The natural history of scar maturation in humans has been described by Bond et al. (2008b) in a male European Continental Ancestry Group (ECAG). It is important that the natural history of scar maturation in humans is established for all skin types. This study therefore aims to describe clinically and histologically the maturation of scars in male volunteers from the African Continental Ancestry Group (ACAG).This study was performed as a single centre, methodology trial. Three incisions and a punch biopsy were carried out on each arm. Monthly assessments of the resultant scars included: investigator scar assessments; scar photography; VAS scoring by an Independent External Scar Assessment Panel; and objective measures of colour and scar mechanics. At various time points scars were excised for histology. Sixty male subjects of African Continental Ancestry between the ages of 18-56 years were recruited to take part in the study. The clinical appearance of a scar in the ACAG improves with time. Scar colour mismatch decreases and the mechanical properties of scars improve with time. Scar width increased over the 12 months. With the exception of scar contour and scar redness, a steady state was not achieved. Volunteer skin type was shown to influence the resulting scar appearance and not age. The histology of scar maturation in the ACAG over 12 months was described and scars classified into three groups each displaying a different rate of longitudinal progression of scar maturation. The process of collagen maturation is still ongoing at month 12; many scars demonstrated a prolonged high turnover state of collagen synthesis and degradation, rete ridge restoration and angiogenesis were still ongoing with persistent inflammation identified in scars up to Month 12. There is a strong correlation shown between the Clinical VAS scores and the Histology VAS scores for the papillary dermis which is of better quality than the reticular dermis. There is some evidence that young people (ACAG) and volunteers with darker skin have poorer scar histology. The spectrophotometry data indicated that the Fitzpatrick Skin Type Classification is a useful method of classifying the varying skin colours of this group of volunteers. In conclusion, scar maturation in the ACAG occurs as a series of defined macroscopic and microscopic stages over the course of 1 year. The process of scar maturation is not complete at 12 months. All scars showed evidence of improvement over the course of the study influenced in part by volunteer skin type and age. Results suggest that scar maturation in this study group occurs at a different rate and is of a different quality, compared to current knowledge of scar maturation in the ECAG.

M.Ed. / A person constitutes his world and determines to a large extent his happiness by means of choices. The individual find himself in a society with a network of relationships wherein several values and views of life are representative. In this complex structure of views and relationships a person can easily feel unfettered in the midst of choices in respect of which he does not feel ready to take a view. It is against this background that a study was made as to the education of responsible choices as a means of coping. The goal of the study was to investigate the making of choices as a means of coping against the background of a fundamental-agogic perspective. It shall also be endeavoured to highlight the educational implications of the findings and to express same in functional terms. To determine what the underlying basis of a person's daily choices is, it is necessary to determine a person essential characteristics from a universally valid perspective. This essential characteristics are then brought in connection with the ground motives which regulate a person's daily existence. In futherance of the universally valid perspective the motives relating to personal aspects and to other people within the ideological context and how such motives are manifested within the specific context are investigated. In futherance of the fenomenologistic view on choices, it will be shown what the educational requirements are when the exercise of choices takes place. It will also be shown concisely how a lack of choice-awareness may be a contributing factor in socioeducational problem areas for instance misbehaviour and suicide amongst the youth. The most important findings from the above mentioned study are the following: It is the task of the educator to make the educant aware that he has, as a human being, a choice potential and to encourage him to make use of such potential. An awareness of choices as a life-skill should underlie the rational making of choices. A persons options are determined by his specific time-space situation and the parameters of his responsibility. Because of the uniqueness of every person's circumstances rigid directives of choices cannot be fundamentally or universally valid. There are however certain singular core matters which are generally present in the education of choices namely: The possibility of education toward choices exists because the exercise of choices is a conscious mental process. Through choices the educant obtains a share in his growth process and will his helplessness be gradually reduced. A person should exercise choices from within the safe basis of a value structure to experience order and security. When the educator makes the educant aware of his choice-potential, he should also unfold the sense of life to him, because choices one makes in relation to meaning of his existence also determines to a great extent the goals of the other choices which he will make. The educant should obtain the opportunity for making choices in a climate of responsible discipline. By utilizing choices as a life skill, a person can answer to his basic motives and anthropological needs. Because of choices a person can establish himself as somebody and can enter into relationships with the others of his existence being the divine, his fellowman and objects.

