<p>Clubfoot is the most common congenital structural deformity that leads to physical impairments in children in many poor developing countries. Inadequately treated or neglected clubfoot has been found to be a common cause of ohysical disability globally among children and young growing adults. Many children are referred to the clinics for treatment but some parents do not comply with the treatment regimen whcih requires attending for consecutive treatment sessions. The purpose of this study was to investigate barriers to treatment attendance parents/caregivers of children with clubfoot encounter in complying with clubfoot treatment during the plaster csting phase in Uganda.</p>

Dyskeratosis congenita (DC) is a multi system disorder that exhibits considerable clinical and genetic heterogeneity. It is characterised by mucocutaneous features, bone marrow failure and a predisposition to cancer. Research has identified mutations affecting several telomerase components and patients often have short telomeres, implicating defective telomere maintenance in this disease. Affected components include dyskerin, NOP10 and NHP2, which together with GAR1 form a protein core common to telomerase and all other H/ACA ribonucleoprotein complexes (H/ACA RNPs). Initially characterised as H/ACA RNP components important for pseudouridylation and rRNA processing, their role in the functionally distinct telomerase complex and telomere maintenance is less defined. In order to better understand their implications in DC, this study investigated the importance of these core proteins for the integrity and function of telomerase in human cells. RNAi knockdown studies demonstrated that dyskerin, NOP10 and NHP2 are necessary for the accumulation of TERC (telomerase RNA component); dyskerin and NOP10 for telomerase activity. Moreover, dyskerin was found to be important for maintaining telomere length over time. The impact of NOP10 and NHP2 missense mutations was also analysed in vitro, which indicated that they impair TERC accumulation. The potential effect on pseudouridylation was also considered in this study; the analysis of other H/ACA RNA levels in these knockdown experiments and in a cohort of patients with DKC1 mutations revealed an irregular and inconsistent impact compared to that observed on TERC. Finally, defective telomere maintenance is heavily implicated as the primary cause of DC and very short telomeres have been proposed as a diagnostic marker. This study investigated telomere length in a patient cohort of unprecedented size. It demonstrated the prevalence of the telomere length defect, but telomere length was not found to correlate with either genetic subtype or disease severity, implicating the rate of telomere shortening as the correlating factor instead.

<p>Clubfoot is the most common congenital structural deformity that leads to physical impairments in children in many poor developing countries. Inadequately treated or neglected clubfoot has been found to be a common cause of ohysical disability globally among children and young growing adults. Many children are referred to the clinics for treatment but some parents do not comply with the treatment regimen whcih requires attending for consecutive treatment sessions. The purpose of this study was to investigate barriers to treatment attendance parents/caregivers of children with clubfoot encounter in complying with clubfoot treatment during the plaster csting phase in Uganda.</p>

Magister Scientiae (Physiotherapy) - MSc(Physio) / Clubfoot is the most common congenital structural deformity that leads to physical impairments in children in many poor developing countries. Inadequately treated or neglected clubfoot has been found to be a common cause of ohysical disability globally among children and young growing adults. Many children are referred to the clinics for treatment but some parents do not comply with the treatment regimen whcih requires attending for consecutive treatment sessions. The purpose of this study was to investigate barriers to treatment attendance parents/caregivers of children with clubfoot encounter in complying with clubfoot treatment during the plaster csting phase in Uganda. / South Africa

Orientador: Renato Passini Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-09T15:30:07Z (GMT). No. of bitstreams: 1 Jannini_AlexandreWolf_M.pdf: 3134011 bytes, checksum: 9cae7dc9e2202285b4be1b0a5ae92bb0 (MD5) Previous issue date: 2008 / Resumo: Introdução: A legislação não permite a interrupção da gestação em casos de malformações fetais incompatíveis com a vida extra-uterina, cabendo ao Poder Judiciário decidir quando há uma solicitação deste tipo. Objetivos: Investigar a opinião de Magistrados e membros do Ministério Público sobre o abortamento nos casos de malformações fetais incompatíveis com a vida extra-uterina, especialmente em relação à anencefalia. Método: Análise parcial de dados obtidos em duas pesquisas realizadas pelo Centro de Pesquisas em Saúde Reprodutiva de Campinas (CEMICAMP), que objetivaram estudar a opinião destes profissionais acerca do aborto induzido. Foram obtidos dados de 1493 Magistrados e 2614 Promotores de