No description available.

no / Following traumatic injury, skin has the capacity to repair itself through a complex cascade of biochemical change. The dermis, which contains a load-bearing collagenous network structure, is remodelled over a long period of time, affecting its mechanical behaviour. This study examines the nanomechanical and viscoelastic properties of the upper dermis from human skin that includes both healthy intact and scarred tissue. Extensive nanoindentation analysis shows that the dermal scar tissue exhibits stiffer behaviour than the healthy intact skin. The scar skin also shows weaker viscoelastic creep and capability to dissipate energy at physiologically relevant frequencies than the adjacent intact skin. These results are discussed in conjunction with a visual change in the orientation of collagenous fibrils in the scarred dermis compared with normal dermis, as shown by atomic force microscopy imaging.

Being the longest-lived rodent, naked mole-rats (NMR; Heterocephalus glaber) are an exceptional model for biogerontological research. However, unlike other rodents, not much is known about their wound healing process. To investigate that, full-thickness wounds were created in the back skin of naked mole rats. Our initial data confirmed that wound closure in NMR skin was achieved primarily by reepithelialization and granulation tissue formation, with only ~26% wound contraction, making them an excellent model to study human cutaneous wound healing. Similar to mice and human skin, changes in wound epithelial tongue included progressive enlargement of wound epithelium, increased proliferation and changes in the expression pattern of epidermal markers including K14, K17, integrin α6 and E-cadherin. Further analysis revealed characteristics of reduced scarring in NMR wounds including low collagen I to III ratio, increased HA expression (HMW) and increased fibronectin expression. Transcriptional profiling of TGFβ isoforms and different pro/anti-inflammatory cytokines revealed a balance in the expression and repression of different cytokines, potentially contributing into reduced scarring. Comparison of RNA-seq data from NMR and human fullthickness wounds revealed a delay in the activation of important biological processes and pathways in NMR skin in response to injury. Further analysis based on cultured human and NMR cells revealed differential regulation of TGFβ signalling pathway between both species. 3-D collagen gel contraction assay revealed that NMR fibroblast showed noticeable contraction but independently of TGFβ treatment, while human fibroblast showed marked increased in gel contraction in the presence of TGFβ. In conclusion, NMR can serve as a very useful model to study human cutaneous wound healing. The reduced scarring in NMR could be a result of multiple factors including HMW-HA, balanced cytokine expression and differential regulation of different TGFβ cytokines as observed in the in vitro studies. / The full text will be available at the end of the embargo: 3rd May 2024

Thanks to pioneering scientists and clinicians, prosthetic devices that are controlled by intra-cortical electrodes recording one's 'thoughts' are a reality today, and no longer merely in the realm of science fiction. However, widespread clinical use of implanted electrodes is hampered by a lack of reliability in chronic recordings, independent of the type of electrodes used. The dominant hypothesis has been that astroglial scar electrically impedes the electrodes. However, recent studies suggest that the impedance changes associated with the astroglial scar are not high enough to interfere significantly impair neural recordings. Furthermore, there is a time delay between when scar electrically stabilizes and when neural recordings fail (typically >1 month lag), suggesting that scar, per se, does not cause chronic recording unreliability. In this study, an alternative hypothesis was tested in a rat model, namely, that chronic inflammation surrounding microelectrodes causes a local neurodegenerative state. Chronic inflammation was varied in three ways: 1) stab wound control, 2) age-matched control, and 3) inter-shank spacing of a multishank electrode. The results of this study suggest that chronic inflammation, as indicated by activated microglia and reactive astrocytes, is correlated with local neurodegeneration, marked by neuron cell death and dendritic loss. Surprisingly, axonal pathology in the form of hyperphosphorylation of the protein Tau (the hallmark of many tauopathies, including Alzheimer's Disease) was also observed in the immediate vicinity of microelectrodes implanted for 16 weeks. Additionally, work is presented on a fast, non-invasive method to monitor the astrocytic response to intra-cortical electrodes using electrical impedance spectroscopy. This work provides a non-invasive monitoring tool for inflammation, albeit an indirect one, and fills a gap which has slowed the development of strategies to control the inflammatory tissue response surrounding microelectrodes and thereby improve the reliability of chronic neural recordings. The results of these experiments have significance for the field of neuroengineering, because a more accurate understanding of why recordings fail is integral to engineering reliable solutions for integrating brain tissue with microelectrode arrays.

