and to increase the understanding of underlying factors influencing the outcome of surgery.Patients undergoing surgery for UNE at a tertiary referral hospital were retrospectively evaluated (Linköping cohort; n=202). Comorbidity was extensive. Patients treated with simple decompression (SD) had a lower rate of complications than those with transposition surgery. Emerging neurogenic pain was the most common complication, with a two-fold risk for smokers. Scores from the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire revealed no differences between the surgical groups. Satisfaction with surgery was relatively low (53%), however only 8% stated that they would not go through the same surgical procedure again.Images from magnetic resonance imaging (MRI), performed in conjunction with surgery (Linköping cohort; 62 patients), were re-evaluated by a neuroradiologist. Spinal nerve root pathology contributing to the ulnar nerve (C8-Th1) was rare (1/62 patients), however, nerve root affections at other levels were common (26/62). No relation between cervical pathology and patient-reported outcome was seen.The Linköping cohort was combined with two cohorts from Region Skåne to evaluate time before return to work (RTW) after surgery for UNE (n=635 in total). RTW within 6 weeks was more common among older, SD and non-manual workers. Those who were unemployed were on sick leave longer than the rest of the population. Transposition of the ulnar nerve was the only predictor for prolonged RTW in the regression model.Patients with pain in conjunction with surgery were studied both in a retrospective observational study and in a qualitative study. Questionnaires obtained from the pain management clinic revealed a high prevalence of kinesiophobia, potential depression and/or anxiety, low life satisfaction and low overall health status. Patients with severe postoperative pain were younger and more often had bilateral surgery compared to the reference population. The narratives from the qualitative study revealed that chronic pain in conjunction with surgery for UNE affects most aspects of daily life and contributes to a heavy burden for the individual.In summary, patients surgically treated for UNE in a real-life setting constitute a heterogeneous population with wide variation in comorbidity and outcome of surgery. Pain after surgery can have a great impact on the individual and should be considered as an outcome. A biopsychosocial approach should be applied when treating patients with pain.
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| 8. |
- Lundin, Anna-Carin
(författare)
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Tendinosis in Trigger Finger
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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| 9. |
- Pourhamidi, Kaveh, 1985-
(författare)
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Peripheral nerve function : metabolic features, clinical assessment, and heat shock protein 27
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peripheral neuropathy is a common complication among patients with diabetes mellitus, but whether peripheral neuropathy is present in individuals with impaired glucose tolerance (IGT) is debatable. In order to identify and diagnose peripheral neuropathy correctly, it is important to evaluate diagnostic tools that can be implemented in routine health care to assess both large and small nerve fibre function. There is currently limited knowledge about neuroprotective factors that could be useful for measuring peripheral nerve function in individuals at risk of developing neuropathy such as those with diabetes mellitus. Thus, studies are needed to investigate potential neuroprotective factors in relation to peripheral nerve function in humans.Objectives: The overall goal of this thesis was to study the metabolic features and clinical assessment of peripheral nerve function and the potential relationship between the neuroprotective factor heat shock protein 27 (HSP27) and peripheral nerve function.Methods: Thirty-nine participants with normal glucose tolerance (NGT) and 29 participants with IGT were recruited from the population-based Västerbotten Intervention Programme in 2003–2004. Patients with type 2 diabetes mellitus (T2DM, n = 51) were recruited from primary health care centres. NGT and IGT individuals underwent two separate oral glucose tolerance tests to verify their glucose status. The peripheral nerve function in the lower limb was assessed by nerve conduction studies, neuropathy disability scoring, quantitative sensory tests, and skin biopsies with subsequent quantification of intraepidermal nerve fibre density (IENFD). The concentrations of HSP27 in serum were determined in the NGT, IGT, and T2DM individuals. Patients with type 1 diabetes mellitus (T1DM) were recruited from the Diabetes Clinic, Skåne University Hospital in Malmö, Sweden (n = 27) in 1992 and were followed-up in 2005. Baseline and follow-up concentrations of HSP27 were determined in T1DM patients as well as in healthy non-diabetic controls (n = 397). The T1DM patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Delta changes in HSP27 concentrations and small and large nerve fibre function were calculated.Results: There was no difference between IGT and NGT in sural nerve