Microdeletion syndromes disclose replication timing alterations of genes unrelated to the missing DNA

<p>Abstract</p> <p>Background</p> <p>The temporal order of allelic replication is interrelated to the epigenomic profile. A significant epigenetic marker is the asynchronous replication of monoallelically-expressed genes versus the synchronous replication of biallelically-expressed genes. The present study sought to determine whether a microdeletion in the genome affects epigenetic profiles of genes unrelated to the missing segment. In order to test this hypothesis, we checked the replication patterns of two genes – <it>SNRPN</it>, a normally monoallelically expressed gene (assigned to 15q11.13), and the <it>RB1</it>, an archetypic biallelically expressed gene (assigned to 13.q14) in the genomes of patients carrying the 22q11.2 deletion (DiGeorge/Velocardiofacial syndrome) and those carrying the 7q11.23 deletion (Williams syndrome).</p> <p>Results</p> <p>The allelic replication timing was determined by <it>fluorescence in situ hybridization </it>(FISH) technology performed on peripheral blood cells. As expected, in the cells of normal subjects the frequency of cells showing asynchronous replication for <it>SNRPN </it>was significantly (P < 10^-12) higher than the corresponding value for <it>RB1</it>. In contrast, cells of the deletion-carrying patients exhibited a reversal in this replication pattern: there was a significantly lower frequency of cells engaging in asynchronous replication for <it>SNRPN </it>than for <it>RB1 </it>(P < 10^-4and P < 10^-3for DiGeorge/Velocardiofacial and Williams syndromes, respectively). Accordingly, the significantly lower frequency of cells showing asynchronous replication for <it>SNRPN </it>than for <it>RB1 </it>is a new epigenetic marker distinguishing these deletion syndrome genotypes from normal ones.</p> <p>Conclusion</p> <p>In cell samples of each deletion-carrying individual, an aberrant, reversed pattern of replication is delineated, namely, where a monoallelic gene replicates more synchronously than a biallelic gene. This inverted pattern, which appears to be non-deletion-specific, clearly distinguishes cells of deletion-carriers from normal ones. As such, it offers a potential epigenetic marker for suspecting a hidden microdeletion that is too small to be detected by conventional karyotyping methods.</p

Molecular imaging of cell death in vivo by a novel small molecule probe

Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo

Performance of two head injury decision rules evaluated on an external cohort of 18,913 children

The Pediatric Emergency Care Applied Research Network (PECARN) decision rule demonstrates high sensitivity for identifying children at low risk for clinically important traumatic brain injury (ciTBI). As with the PECARN rule, the Israeli Decision Algorithm for Identifying TBI in Children (IDITBIC) recommends proceeding directly to computed tomography (CT) in children with Glasgow Coma Score (GCS) lower than 15. The aim was to assess the diagnostic accuracy of two clinical rules that assign children with GCS lower than 15 at presentation directly to CT

The influence of an accredited pediatric emergency medicine program on the management of pediatric pain and anxiety

Abstract Background The emergency department (ED) setting is an environment where children may experience intense physical pain and emotional stress. This study sought to determine the availability of pain and anxiety management practices in all Israeli emergency departments which accept children, specifically looking for differences between accredited pediatric emergency medicine departments and others. Methods A cross-sectional survey of all Israeli emergency departments that accept children was performed. One person at each institution was approached to complete the survey. Data were collected between May and June 2016 using an electronic survey tool. Results Responses were collected from 21 of 22 hospitals (95% response rate). Commonly available in all types of emergency departments were nurse ordered analgesia, medical clowns (in 95% of the hospitals), topical analgesia and oral sucrose solution. The accredited pediatric emergency medicine departments showed a tendency for more frequent use of all pharmacologic methods for pain and anxiety relief, specifically oxycodone and ketamine. Conclusions Overall, Israeli emergency departments have similar access to pharmacologic and non-pharmacologic pain and anxiety management strategies in children, but gaps still exist, especially where not all attending physicians are pediatric emergency medicine trained. We suggest that certified pediatric emergency medicine physicians should advise all emergency departments that accept children to promote the use of the various methods of pain and anxiety reduction

An Unusual Cause of Small Bowel Obstruction in a Child: Ingested Rhubarb

Small bowel obstruction is rarely caused by bezoars concretions formed from undigested foreign material in the gastrointestinal tract. An important cause of bezoars is phytobezoars, formed from vegetables or fruits. A four-year-old boy presented to our emergency department with symptoms of acute intestinal obstruction. Upright plain abdominal radiography revealed multiple air fluid levels. Ultrasound showed no abnormalities, and because of worsening symptoms computed tomography of abdomen was performed. It showed intraluminal obstruction of the terminal ileum. Exploratory laparotomy revealed a phytobezoar consisting of undigested rhubarb. The mass was milked through the large bowel and out the anus. Although rare in humans, bezoars are a well-documented cause of small bowel obstruction and should be considered when intraluminal bowel obstruction occurs. Bezoars causing small bowel obstruction may require surgical treatment.Peer Reviewe

Binge drinking among young adults in an urban tertiary care emergency department in Israel

Abstract Background Alcohol use is a major preventable public health problem with serious health and social consequences especially among youth. In Israel, alcohol use has become an emerging problem during the last decade, and its use has increased among adolescents and young adults. Binge drinking is the common pattern of alcohol consumption among young adults who drink for recreational purposes. The present survey was conducted among 16–35 years old visitors to the ED. The aim was specifically to identify binge drinkers in order to assess the scope of the need for a brief counseling intervention among young people who arrive intoxicated to a large tertiary care urban ED in Israel. Methods The survey was conducted throughout a 1 week period (24 h per day) at the general EDs in a large, tertiary care center, situated in Tel Aviv. During the survey week, 946 individuals, aged 16-35, visited the ED and 573 (63%) of them were approached for an interview. 89% of those approached agreed to be interviewed. Consenting patients [N = 348] were asked whether they drink any alcohol, how often they drink and how much. Results About one fifth of those interviewed were in the habit of consuming more than four units of alcohol per occasion. Drinking several times a week or every day was reported by 19% of the males and 26% of the females. Frequency of the drinking episodes was highly correlated with the number of units of drink per occasion. Conclusions The study found a very high rate of binge drinking among ED visitors, and this suggests a need for large scale ED-based interventions. As binge drinkers are at elevated risk for accidents, violence and related problems, effective ED-based interventions could make an important contribution to public health. Accordingly, Israel is in the process of assessing the effectiveness of a large-scale ED-based counseling intervention. Trial registration Trial registration number 0230-13-TLV