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

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Composição do liquido cefalorrraqueano do recem-nascido normal: citometria, proteinorraquia e bilirrubinorraquia em 79 casos

Estudo do LCR de recém-nascidos a termo e de parto normal, sem intercorrências perinatais, para verificar o quanto a xantocromia é devida à bilirrubinorraquia. Foi verificado que a bilirrubinorraquia é constante na primeira semana de vida e que sua concentração: não guarda relação com a concentração proteica total do LCR e/ou com os níveis de bilirrubina no soro; não sofre influência do número de hemácias e/ou de leucócitos presente na amostra. Os valores encontrados no LCR quanto ao número de leucócitos e de hemácias e às concentrações de proteínas totais e de bilirrubina são analisados na caracterização do LCR do recém-nascido normal na primeira semana de vida

Development and Evaluation of Electronic Social Needs Assessment and Resource Connection Tool in Facilitating Utilization of Community Services That Address Upstream Health

Background: Social determinants of health (SDOH) put some groups who access care at student-run free clinics (SRFCs) at higher risk for adverse medical outcomes. Free or low-cost community services supplement clinic-based interventions, but access is limited by knowledge, transportation, language, and/or trust. Social needs assessments may be electronically paired with resource connection tools to connect patients to local, validated resources. The objective of this pilot study was to evaluate the SDOH screen and resource connection tool developed at a SRFC. Methods: The tool was piloted with a convenience sample of 40 patients with scheduled outpatient appointments at a SRFC in Miami, Florida. Participants were given information about a variety of services and screened for high-risk situations such as human trafficking. Follow-up survey via telephone at 2-4 weeks identified survey acceptability, successful connections, and barriers to access. Results: Forty participants completed the assessment. All participants were counseled regarding exercise and nutrition and requested information about more than one resource. Sixty percent (n=24) were successfully contacted for follow-up. Of these, 29% (n=7) were able to connect with one or more recommended resources. Reasons given for failure to access resources included lack of time or transportation, health issues, and lack of response from contacted organizations. Conclusions: Social needs assessments may be implemented in SRFCs to identify high-risk needs, facilitate linkage to local organizations that meet these needs, gather data to guide future programming, and provide education and counseling. Stronger connections with local organizations and closed loop referrals may be needed to facilitate connection to community resources

Impact of nucleos(t)ide reverse transcriptase inhibitors on blood telomere length changes in a prospective cohort of aviremic HIV-infected adults

[Background]: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown.[Methods]: A prospective cohort of human immunodeficiency virus (HIV)–infected participants with suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF.[Results]: A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides [of whom 69 were receiving abacavir], 25 were receiving a nucleos[t]ide reverse transcriptase inhibitor [N{t}RTI]–sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside.[Discussion]: In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.This work was supported by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (grants PI13/01467 and PI14/01495 [supported by the European Regional Development Fund], Rio Hortega fellowship [to R. d. M.], and predoctoral fellowship [to N. S.-A.]).Peer reviewe

Root caries in areas with and without fluoridated water at the Southeast region of São Paulo State, Brazil

This study aimed to investigate root caries prevalence in areas with and without water fluoridation at the Southeast region of São Paulo State, in the adult population, employees of public and private schools, and elderly population. Epidemiological surveys were conducted according to the World Health Organization guidelines (1997), including 1,475 dentate individuals aged 35 to 44 years and 65 to 74 years, living in cities representing the southeast of São Paulo State, with (n=872) or without (n=603) fluoridated water supply. Statistical analysis was performed by Mann-Whitney and Chi-square tests at a significance level of 5%. The prevalence of root caries was 15.6% for the 35-44-year-old age group and 31.8% for the 65-74-year-old age group . There were no statistically significant differences (p>0.05) in the occurrence of root caries according to water fluoridation, although individuals living at non-fluoridated areas presented higher percentage of missing teeth; also, there was higher mean number of intact roots at fluoridated areas (p<0.05). Most individuals with gingival recession, both adults and elderly, did not have root caries experience. In this study, root caries prevalence was lower in areas with fluoridated water. Due to the reduced prevalence of edentulism and increased number of people keeping their natural teeth for a longer period, a future increase in root caries is expected, highlighting the importance of studies related to water fluoridation and its relationship with the oral health of adults and elderly, especially referring to tooth root