Orientador: Miguel de Arruda / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Educação Física / Made available in DSpace on 2018-08-24T03:49:18Z (GMT). No. of bitstreams: 1 GomezCampos_RossanaAnelice_D.pdf: 1709692 bytes, checksum: 7ee06ef2cd6aa9b11142d3f018b6f1e8 (MD5) Previous issue date: 2014 / Resumo: Objetivo: O estudo teve por objetivo geral avaliar o crescimento físico e a maturação somática de crianças e adolescentes da Rede de Ensino Fundamental de Campinas. Os objetivos específicos foram: a) comparar o crescimento físico com a referência internacional do CDC-2012 e construir os valores referenciais para as crianças e adolescentes; e b) validar a técnica de predição da maturação somática (Mirwald) e desenvolver uma equação para determinar o Pico de velocidade de crescimento de forma transversal. Metodologia: Foi realizado um estudo descritivo transversal. A amostra foi constituída por 6531 indivíduos, sendo selecionados de forma probabilística (estratificado) 3315 meninos e 3216 meninas entre 6 a 17 anos de idade (IC=95%). Foram avaliadas as variáveis de idade decimal, peso corporal, estatura e estatura tronco-cefálica. Calculou-se o Índice de Massa Corporal (IMC) e Pico de velocidade de crescimento (anos de velocidade) para ambos os sexos. O tratamento estatístico utilizado consistiu em analisar a média, desvio padrão, rango, coeficiente de Pearson (r), regressão múltipla (R2), Plotagem de Bland-Altman, Teste t, com um nível significante de 5%, e para construir as curvas utilizou-se o método LMS. Resultados: Em relação ao crescimento físico os meninos de Campinas apresentam menor peso e estatura em relação aos da referência (9-17 anos), estatura (7-14 anos) e IMC (11-17 anos) (p<0,05). Quanto à maturação somática, observaram-se altos valores de correlação entre idade e as variáveis antropométricas em meninos (r=0,56-0,96) e meninas (r=0,57-0,98). Na validação interna e externa não houve diferenças significantes (p>0,05) e verificou-se aceitável concordância entre o critério e as equações desenvolvidas para os escolares de ambos os sexos. Conclusões: O estudo constatou que os valores absolutos de peso, estatura e IMC das crianças de Campinas são substancialmente inferiores quando comparados com a referência CDC-2012, e que, a equação do Pico de Velocidade de Crescimento é válida para determinar a maturação somática (Mirwald) dos escolares de Campinas. Para avaliar a trajetória do crescimento físico, os resultados sugerem o uso de padrões regionais, e quanto à maturação somática, pode-se utilizar tanto a equação do Mirwald, quanto, as equações desenvolvidas no presente estudo / Abstract: The study was designed to evaluate the overall physical growth and somatic maturation of children and adolescents Network Elementary School Campinas. The specific objectives were: a) compare the physical growth with the international reference the CDC -2012 and build the reference values for children and adolescents and b) to validate the technique for prediction of somatic maturation (Mirwald) and develop an equation to determine peak growth velocity transversely. Methodology: A descriptive cross-sectional study was developed. The show consisted of 6531 individuals were selected in a probabilistic manner (stratified) 3315 boys and 3216 girls aged 6-17 years (95% CI). Decimal variables age, body weight, height and head stem height were evaluated. We calculated the Body Mass Index (BMI) and peak velocity (speed years) for both sexes. The statistical approach used was to analyze media , standard deviation, range, coefficient of Pearson (r), multiple regression (R2), Bland, Altman, t test, ANOVA (one way), with a significance level of 5 % and curves used to build up the LMS method. Results: In terms of physical growth of prairie boys have lower weight and height relative to the reference (9-17 years), height (7-14 years) and BMI (11-17 years) (p<0.05). As for somatic maturation observed high values of correlation between age and anthropometric variables in boys (r = 0.56-0.96) and girls (r = 0.57 to 0.98), determining acceptable agreement between the benchmark criteria and the equations developed (CI = 95 %). Conclusions: The absolute values of weight, height and BMI for children in Campinas are substantially lower than the CDC -2012 reference, and the equation of the peak height velocity to determine the somatic maturation (Mirwald) is valid for the school Municipal City Hall of Campinas. The results suggest the use of regional standards for assessing the physical growth trajectory, and the somatic maturation, one can use the equation of Mirwald as well as the equations developed in this study to determine the somatic maturation / Doutorado / Biodinamica do Movimento e Esporte / Doutora em Educação Física

The purpose of this study was to: (1) determine the correlation between academic intelligence and social maturity at the elementary school level; and (2) indicate the degree of social competency attained at various selected intellectual levels.

