M.Tech. / Striae are linear scars in the dermis which arise from rapid stretching of the skin over weakened connective tissue (de Angelis & Adatto, 2010). Striae occur when collagen production cannot keep pace with a sudden growth of the underlying tissues. Striae have no medical consequences but are frequently distressing to those afflicted. These disfiguring marks are usually caused by excessive stretching of the skin that may occur with pregnancy, adolescent growth spurts, obesity and weightlifting (Kang & Arbor, 1998). Striae usually appear on the abdomen, thighs, buttocks, breasts and extremities. Patients’ quality of life can be enhanced with the effective management of these unsightly marks. Modalities of treatments that exist for the treatment of striae have been advocated with varying success and side effects (Manuskiatti et al., 2010). The aim of this study was to determine the efficacy of the topical application of a homoeopathic preparation Thiosinaminum 1X on the appearance of striae. The research was a double-blind placebo controlled study which took place at the Homoeopathy Health Centre which is located at the University of Johannesburg(Doornfontein campus). Forty female participants aged between eighteen and thirty-five were randomly selected to take place in the study. The study was conducted over a period of twelve weeks. On recruitment, the participants were required to read and sign the information sheet (Appendix A) and consent form (Appendix B) assisted by the researcher. Participants were asked to complete a questionnaire (Appendix C) to determine contributing factors e.g. duration of the stretch marks, the cause of the stretch marks and any disease that may contribute to the formation of stretch marks. A pertinent case and vital signs were taken at the initial consultation to eliminate any pathologies. All potential participants were required to present with stretch marks on the thighs or buttocks present for at least 6 months prior to the study. The stretch marks needed to have had a minimum length of 50mm and a maximum length of a 100mm. The researcher was responsible for choosing the designated area that was treated. The most distinct striae were selected by the researcher according to criteria for treatment. The researcher took photographs of the treatment areas at the commencement of the study and this was repeated at the end of the study (Appendix I). The length of the most prominent stretch mark (according to criteria) below was also measured on the commencement of the study. To physically iv measure the most prominent stretch mark a string and a ruler was utilized. The same ruler and ball of string was used each time to ensure validity of the results. A new piece of string was cut and tied in a knot at the tip and placed on the stretch mark itself to mould to its shape and thereafter it was placed on a ruler to determine the measurements in millimeters. To ensure that the same stretch mark was measured every time, the researcher measured out the distance between the stretch mark and a defined anatomical point for all the participants. The stretch mark was traced using plotting paper. The participants were required to apply the cream twice daily for the duration of the study. Participants were able to rate their satisfaction on a monthly basis by completing a questionnaire. The results of the study indicated that there was no improvement in the length of striae however there was more improvement in satisfaction ratings throughout the study from the experimental group.

No / Recurrent fires have a considerable potential to influence the structure and composition of savanna vegetation. In Mole National Park in Ghana, the policy is to burn the vegetation annually early in the dry season. This study aimed to assess the effects of these perennial fires on the trees and shrubs of the Park. To achieve this, scars on tree bole bases as well as mortality and top-kill to trees ¿ 2 m tall resulting from perennial fires were assessed in twenty 50 m x 50 m plots in the savanna vegetation near Grupe camp at the south-western section of the Park. Fire scars on tree bole bases were widespread, but were significantly more frequent on large trees (> 5 m tall) than small ones (< 2 m tall). Also, certain tree species, notably Burkea africana and Detarium microcarpum were more prone to scarring. The greater proportion of the scars had reached an advanced stage and the affected individuals were either moribund or were likely to be killed by subsequent fires or toppled by the wind. Contrary to the popular opinion that fire generally affects tree recruitment and not adult survival, fire-induced mortality and top-kill to large trees (> 5 m tall) was widespread among all the tree species, particularly Acacia dudgeoni, Burkea africana, Detarium microcarpum and Vitellaria paradoxa. These fire impacts will likely lead to changes in the relative abundance of the constituent tree species as well as a decline in the density of woody elements in the plant community as a whole unless burning frequency is reduced. The areas for which these predicted vegetation changes are valid can be generalized to include the vegetation in the northern half of the Park where similar conditions of high fuel load and intense fires are likely to prevail.

