CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Supplementary Material for: Analysis of p16_{<i>CDKN2A</i>} Methylation and HPV-16 Infection in Oral Mucosal Dysplasia

<i>Objective:</i> The purpose of this study was to investigate the relationship between <i>p16</i>_{<i>CDKN2A</i>} methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1). Finally, we tested whether HPV-16/18 or the <i>dmt3b</i> (C46359T) polymorphism is associated with <i>p16</i>_{<i>CDKN2A</i>} methylation status. <i>Methods:</i> To test the hypothesis, a case-control study with 72 (control, n = 24; ED, n = 48) tissue samples from subjects was performed. Methylation-specific PCR, RFLP, and immunohistochemical analyses were performed to evaluate <i>p16</i>_{<i>CDKN2A</i>} methylation status, <i>dmt3b</i> (C46359T) genotyping, and protein levels, respectively. <i>Results:</i> The methylation of <i>p16</i>_{<i>CDKN2A</i>} and HPV-16 was associated with ED gradation (p = 0.001 and 0.002, respectively). In addition, most HPV-16-positive samples (77.8%) exhibited <i>p16</i>_{<i>CDKN2A</i>} methylation; however, changes in DNMT3B and DNMT1 protein levels were not observed in HPV-positive samples. Neither HPV-18 nor the <i>dmt3b</i> polymorphism was associated with <i>p16</i>_{<i>CDKN2A</i>} methylation. <i>Conclusions:</i> There is an association between the presence of HPV-16 in ED and the occurrence of <i>p16</i>_{<i>CDKN2A</i>} methylation. Both variables are also associated with ED development, but further studies are necessary to clarify if they operate independently and if they have any impact on OD malignization

Cálcio, fósforo e proteína total no sangue de frangos de corte em função de níveis de balanço eletrolítico da ração

Determinaram-se os melhores valores do balanço eletrolítico (BE) de dietas para frangos quanto aos teores de cálcio, fósforo e proteína total no sangue de frangos de corte aos 42 dias de idade. Foram utilizadas 1728 aves de marca comercial, machos. As aves foram alimentadas com duas dietas basais, 20 ou 23% de proteína bruta (PB), na fase inicial, e uma única ração basal, 20% de PB, na fase de crescimento, combinadas com níveis de balanço eletrolítico de 0; 50; 100; 150; 200; 250; 300 e 350mEq/kg. Foi utilizado delineamento experimental inteiramente ao acaso, em arranjo fatorial, com seis repetições de 18 aves cada e 96 unidades experimentais. Foi escolhida uma ave em cada unidade experimental para a coleta de sangue. Foram avaliados os teores de cálcio, fósforo e proteínas totais no sangue dessas aves aos 42 dias de idade. Os melhores valores de BE estimados para o teor de proteína total no sangue foram de 101 e 131mEq/kg da dieta, para planos nutricionais de 20-20% e 23-20% de PB, respectivamente. Para os teores plasmáticos de cálcio e fósforo, não foram encontradas diferenças entre os níveis de BE estudados

Diagnostic investigation of 100 cases of abortion in sheep in Uruguay: 2015-2021.

Abstract: The aim of this work was to identify causes of abortion through laboratory investigations in sheep flocks in Uruguay. One hundred cases of abortion, comprising 58 fetuses, 36 fetuses with their placentas, and 6 placentas were investigated in 2015?2021. Cases were subjected to gross and microscopic pathologic examinations, and microbiological and serological testing for the identification of causes of abortion, including protozoal, bacterial, and viral pathogens. An etiologic diagnosis was determined in 46 (46%) cases, including 33 (33%) cases caused by infectious pathogens, as determined by the detection of a pathogen along with the identification of fetoplacental lesions attributable to the detected pathogen. Twenty-seven cases (27%) were caused by Toxoplasma gondii, 5 (5%) by Campylobacter fetus subspecies fetus, and 1 (1%) by an unidentified species of Campylobacter. Fourteen cases (14%) had inflammatory and/or necrotizing fetoplacental lesions compatible with an infectious etiology. Although the cause for these lesions was not clearly identified, T. gondii was detected in 4 of these cases, opportunistic bacteria (Bacillus licheniformis, Streptococcus sp.) were isolated in 2 cases, and bovine viral diarrhea virus 1 subtype i (BVDV-1i) was detected in another. Campylobacter jejuni was identified in 1 (1%) severely autolyzed, mummified fetus. BVDV-2b was identified incidentally in one fetus with an etiologic diagnosis of toxoplasmosis. Microscopic agglutination test revealed antibodies against ?1 Leptospira serovars in 15/63 (23.8%) fetuses; however, Leptospira was not identified by a combination of qPCR, culture, fluorescent antibody testing nor immunohistochemistry. Neospora caninum, Chlamydia abortus, Chlamydia pecorum, Coxiella burnetii and border disease virus were not detected in any of the analyzed cases. Death was attributed to dystocia in 13 (13%) fetuses delivered by 8 sheep, mostly from one highly prolific flock. Congenital malformations including inferior prognathism, a focal hepatic cyst, and enterohepatic agenesis were identified in one fetus each, the latter being the only one considered incompatible with postnatal life. Toxoplasmosis, campylobacteriosis and dystocia were the main identified causes of fetal losses. Despite the relatively low overall success rate in establishing an etiologic diagnosis, a systematic laboratory workup in cases of abortion is of value to identify their causes and enables zoonotic pathogens surveillance