No description available.

No / There is evidence that both the herb Sanicle and the cytokine TGF- β3 can be beneficial in enhancing wound repair. In this study 3T3 fibroblast cells were cultured and the confluent monolayers were wounded (scarred) using a disposable plastic pipette. Various amounts of TGF-β3 (a growth factor) and Sanicle extract were applied to the cell monolayers. TGF-β3 was applied at concentrations of 50ng/ml, 5ng/ml, 500pg/ml, 50pg/ml and 5pg/ml to five different culture flasks with one additional flask acting as control. Sanicle was applied at concentrations of 100μg/ml, 10μg/ml, 1μg/ml, 100ng/ml and 10ng/ml with one additional flask as a control. The cells were imaged over a period of 20 hours with or without presence of TGF-β3 and Sanicle. The results indicated that although there were no significant increases in the rate of wound closure in relation to application of TGF-β3, there is an indication that TGF-β3 may enhance model wound closure at optimum working concentration between 5ng/ml and 50ng/ml. However, the sanicle extract did not stimulate enhanced repair of the model in vitro wound, but instead seemed to promote cell death along the wound margin. These results indicate that sanicle may be used in the care of wounds, but not as a growth promoter, but because it acts as an antibiotic agent, and possibly because it aids wound debridement.

TGF-β isoforms are important signalling molecules in wound repair in the skin. Transforming growth factor β3 (TGF-β3) has been implicated in scarless healing. In both animal and human models the application of exogenous TGF-β3 causes a reduction in the inflammatory response and improves the architecture of the neodermis. Research into the influence of TGF-β on scarring has tended to focus on fibroblasts. However, keratinocytes play a major role in scarring both indirectly, as a result of their influence over the behaviour of fibroblasts and also by directly influencing wound contraction. Thus, experiments were carried out to investigate the influence of TGF-β3 on the behaviours of a keratinocyte cell line (HaCaT). Incubation with TGF-β3 increased cell spreading and appeared to reduce cell-surface contacts indicated by both SPR imaging and a detachment assay. TGF-β3 also caused a decreased cell alignment response to microcontact printed protein patterns, in part due to the deposition of laminin which is associated with the TGF-β induced cell migration. There is evidence that TGF-β isoforms differentially influence the outcome of wound healing. Similar to the results produce following addition of exogenous TGF-β3, the neutralisation of TGF-β1 and 2 has been shown to reduce scar formation in the adult wounds. During reepithelialisation keratinocytes experience a dynamic environment. Both extracellular matrix proteins and growth factors influence the progression of wound repair which includes both cell migration and proliferation. Few studies have examined collective cell behaviour in response to TGF-β isoforms and ECM coated substrates. Thus both wound closure and cell proliferation assays were conducted for different ECM proteins fibronectin, laminin and collagen type I and for TGF-β1, 2 and 3. Rates of wound closure were significantly reduced on laminin coated substrates while cell proliferation rates were increased. TGF-β2 and 3 induced significant increases in wound closure rates. This appeared to correspond with an increase in the number of cells independently migrating out from the wound margins. Only TGF-β3 caused a significant decrease in cell proliferation over a 4 day period. Laminin332 deposition is central to the reepithelialisation process and is known to be induced in response to TGF-β. Thus experiments were carried out to investigate HaCaT cell laminin332 deposition in response to TGF-β1, 2 and 3. Both an immunofluorescence staining technique and an ELISA based semi-quantification method was used. Following 4 day incubation all TGF-β isoforms significantly increased laminin332 deposition; however TGF-β2 and 3 caused the most significant increases. Integrin receptors enable cell-matrix interactions during wound repair. TGF-β is known to influence the expression of integrin subunits. Thus, experiments were carried out to compare the influence of each TGF-β isoform on the expression of subunits β3, β2, β5, β1 and β4. All TGF-β isoforms significantly increased all subunit expression. TGF-β3 caused the most significant increase in β4 and both TGF-β2 and 3 caused the most significant increase in β2. While there were differences in cell responses to each isoforms, TGF-β3 did not stand out from the other two isoforms. Interestingly, TGF-β2 shared more similarities with TGF-β3 than it did with TGF-β1, in its role in enhancing wound closure and LN332 deposition. These comparative studies have shown that differences exist in the way TGF-β isoforms influence HaCaT cell behaviour, namely migration, laminin deposition and integrin expression.