Many surgical procedures in the head and neck regions produce visible scarring. The most common of these surgeries are tracheotomies and thyroidectomies. The recent COVID-19 pandemic has caused an increase in tracheotomy scars, particularly in those who survived severe infection with the disease and required long-term ventilation. Individuals with neck scars are at an increased risk of health consequences such as reduced quality of life, depression, and negative body image. Research on attitudes toward and reactions to individuals with such scarring is limited. The purpose of this study is to examine how people rate images of scarred individuals on personality and attractiveness attributions. In addition, dermatography, or medical tattooing, is an emerging cosmetic intervention used to mask scarring, and has demonstrated positive outcomes in cases of breast cancer. This study further aims to examine how people rate images of individuals with scars covered with medical tattoos. Personality attributions were measured using the Five Factor Scale and various dimensions of attractiveness were measured using the Interpersonal Attraction Scale. Acceptability of medical tattooing as a cosmetic intervention for head and neck scars was also examined using the Decision Satisfaction Scale. Participants consisted of 456 young adults and were presented with two series of images, each consisting of a young adult, the young adult with a neck scar, and the young adult with a tattoo covering the scar. Participants were asked to rate each image directly after viewing. We hypothesized that those without scars and those with medical tattoos would be rated more positively on personality and attraction scales than would those with scars. Multivariate analysis confirms scarring and medical tattoos influence personality attributions. Non-scarred individuals were rated more positively in perceived Agreeableness and Conscientiousness traits when compared to scarred individuals. However, when compared to non-scarred individuals, scarred individuals were rated more positively on the Openness to Experience trait. This demonstrates the variability of impressions that a neck scar can elicit. Reactions to scars covered with tattoos were mixed. Medical tattoo recipients were rated more positively on Extraversion and Openness to Experience traits compared to scarred individuals. They were also rated lower on Conscientiousness compared to scarred individuals. Acceptability of medical tattooing was higher in participants who reported lower levels of religiosity and higher levels of social media use. This study highlights the varying effects that head and neck scars can have on appearance and the use of medical tattooing in clinical practice.