This study was undertaken to evaluate fertilization and early embryo development of in vitro matured (IVM) horse oocytes following transfer with homologous sperm to the oviduct of estrous ewes. A total of 1023 follicles (5.1 per ovary) were found after processing 202 slaughterhouse ovaries by aspiration and subsequent slicing. Most follicles (79%) were less than 20-mm in diameter. Six hundred sixty-seven oocytes were recovered (3.3 per ovary; recovery rate, 65%). About two-thirds of oocytes were recovered by slicing, which yielded twice the number of oocytes as aspiration. Sixty four percent cumulus oocyte complexes (COCs) recovered by each method were grade A and the overall distribution of oocytes by grade was not affected by the method of recovery. Oocytes underwent IVM for an average of 41-h and were subjected to either in vitro fertilization (IVF) or xenogenous gamete intrafallopian transfer (XGIFT). At the onset of IVM, 83% COCs had compact cumulus investment. At the end of IVM, 78% COCs showed cumulus expansion. The expansion score was not improved with increasing the IVM duration from 32.3 to 50.3 h. Five (15%) IVF oocytes showed changes indicative of fertilization and two cleaved to 3 and 4-cell stages. Oviducts of 16 ewes were use for XGIFT, which involved surgical transfer of an average of 13 oocytes with 40x103 capacitated spermatozoa per oocyte. Of 259 oocytes transferred, 36 (14%) were recovered between 2 to 7 d post XGIFT and 13 (36%) showed cleavage ranging from the 2-cell to hatching blastocyst stage. The ovarian status of ewes and ligation of the uterotubal junction (UTJ) at the time of XGIFT, or the duration gametes were allowed to reside in the uterine tube, did not affect the recovery and cleavage rate. However, the most advanced stage embryos were recovered from ewes ovulating shortly after XGIFT. Fertilization following XGIFT was further demonstrated by the detection of ZFY loci in one embryo. This study demonstrated, for the first time, that horse embryos could be produced in a non-equine species. However, further studies focusing on the establishment of pregnancy in the mare using such embryos and improvement of the recovery and fertilization rates following XGIFT are recommended for use of XGIFT in horse assisted reproduction. / Master of Science

Aging is a major risk factor for a variety of diseases, including metabolic disease and cancer. Accumulating evidence suggests that the regulation of developmental traits might have long-term effects on aging and health conditions later in life. The current project focuses on understanding the underlying genetic and molecular mechanisms. Nuclear receptor interacting protein 1 (NRIP1, also named RIP140) is a key regulator that modulates transcriptional activity of variety of transcription factors, including estrogen receptor and NF-κB. We previously identified that NRIP1 plays an important role in development and aging. The global depletion of Nrip1 (Nrip1-/-) significantly reduced pre-weaning survival, delayed female sexual maturation, improved insulin sensitivity at young, middle, and old age, as well as increased the longevity of female mice. In the current project, using adipose tissue- derived stem cells (ASCs), we found that the benefits of suppressing NRIP1 on aging and longevity may be related to reduced inflammation, delayed cell senescence and cell growth, and improved stem cell maintenance. The elucidation of the role of NRIP1 in female reproduction, metabolism, inflammation, and cell senescence, encouraged us to further investigate the role of NRIP1 in breast cancer. Importantly, epidemiological studies of human populations found that an early age at menarche significantly associates with risk of breast cancer (BC). During development, depletion of NRIP1 delays female sexual maturation and suppresses the development of mammary glands. Our previous study showed that NRIP1 expression was elevated in breast cancer, and that the depletion of NRIP1 could suppress the onset and progression of breast cancer. Combining this study with the findings of suppressed inflammation and delayed cell senescence, we hypothesized that Nrip1 knockout may have anti-BC effect by improving the stroma cell function and lowering the inflammation in local microenvironment. In this study, we found that NRIP1 is not only involved in tumorigenesis of breast cancer, but also in the cancer progression and the development of drug resistance. Interestingly, suppressing Nrip1 in a tamoxifen-resistant breast cell line restored drug sensitivity. The mechanism of anti-cancer effect may be related to suppressed NF-κB expression and activity, as well as reduced expression of aromatase.While identifying genes that are involved in development and longevity is important to aging research, searching for geroprotective drugs for clinical use may be a more realistic way to improve metabolic traits and delay aging in humans. Metformin is a widely used drug for treating type 2 diabetes (T2D) that has a good safety profile. Also, metformin treatment has been linked to a reduced risk of cancer and cancer-related mortality in retrospective investigations. In this study, heterogeneous mice (UM-HET3) were treated with metformin between the ages of 15 and 56 days. The results show that body weight and food consumption were increased, and sexual maturation was delayed in females. Tail length and circulating insulin-like growth factor 1 (IGF1) levels were significantly increased. Glucose tolerance was improved, but no significant difference in insulin tolerance was found. Circulating adiponectin and insulin levels were altered by metformin treatment. Analysis of quantitative insulin sensitivity check index (QUICKI) suggests that metformin treatment increased insulin sensitivity. These results revealed that treating mice early in life with metformin alters development and metabolism. Importantly, the effects of metformin treatment at an early age may have long-term impacts on health and aging-related traits.