Justiça. Foi constituído um banco de dados com as informações de interesse das pesquisas originais, analisado com auxílio do programa estatístico SAS versão 9.02, envolvendo análise bivariada e múltipla, por regressão logística. Resultados: Para 78,5% dos Magistrados e 82,6% dos membros do Ministério Público, a interrupção da gestação deveria ser permitida nos casos de qualquer malformação fetal incompatível com a vida extra-uterina. Em casos de diagnóstico de anencefalia, estes valores foram de 79,2% e 84,1%, respectivamente. Na análise multivariada, as variáveis associadas à opinião dos pesquisados foram a religiosidade, importância da religião e das concepções religiosas pessoais sobre as respostas dadas, experiência de gravidez indesejada que resultou em aborto, sexo, estado marital e o fato de possuir filhos. Conclusões: A grande maioria dos Magistrados e membros do Ministério Público foi favorável ao abortamento nas hipóteses estudadas, sendo as variáveis ligadas à religião as que mais influenciaram seu posicionamento / Abstract: Introduction: In Brazil abortion in cases of fetal malformation or anencephaly is prohibited by law. Pregnant women who want to perform an abortion in such cases must seek for a judicial order. Objectives: Evaluate the opinion of brazilian magistrates and Prosecutors about abortion in cases of fetal malformation incompatible with life and anencephaly. Methodology: It was a partial data analysis from data obtained in two researchs carried out by Centro de Pesquisas em Saúde Reprodutiva de Campinas (CEMICAMP ), to evaluate the opinion and conduct of these professionals about induced abortion. There were data from 1453 Magistrates and 2614 Prosecutors. It was made a data bank with data from the original studies, that was processed and analyzed using the statistical package SAS version 9.02. Results: For 78.5% of the Magistrates and 82.6% of the Prosecutors abortion should be permitted in cases of severe fetal malformation incompatible with life. In cases of anencephaly abortion should be permitted for 79.2% of the Magistrates and for 84.1% of the Prosecutors. Religiosity, influence of religion and personal religious convictions among responses, experience with unwanted pregnancy that ended in abortion, gender, marital status and the fact of having children had shown, in multivariable analysis, association with the opinion about abortion in the hypothesis studied. Conclusion: The great majority of Magistrates and Prosecutors had a favorable opinion about abortion in both hypothesis evaluated. Variables associated with religion had the strongest association with the opinion about abortion in cases of fetal malformation and anencephaly.Abstract: Introduction: In Brazil abortion in cases of fetal malformation or anencephaly is prohibited by law. Pregnant women who want to perform an abortion in such cases must seek for a judicial order. Objectives: Evaluate the opinion of brazilian magistrates and Prosecutors about abortion in cases of fetal malformation incompatible with life and anencephaly. Methodology: It was a partial data analysis from data obtained in two researchs carried out by Centro de Pesquisas em Saúde Reprodutiva de Campinas (CEMICAMP ), to evaluate the opinion and conduct of these professionals about induced abortion. There were data from 1453 Magistrates and 2614 Prosecutors. It was made a data bank with data from the original studies, that was processed and analyzed using the statistical package SAS version 9.02. Results: For 78.5% of the Magistrates and 82.6% of the Prosecutors abortion should be permitted in cases of severe fetal malformation incompatible with life. In cases of anencephaly abortion should be permitted for 79.2% of the Magistrates and for 84.1% of the Prosecutors. Religiosity, influence of religion and personal religious convictions among responses, experience with unwanted pregnancy that ended in abortion, gender, marital status and the fact of having children had shown, in multivariable analysis, association with the opinion about abortion in the hypothesis studied. Conclusion: The great majority of Magistrates and Prosecutors had a favorable opinion about abortion in both hypothesis evaluated. Variables associated with religion had the strongest association with the opinion about abortion in cases of fetal malformation and anencephaly / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

This diploma thesis follows the bachelor thesis and it?s task is to processing analysis of the occurrence of PSE meat in a population of the Czech white breed as a pigs stress syndrome impact. General problem of congenital diseases is processed in literature review. Further, this work deals with pigs stress syndrome and stress, which causes the meat defects as an external factor. Molecular - genetic methods, which are used in the practical part, are described as well. The research focused on genotyping of loci selected panel of samples, to determine the frequency of alleles and genotypes of selected locus and the statistical relationship between genotype and expression of PSE meat. Results were statistically processed and evaluated at the end.

