Is there still space for the implementation of antisepsis and disinfection to prevent rotavirus and norovirus gastroenteritis outbreaks?

No summar

Is there still space for the implementation of antisepsis and disinfection to prevent rotavirus and norovirus gastroenteritis outbreaks?

No summar

CUGC for hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome

From 1999 to date, 50 affecting function variants have been identified and associated to HHH syndrome [1–5]. As it is not available in the literature a complete up-to-date list of disease-causing variants for SLC25A15 gene, we included this information as a Supplementary Excel sheet (See Supplementary Material File #1): this list was created by using LOVD and ClinVar databases and liked to the relevant literature reference. Reported variants consist of: 29 missense variants, 4 frameshift, 11 nonsense, 2 splicing, 2 small deletion, 1 in frame insertion, 1 gross deletion

Vemurafenib treatment of pleomorphic xanthoastrocytoma in a child with Down syndrome

Brain tumors are the most common solid neoplasms of childhood, but they are very rarely reported in children with Down Syndrome (DS), who develop more commonly different types of malignancies. In particular, we hereby report the case of an 8-years-old child with DS that presented to our attention for neurological and endocrinological issues. Brain imaging revealed the presence of a mass that was partially resected revealing a histological diagnosis of Pleomorphic Xanthoastrocytoma (PXA), a rare WHO grade II tumor extending from the diencephalic region into the surrounding brain tissue. These tumors can harbor the BRAF mutation p.V600E, targetable by the specific inhibitor Vemurafenib. After confirming the presence of the mutation in the tumor, the patient was treated with Vemurafenib. The treatment proved to be effective, leading to a partial response and a stabilization of the disease. Usually, in patients with DS a reduction of the dose of chemotherapeutic drugs is necessary. Vemurafenib was instead well-tolerated as the only observed adverse effect was grade I skin toxicity. This is, to our knowledge, the first case of a PXA reported in a child with DS and the first DS patient treated with Vemurafenib

COVID-19 and genetic variants of protein involved in the SARS-CoV-2 entry into the host cells

The recent global COVID-19 public health emergency is caused by SARS-CoV-2 infections and can manifest extremely variable clinical symptoms. Host human genetic variability could influence susceptibility and response to infection. It is known that ACE2 acts as a receptor for this pathogen, but the viral entry into the target cell also depends on other proteins. The aim of this study was to investigate the variability of genes coding for these proteins involved in the SARS-CoV-2 entry into the cells. We analyzed 131 COVID-19 patients by exome sequencing and examined the genetic variants of TMPRSS2, PCSK3, DPP4, and BSG genes. In total we identified seventeen variants. In PCSK3 gene, we observed a missense variant (c.893G>A) statistically more frequent compared to the EUR GnomAD reference population and a missense mutation (c.1906A>G) not found in the GnomAD database. In TMPRSS2 gene, we observed a significant difference in the frequency of c.331G>A, c.23G>T, and c.589G>A variant alleles in COVID-19 patients, compared to the corresponding allelic frequency in GnomAD. Genetic variants in these genes could influence the entry of the SARS-CoV-2. These data also support the hypothesis that host genetic variability may contribute to the variability in infection susceptibility and severity

Low-grade gliomas in patients with Noonan syndrome: case-based review of the literature

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling

Pelvic trauma : WSES classification and guidelines

Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be ultimately based on the physiology of the patient and the anatomy of the injury. This paper presents the World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines.Peer reviewe

Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects

KDM4B is a lysine-specific demethylase with a preferential activity on H3K9 tri/di-methylation (H3K9me3/2)-modified histones. H3K9 tri/di-demethylation is an important epigenetic mechanism responsible for silencing of gene expression in animal development and cancer. However, the role of KDM4B on human development is still poorly characterized. Through international data sharing, we gathered a cohort of nine individuals with mono-allelic de novo or inherited variants in KDM4B. All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had anomalies on brain imaging ranging from agenesis of the corpus callosum with hydrocephalus to cystic formations, abnormal hippocampi, and polymicrogyria. In mice, lysine demethylase 4B is expressed during brain development with high levels in the hippocampus, a region important for learning and memory. To understand how KDM4B variants can lead to GDD in humans, we assessed the effect of KDM4B disruption on brain anatomy and behavior through an in vivo heterozygous mouse model (Kdm4b+/-), focusing on neuroanatomical changes. In mutant mice, the total brain volume was significantly reduced with decreased size of the hippocampal dentate gyrus, partial agenesis of the corpus callosum, and ventriculomegaly. This report demonstrates that variants in KDM4B are associated with GDD/ intellectual disability and neuroanatomical defects. Our findings suggest that KDM4B variation leads to a chromatinopathy, broadening the spectrum of this group of Mendelian disorders caused by alterations in epigenetic machinery