Ligament tears are more prevalent than all other knee injury pathologies, and contribute significantly to musculoskeletal joint pain and disability reported worldwide. Despite current soft tissue reconstruction techniques, the injured ligament fails to regenerate due to dysregulated cell-extracellular matrix (ECM) interactions that culminate in scar formation. Hallmarks of scar formation, or fibrotic healing include disorganized ECM, pathological stiffness or tissue rigidity, and the accumulation and persistence of myofibroblasts. A primary driver of fibrosis, myofibroblasts are characterized by high contractility, excessive deposition of collagen type I, coupled with inflammatory and fibrotic signaling. Notably these cells are critical early on in the response to injury, by aiding in the contracture of the wound bed and depositing collagen to repair the injury site. However, myofibroblasts are not capable of fully regenerating the native ligamentous matrix, and resolution of the phenotype is necessary in order to cue surrounding cells, prevent chronic inflammation and aberrant tissue remodeling. Persistence of the myofibroblast phenotype thus leads to a ligament scar that is functionally weaker than the healthy tissue matrix, characterized by significantly different histological, biochemical, and biomechanical properties. The consequential instability of this scar disrupts load distribution within the knee joint and increases the risk of subsequent injury, osteochondral degeneration, and ultimately, the development of post-traumatic osteoarthritis. Therefore, there is a critical need for strategies that target the inflammatory and fibrotic myofibroblast phenotypes for soft tissue healing. It follows that the overarching goal of this thesis is to engineer an immunomodulatory matrix to regulate myofibroblast activation and downstream fibrogenic signaling. To this end, models of soft tissue fibrotic repair are explored in order to test the central hypothesis that cues from the repairing ECM play an important role in regulating myofibroblast activation and persistence. Specifically, this thesis will compare myofibroblast differentiation and signaling in three in vitro models of tissue repair: 1) 2D on tissue culture polystyrene (TCPS), and two 3D models namely 2) collagen hydrogel and 3) electrospun collagen fiber matrices. As expected, on the 2D model, a persistent myofibroblast phenotype could be generated over time with an optimized transforming growth factor beta 1 (TGF-β1) stimulation protocol. To create repair-relevant 3D matrix models, we engineered collagen hydrogels with controlled mechanical properties, as well as electrospun fiber platforms that isolate key matrix factors including, collagen content, stiffness, fiber diameter, and alignment. These models emulate the connective tissue repair process via recapitulating the increasing matrix stiffness and fiber assembly of the early (granulation tissue), proliferative, and remodeling stages of the repair. Myofibroblast differentiation potential, parallel inflammatory and fibrotic cytokine secretion, as well as matrix remodeling potential were observed to be dependent on matrix model parameters. Moreover, single-cell resolution RNA sequencing revealed heterogenous myofibroblast populations within the context of response to engineered collagenous substrates. Specifically, myofibroblast accumulation was observed on hydrogel substrates that recapitulate the pathologically stiff mechanics and disorganization of fibrotic scar tissue while architectural cues of engineered fiber substrates prevented myofibroblast differentiation in a diameter and alignment-dependent manner. Moreover, nanoscale fibers elicited the greatest anti-fibrotic and anti-inflammatory properties compared to microscale fibers and stiff collagen-based hydrogels. Throughout, this thesis also explores the contribution of NF-κB signaling to myofibroblast plasticity and persistence using engineered collagen-based platforms, highlighting the dynamic role of myofibroblasts as critical immunoregulating cells. The NF-κB signaling pathway is implicated in a broad array of fibrotic and chronic inflammatory conditions, and more recently has been associated with survival of persistent myofibroblast populations in soft-tissue fibrosis and tendon degeneration models. In this thesis, NF-κB activation was seen to be related to the persistent myofibroblast phenotype and increase over time in both 2D TCPS and 3D collagenous hydrogel matrices that mimic pathologically stiff scar tissue, while a temporally dependent activation pattern was observed in electrospun collagen fiber-based models. At the transcriptional level, NF-κB survival signaling was significantly enriched in myofibroblast populations supported by TCPS and stiff collagen-based hydrogels but downregulated on soft hydrogels and fibers with decreasing fiber diameter that prevented robust myofibroblast differentiation at single cell resolution. Building upon these new insights regarding matrix cues that drive myofibroblast activation, we designed an immunomodulatory matrix that mediates small molecule release targeting NF-κB inhibition. The immunomodulatory matrix achieved robust amelioration of the myofibroblast phenotype as well as reduced the secretion of key inflammatory and fibrotic cytokines by these cells. Moreover, a similar anti-fibrotic response was seen for human ligament fibroblasts treated with these matrices. Collectively, this thesis work presents a systematic evaluation of myofibroblast plasticity and persistence within the context of 2D (TCPS), 3D (collagen-based hydrogels), and finally 3D with defined microarchitectural cues (electrospun collagen-based fibers) that recapitulate the progressive stages of scar-mediated healing, and reveals NF-κB as a promising target for reducing myofibroblast persistence. Moreover, the immunomodulatory control of myofibroblast plasticity and persistence via matrix cues coupled with NF-κB inhibition informs future strategies for true ligament healing.

No description available.

付記する学位プログラム名: 京都大学卓越大学院プログラム「先端光・電子デバイス創成学」 / 京都大学 / 新制・課程博士 / 博士(理学) / 甲第23694号 / 理博第4784号 / 新制||理||1685(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 川上 則雄, 教授 柳瀬 陽一, 教授 高橋 義朗 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

