Lower Extremity Polydactyly Does Not Disturb Finding One's Feet

Little is known about functional outcomes in children with treated lower extremity polydactyly (LEP). No classification system has been shown to be prognostically useful for functional outcomes. This study investigates whether children with treated LEP learn to walk at an age comparable to the population and whether the SAM (severity of syndactyly, axis deviation and metatarsal involvement) classification system is prognostically useful. In a retrospective cohort of 18 patients, we tested for associations between patient characteristics and SAM scores, age at learning to walk, and ability to fit off-the-shelf shoes. The proportion of children with treated LEP able to walk at 18 months of age was compared with the general population. We found no association between the age at which the 17 participants learned to walk and the severity of syndactyly (p =. 214), axis deviation (p =. 723) and metatarsal involvement (p =. 781), nor between the proportion of patients able to wear off-the-shelf shoes compared to those requiring extra wide off-the-shelf shoes and the severity of syndactyly (p = 1.000), axis deviation (p = 1.000) and metatarsal involvement (p = 1.000). We found a trend between older age at surgery and the need for extra wide off-the-shelf shoes (OR = 1.008, p =. 080). We found no significant difference in the proportion of children able to walk at 18 months between our patients (proportion = 1.00) and the general population (proportion = 0.95) (p = 1.000). We found no significant association between different SAM scores and functional outcomes, and none in the proportion of children able to walk at 18 months between treated LEP patients and the general population.</p

On-call abdominal ultrasonography:the rate of negative examinations and incidentalomas in a European tertiary care center

OBJECTIVES: To determine the proportions of abdominal US examinations during on-call hours that are negative and that contain an incidentaloma, and to explore temporal changes and determinants. METHODS: This study included 1615 US examinations that were done during on-call hours at a tertiary care center between 2005 and 2017. RESULTS: The total proportion of negative US examinations was 49.2% (795/1615). The total proportion of US examinations with an incidentaloma was 8.0% (130/1615). There were no significant temporal changes in either one of these proportions. The likelihood of a negative US examination was significantly higher when requested by anesthesiology [odds ratio (OR) 2.609, P = 0.011], or when the indication for US was focused on gallbladder and biliary ducts (OR 1.556, P = 0.007), transplant (OR 2.371, P = 0.005), trauma (OR 3.274, P < 0.001), or urolithiasis/postrenal obstruction (OR 3.366, P < 0.001). In contrast, US examinations were significantly less likely to be negative when requested by urology (OR 0.423, P = 0.014), or when the indication for US was acute oncology (OR 0.207, P = 0.045) or appendicitis (OR 0.260, P < 0.001). The likelihood of an incidentaloma on US was significantly higher in older patients (OR 1.020 per year of age increase, P < 0.001) or when the liver was evaluated with US (OR 3.522, P < 0.001). DISCUSSION: Nearly 50% of abdominal US examinations during on-call hours are negative, and 8% reveal an incidentaloma. Requesting specialty and indication for US affect the likelihood of a negative examination, and higher patient age and liver evaluations increase the chance of detecting an incidentaloma in this setting. These data may potentially be used to improve clinical reasoning and restrain overutilization of imaging

Does FDG-PET/CT for incidentally found pulmonary lesions lead to a cascade of more incidental findings?

OBJECTIVE: To determine the frequency, nature, and downstream healthcare costs of new incidental findings that are found on whole-body FDG-PET/CT in patients with a non-FDG-avid pulmonary lesion ≥10 mm that was incidentally found on previous imaging.MATERIALS AND METHODS: This retrospective study included a consecutive series of patients who underwent whole-body FDG-PET/CT because of an incidentally found pulmonary lesion ≥10 mm.RESULTS: Seventy patients were included, of whom 23 (32.9 %) had an incidentally found pulmonary lesion that proved to be non-FDG-avid. In 12 of these 23 cases (52.2 %) at least one new incidental finding was discovered on FDG-PET/CT. The total number of new incidental findings was 21, of which 7 turned out to be benign, 1 proved to be malignant (incurable metastasized cancer), and 13 whose nature remained unclear. One patient sustained permanent neurologic impairment of the left leg due to iatrogenic nerve damage during laparotomy for an incidental finding which turned out to be benign. The total costs of all additional investigations due to the detection of new incidental findings amounted to €9903.17, translating to an average of €141.47 per whole-body FDG-PET/CT scan performed for the evaluation of an incidentally found pulmonary lesion.CONCLUSION: In many patients in whom whole-body FDG-PET/CT was performed to evaluate an incidentally found pulmonary lesion that turned out to be non-FDG-avid and therefore very likely benign, FDG-PET/CT detected new incidental findings in our preliminary study. Whether the detection of these new incidental findings is cost-effective or not, requires further research with larger sample sizes.</p