TGF-β isoforms are important signalling molecules in wound repair in the skin. Transforming growth factor β3 (TGF-β3) has been implicated in scarless healing. In both animal and human models the application of exogenous TGF-β3 causes a reduction in the inflammatory response and improves the architecture of the neodermis. Research into the influence of TGF-β on scarring has tended to focus on fibroblasts. However, keratinocytes play a major role in scarring both indirectly, as a result of their influence over the behaviour of fibroblasts and also by directly influencing wound contraction. Thus, experiments were carried out to investigate the influence of TGF-β3 on the behaviours of a keratinocyte cell line (HaCaT). Incubation with TGF-β3 increased cell spreading and appeared to reduce cell-surface contacts indicated by both SPR imaging and a detachment assay. TGF-β3 also caused a decreased cell alignment response to microcontact printed protein patterns, in part due to the deposition of laminin which is associated with the TGF-β induced cell migration. There is evidence that TGF-β isoforms differentially influence the outcome of wound healing. Similar to the results produce following addition of exogenous TGF-β3, the neutralisation of TGF-β1 and 2 has been shown to reduce scar formation in the adult wounds. During reepithelialisation keratinocytes experience a dynamic environment. Both extracellular matrix proteins and growth factors influence the progression of wound repair which includes both cell migration and proliferation. Few studies have examined collective cell behaviour in response to TGF-β isoforms and ECM coated substrates. Thus both wound closure and cell proliferation assays were conducted for different ECM proteins fibronectin, laminin and collagen type I and for TGF-β1, 2 and 3. Rates of wound closure were significantly reduced on laminin coated substrates while cell proliferation rates were increased. TGF-β2 and 3 induced significant increases in wound closure rates. This appeared to correspond with an increase in the number of cells independently migrating out from the wound margins. Only TGF-β3 caused a significant decrease in cell proliferation over a 4 day period. Laminin332 deposition is central to the reepithelialisation process and is known to be induced in response to TGF-β. Thus experiments were carried out to investigate HaCaT cell laminin332 deposition in response to TGF-β1, 2 and 3. Both an immunofluorescence staining technique and an ELISA based semi-quantification method was used. Following 4 day incubation all TGF-β isoforms significantly increased laminin332 deposition; however TGF-β2 and 3 caused the most significant increases. Integrin receptors enable cell-matrix interactions during wound repair. TGF-β is known to influence the expression of integrin subunits. Thus, experiments were carried out to compare the influence of each TGF-β isoform on the expression of subunits α3, α2, α5, β1 and β4. All TGF-β isoforms significantly increased all subunit expression. TGF-β3 caused the most significant increase in β4 and both TGF-β2 and 3 caused the most significant increase in α2. While there were differences in cell responses to each isoforms, TGF-β3 did not stand out from the other two isoforms. Interestingly, TGF-β2 shared more similarities with TGF-β3 than it did with TGF-β1, in its role in enhancing wound closure and LN332 deposition. These comparative studies have shown that differences exist in the way TGF-β isoforms influence HaCaT cell behaviour, namely migration, laminin deposition and integrin expression. / EPSRC and DTA grant

The experience of unemployment puts individuals at risk of long-term negative scarring and the longer the unemployment spell, the greater the risk of negative scarring. In Sweden, labour market policies aim at reducing such risks in the form of unemployment benefits, active matching and active labour market policy programmes (ALMPs). However, there is frequent discussion regarding the extent to which these kinds of policies actually reduce the risk of negative scarring. It is often argued that the programmes are of poor quality, particularly during economic downturns, and participants are often not motivated for the task. Likewise, it is claimed that unemployment insurance tends to counteract a quick return to the regular labour market. One problem related to labour market