Spinal Muscular Atrophy (SMA), traditionally described as a predominantly childhood form of motor neuron disease, is a leading genetic cause of infant mortality. Although motor neurons are undoubtedly the primary affected cell type, SMA is now widely recognised as a multisystem disorder, where a variety of organs and systems in the body are also affected. Vascular perfusion abnormalities have previously been reported in both patients and mouse models of SMA, however it remains unclear whether these defects are secondary to the motor neuron pathology for which this disease is known. Through analysis of the 'Taiwanese' murine model of severe SMA (Smn-/-;SMN2tg/0, Smn-/+) we report significant vascular defects in the retinas of SMA mice, a tissue devoid of motor neurons, thus providing strong evidence that these vascular defects are independent of motor neuron pathologies. We show that restoration of Smn levels by antisense oligonucleotide treatment at birth significantly ameliorates retinal vascular defects. Next, we report defects in the neural retina, with a significant decrease in key neural cells in SMA mice. A similar vascular pathology was expected in the spleen of SMA mice given that the spleen is small and pale in appearance; however, the density of the intrinsic vasculature remained unchanged. We report that the spleen is disproportionately small in SMA mice, correlated to low levels of cell proliferation, increased cell death, and multiple lacunae. The SMA spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganized fibrotic architecture. Histologically distinct white pulp fails to form and this is reflected in an almost complete absence of B lymphocytes necessary for normal immune function. Taken together, these results highlight both the vascular and immune systems as key targets of SMA pathology that should be considered during treatment of this disease.

M.Cur. (Midwifery and Neonatal Nursing) / The purpose of this study is to determine the experiences of the parents after the death of a congenital abnormal baby. Parents who have lost a baby go through a process of grief. This also applies to parents of a baby with congenital abnormalities. Parents whose congenital abnormal baby dies, not only grieve because of the abnormality of their baby, but also because it died Unstructured in-depth interviews were held with six couples within a year after the death of their babies. The experiences of the six couples were afterwards compared. A literature study was undertaken in order to determine what the conclusions of other researchers field were. The result of the literature study was compared with that of the present study. Recommendations are made at the end of this study on the practical applications, education and further research that can be undertaken on this subject.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

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The dissertation examines the appearance and meanings of corporeal anomaly in the arts of Postclassic Mexico (AD 900–1521). Drawing specifically upon those categories of the human or divine body that are regularly termed aberrant, grotesque, or otherwise “deformed” by scholars of Mesoamerican art, the images discussed here include dwarfs, hunchbacks, twins, animal-human hybrids, disfigured deities, and disembodied limbs, among others. While similarly distinctive images can be identified among earlier Mesoamerican artistic traditions, the variety of idiosyncratic bodies that pervade the arts of the Postclassic period, in addition to the breadth of available historical sources, make it the ideal lens through which to analyze many of the most fundamental issues of indigenous Mexican visual culture. Relative to Classic Maya art, a tradition of naturalism and linear elegance greatly resembling that of early modern European painting and sculpture, the art of the ancient Mixtecs, Toltecs, and Nahuas (Aztecs) is sometimes perceived as rigid, laconic, and hulking—even brutish—by comparison. Featuring complex figural abstractions and esoteric symbolism, these later traditions are further distinguished by the specificity of their physical deformations, including twisted faces, palsied limbs, contorted spines, extra appendages, and other unnatural anatomies. Consequently, Postclassic art offers an inventory of difference that is unique not only among Mesoamerican art but among Western traditions as well, making it doubly challenging to interpret its motivations and significance. However, by analyzing the role of such extraordinary bodies within the broader anthropocentric worldviews of ancient Mesoamerica, this study offers useful strategies for unpacking the complex religious, political, and formal motivations that govern much of Postclassic visual culture. As I argue, extraordinary bodies share a common identity as transformational characters occupying specifically transitory states. As shape-shifters, gatekeepers, divine conduits, and shepherds, it is in the liminal regions of existence—the “betwixt and between” of reality and myth—where such figures live and serve as the custodians of heaven and earth. With tremendous regularity, their irregular forms indicate and define the various “borderlands” of Mesoamerican ideology, from the hinterlands of the urban center to the margins and gutters of hand-painted books. In short, a distinctly Postclassic notion of physical deformation stands at the threshold between creation and dissolution, center and periphery, life and death.

Major developmental defects occur in 100,000 to 200,000 children born each year in the United States of America. 97% of these defects are from unidentified causes. Many fetal outcomes (e.g., developmental defects), result from interactions between genetic and environmental factors. The lifetime effects from prenatal exposures with low impact (e.g., air pollution) are often understudied. Even when these exposures are studied, the focus is often placed on immediate effects of the exposure (e.g., fetal anomalies, miscarriage rates) leaving lifetime effects largely unexplored. This makes prolonged (or lifetime) effects of low-impact exposures an understudied research area. Included in this set of low-impact exposures is seasonal variance at birth. This thesis measures the effects of seasonal variance at birth on lifetime disease risk at both the population-level and molecular-levels. Four aims, comprising this thesis study, were conducted that utilize data from pharmacology, clinical care (Electronic Health Records) and genetics. These aims included: 1.) Development of an Algorithm to Reveal Diseases with a Prenatal/Perinatal Seasonality Component (described in chapter 2); 2.) Investigation of Climate Variables that Affect Lifetime Disease Risk By Altering Environmental Drivers (described in chapters 3 and 4); 3.) Discovery of Genes Involved in Birth Season – Disease Effects (described in chapter 5) and 4.) Investigation of Pharmacological Inhibitors As Phenocopies of the Birth Season – Disease Effect (described in chapters 6 and 7). Knowledge gained from these four areas, through seven distinct studies, establishes that birth season is a causal risk factor in a number of common diseases including cardiovascular diseases.

