Molecular Analysis Of The Ctsk Gene In A Cohort Of 33 Brazilian Families With Pycnodysostosis From A Cluster In A Brazilian Northeast Region

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceara State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis. Methods: The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceara, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents. Results: We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceara State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceara (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceara have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast. Conclusions: The high frequency of pycnodysostosis in Ceara State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceara, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceara, suggestive of a founder effect.21CNPq [402008/2010-3, 590148/2011-7]CAPES [3300017023p6]Fapesp [2015/22145-6]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Disseccao da arteria carotida interna em paciente com sindrome de Ehlers-Danlos tipo IV: diagnostico e manejo

Ehlers-Danlos syndrome (EDS) type IV, also known as vascular EDS, is an inherited connective tissue disorder with an estimated prevalence of 1/100,000 to 1/250,000. In EDS type IV, vascular complications may affect all anatomical areas, with a preference for large- and medium-sized arteries. Dissections of the vertebral and carotid arteries in their extra- and intra-cranial segments are typical. The authors report the case of a patient with EDS type IV for whom the diagnosis was established based on clinical signs and who developed internal carotid artery dissection at the age of 44 years. In the absence of a specific treatment for EDS type IV, medical interventions should focus on symptomatic relief, prophylactic measures, and genetic counseling. Invasive imaging techniques are contraindicated, and a conservative approach to vascular complications is usually recommended.A síndrome de Ehlers-Danlos (EDS) tipo IV, também conhecida como EDS tipo vascular, é uma doença genética do tecido conjuntivo com prevalência estimada entre 1/100.000 e 1/250.000. Na EDS tipo IV, as complicações vasculares podem afetar todas as áreas anatômicas, com comprometimento preferencial de artérias de médio e grande diâmetros. Dissecções das artérias vertebrais e carótidas em seus segmentos intra e extracranianos são típicas. Os autores relatam o caso de uma paciente com EDS tipo IV na qual o diagnóstico sindrômico foi realizado com base nos achados clínicos e que desenvolveu dissecção da artéria carótida interna aos 44 anos. Na ausência de um tratamento específico para EDS tipo IV, a intervenção médica deve ser voltada para o tratamento sintomático, para medidas profiláticas e para o aconselhamento genético. Técnicas de imagem invasivas são contraindicadas e, geralmente, recomenda-se uma abordagem conservadora ao cuidar das complicações vasculares.Universidade Federal de Sao Carlos Departamento de MedicinaUniversidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP, Depto. de MedicinaSciEL

Structure and reactive properties of Nb-impregnated two-dimensional pillared MWW zeolites for total oxidation of volatile organic compounds

[EN] In this work, the structure and reactive properties of niobium (Nb)-impregnated MWW-type materials were evaluated for gas-phase total oxidation of volatile organic compounds, including BTX (benzene, toluene and o -xylene). The role of the type of structure (two or three-dimensional) and the loading of Nb were considered. The results indicated most Nb species with a tetrahedral coordination on the external surfaces of both two- and threedimensional zeolites, together with a minimal contribution of octahedral extra-framework Nb2O5 species. The texture and Nb content played a key role in the gas-phase total oxidation of BTX. With the same Nb content (5 wt %), the pillared zeolite exhibited a higher specific surface, larger pore volume and mesopores between the MWW nanosheets when compared to the MCM-22 zeolites, which resulted in high accessibility of the reactant molecules to the active sites, reflected in higher BTX conversion at lower and higher temperatures (50-300 degrees C). The best performance was achieved with the pillared zeolite (10 wt% Nb), reaching a BTX conversion at 300 degrees C of 92%, 69% and 58%, respectively. The catalyst was stable for up to 30 h of reaction.A.J.S. thanks the Cordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil; Finance Code 001) and the Programa de Pos-Graduacao em Quimica of the Universidade Federal do Rio Grande do Sul (PPGQ-UFRGS) . C.W.L. thanks the PRH 50.1 - ANP/FINEP Human Resources Program for the Visiting Researcher Fellowship. This research used resources of the Advanced Photon Source, a user facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, and was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357 and by the Canadian Light Source and its funding partners. U.D thanks the MAT2017-82288-C2-1-P Project.A. Schwanke; RB; Wittee Lopes, C.; Debora Motta Meira; Díaz Morales, UM.; Sibele B. Pergher; Katia Bernardo-Gusmao (2021). Structure and reactive properties of Nb-impregnated two-dimensional pillared MWW zeolites for total oxidation of volatile organic compounds. Microporous and Mesoporous Materials. 327:1-11. https://doi.org/10.1016/j.micromeso.2021.111425S11132