The occurrence of wildfire is influenced by a suite of factors ranging from "top-down" influences (e. g., climate) to "bottom-up" localized influences (e. g., ignitions, fuels, and land use). We carried out the first broad-scale assessment of wildland fire patterns in northern Mexico to assess the relative influence of top-down and bottom-up drivers of fire in a region where frequent fire regimes continued well into the 20th century. Using a network of 67 sites, we assessed (1) fire synchrony and the scales at which synchrony is evident, (2) climate drivers of fire, and (3) asynchrony in fire regime changes. We found high fire synchrony across northern Mexico between 1750 and 2008, with synchrony highest at distances < 400 km. Climate oscillations, especially El Nino-Southern Oscillation, were important drivers of fire synchrony. However, bottom-up factors modified fire occurrence at smaller spatial scales, with variable local influence on the timing of abrupt, unusually long fire-free periods starting between 1887 and 1979 CE. Thirty sites lacked these fire-free periods. In contrast to the neighboring southwestern United States, many ecosystems in northern Mexico maintain frequent fire regimes and intact fire-climate relationships that are useful in understanding climate influences on disturbance across scales of space and time.

Pentoxifilina (PTF), um derivado da metilxantina, tem ação terapêutica como agente antifibrótico. In vitro, a PTF causa inibição na produção de colágeno, glicosaminoglicanos e fibronectina, bem como promove acentuada redução na proliferação dos próprios fibroblastos de quelóides. A PTF na concentração de 1.000 g/mL foi seletiva no controle da inibição da síntese protéica pelos fibroblastos. O objetivo deste estudo foi verificar o comportamento in vitro de fibroblastos oriundos de cicatrizes hipertróficas (HSHF) e de pele não-cicatricial (NHF) na presença e ausência de PTF (1.000 g/mL), quanto à: proliferação celular, produção de colágeno e capacidade dos fibroblastos gerarem contração em modelo experimental de matriz de colágeno. Para tanto, foram utilizados fibroblastos cultivados a partir de amostras de cicatrizes hipertróficas e pele não-cicatricial doadas, com finalidade de pesquisa, pelo banco de Tecidos do Instituto Central do Hospital das Clínicas da FMUSP. Culturas celulares expostas a PTF apresentaram diminuição na proliferação celular em HSHF (46,35%) e em NHF (37,73%) (p<0,0001). Na presença de PTF, foi observada seletividade de inibição na síntese de colágenos, havendo inibição mais expressiva de colágeno tipo III em HSHF e de colágeno tipo I em NHF (p<0,0001). O modelo experimental de matriz de colágeno povoada por fibroblastos de cicatriz hipertrófica apresentou contração menor (12%) na presença de PTF (p<0,0001), em relação à sua ausência / Fibroblasts are thought to be partially responsible for the persisting contractile forces that result in burn contractures. Using a monolayer and fibroblast populated collagen lattice (FPCL) three-dimensional (3D) model we subjected hypertrophic scar and non-cicatricial fibroblasts to the antifibrogenic agent pentoxifylline (PTF) 1000g/mL attempting to reduce proliferation, collagen type I and III synthesis and contraction in this 3D model. Fibroblasts were isolated from post burn hypertrophic scars (HSHF) and non-scarred skin (NHF). Cells were grown in monolayer or incorporated into FPCL\'s and exposed to PTF. In monolayer, cell number proliferation was reduced (46.35% in HSHF group and 37.73% in NHF group) p<0,0001. The PTF also demonstrated to be selective on collagen type I and III synthesis inhibition suggesting higher inhibition of collagen type III on HSHF group and more evident inhibition of type I on NHF group. FPCL\'s containing PTF had surface areas reduced in about 12% p<0,0001. PTF showed inhibition effects on cell proliferation and reduced contraction in both HSHF and NHF