policies is that it has been difficult to examine the impact of such policies. Studies often present results that appear scattered due to differences in what is actually being measured and methodological problems. The uniqueness of this thesis is that it is based on a large-scale longitudinal register of data that has provided important empirical information regarding the long-term effects of labour market policy investments. The quality of data has also enabled the use of evaluation techniques which largely can help to reduce the uncertainty of the findings. More precisely, the research questions examine (1) in what way the level of unemployment benefit functions as protection against unemployment scarring, (2) in what way the ALMPs protect long-term unemployed people from long-term unemployment scarring, (3) at what point in a business cycle the ALMPs are efficient and finally, (4) for whom do the ALMPs function to reduce the risk of negative scarring. In this thesis, scarring effects are measured as the risk of labour market exit, the risk of labour market instability and the risk of future negative wage trajectories. The methods used in most studies are Cox regressions in combination with instrumental variable analysis (the Heckman two-step procedure). The empirical findings indicate that ALMPs worked well to reduce such negative effects both in times of booms (1999) and recessions (1993) and particularly among the youngest and oldest actors on the labour market. They also function particularly well for people with a low level of education. However, it is important not to exclude unemployed people who have a high level of education, in the belief that ALMPs have nothing to offer them, since such people are particularly helped by ALMPs as regards reducing the risk of future labour market instability. It was also found that generous unemployment benefit helped to reduce the risk of future negative wage scarring. In addition to these findings, some mechanisms were identified which proved to be important tools for transforming policies into valuable resources for the unemployed. In this thesis, the value of the findings of these mechanisms is discussed from the perspective of the capability approach. Even if the same investments were made in all unemployed persons, the participants would respond differently to the investment. Some reasons for the inequality in outcomes were found within the programmes and were due to heterogeneity in the unemployment group but some reasons can actually be explained by the converters (mechanisms) that were identified in the studies. Thus, the results emphasise the importance of investing in labour market policies, particularly during economic downturns. This is the time when cuts in unemployment benefit do not help the unemployed back to the labour market since there are very few available jobs to apply for. It is also the time when the long-term unemployed should participate in ALMP-training in order to be prepared for new challenges when the labour market improves again. As a matter of fact, the results show that skills from ALMP-training have a bridging effect which indicates that these skills will be valuable on the labour market for at least another five years after the year of investment. The findings in this thesis are controversial since they differ from most research findings from the beginning of the 1990s which point to poor micro level outcomes. However, the long-term approach of this thesis is the main explanation for these new and different results.  It is argued here that a long-term approach is needed to find out the long-term effects because ALMP participation, particularly ALMP-training, is meant to be a long-term investment in human capital. A long period of time needs to pass between ALMP-investment and evaluation before the effects can show. Reported effects from ALMP investments at the beginning of the 1990s have often been measured on a short-term basis. It is not suggested that short-term effects should be ignored but it is argued that a short-term analysis provides only a fragmental description of reality, and long-term effects should be given greater priority than is usually the case since they affect the labour market prospects of the individuals over a long period of time. This thesis dispels the “myth” about the negative effects generated from ALMPs during the 1990s.