<div><p>Zika virus (ZIKV) is a mosquito-borne pathogen that stayed unnoticed for over half a century. Only after the 2015-16 Brazilian outbreak did the severity of the infectious outcome, particularly the Congenital Zika Syndrome, become apparent. ZIKV is associated with severe neurodevelopmental impairments in human fetuses, including microencephaly, ventriculomegaly, retinopathy, and sensorineural hearing loss. Though the pandemic is now under control in the Latin American countries, several tropical countries could still be at risk of widespread infection. This warrants a better understanding of the congenital Zika syndrome; this project attempts to contribute towards this goal.</p><p><br></p><p>Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in non-uniform periventricular infection 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influence neuroepithelial patterning at a distance through secretion of morphogens. ZIKV infection reduced transcript levels for 3 morphogens, SHH, BMP7, and FGF8, expressed at the midbrain basal plate, hypothalamic floor plate, and isthmus, respectively. Levels of Patched1, a SHH-pathway downstream gene, were also reduced and a SHH-dependent cell population in the ventral midbrain was shifted in position. Thus, the diminishment of signaling centers through ZIKV-mediated apoptosis may yield broader, non-cell autonomous changes in brain patterning.</p><p><br></p></div><p>Sensorineural hearing loss is a relatively understudied consequence of congenital Zika syndrome, and balance disorders are essentially unreported to date. ZIKV pathogenesis was explored in the developing inner ear using the accessible chicken embryo model system. One goal was to assess the spatiotemporal susceptibility of otic epithelial-derived structures to ZIKV infectivity. Direct injections of the inner ear or the inner ear primordium were performed <i>in ovo</i>with subsequent harvests at 2 to 8 days-post-infection. The degree of infection in sensory/prosensory organs was evaluated histologically to determine the susceptibility of one auditory and five vestibular organs. ZIKV infection of the sensory as well as non-sensory epithelia was observed at most stages of analysis, with no apparent preference for one over the other. The lagena, the ventral most tip of the chicken inner ear, and the endolymphatic sac/duct were least frequently infected. In this report, two novel findings in sequela of ZIKV infection are presented: the vestibular labyrinth can present with stalled canal morphogenesis, and the auditory ganglion can be severely shrunken, perhaps due to an increased cell death upon early ZIKV infection of the inner ear.</p><p><br></p><p>Additional methods of peripheral infection in the chicken embryos were tested to examine ZIKV transmission to the central nervous system: E3 blood vessel, E4 limb bud, and E10 chorioallantoic membrane infections. Although none of these methods resulted in a histologically significant infection of the developing brain 3 to 6 days-post-infection, evidence of ZIKV genome replication and viremia was detected in several tissue types.<br></p>

Made available in DSpace on 2014-08-20T14:37:57Z (GMT). No. of bitstreams: 1 dissertacao_leticia_fiss.pdf: 2050441 bytes, checksum: becde768d58c37eaecc13d2d83140f38 (MD5) Previous issue date: 2009-03-03 / Hereditary hydrancephaly and cerebellar hypolasia are reported in Murrah buffalos. Six calves, one female and 5 male out of 128 born between 2004 and 2008 in a farm in southern Brazil were affected. All affected calves were offspring from the same bull. No affected buffaloes were observed in the descendants of other three bulls used in the farm. Main clinical signs were depression, blindness, difficulty or impossibility to standing up, wide-based stance, and intention tremors. There is mild doming of the skull. The brain was smaller than normal. The cerebral cortex was almost complete absent leaving only membranous sacs fluid filled. The gyri were absent or narrower than normal in the occipital cortex. On the cut of the telencephalic cortex cavities were observed in the subcortical white matter. Smaller