Fluorescence spectroscopy as a tool to detect and evaluate glucocorticoid-induced skin atrophy

Topical glucocorticoid (GC) therapy has been successfully used in the treatment of several common cutaneous diseases in clinical practice for a long time, and skin atrophy is one of the most typical cutaneous side effects of this therapy. The aim of this study was to evaluate the potential of noninvasive fluorescence spectroscopy (FS) technique in the detection and classification of GC-induced skin atrophy. A total of 20 male Wistar rats were used in the experimental protocol under controlled environmental conditions and with free access to food. One group received topical application of clobetasol propionate 0.05% for 14 days to induce cutaneous atrophy (atrophic group) and the other (control) group received only vehicle application following the same protocol and schedule. Histological analyses and FS measurements with laser excitation at both 532 nm and 408 nm were obtained on days 1 and 15. The FS results were classified as "normal" or "atrophic" according by histological analysis. Fluorescence spectra obtained with excitation at 408 nm allowed a clear distinction between the control and atrophic groups, and were more informative than the those obtained at 532 nm. Our results reveal that, if correctly applied, FS allows noninvasive evaluation of corticosteroid-induced skin atrophy, and thus represents an important step towards better monitoring of undesirable side effects of cutaneous therapy.CAPES (Brazilian Coordination for the Improvement of Higher Education PersonnelCAPES (Brazilian Coordination for the Improvement of Higher Education Personnelprogram NANOBIOTEC) [23038.027482/2009-60]program NANOBIOTEC

Molecular analysis of the CTSK gene in a cohort of 33 brazilian families with Pycnodysostosis from a cluster in a brazilian northeast region

Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceara State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis. The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceara, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents. We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceara State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceara (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceara have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast. The high frequency of pycnodysostosis in Ceara State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceara, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceara, suggestive of a founder effect21CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP402008/2010-3; 590148/2011-73300017023p62015/22145-

Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region

Background: Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceara State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis. Methods: The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceara, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents. Results: We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceara State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceara (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceara have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast. Conclusions: The high frequency of pycnodysostosis in Ceara State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceara, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceara, suggestive of a founder effect.CNPq [402008/2010-3, 590148/2011-7]CAPES [3300017023p6]Fapesp [2015/22145-6]Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, Skeletal Dysplasia Grp, Campinas, SP, BrazilChildrens Hosp Albert Sabin, Fortaleza, Ceara, BrazilMed Sci Fac Juazeiro do Norte FMJ, Juazeiro Do Norte, CE, BrazilUniv Estadual Campinas, Dept Med Genet, Fac Med Sci, Perinatal Genet Program, Campinas, SP, BrazilUniv Fed Campina Grande, Campina Grande, PB, BrazilChildrens Clin, City Hall Guarulhos, Guarulhos, SP, BrazilFed Univ Sao Carlos UFSCAR, Dept Med, Sao Carlos, SP, BrazilUniv Sao Paulo FCMUSP, Fac Med Sci, Childrens Inst, Med Genet Unit, Sao Paulo, SP, BrazilChildrens Hosp Juvencio Mattos, Sao Luis, MA, BrazilClin Hosp Porto Alegre, Med Genet Serv, Porto Alegre, RS, BrazilUniv Fed Sao Paulo, Ctr Genet Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Ctr Genet Med, Sao Paulo, SP, BrazilCNPq:402008/2010-3590148/2011-7CAPES: 3300017023p6]FAPESP:2015/22145-6Web of Scienc