Using data from the Third National Health and Nutrition Examination Survey, we assessed measures of puberty in U.S. girls in relation to blood lead levels to determine whether sexual maturation may be affected by current environmental lead exposure. The study sample included 1,706 girls 8-16 years old with pubic hair and breast development information; 1,235 girls 10-16 years old supplied information on menarche. Blood lead concentrations (range = 0.7-21.7 pg/dL) were categorized into three levels: 0.7-2.0, 2.1-4.9, and 5.0-21.7 μg/dL. Sexual maturation markers included self-reported attainment of menarche and physician determined Tanner stage 2 pubic hair and breast development. Girls who had not reached menarche or stage 2 pubic hair had higher blood lead levels than did girls who had. For example, among girls in the three levels of blood lead described above, the unweighted percentages of 10-year-olds who had attained Tanner stage 2 pubic hair were 60.0, 51.2, and 44.4%, respectively, and for girls 12 years old who reported reaching menarche, the values were 68.0, 44.3, and 38.5%, respectively. The negative relation of blood lead levels with attainment of menarche or stage 2 pubic hair remained significant in logistic regression even after adjustment for race/ethnicity, age, family size, residence in metropolitan area, poverty income ratio, and body mass index. In conclusion, higher blood lead levels were significantly associated with delayed attainment of menarche and pubic hair among U.S. girls, but not with breast development.

Affinity maturation increases the affinity of B-cell derived antibodies to their cognate antigens. In this study, we characterized the kinetic, structural, dynamic and thermodynamic evolution of antibodies during affinity maturation. Through single B-cell cell sorting, paired heavy and light chain sequencing, phylogenetic analysis, antibody expression, and physicochemical characterization, we were able to longitudinally analyze the stages of affinity maturation of anti-PA (B.anthracis protective antigen) antibodies. Following repeated immunizations, we observed up to an 10,000-fold increase in antibody affinity, mainly through a decrease in the off-rates. For detailed maturation analysis, we chose three antibodies lying along a single clonal branch--the clone’s unmutated common ancestor (UCA), a medium affinity antibody (MAAb) appearing after second immunization, and a high-affinity antibody (HAAb) appearing after third immunization. Most of the mutations that occur between the UCA and HAAb resulted in key changes to structural conformation. In particular, mutations change residues in the CDR-H3 region inducing the folding of the CDR-loops into a conformation that is more complementary to PA. This advantageous new antibody conformation is preserved in the unbound state, indicating that though the UCA and MAAb appear to use an induced fit and/or conformational selection mechanism, the HAAb is more rigidly lock-and-key. Thermodynamic results support this interpretation. In the first maturation step from UCA to MAAb, enthalpic improvement indicates optimization of noncovalent interactions. The second step from MAAb to HAAb predominantly involves entropic improvement by which the advantageous conformation made accessible in the first step is made more dominant via the narrowing of effectively accessible conformations, which allows better contact with PA. This is also reflected by a less significant improvement in the enthalpic component of PA-binding. Studies examining the evolving protein-dynamic characteristics further support this interpretation. In summary, we observed that a single energetic component is not responsible for increased affinity in the maturation pathways we studied. From UCA to MAAb, affinity increases through optimization of noncovalent interactions. From MAAb to HAAb, affinity increase is achieved through changes that stabilize the favorable conformation in the unbound state. A better understanding of affinity maturation can have implications for antibody engineering and vaccine development.

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