La cicatrisation et la régénération sont les deux processus de réparation observés dans le règne animal. Toutefois, les mammifères ne sont susceptibles de réparer une blessure que par la constitution d'une cicatrice qui ne restitue point la structure et les propriétés du tissu initial. Dans un contexte de brûlure profonde, la cicatrisation, le plus souvent excessive, peut retentir négativement sur la vie de l'individu. A cette aune, nous nous somme proposé de mettre au point des thérapies innovantes, dans un modèle murin de brûlure, dans le but de réduire ou de réorienter une réaction cicatricielle anormale. La première stratégie était une thérapie cellulaire basée sur l'utilisation des cellules stromales mésenchymateuses du tissu adipeux. Bien que les études effectuées aient révélé des aptitudes immunomodulatrices encourageantes, l'utilisation de ces cellules n'a pas apporté de résultats probants pour prétendre combattre la cicatrisation excessive de notre modèle. La seconde stratégie s'appuyait sur les enseignements tirés de la première approche et de la régénération animale. Les brûlures ont été traitées par des jets de plasma froid à pression atmosphérique. La prise en charge des lésions par ce nouvel outil entraina singulièrement une diminution de la zone cicatricielle. Les expériences montrèrent que le plasma circonscrivit la cicatrisation par l'atténuation de l'inflammation et du dépôt matriciel subséquent ; il en résulta une fibrose dermique quasi-inexistante, l'émergence de follicules pileux en régénération et une récupération de l'hypoderme. En conclusion, le plasma froid améliore significativement la cicatrisation des brûlures profondes. / Scarring and regeneration are both repair processes observed in the animal kingdom, even though mammals always heal by a scar tissue formation that never restitute the initial tissue structure and properties. Burns healing can become abnormal and may subsequently affect the person's daily life. Considering pathological healings, we developed innovative regenerative medicine strategies to reduce or redirect the wound healing process towards a better issue in a mouse model of skin burn. First, we performed a cell therapy based on the administration of adipose mesenchymal stromal cells. Although the experiments showed promising immunomodulatory abilities, such cells failed to provide convincing results in our model of excessive burn healing. The second intent was designed after findings from the first approach and knowledge from regenerative models. Deep skin burns were treated by cold atmospheric plasma. We found that plasma-treated lesions were repaired by a considerably diminished scar. Experiments showed that the plasma treatment resulted in almost inexistent fibrosis through a reduction of inflammation and matrix deposition, emergence of regeneration follicles regeneration and a better restitution of hypodermis. In conclusion, cold atmospheric plasma significantly improves healing when applied on skin burns.

疤痕效應(Scarring Effect)所指的當一個人的就業歷程出現失業，失業將會對往後的就業歷程產生長期性的影響，且影響的範圍相當廣，包含收入、就業狀況、身心健康等等。然而，在所有年齡層中，青年是最容易失業且待在勞動市場中時間最長的群體。 　　本研究將在疤痕效應的理論基礎上探討：台灣青年在失業後是否會影響終生的就業歷程、造成長期性工作貧窮的現象。本研究試著從青年找不到適得其所的工作時，其實際工作狀況和生活來理解失業的成因及長期性影響。 　　本研究採取多元方法的研究設計，透過「人力運用擬-追蹤調查資料庫」以及「華人家庭動態資料庫」比較15-29歲有失業經驗的青年及無失業經驗青年，往後薪資及就業狀況，觀察失業的短期性及長期性的影響。並以深度訪談的方式，訪談七位不同背景且在15-29歲期間有3個月以上失業經驗的受訪者，透過訪談青年失業理解連續性脈絡，藉此理解疤痕效應的成因及疤痕效應造成影響的詳細情形。 　　實證結果發現不論觀察期長短，有失業經驗的青年的收入漲幅普遍會低於沒有失業經驗的青年，失業確實會對收入水準造成長期影響。就業情形的差異上，有失業經驗青年陷入再度失業的機率普偏高於無失業經驗青年陷入失業的機率。 　　訪談結果發現疤痕效應的原因有(一)工作經驗不足，無法進入職場；(二)雇主對過短工作經驗的負面評價；(三)人力資本難以積累；(四)社會關係封閉，難以向外得到援助；(五)工作經驗的中斷。 　　本研究透過疤痕效應的理論，指出失業對青年所造成的長期性影響。藉由實證數據及訪談結果，深入理解青年失業所造成的長期性影響及成因，作為解決青年失業問題及工作貧窮上的政策參考。 / The “Scarring Effect” means the unemployment of a person's career path, which will have a long-term impact on the future career path, and have the influence of a wide range, including income, employment status, physical and mental health and so on. However, youth have the highest unemployment rate in all ages and have the longest time in the labor market. 　　This study will explore the theory of scarring effect: whether unemployment will affect Taiwanese youth’s lifetime career path after unemployment, resulting in long-term poverty. This study tries to understand the causes and long-term effects of unemployment from the time when youth find jobs that are not suitable for them. 　　This study is based on a multimethod research approach to compare youth from 15 to 29 years old with unemployed experience and young people with no unemployment experience. Through "Manpower Utilization Quasi-longitudinal Survey" and the “Panel Study of Family Dynamics" in subsequent earnings and employment status, we observe the short-term and long-term effects of unemployment. And through deep-interviews with seven different backgrounds and those who had more than three months of unemployment experience during the 15-29 year old period, we understand the continuity of unemployment, the causes of scar effects and the details of the impact. 　　