bilateral and symmetric cavities, containing fluid (porencephaly), were also observed in the basal nuclei. The lateral ventricles were dilated (hydrocephalum ex-vacuo). The cerebellum was smaller than normal. The brain stem appears normal, except by a side reduction in relation with the brain of a control calf. Upon histologic examination, in all buffalos, cavities of the subcortical white matter were limited by normal nervous tissue. Within cavities, residues of white matter sometimes bordered by ependymal cells were observed. The cortex was thin. Gitter cells, axonal spheroids, and gliosis were occasionally observed. Cerebellar disorganization, characteristic of cerebellar hypoplasia, and hypomyelinogenesis were observed in the cerebellum. Imuno-histochemistry and serologic tests were negative for bovine virus diarrhea and blue tongue viruses. These results associated with epidemiologic data suggest that the disease is a hereditary hydrancephaly and cerebellar hypoplasia, probably transmitted by a recessive autossomic gen. / Descreve-se a ocorrência de hidranencefalia e hipoplasia cerebelar congênita em búfalos da raça Murrah. Foram afetados seis bezerros, 5 fêmeas e 1 macho de um total de 128 nascidos entre 2004 e 2008 em uma propriedade no município de Capão do Leão, Rio Grande do Sul. Todos os búfalos afetados eram filhos do mesmo touro. A enfermidade não foi observada nos búfalos filhos de outros três touros utilizados na propriedade. Os sinais clínicos caracterizaram-se por depressão profunda, cegueira, estação em base larga, dificuldade ou impossibilidade de andar e tremores. O crânio apresentava forma de cúpula. Os encéfalos estavam diminuídos de tamanho e os hemisférios telencefálicos estavam quase que totalmente ausentes apresentando-se como sacos membranosos preenchidos por líquido. Havia resquícios de giros e sulcos no córtex occipital. Ao corte do encéfalo no córtex telencefálico remanescente observavam-se cavidades císticas bilaterais e simétricas na substância branca subcortical e nos núcleos basais que também continham líquido em seu interior (porencefalia). Os ventrículos laterais estavam dilatados (hidrocefalia ex-vacuo). O cerebelo e o tronco encefálico estavam diminuídos de tamanho em comparação ao cerebelo e ao tronco encefálico de um búfalo controle. Histologicamente em todos os búfalos afetados havia cavidades delimitadas por tecido nervoso de aspecto normal. Nestas cavidades havia eventualmente a presença de resquícios de substância branca, algumas vezes delimitadas por células ependimárias. O córtex estava delgado. Ocasionalmente, nestas áreas havia a presença de substância branca rarefeita com células gitter, esferóide axonais e gliose. No cerebelo observou-se desorganização celular e hipomielinogênese características de hipoplasia cerebelar. A imuno-histoquímica do tecido nervoso dos búfalos afetados e a sorologia do rebanho de búfalos realizados para os vírus da diarréia viral bovina e da língua azul foram negativos. Ess resultados associados a epidemiologia sugerem que a enfermidade é hereditária e causada por um gene recessivo autossômico.

Abstract Organogenesis involves precursor cells proliferation, differentiation along with their coordinated organization into precise multicellular arrangements by planar cell polarity (PCP) pathways. The beta-catenin independent/non-canonical type of Wnt-11 signaling has been known as a PCP modulator during development. In this thesis were analyzed the roles of Wnt-11 in heart and kidney development by using in vivo functional genomics technologies. We show that the Wnt-11 gene is important for murine ventricular myocardium development, since Wnt-11 deficiency in early cardiogenesis leads to impaired organization and maturation of mouse ventricular cardiomyocytes, causing primary cardiomyopathy with in utero lethality. Wnt-11 coordinates the co-localized expression of the cell adhesion molecules N-cadherin and β-catenin, which are critical for the spatially specific organization of cardiomyocytes. We show that Wnt-11 deficiency causes primary hypertrophic and noncompaction cardiomyopathy in adult mice, with