Our objective is to report mortality rates for ponderosa pine trees in Oregon ten to eleven years after removing a fire-scarred partial cross-section from them, and five years after an initial survey of post-sampling mortality. We surveyed 138 live trees from which we removed fire-scarred partial crosssections in 1994/95 and 387 similarly sized, unsampled neighbor trees of the same species. These trees were from 78 plots distributed over about 5,000 ha at two sites in northeastern Oregon. The annual mortality rate for sectioned trees from 1994/95 to 2005 was 3.6% compared to 2.1% for the neighbor trees. However, many of the trees that died between 2000 and 2005 were likely killed by two prescribed fires at one of the sites. Excluding all trees in the plots burned by these fires (regardless of whether they died or not), the annual mortality rate for sectioned trees was 1.4% (identical to the rate from 1994/95 to 2000) compared to 1.0% for neighbor trees. During these fires, a greater proportion of sectioned trees died than did catfaced neighbor trees (80% versus 64%) but the difference was not significant.

Corticosteróides injetáveis têm sido usados em fonocirurgia com o intuito de se prevenir fibrose da prega vocal pelos seus efeitos na cicatrização e assegurar uma melhor qualidade vocal. O objetivo deste estudo é avaliar histologicamente os efeitos da infiltração de dexametasona no processo agudo de cicatrização, 3 e 7 dias após uma lesão induzida cirurgicamente na prega vocal de coelhos, através da análise quantitativa da reação inflamatória e da deposição de colágeno. Uma incisão cirúrgica foi realizada nas pregas vocais de 12 coelhos, seguido da injeção de 0,1ml de dexametasona na prega vocal esquerda. A prega vocal direita não recebeu nenhuma injeção e serviu como grupo controle. As laringes foram coletadas 3 e 7 dias após a cirurgia. As pregas vocais foram histologicamente analisadas com hematoxilina-eosina para quantificar a resposta inflamatória e picrossírius-red para quantificar a deposição de colágeno. Quantitativamente, não houve diferença significativa na resposta inflamatória das pregas vocais com corticosteróide em relação ao controle. A deposição de colágeno no grupo com corticóide foi estatisticamente menor em 3 dias e permaneceu menor em 7 dias após a lesão cirúrgica (p=0,002). Esses resultados sugerem que os corticosteróides diminuem a deposição do colágeno no processo agudo da cicatrização / Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold due to their effects on wound healing, and to assure better voice quality. The aim of this study is to evaluate histologically the effects of dexamethasone infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically-induced injury, by quantification of the inflammatory reaction and collagen deposition. A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 ml dexamethasone (4 mg/ml) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histological analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for quantification of collagen deposition. There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and the control folds. However, collagen deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after the injury (p = 0.002). The present results suggest that dexamethasone reduces collagen deposition during acute vocal fold wound healing

A água doce e potável representa um dos maiores desafios da humanidade. A tendência é reconhecer a água como um elemento natural de valor econômico, jurídico e social, cuja ameaça de escassez começa a ser debatida com maior interesse pela Organização das Nações Unidas. E os reservatórios de água doce e potável demandam uma proteção ambiental complexa, por conjugar o uso racional e a necessidade de desenvolvimento econômico e social. Por isso, nesse trabalho, propomos discutir sobre as formas de assegurar a continuidade do abastecimento das águas subterrâneas, para que possam servir às gerações futuras. / The sweet and drinking water represent one of the greatest challenges of humankind. The trend is to acknowledge water as a natural element with economic, legal and social values, which threat of scarcity commences to debate with larger interest for the United Nations Organization. And the reservoirs of sweet and drinking water demand a complex environmental protection, for conjugating the rational use and the necessity of economical and social development. Therefore, in that paper, we propose to discuss the means to legally ensure the continuity of subterranean water supply, so that they can attend the future generations.