The empirical results show that regardless of the length of the observation period, the income growth of youth with unemployed experience is generally lower than which of those without unemployed experience. Unemployment will indeed have a long-term impact on income levels. The difference in employment status, the re-unemployment rate of the youth with unemployment experience is higher than which of youth without unemployment experience. 　　The results of interviews finds that the cause of scarring effects are contributed to (1)Lack of working experiences to get work. (2)Employer have negative impression on short working experience.(3)The difficulty of accumulating human capital.(4) Closed social relationships, which is difficult to get assistance from others. (5)Interruption of work experience. 　　This study, through the theory of scarring, points out the long-term effects of unemployment on youth. Through empirical data and interviews, we will understand the long-term impact and causes of youth unemployment as a policy reference to solve the problem of youth unemployment and working poverty.

Myocardial scar, a non-viable tissue which occurs on the myocardium due to the insufficient blood supply to the heart muscle, is one of the leading causes of life-threatening heart disorders, including arrhythmias. Analysis of myocardial scar is important for predicting the risk of arrhythmia and locations of re-entrant circuits in patients’ hearts. For applications, such as computational modeling of cardiac electrophysiology aimed at stratifying patient risk for post-infarction arrhythmias, reconstruction of the intact geometry of scar is required. Currently, 2D multi-slice late gadolinium-enhanced magnetic resonance imaging (LGEMRI) is widely used to detect and quantify myocardial scar regions of the heart. However, due to the anisotropic spatial dimensions in 2D LGE-MR images, creating scar geometry from these images results in substantial reconstruction errors. For applications requiring reconstructing the intact geometry of scar surfaces, 3D LGE-MR images are more suited as they are isotropic in voxel dimensions and have a higher resolution. While many techniques have been reported for segmentation of scar using 2D LGEMR images, the equivalent studies for 3D LGE-MRI are limited. Most of these 2D and 3D techniques are basic intensity threshold-based methods. However, due to the lack of optimum threshold (Th) value, these intensity threshold-based methods are not robust in dealing with complex scar segmentation problems. In this study, we propose an algorithm for segmentation of myocardial scar from 3D LGE-MR images based on Markov random field based continuous max-flow (CMF) method. We utilize the segmented myocardium as the region of interest for our algorithm. We evaluated our CMF method for accuracy by comparing its results to manual delineations using 3D LGE-MR images of 34 patients. We also compared the results of the CMF technique to ones by conventional full-width-at-half-maximum (FWHM) and signal-threshold-to-reference-mean (STRM) methods. The CMF method yields a Dice similarity coefficient (DSC) of 71 +- 8.7% and an absolute volume error (|VE|) of 7.56 +- 7 cm3. Overall, the CMF method outperformed the conventional methods for almost all reported metrics in scar segmentation. We present a comparison study for scar geometries obtained from 2D vs 3D LGE-MRI. As the myocardial scar geometry greatly influences the sensitivity of risk prediction in patients, we compare and understand the differences in reconstructed geometry of scar generated using 2D versus 3D LGE-MR images beside providing a scar segmentation study. We use a retrospectively acquired dataset of 24 patients with a myocardial scar who underwent both 2D and 3D LGE-MR imaging. We use manually segmented scar volumes from 2D and 3D LGE-MRI. We then reconstruct the 2D scar segmentation boundaries to 3D surfaces using a LogOdds-based interpolation method. We use numerous metrics to quantify and analyze the scar geometry including fractal dimensions, the number-of-connected-components, and mean volume difference. The higher 3D fractal dimension results indicate that the 3D LGE-MRI produces a more complex surface geometry by better capturing the sparse nature of the scar. Finally, 3D LGE-MRI produces a larger scar surface volume (27.49 +- 20.38 cm3) than 2D-reconstructed LGE-MRI (25.07 +- 16.54 cm3).