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Thesis (Ph. D.)--Texas State University-San Marcos, 2007. / Vita. Includes bibliographical references (leaves 111-129).

Orientador: Vera Lucia Gil da Silva Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T16:23:58Z (GMT). No. of bitstreams: 1 Monlleo_IsabellaLopes_D.pdf: 6807937 bytes, checksum: a28121a53a2b35d8afe389692c026003 (MD5) Previous issue date: 2008 / Resumo: As primeiras ações para inclusão da atenção a pessoas com anomalias craniofaciais (ACF) no Sistema Único de Saúde (SUS) ocorreram na década de 1990 e culminaram com a criação da Rede de Referência no Tratamento de Deformidades Craniofaciais (RRTDCF). Esta rede foi avaliada por Monlleó em 2004, momento em que foram identificados centros de atendimento a pessoas com ACF vinculados ao SUS, mas não à RRTDCF. Objetivos: (1) avaliar os centros de ACF não-RRTDCF; (2) discutir a política de atenção à saúde para ACF do Brasil; (3) elaborar cadastro dos centros estudados e (4) elaborar proposta de banco de dados de fendas orofaciais para o Brasil. Resultados: 82 centros de atendimento a pessoas com ACF participaram da avaliação. Estes centros estão concentrados no Sudeste e em universidades e compreendem serviços isolados, multiprofissionais e associações de pais. Apenas seis serviços multiprofissionais seguem critérios internacionais de composição de equipes. Nestes, odontólogos e cirurgiões são os especialistas mais freqüentes. Geneticistas clínicos estão envolvidos com aconselhamento genético em 35 serviços, enquanto em 30, outros profissionais realizam esta atividade. Sessenta e dois centros aderiram ao cadastro proposto. O banco de dados consiste em um projeto de registro clínico e familial de pessoas com fendas orofaciais atendidas em unidades da RRTDCF. Em torno deste, cinco projetos satélites foram elaborados: (1) banco de DNA; (2) avaliação da organização interna das unidades; (3) banco de profissionais de saúde e de protocolos de tratamento; (4) estudos de seguimento pós-cirúrgico, morbidade e mortalidade; (5) avaliação de satisfação dos usuários. Conclusões: os centros não-RRTDCF se sobrepõem à RRTDCF quanto à distribuição, procedimentos, clientela e financiamento. Iniqüidades, disparidades regionais e falta de integralidade permanecem como problemas. Acredita-se que a superação desses problemas requer a reformulação da política de atenção a pessoas com ACF e, para tanto, apresentam-se diretrizes. O cadastro de centros é uma ferramenta pública para minorar dificuldades de acesso a informações. Por sua vez, o banco de dados poderá fornecer subsídios para avaliação contínua dos serviços e para a reformulação da política de saúde para ACF no SUS / Abstract: Health care for persons with craniofacial anomalies (CFA) officially started in Brazil in the nineties. It was consolidated through the Reference Network for Craniofacial Treatment (RRTDCF). The RRTDCF was evaluated by Monlleo in 2004 when several non-RRTDCF units operating in the Unified Health System (SUS) were identified. Aims: (1) to evaluate health care provided through non-RRTDCF units; (2) to inform the debate about craniofacial health care policy in Brazil; (3) to build up a record on CFA units; (4) to build up a Brazilian database on orofacial clefts. Results: 82 non-RRTDCF units took part of the survey. They are mainly located in the southeast, and in universities. They are funded by the government and comprise independent clinics, multiprofessional teams and parental associations. Only 6 multiprofessional units meet the international criteria for minimal CFA teams. Clinical geneticists are involved in genetic counselling in 35 units, however in 30 it is provided by untrained professionals. Sixty two units agreed to participate in the national record proposed. The Brazilian database on orofacial clefts was designed to record clinical and familial information on patients assisted through the RRTDCF. Additionally, five satellite projects were built: (1) biobank of DNA; (2) general care assessment; (3) database of healthcare professionals and assessment of treatment protocols; (4) follow-up studies on surgical treatment and morbidity/mortality and (5) patient/parent satisfaction studies. Conclusion: non-RRTDCF units overlap RRTDCF regarding distribution, treatment provided, type of CFA treated, and funding. The current system does not ensure equity and coordination of care, and keeps up regional disparities. It is believed that these problems may be overcome through changes in the current national health policy for CFA in Brazil and suggestions are given in this regard. The national record on CFA units is a tool in the public interest and can improve equity of access to services. The database, on the other hand, is an achievable strategy to set up appraisal and audit systems and to support the reformulation of health policy for persons with CFA in the SUS / Doutorado / Genetica Medica / Doutor em Ciências Médicas

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