Orientador: Aristides Augusto Palhares Neto / Resumo: Introdução: A cicatriz desempenha um importante papel no resultado final de uma cirurgia. Muitos fatores são implicados no processo de cicatrização patológica, e diversos produtos e curativos foram desenvolvidos para prevenção de cicatriz hipertrófica e quelóide, porém poucos tem evidências que o suportem. Objetivos: Comparar o resultado da cicatriz cirúrgica após utilização da fita de silicone e da fita microporosa. Métodos: Realizamos um ensaio clínico controlado, cego e randomizado, onde um lado da incisão foi randomizado para receber a fita de silicone e o outro lado recebeu o tratamento controle (fita adesiva microporosa). Foram selecionadas pacientes submetidas a abdominoplastia ou mastoplastia de aumento com implantes de silicone no período de maio a outubro de 2016. A Escala de Cicatrização de Vancouver foi utilizada para avaliar as cicatrizes. Resultados: Foram selecionadas para o estudo 17 pacientes. A idade média das pacientes foi de 31,4 ± 6,7, sendo a mínima de 20 e a máxima de 45 anos. Vemos na comparação dos tipos de curativo que os valores de p foram próximos a 5%, sugerindo uma associação do uso da fita de silicone com melhores resultados estéticos e funcionais da cicatriz em relação à fita microporosa. Notamos também que os dois tipos de curativo tiveram uma redução significativa em seus escores do primeiro para o terceiro mês (traduzindo uma melhora no aspecto da cicatriz), porém a fita de silicone teve uma redução superior à fita microporosa (45,6% e 39,2%... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Anaplastic Lymphoma Kinase (ALK) is a Receptor Tyrosine Kinase (RTK) and an oncogene associated with several human diseases, but its normal function in humans and other vertebrates is unclear. Drosophila melanogaster has an ALK homolog, demonstrating that the RTK has been conserved throughout evolution. This makes Drosophila a suitable model organism for studying not only Drosophila ALK function, but also to study mammalian forms of ALK. In Drosophila the ligand Jeb activates ALK, initiating signaling crucial for visceral mesoderm development. The activating ligand for mammalian ALK is unclear, and for this reason Drosophila was employed in a cross-species approach to investigate whether Drosophila Jeb can activate mouse ALK. Jeb is unable to activate mouse ALK, and therefore mouse ALK is unable to substitute for and rescue the Drosophila ALK mutant phenotype. This suggests that there has been significant evolution in the ALK-ligand relationship between the mouse and Drosophila. In humans ALK has recently been shown to be involved in the development of neuroblastoma, a cancer tumor in children. I have developed a Drosophila model for examining human gain of function ALK mutants found in neuroblastoma patients. The various ALK variants have acquired point mutations in the kinase domain that have been predicted to activate the RTK in a constitutive and ligand independent manner. When expressed in the fly eye, active human ALK mutants result in a rough eye phenotype, while inactive wild type ALK does not, due to the lack of an activating ligand in the fly. In this way  several of the ALK mutations identified in neuroblastoma patients could be confirmed to be activated in a ligand independent manner. Moreover, a novel ALK mutant; ALKF1174S, was discovered in a neuroblastoma patient and was in the Drosophila model shown to be a gain of function mutation, and a previously predicted gain of function mutation; ALKI1250T, was shown to be a kinase dead mutation. This fly model can also be used for testing ALK selective inhibitors, for identifying activating ligands for human ALK and for identifying conserved components of the ALK signaling pathway. Gut musculature development in Drosophila is dependent on ALK signaling, while somatic muscle development is not. Proteins of the Wasp-Scar signaling network regulate Arp2/3-complex mediated actin polymerization, and I have investigated their function in visceral and somatic muscle fusion. I found that Verprolin and other members of this protein family are essential for somatic but not visceral muscle development. Despite fusion defects in both tissues in Verprolin and other examined mutants, gut development proceeds, suggesting that fusion is not crucial for visceral mesoderm development. Hence the actin polymerization machinery functions in both somatic and visceral muscle fusion, but this process only appears to be essential in somatic muscle development. / Exploiting Drosophila as a model system for studying Anaplastic Lymphoma Kinase in vivo