conduction, intraepidermal nerve fibre density, or thermal thresholds. The biothesiometer had a sensitivity of 82% and a specificity of 72% in identifying peripheral neuropathy with a cut-off value of ≥24.5 V at the medial malleolus. Adding the quantification of IENFD to the combination of the tuning fork and biothesiometer increased the diagnostic sensitivity from 81% to 95%, the negative predictive value from 87% to 94%, and the positive likelihood ratio from 1.8 to 1.9 when identifying small nerve fibre dysfunction. T2DM patients had lower HSP27 concentrations (mean HSP27 = 412 pg/mL, 95% CI 284–598 pg/mL) than NGT (mean HSP27 = 722 pg/mL, 95% CI 564–922 pg/mL) and IGT (mean HSP27 = 1010 pg/mL, 95% CI 638–1300 pg/mL) individuals (p <0.05 for both comparisons). T1DM patients had lower HSP27 concentrations at baseline (mean HSP27 = 547 pg/mL, 95% CI 421–711 pg/mL) and at follow-up (mean HSP27 = 538 pg/mL, 95% CI 417–693 pg/mL) compared to healthy controls (mean HSP27 = 785 pg/mL, 95% CI 732–842 pg/mL), p <0.05 for both comparisons). High concentrations of HSP27 were associated with better large nerve fibre function (Odds ratio = 2.51, 95% CI 1.25–5.05, p <0.05). Deteriorating large nerve fibre function correlated with decreasing HSP27 concentrations over time in T1DM patients (r = 0.50, p = 0.01).Conclusions: Measures of large and small nerve fibre function in IGT individuals do not differ significantly from NGT individuals. The existence of peripheral neuropathy as a consequence of IGT is not likely, and extensive control of neuropathy in IGT individuals is not advocated by this thesis. The biothesiometer is a useful clinical tool to identify peripheral neuropathy in routine health care. Quantification of IENFD using skin biopsies in combination with methods measuring vibrotactile sense, such as the biothesiometer and the tuning fork, increase the diagnostic usefulness of identifying small nerve fibre dysfunction. High HSP27 concentrations are associated with better peripheral large nerve fibre function. Patients with diabetes mellitus have lower HSP27 concentrations than healthy non-diabetic controls, and deterioration of large nerve fibre function correlates with a decrease in HSP27 concentrations over time in T1DM. This could be indicative of insufficient neuroprotection in patients with diabetes mellitus.
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| 10. |
- Dahlin, Sandra
(författare)
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Deactivation of emission control catalysts for heavy-duty vehicles : Impact of biofuel and lube oil-derived contaminants
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Catalytic emission control is used to reduce the negative impact of pollutants from diesel exhausts on our health and on the environment. For a heavy-duty truck, such a system consists of a diesel oxidation catalyst (DOC), a diesel particulate filter (DPF), a selective catalytic reduction (SCR) catalyst, and an ammonia slip catalyst (ASC). Due to greenhouse-gas induced global warming, it is necessary to decrease the emissions of such gases. Two strategies for this reduction are: 1) to produce engines that are more fuel efficient, 2) to use sustainably produced renewable fuels such as biodiesel and HVO. However, both these strategies may pose additional challenges for the emission control system: a colder exhaust due to the higher fuel-efficiency requires the use of highly active catalysts; catalyst deactivation related to impurities in biofuels, which requires very robust catalysts. The objective of this thesis was to study the impact of biofuel as well as lubrication oil-related contaminants on the performance of emission control catalysts (DOC and SCR catalysts) for heavy-duty diesel engines. The main focus has been on the low-temperature performance of V2O5-WO3/TiO2 (VWTi) and Cu-SSZ-13 SCR catalysts. Results from the project have shown that both Cu-SSZ-13 and VWTi catalysts capture and can be deactivated by phosphorus (P), while only the Cu-SSZ-13 is deactivated by sulfur (S). The degree of the P-related deactivation depends on the concentration in the catalyst, which depends on content of P in the exhaust and the exposure time, as well as the type of catalyst. S-deactivation of Cu-SSZ-13 is observed at low temperatures, where un-poisoned Cu-SSZ-13 are significantly more active than VWTi catalysts. As a contrast, the VWTi-performance can even be improved by sulfur; but alkali metals are severe poisons to VWTi catalysts. Partial performance-recovery of S-poisoned Cu-SSZ-13 can be obtained by exposing it to sulfur-free exhausts at elevated temperatures. The use of an upstream DOC, providing fast SCR conditions to the SCR catalyst, considerably improves the low-temperature performance of the VWTi, as well as sulfur-poisoned Cu-SSZ-13 catalysts. An upstream DOC also protects the SCR catalysts from phosphorus deactivation, as it can trap large amounts of P. However, if too much phosphorus is captured by the DOC, severe deactivation of this catalyst results, which lowers the overall performance of the exhaust treatment system. Insights from this project will guide the development of robust exhaust treatment systems for various applications. Additionally, it could aid in developing more durable emission control catalysts.