consequences for regional myocardium function. The Wnt family of secreted signals has been implicated in kidney tubule development and tubular cystic diseases such as polycystic kidney disease. We show here that Wnt-11 is expressed in mature nephrons and is involved in late steps of nephrogenesis, since the kidney tubule organization is deregulated in Wnt-11 deficient kidneys, to enlarged lumen with increased convolution. These tubule abnormalities are associated with glomerular microcyst formation and kidney failure. Wnt-11 deficiency reduced significantly Wnt-9b expression, a critical signal for PCP-mediated kidney tubule elongation. In the cortical region this associated with reduced expression of nephron and stromal progenitor cell marker. The results in this thesis point out that Wnt-11 function is required for proper myocardium organization and maturation as well as proper morphogenesis of the kidney tubules during the embryonic and postnatal developmental stages. Wnt-11 knockout phenotypes depend on the genetic background, similarly to human congenital disease. This data may be relevant for human congenital cardiomyopathy and glomerulocystic kidney disease studies. / Tiivistelmä Alkion sisäelinten kehityksen aikana esisolut lisääntyvät ja erilaistuvat muodostaen tarkoin määriteltyjä monisoluisia rakenteita. Muodostuvan kudosrakenteen määrittelyssä erilaiset solusignaalit ovat keskeisessä asemassa. Yksi näistä on nk. Wnt signaali perhe. Wnt perheeen jäsen Wnt-11 tehtävät on huonosti tunnettu. Wnt-11 viestittää ilmeisesti nk. planaaristen solupolariteettireittien (PCP) avulla, joka on beeta-kateniinista riippumattoman nk. ei-kanonisen Wnt signaali. Väitöskirjatyössä selvitettiin Wnt-11:n vaikutuksia sydämen ja munuaisten kehitykseen in vivo funktionaalisten genomisten menetelmien avulla. Ihmisen synnynnäiset kardiomyopatiat ovat sydänlihaksen ensisijaisia vaurioita, joiden taustalla on sydänlihaksen kehityshäiriö. Tutkimuksessa osoitetaan, että Wnt-11-geenillä on tärkeä merkitys hiiren sydänkammion kehitykselle, koska Wnt-11-geenin puute sydämen varhaisen kehityksen vaiheessa johtaa sydänlihassolujen järjestäytymisen ja kypsymisen häiriintymiseen, jolloin seurauksena on ensisijaisesta kardiomyopatiasta johtuva sikiökuolema. Wnt-11 koordinoi kahden solukiinnitysmolekyylin, N-kadheriinin ja β-kateniinin, samanaikasta ilmentymistä. Kyseiset molekyylit ovat keskeisen tärkeitä sydänlihasssolujen spatiaalisen järjestäytymisen kannalta. Tutkimuksessa osoitetaan, että Wnt-11-puutos aiheuttaa aikuisilla hiirillä ensisijaista sydänlihaksen liikakasvua ja trabekuloivaa kardiomyopatiaa, mikä vaikuttaa sydänlihaksen toimintaan. Tuloksilla voi olla merkitystä tutkittaessa ihmisen synnynnäisiä kardiomyopatioita. Wnt-signaaliperheen on osoitettu olevan yhteydessä munuaisputken kehitykseen ja sen sairauksiin, kuten munuaisten monirakkulatautiin. Väitöstutkimuksessa osoitetaan, että Wnt-11 ilmentyy kypsissä nefroneissa ja että se osallistuu nefrogeneesiin myöhempiin vaiheisiin, koska munuaisputken kehityksen säätely on poikkeavaa niissä munuaisissa, joista Wnt-11 puuttuu. Seurauksena on laajentunut, normaalia poimuttuneempi luumen. Munuaisputken poikkeavuuksilla oli yhteyttä munuaiskerästen mikrokystien muodostumiseen sekä munuaisten vajaatoimintaan. Wnt-11 -puute vähensi huomattavasti Wnt-9b-ilmentymistä, joka on PCP-välitteisen munuaisputken pidentymisen kannalta keskeisen tärkeä signaali. Kortikaalialueella Wnt9b:n vaimennussäätely liittyi poikkeavaan solujen lisääntymiseen, apoptoosiin ja kypsymiseen sekä vähentyneeseen nefroni- ja stroomakantasolujen merkkiaineen ilmentymiseen. Väitöskirjatutkimuksen tulokset viittaavat siihen, että Wnt-11 -toiminto on välttämätön sydänlihaksen normaalin muodostumisen ja kypsymisen sekä munuaisputken normaalin morfogeneesin kannalta sikiövaiheen ja syntymän jälkeisen kehityksen aikana. Wnt-11 -poistogeenisen hiiren fenotyypi riippuu geneettisestä tausta, samaan tapaan kuin ihmisen synnynnäisissä sairauksissa. Väitöstutkimuksesta saatavalla tiedolla voi olla merkitystä tutkittaessa ihmisen synnynnnäistä kardiomyopatiaa ja munuaisten monirakkulatautia.