Submitted by ANA LUÍZA ALVES PINTO LUNA null (analualves@hotmail.com) on 2017-09-25T18:42:11Z No. of bitstreams: 1 DISSERTAÇÃO MESTRADO Ana Luiza Alves Pinto Luna.pdf: 1782319 bytes, checksum: 832d2855b5d3e28f440d7df38d89674c (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-09-27T20:31:58Z (GMT) No. of bitstreams: 1 luna_alap_me_bot.pdf: 1782319 bytes, checksum: 832d2855b5d3e28f440d7df38d89674c (MD5) / Made available in DSpace on 2017-09-27T20:31:58Z (GMT). No. of bitstreams: 1 luna_alap_me_bot.pdf: 1782319 bytes, checksum: 832d2855b5d3e28f440d7df38d89674c (MD5) Previous issue date: 2017-08-25 / Introdução: A cicatriz desempenha um importante papel no resultado final de uma cirurgia. Muitos fatores são implicados no processo de cicatrização patológica, e diversos produtos e curativos foram desenvolvidos para prevenção de cicatriz hipertrófica e quelóide, porém poucos tem evidências que o suportem. Objetivos: Comparar o resultado da cicatriz cirúrgica após utilização da fita de silicone e da fita microporosa. Métodos: Realizamos um ensaio clínico controlado, cego e randomizado, onde um lado da incisão foi randomizado para receber a fita de silicone e o outro lado recebeu o tratamento controle (fita adesiva microporosa). Foram selecionadas pacientes submetidas a abdominoplastia ou mastoplastia de aumento com implantes de silicone no período de maio a outubro de 2016. A Escala de Cicatrização de Vancouver foi utilizada para avaliar as cicatrizes. Resultados: Foram selecionadas para o estudo 17 pacientes. A idade média das pacientes foi de 31,4 ± 6,7, sendo a mínima de 20 e a máxima de 45 anos. Vemos na comparação dos tipos de curativo que os valores de p foram próximos a 5%, sugerindo uma associação do uso da fita de silicone com melhores resultados estéticos e funcionais da cicatriz em relação à fita microporosa. Notamos também que os dois tipos de curativo tiveram uma redução significativa em seus escores do primeiro para o terceiro mês (traduzindo uma melhora no aspecto da cicatriz), porém a fita de silicone teve uma redução superior à fita microporosa (45,6% e 39,2% respectivamente). Conclusão: A fita de silicone parece ser discretamente mais efetiva em promover melhoria da cicatriz cirúrgica a médio prazo, com base na Escala de Cicatrização de Vancouver, em relação à fita microporosa. Ambas as fitas apresentaram melhora no escore do terceiro mês de pós-operatório quando comparados ao primeiro mês, porém a fita de silicone apresentou uma redução superior. Os pontos de maior diferença constaram na pliabilidade, altura e vascularização. Quanto aos efeitos adversos, ambos os curativos apresentaram como intercorrência o surgimento de rash cutâneo, sendo que o surgimento foi maior com o uso da fita de silicone (RR=2). / Introduction: The scar plays an important role on result of any surgery. Many factors are implied in the pathologic scar healing process. Lots of dressings and products have been developed to prevent formation of hypertrophic scar and keloids, but few have been supported by evidence. Objective: To compare the surgical scar result after using silicone-gel sheeting and microporous tape. Methods: We’ve performed a blind and randomized clinical trial, using the silicone-gel sheeting on one side of the surgical incision and the control-treatment on the opposite site (microporous tape). Selected patients underwent abdominoplasty or augmentation mastoplasty with silicone implants from May to October of 2016. The Vancouver Scar Scale (VSS) was assessed to evaluate the scars. Results: Seventeen patients were selected for the study. The mean age was 31,4 ± 6,7, with the youngest at 20 and the oldest with 45 years-old. Comparing the two dressing types, we found that p values were close to 5%, suggesting that the siliconegel sheeting promotes better aesthetic and functional results over the microporous tape. We also noticed that both dressings had a significant reduction on the VSS score from the first to the third month of post-operative, although the silicone-gel sheeting had a superior reduction (45,6% and 39,2%). Conclusion: Silicone-gel sheeting appears to be slightly more effective in promoting mid-term improvement of surgical scar, related to the VSS, and compared to microporous tape. Both dressings provided an upgrade on VSS score from the first to the third post-operative month evaluation, but the silicone-gel sheeting was superior. Most of the difference relied on pliability, height and vascularization. As to the side effects, both dressings presented with skin rash, but the silicone-gel sheeting had a higher occurrence (RR=2).