Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, congenital heart defects and distinctive facies. The disorder is genetically heterogeneous with approximately 50% of patients having PTPN11 mutations. Prenatally, the diagnosis of NS has been suspected following certain ultrasound findings, such as cystic hygroma, increased nuchal translucency (NT) and hydrops fetalis. Studies of fetuses with cystic hygroma have suggested an NS prevalence of 1-3%. A retrospective review was performed to assess the utility of PTPN11 testing based on prenatal sonographic findings (n = 134). The most commonly reported indications for testing were increased NT and cystic hygroma. Analysis showed heterozygous missense mutations in 12 fetuses, corresponding to a positive test rate of 9%. PTPN11 mutations were identified in 16% and 2% of fetuses with cystic hygroma and increased NT, respectively. Among fetuses with isolated cystic hygroma, PTPN11 mutation prevalence was 11%. The mutations observed in the three fetuses with hydrops fetalis had previously been reported as somatic cancer mutations. Prenatal PTPN11 testing has diagnostic and possible prognostic properties that can aid in risk assessment and genetic counseling. As NS is genetically heterogeneous, negative PTPN11 testing cannot exclude the diagnosis and further study is warranted regarding the other NS genes.

A new technique has been applied to the study of the RNA secondary structure unwinding activity of the eukaryotic initiation factors (eIFs) 4F, 4A, and 4B. Secondary structures were generated at the 5' ends of reovirus and globin mRNA molecules by hybridization with 32P-labeled cDNA molecules 15 nucleotide residues long. The dissociation of the labeled cDNAs from the mRNAs was assayed by a gel filtration chromatography procedure which separates the free cDNAs from mRNAs and mRNA/cDNA hybrids. When the three factors were tested alone, only eIF-4F stimulated dissociation of hybrids. The combination of eIF-4A plus eIF-4B also exhibited a strong hybrid dissociating activity, which was markedly temperature dependent. Under optimum conditions, up to 90% of the hybrid structures are disrupted in 60 min. These results demonstrate for the first time that stable double-stranded regions can be melted and dissociated by eIFs. They also characterize more precisely the first step in the structure unwinding reaction.

Evidence before this study: Acute appendicitis is the most common general surgical emergency in children. Its diagnosis remains challenging and children presenting with acute right iliac fossa (RIF) pain may be admitted for clinical observation or undergo normal appendicectomy (removal of a histologically normal appendix). A search for external validation studies of risk prediction models for acute appendicitis in children was performed on MEDLINE and Web of Science on 12 January 2017 using the search terms ["appendicitis" OR "appendectomy" OR "appendicectomy"] AND ["score" OR "model" OR "nomogram" OR "scoring"]. Studies validating prediction models aimed at differentiating acute appendicitis from all other causes of RIF pain were included. No date restrictions were applied. Validation studies were most commonly performed for the Alvarado, Appendicitis Inflammatory Response Score (AIRS), and Paediatric Appendicitis Score (PAS) models. Most validation studies were based on retrospective, single centre, or small cohorts, and findings regarding model performance were inconsistent. There was no high quality evidence to guide selection of the optimum model and threshold cutoff for identification of low-risk children in the UK and Ireland. Added value of this study: Most children admitted to hospital with RIF pain do not undergo surgery. When children do undergo appendicectomy, removal of a normal appendix (normal appendicectomy) is common, occurring in around 1 in 6 children. The Shera score is able to identify a large low-risk group of children who present with acute RIF pain but do not have acute appendicitis (specificity 44%). This low-risk group has an overall 1 in 30 risk of acute appendicitis and a 1 in 270 risk of perforated appendicitis. The Shera score is unable to achieve a sufficiently high positive predictive value to select a high-risk group who should proceed directly to surgery. Current diagnostic performance of ultrasound is also too poor to select children for surgery. Implications of all the available evidence: Routine pre-operative risk scoring could inform shared decision making by doctors, children, and parents by supporting safe selection of lowrisk patients for ambulatory management, reducing unnecessary admissions and normal appendicectomy. Hospitals should ensure seven-day-a-week availability of ultrasound for medium and high-risk patients. Ultrasound should be performed by operators trained to assess for acute appendicitis in children. For children in whom diagnostic uncertainty remains following ultrasound, magnetic resonance imaging (MRI) or low-dose computed tomography (CT) are second-line investigations.

Living fungal mycelium with abolished ability to form fruiting bodies is a self-healing substance, which is particularly valuable for further engineering and development as materials sensing environmental changes and secreting signals. Suppression of fruiting body formation is also a useful tool for maintaining the stability of a mycelium-based material with ease and lower cost. The objective of this study was to provide a biochemical solution to regulate the fruiting body formation, which may replace heat killing of mycelium in practice. The concentrations of glycogen synthase kinase-3 (GSK-3) inhibitors, such as lithium chloride or CHIR99021 trihydrochloride, were found to directly correlate with the development of fruiting bodies in the mushroom forming fungi such as Coprinopsis cinerea and Pleurotus djamor . Sensitive windows to these inhibitors throughout the fungal life cycle were also identified. We suggest the inclusion of GSK-3 inhibitors in the cultivation recipes for inhibiting fruiting body formation and regulating mycelium growth. This is the first report of using a GSK-3 inhibitor to suppress fruiting body formation in living fungal mycelium-based materials. It provides an innovative strategy for easy, reliable, and low cost maintenance of materials containing living fungal mycelium.

The purpose of this study was to estimate the prevalence of perimenstrual symptoms in professionally employed women. Questionnaires were administered to all female nurses working at least 32 hr/wk in 7 different hospitals on the West Coast between October, 1987 and June, 1988. Of the 760 respondents, 594 were currently menstruating and met inclusion criteria. Symptoms frequently experienced by a majority of women included weight gain/swelling, anxiety/tension/irritability, fatigue, cramps, breast pain, mood swings, and food cravings. Symptoms were more prevalent in women under 30 years. Compared to white women, fewer Asians reported cramps and weight gain/swelling. More single women reported food cravings and depression/crying. Parity, cycle regularity, menses duration, and endometriosis were associated with perimenstrual cramps. Fewer women over 30 yrs experienced skin disorders and depression/crying. The only symptom experienced by more than 60% of women in all age groups was weight gain/swelling.