MicroRNAs can generate thresholds in target gene expression

MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.National Institutes of Health (U.S.). Director's Pioneer Award (1DP1OD003936)National Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874)United States. Public Health Service (Grant R01-CA133404)United States. Public Health Service (Grant R01-GM34277)National Cancer Institute (U.S.) (PO1-CA42063)National Cancer Institute (U.S.) Cancer Center Support (Grant P30-CA14051)Howard Hughes Medical Institute. Predoctoral FellowshipCleo and Paul Schimmel Foundation. FellowshipNatural Sciences and Engineering Research Council of Canada PGS Scholarshi

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed

Detection of clonal mast cell disease in wasp venom allergic patients with normal tryptase

Background: Clonal mast cell disease (CMD) is an underlying aggravating condition in wasp venom allergy (WVA) which requires a different treatment strategy. CMD is increasingly recognized in patients with normal basal serum tryptase (bsT). However, methods to identify at risk patients have not yet been assessed in large cohorts of WVA patients with normal bsT. Methods: This retrospective study evaluated the reliability of the REMA score in detecting CMD in a cohort of grade IV WVA patients with normal bsT and assessed the added value of other clinical parameters, KIT D816V mutation analysis in peripheral blood (PB) and the diagnosis of hereditary alpha tryptasemia (HAT). All patients had a conclusive bone marrow evaluation that demonstrated or excluded underlying CMD. Results: In total 35 CMD and 96 non-CMD patients were included. REMA score had a sensitivity of 72% (95% CI 56%-88%) and specificity of 79% (95% CI 70%-87%) in this cohort. Loss of consciousness during systemic reaction and bsT between 6.3 and 11.4 ng/ml were additional parameters independently associated with CMD. Sensitivity of KIT in PB was relatively low, 56% (95% CI 36%-75%), but had added value as screening method in patients with a low REMA score due to 100% specificity. Conclusion: The REMA score is a relatively reliable method to detect patients at risk of CMD among WVA patients with normal bsT. KIT mutation analysis in PB could serve as additional screening method in patients with low REMA scores

A Smart Computational Tool for Personalized Coronary Blood Flow Settings During Normothermic &lt;i&gt;Ex Situ&lt;/i&gt; Heart Perfusion

Myocardial edema significantly develops during current subnormothermic ex situ heart perfusion (ESHP) procedures, resulting in myocardial function decline during prolonged perfusion. A relatively high coronary blood flow (CBF) during ESHP is thought to be responsible for this high degree of myocardial edema formation. In this study, we present a novel tool to calculate CBF based on individual donor (sex and body weight) and perfusate (hemoglobin concentration, oxygen saturation, partial pressure of oxygen [PO2]) characteristics. The tool continuously evaluates the balance between myocardial oxygen consumption (MVO2) and delivery to facilitate adequate and preventing excess perfusion. Taking this personalized approach, the CBF can potentially be lowered while still providing sufficient oxygen to the donor heart. Furthermore, the tool automatically calculates MVO2, ΔPO2, and coronary vascular resistance during ESHP, which aids in the qualitative assessment of the heart before transplantation.</p

Eindrapport VC3BI commissie

De commissie VC3BI (Verkenningscommissie 3: Bachelors Informatiewetenschappen) heeft sinds eind 2014 de beoogde samenwerking verkend bij de in totaal zes Bacheloropleidingen in informatiewetenschappen aan UvA en VU. Bij de UvA gaat het om de opleidingen Informatica (INF), Informatiekunde (IK) en Kunstmatige Intelligentie (KI), bij de VU om Computer Science (CS), Information, Multimedia &amp; Management (IMM), en Lifestyle Informatics (LI)

Circular RNAs in Cardiovascular Diseases: Regulation and Therapeutic Applications

Cardiovascular disease is one of the leading causes of mortality worldwide. Recent studies have shown that circular RNAs (circRNAs) have emerged as important players in the prevention and treatment of cardiovascular diseases. circRNAs are a class of endogenous noncoding RNAs that are generated by back-splicing and are involved in many pathophysiological processes. In this review, we outline the current research progress on the regulatory roles of circRNAs in cardiovascular diseases. Further, new technologies and methods available for identifying, validating, synthesizing, and analyzing circRNAs, as well as their applications in therapeutics, are highlighted here. Moreover, we summarize the increasing insights into the potential use of circRNAs as circulating diagnostic and prognostic biomarkers. Finally, we discuss the prospects and challenges of circRNA therapeutic applications for cardiovascular disease therapy, with a particular focus on developing circRNA synthesis and engineering delivery systems