No description available.

Le but de notre étude visait à déterminer si les matrices ECM (extracellular matrix) préparés à partir d'un modèle vertébré (Axolotl) capables de régénérer ses tissus suite à une blessure sont plus efficaces pour stimuler les réponses régénératives chez les animaux non régénérant (par exemple les mammifères). Nous avons testé la capacité de matrice ECM axolotl à améliorer la guérison des plaies cutanées dans des souris et nous les avons comparés à une matrice disponible commercialement (échafaudage Symbios PerioDerm) pour leur efficacité à favoriser la guérison des plaies. Des lésions d'excision ont été créées sur le dos de souris et les animaux ont été regroupés dans différents groupes; a-) ECM de peau axolotl décellularisée (groupe Axolotl), b-) matrice de derme acellulaire Symbios Perioderm (groupe PerioDerm), c-) grillage en titane (groupe témoin); respectivement. Les tissus des plaies ont été récoltés à des moments précis : 7 jours et 30 jours après la blessure pour évaluer la guérison des plaies. La guérison des blessures ayant reçu les différentes matrices a été comparées entre elles en utilisant le test de transillumination et des analyses histologiques. Les résultats indiquent que la ECM de peau d’axolotl décellularisée est bien tolérée par les souris, car aucun rejet n'a été observé. Le groupe qui a reçu l'ECM de la peau axolotl décellularisé a démontré une réépithélialisation, une densité cellulaire, une teneur en collagène (avec une organisation similaire à un tissu intact) et une vascularisation (angiogenèse) élevées par rapport aux groupes PerioDerm et témoins. La présence de follicules pileux était également observé dans le groupe axolotl (qui n'est pas présent dans PerioDerm et groupes de contrôle). Sur la base de nos résultats, l'hypothèse de base semble être correcte en ce qu'une matrice ECM provenant d'un régénérateur puissant semble favoriser la guérison plus efficacement chez les animaux normalement non régénérants. Cependant, des recherches supplémentaires devront être menées pour confirmer ces résultats. / The aim of our study sought to determine whether ECM scaffolds prepared from a vertebrate model (Axolotl) capable of regenerating tissues following injury are more effective at stimulating regenerative responses in non-regenerating animals (e.g., mammals). We tested the ability of axolotl decellularized ECM scaffolds to improve skin wound healing in mammalian models and compare the axolotl skin ECM scaffold to a commercially available one (Symbios PerioDerm scaffold) for efficiency in promoting wound healing. Excisional lesions were created on the back of mice, and animals in different groups were treated by; a-) decellularized axolotl skin ECM (Axolotl group), b-) Symbios Perioderm acellular dermis scaffold (PerioDerm group), d-) Titanized mesh only (Control group); respectively. Wound tissues were harvested at time points: 7- and 30-days post-wounding to assess the scaffolds impact on wound healing. Wound healing was compared between the Axolotl, PerioDerm and Control groups using transillumination test and histological analyses, Results indicate that the decellularized axolotl skin ECM is well tolerated by mammalian models, as no immune rejection was observed. The axolotl group that received the decellularized Axolotl Skin ECM demonstrated high reepithelialization, cellular density, collagen content (in a porous pattern similar to intact skin), vascularization (angiogenesis) compared to PerioDerm and control groups. The presence of hair follicles was also observed in the axolotl group (which is not present in PerioDerm and control groups). Based on our results, the basic hypothesis appears to be correct in that an ECM scaffold from a strong regenerator seems to promote healing more efficiently in non-regenerating animals. However, further research should be conducted to confirm these findings.