Umbilical Cord Care: Cord Detachment and Prevention of Infection

There are nearly 4 million neonatal deaths worldwide each year, with one-third of those related to infections. The longer the umbilical cord remains attached, the more likely an infection will develop. Uneducated guardians may utilize improper cleaning techniques, which increases infection rates. Guardians desire to know the best method of care for their neonate

Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype

PURPOSE: Despite a few recent reports of patients harboring truncating variants in NSD2, a gene considered critical for the Wolf–Hirschhorn syndrome (WHS) phenotype, the clinical spectrum associated with NSD2 pathogenic variants remains poorly understood. METHODS: We collected a comprehensive series of 18 unpublished patients carrying heterozygous missense, elongating, or truncating NSD2 variants; compared their clinical data to the typical WHS phenotype after pooling them with ten previously described patients; and assessed the underlying molecular mechanism by structural modeling and measuring methylation activity in vitro. RESULTS: The core NSD2-associated phenotype includes mostly mild developmental delay, prenatal-onset growth retardation, low body mass index, and characteristic facial features distinct from WHS. Patients carrying missense variants were significantly taller and had more frequent behavioral/psychological issues compared with those harboring truncating variants. Structural in silico modeling suggested interference with NSD2’s folding and function for all missense variants in known structures. In vitro testing showed reduced methylation activity and failure to reconstitute H3K36me2 in NSD2 knockout cells for most missense variants. CONCLUSION: NSD2 loss-of-function variants lead to a distinct, rather mild phenotype partially overlapping with WHS. To avoid confusion for patients, NSD2 deficiency may be named Rauch–Steindl syndrome after the delineators of this phenotype

10 years of CEMARA database in the AnDDI-Rares network: a unique resource facilitating research and epidemiology in developmental disorders in France

Background : In France, the Ministry of Health has implemented a comprehensive program for rare diseases (RD) that includes an epidemiological program as well as the establishment of expert centers for the clinical care of patients with RD. Since 2007, most of these centers have entered the data for patients with developmental disorders into the CEMARA population-based registry, a national online data repository for all rare diseases. Through the CEMARA web portal, descriptive demographic data, clinical data, and the chronology of medical follow-up can be obtained for each center. We address the interest and ongoing challenges of this national data collection system 10 years after its implementation. Methods : Since 2007, clinicians and researchers have reported the “minimum dataset (MDS)” for each patient presenting to their expert center. We retrospectively analyzed administrative data, demographic data, care organization and diagnoses. Results : Over 10 years, 228,243 RD patients (including healthy carriers and family members for whom experts denied any suspicion of RD) have visited an expert center. Among them, 167,361 were patients affected by a RD (median age 11 years, 54% children, 46% adults, with a balanced sex ratio), and 60,882 were unaffected relatives (median age 37 years). The majority of patients (87%) were seen no more than once a year, and 52% of visits were for a diagnostic procedure. Among the 2,869 recorded rare disorders, 1,907 (66.5%) were recorded in less than 10 patients, 802 (28%) in 10 to 100 patients, 149 (5.2%) in 100 to 1,000 patients, and 11 (0.4%) in > 1,000 patients. Overall, 45.6% of individuals had no diagnosis and 6.7% had an uncertain diagnosis. Children were mainly referred by their pediatrician (46%; n = 55,755 among the 121,136 total children referrals) and adults by a medical specialist (34%; n = 14,053 among the 41,564 total adult referrals). Given the geographical coverage of the centers, the median distance from the patient’s home was 25.1 km (IQR = 6.3 km-64.2 km). Conclusions : CEMARA provides unprecedented support for epidemiological, clinical and therapeutic studies in the field of RD. Researchers can benefit from the national scope of CEMARA data, but also focus on specific diseases or patient subgroups. While this endeavor has been a major collective effort among French RD experts to gather large-scale data into a single database, it provides tremendous potential to improve patient care

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Prehistoria de la costa extremo-sur del Perú

Las excavaciones conducidas en la Quebrada de los Burros (dpto. de Tacna) entre 1995 y 2009, han descubierto un campamento de pescadores-recolectores (QLB) ocupado entre 10000 y 7000 a. P. durante el Holoceno temprano y medio. Seis niveles sucesivos de ocupación han sido excavados por decapado, cada uno contando con terraplenes acondicionados, vestigios de abrigos construidos, fogones, áreas de actividad y acumulaciones de desechos alimenticios de origen marino, mezclados con restos de fauna terrestre. Dos entierros humanos fueron también descubiertos. Desde el inicio de la ocupación, los ocupantes dominan perfectamente el medio marítimo pero explotan también las lomas. Los instrumentos de piedra y hueso atestiguan un ajuar muy sofisticado de pesca, recolección y caza. Al final de la ocupación, ya practican horticultura. Dos fases de ocupación fueron singularizadas, la primera durante el Holoceno temprano (ca. 10000 a 8000 a. P.), la segunda durante el Holoceno medio (ca. 8000 a 7000 a. P.). Los análisis efectuados (paleoclimatológicos, zoológicos y botánicos, esclerocronológicos e isotópicos) sugieren para la Fase I una sucesión de ocupaciones breves y posibles contactos con las tierras altas y, al contrario, una ocupación más intensa y casi permanente a lo largo del año para la Fase II, durante la cual las materias primas líticas proceden de sectores cercanos. Una contemporaneidad con los más antiguos sitios chilenos de la cultura Chinchorro está confirmada

Toutes des grosses putes !

International audienceRevenant sur le sens et l'usage de l'insulte « grosse pute », prononcée par un policier sur le répondeur d’une femme de 34 ans qui venait de porter plainte pour agression sexuelle, plusieurs universitaires expriment leur solidarité avec « toutes les “grosses putes” qui viendraient se présenter dans des commissariats et y subiraient le même traitement qu’Élodie.

Toutes des grosses putes !

International audienceRevenant sur le sens et l'usage de l'insulte « grosse pute », prononcée par un policier sur le répondeur d’une femme de 34 ans qui venait de porter plainte pour agression sexuelle, plusieurs universitaires expriment leur solidarité avec « toutes les “grosses putes” qui viendraient se présenter dans des commissariats et y subiraient le même traitement qu’Élodie.

Toutes des grosses putes ! [Tribune, Club de Mediapart]

International audienceRevenant sur le sens et l'usage de l'insulte « grosse pute », prononcée par un policier sur le répondeur d’une femme de 34 ans qui venait de porter plainte pour agression sexuelle, plusieurs universitaires expriment leur solidarité avec « toutes les “grosses putes” qui viendraient se présenter dans des commissariats et y subiraient le même traitement qu’Élodie.

Toutes des grosses putes !

International audienceRevenant sur le sens et l'usage de l'insulte « grosse pute », prononcée par un policier sur le répondeur d’une femme de 34 ans qui venait de porter plainte pour agression sexuelle, plusieurs universitaires expriment leur solidarité avec « toutes les “grosses putes” qui viendraient se présenter dans des commissariats et y subiraient le même traitement qu’Élodie.