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| 11. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 12. |
- Welin, Dag, 1978-
(författare)
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Neuroprotection and axonal regeneration after peripheral nerve injury
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Following microsurgical reconstruction of injured peripheral nerves, severed axons are able to undergo spontaneous regeneration. However, the functional result is always unsatisfactory with poor sensory recovery and reduced motor function. One contributing factor is the retrograde neuronal death, which occurs in the dorsal root ganglia (DRG) and in the spinal cord. An additional clinical problem is the loss of nerve tissue that often occurs in the trauma zone and which requires “bridges” to reconnect separated nerve ends. The present thesis investigates the extent of retrograde degeneration in spinal motoneurons and cutaneous and muscular afferent DRG neurons after permanent axotomy and following treatment with N-acetyl-cysteine (NAC). In addition, it examines the survival and growth-promoting effects of nerve reconstructions performed by primary repair and peripheral nerve grafting in combination with NAC treatment. In adult rats, cutaneous sural and muscular medial gastrocnemius DRG neurons and spinal motoneurons were retrogradely labeled with fluorescent tracers from the homonymous transected nerves. Survival of labeled neurons was assessed at different time points after nerve transection, ventral root avulsion and ventral rhizotomy. Axonal regeneration was evaluated using fluorescent tracers after sciatic axotomy and immediate nerve repair. Intraperitoneal or intrathecal treatment with NAC was initiated immediately after nerve injury or was delayed for 1-2 weeks. Counts of labeled gastrocnemius DRG neurons did not reveal any significant retrograde cell death after nerve transection. Sural axotomy induced a delayed loss of DRG cells, which amounted to 43- 48% at 8-24 weeks postoperatively. Proximal transection of the sciatic nerve at 1 week after initial axonal injury did not further increase retrograde DRG degeneration, nor did it affect survival of corresponding motoneurons. In contrast, rhizotomy and ventral root avulsion induced marked 26- 53% cell loss among spinal motoneurons. Primary repair or peripheral nerve grafting supported regeneration of 53-60% of the motoneurons and 47-49% of the muscular gastrocnemius DRG neurons at 13 weeks postoperatively. For the cutaneous sural DRG neurons, primary repair or peripheral nerve grafting increased survival by 19-30% and promoted regeneration of 46-66% of the cells. Regenerating sural and medial gastrocnemius DRG neurons upregulate transcription of peripherin and activating transcription factor 3. The gene expression of the structural neurofilament proteins of high molecular weight was significantly downregulated following injury in both regenerating and non-regenerating sensory neurons. Treatment with NAC was neuroprotective for spinal motoneurons after ventral rhizotomy and avulsion, and sural DRG neurons after sciatic nerve injury. However, combined treatment with nerve graft and NAC had significant additive effect on neuronal survival and also increased the number of sensory neurons regenerating across the graft. In contrast, NAC treatment neither affected the number of regenerating motoneurons nor the number of myelinated axons in the nerve graft and in the distal nerve stump. In summary, the present results demonstrate that cutaneous sural sensory neurons are more sensitive to peripheral nerve injury than muscular gastrocnemius DRG cells. Moreover, the retrograde loss of cutaneous DRG cells taking place despite immediate nerve repair would still limit recovery of cutaneous sensory functions. Experimental data also show that NAC provides a highly significant degree of neuroprotection in animal models of adult nerve injury and could be combined with nerve grafting to further attenuate retrograde neuronal death and to promote functional regeneration.
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