Die Arbeit befasst sich mit zweierleiZum einen wird der STM-Abbildungsprozess simuliert, indem Probe und Spitze durch zweidimensionale Sommerfeld-Metalle frei waehlbarer Geometrie beschrieben werden und der Tunnelstrom im Transfer-Hamiltonian-Formalismus bestimmt wird. Die Berechnung der Eigenzustaende der Elektroden erfolgt numerisch durch Diskretisierung der Schroedingergleichung im Differenzenverfahren. Ueber die geometrische Entfaltung der erhaltenen Konstantstromprofile mit der Spitzengeometrie werden der Vergleich zum geometrischen (mechanischen) Abtasten gezogen und Moeglichkeiten einer Vermessung von Spitze und Probe diskutiert. Zum anderen wird durch Berechnung von Eigenzustaenden in grossen zweidimensionalen Potentialkaesten (Quantenbillards) endlicher Wandhoehe der Frage nachgegangen, welchen Einfluss klassisch verbotene Gebiete (Aussenraum, Tunnelbarriere) auf Eigenfunktionen in semiklassisch grossen Systemen haben. Betrachtet wird insbesondere ein Gesamtsystem bestehend aus zwei Potentialkaesten, die ueber eine Tunnelbarriere koppeln (¨Quantenbillards endlicher Wandhoehe im Tunnelkontakt¨). Bei einer Reihe von Zustaenden zeigen sich Scars, die aus der Barriere austreten und in diese zuruecklaufen. Das Gesamtsystem ist in hohem Masse nichtintegrabel, ¨sichtbar¨ wird dieses aber nur fuer Bahnen entweder des Kontinuums oder fuer komplexe Orbits. Eine semiklassische Beschreibung dieses Phaenomens mit der gegenwaertigen, auf klassischen Orbits fussenden Theorie periodischer Bahnen ist nicht mehr moeglich. Die Einbeziehung komplexer Orbits oder Bahnen des Kontinuums (¨ungebundener Orbits¨) wird durch diese Ergebnisse angemahnt.

Pentoxifilina (PTF), um derivado da metilxantina, tem ação terapêutica como agente antifibrótico. In vitro, a PTF causa inibição na produção de colágeno, glicosaminoglicanos e fibronectina, bem como promove acentuada redução na proliferação dos próprios fibroblastos de quelóides. A PTF na concentração de 1.000 g/mL foi seletiva no controle da inibição da síntese protéica pelos fibroblastos. O objetivo deste estudo foi verificar o comportamento in vitro de fibroblastos oriundos de cicatrizes hipertróficas (HSHF) e de pele não-cicatricial (NHF) na presença e ausência de PTF (1.000 g/mL), quanto à: proliferação celular, produção de colágeno e capacidade dos fibroblastos gerarem contração em modelo experimental de matriz de colágeno. Para tanto, foram utilizados fibroblastos cultivados a partir de amostras de cicatrizes hipertróficas e pele não-cicatricial doadas, com finalidade de pesquisa, pelo banco de Tecidos do Instituto Central do Hospital das Clínicas da FMUSP. Culturas celulares expostas a PTF apresentaram diminuição na proliferação celular em HSHF (46,35%) e em NHF (37,73%) (p<0,0001). Na presença de PTF, foi observada seletividade de inibição na síntese de colágenos, havendo inibição mais expressiva de colágeno tipo III em HSHF e de colágeno tipo I em NHF (p<0,0001). O modelo experimental de matriz de colágeno povoada por fibroblastos de cicatriz hipertrófica apresentou contração menor (12%) na presença de PTF (p<0,0001), em relação à sua ausência / Fibroblasts are thought to be partially responsible for the persisting contractile forces that result in burn contractures. Using a monolayer and fibroblast populated collagen lattice (FPCL) three-dimensional (3D) model we subjected hypertrophic scar and non-cicatricial fibroblasts to the antifibrogenic agent pentoxifylline (PTF) 1000g/mL attempting to reduce proliferation, collagen type I and III synthesis and contraction in this 3D model. Fibroblasts were isolated from post burn hypertrophic scars (HSHF) and non-scarred skin (NHF). Cells were grown in monolayer or incorporated into FPCL\'s and exposed to PTF. In monolayer, cell number proliferation was reduced (46.35% in HSHF group and 37.73% in NHF group) p<0,0001. The PTF also demonstrated to be selective on collagen type I and III synthesis inhibition suggesting higher inhibition of collagen type III on HSHF group and more evident inhibition of type I on NHF group. FPCL\'s containing PTF had surface areas reduced in about 12% p<0,0001. PTF showed inhibition effects on cell proliferation and reduced contraction in both HSHF and NHF