Lifestyle Risk Score: handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions

Recent studies consider lifestyle risk score (LRS), an aggregation of multiple lifestyle exposures, in identifying association of gene-lifestyle interaction with disease traits. However, not all cohorts have data on all lifestyle factors, leading to increased heterogeneity in the environmental exposure in collaborative meta-analyses. We compared and evaluated four approaches (Naïve, Safe, Complete and Moderator Approaches) to handle the missingness in LRS-stratified meta-analyses under various scenarios. Compared to “benchmark” results with all lifestyle factors available for all cohorts, the Complete Approach, which included only cohorts with all lifestyle components, was underpowered due to lower sample size, and the Naïve Approach, which utilized all available data and ignored the missingness, was slightly inflated. The Safe Approach, which used all data in LRS-exposed group and only included cohorts with all lifestyle factors available in the LRS-unexposed group, and the Moderator Approach, which handled missingness via moderator meta-regression, were both slightly conservative and yielded almost identical p values. We also evaluated the performance of the Safe Approach under different scenarios. We observed that the larger the proportion of cohorts without missingness included, the more accurate the results compared to “benchmark” results. In conclusion, we generally recommend the Safe Approach, a straightforward and non-inflated approach, to handle heterogeneity among cohorts in the LRS based genome-wide interaction meta-analyses.Subject terms: Genetics, Risk factors     

DADOS-Survey: an open-source application for CHERRIES-compliant Web surveys

Background  

The Internet has been increasingly utilized in biomedical research. From online searching for literature to data sharing, the Internet has emerged as a primary means of research for many physicians and scientists. As a result, Web-based surveys have been employed as an alternative to traditional, paper-based surveys. We describe DADOS-Survey, an open-source Web-survey application developed at our institution that, to the best of our knowledge, is the first to be compliant with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). DADOS-Survey was designed with usability as a priority, allowing investigators to design and execute their own studies with minimal technical difficulties in doing so.     

Molecular cloning and characterization of actin genes from Echinococcus granulosus

An Echinococcus granulosus genomic library has been screened with a mouse β-actin cDNA probe. Two clones carrying DNA fragments of about 15 kb, possibly derived from the same genome region, have been isolated. This 15-kb genomic region includes 2 actin-related sequences (EgactI and EgactII) separated by about 4 kb. The nucleotide sequences of both genes were determined. The EgactI sequence presents no introns, but an intron of 591 bp was observed in the EgactII sequence. The genes potentially encode 375 and 376 amino-acid-long actins, respectively, with a homology of 85.3%. The deduced amino acid sequences from both genes were compared to the actin sequences from other organisms, showing similarities ranging from 63.5% to 90.6%. The nucleotide sequence of a partial actin cDNA clone has been determined. The deduced amino acids sequence showed a homology of 90.3% and 88.0% in relation to the EgactI and EgactII sequences respectively, suggesting the existence of at least one more actin gene in E. granulosus. This hypothesis is reinforced by the number of bands detected in the Southern blot analysis. Experiments based on the amplification of DNA segments using 3′-specific actin primers indicate that the EgactI gene is transcribed in protoscoleces.     

Microhardness of superficial and deep sound human dentin

Our purpose in this study was to determine the microhardness of superficial and deep dentin by means of two indentation methods (Knoop and Vickers) under two different applied loads. Twelve dentin discs approximately 2-mm thick were obtained from both superficial and deep dentin by transversally sectioning the crowns of sound, extracted human third molars with a diamond blade under water irrigation. Dentin surfaces were sequentially polished, and indentations (n = 20 per surface) were performed with either Vickers indentor at loads of 300 and 500 g, respectively, or Knoop indentor at loads of 50 and 100 g, respectively. Average Vickers hardness number (VHN) and Knoop hardness number (KHN) were calculated and treated with two-way analysis of variance (ANOVA) and Student's t test. Microhardness of dentin was not influenced by the different loads applied for both indentation methods. Knoop hardness was significantly higher for superficial than for deep dentin (p < 0.05). Conversely, Vickers hardness was not significantly different for both substrates (p > 0.05). Differences in dentin hardness as a function of depth exist, but they might not be relevant, and no alteration of the distribution of stresses along the adhesive interface is expected.     

Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract

BACKGROUND: Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions. OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a standardized hazelnut extract in patients allergic to hazelnut. METHODS: This was a randomized, double-blind, placebo-controlled study. Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results. Patients were then randomly assigned into 2 treatment groups (hazelnut immunotherapy or placebo). Efficacy was assessed by double-blind, placebo-controlled food challenge after 8 to 12 weeks of treatment. Blood samples were drawn for measurement of specific IgE, IgG(4), and serum cytokines before and after treatment. RESULTS: Twenty-three patients were enrolled and divided into 2 treatment groups. Twenty-two patients reached the planned maximum dose at 4 days. Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4) and IL-10 levels after immunotherapy in only the active group. CONCLUSION: Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment.     

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

Background  

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process.     

Relationship between chamber mechanical properties and mean pressure-mean flow diagram of the left ventricle

We undertook a theoretical analysis of the source resistance of the left ventricle represented in a mean pressure-mean flow diagram, using the chamber properties established in terms of the pressure-volume relationship. This analysis showed that pairs of points should lie above the linear function proposed by Elzinga and Westerhof. A third-order polynomial function would theoretically explain better than a linear relation or a parabolic fit the curved shape of experimentally obtained relationships. The analysis resolves the discrepancy between Elzinga and Westerhof's theoretical concept of linear source resistance and the actual nonlinear relationship.     

Diagnostic performance of arginase activity in colorectal cancer

Arginase activity was measured in serum and biopsy from healthy individuals and colorectal cancer patients. Arginase activity in tumor samples (87±7.7 U/g tissue) was significantly higher than in controls (40.7±3.3 U/g tissue). However, serum arginase activity did not show any significant change in both groups. Finally, the micromethod used to quantify arginase activity in this study is superior to other methods because it has increased sensitivity, requires less sample, and is less time-consuming. Arginase differences are significant, according to the t-test (P<0.05). Received: 14 September 2001 / Accepted: 6 February 2002     

Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C‐terminal amino acid sequence

Defects in the gene encoding synaptotagmin 2 (SYT2) have been linked to a presynaptic congenital myasthenic syndrome (CMS) and motor neuropathies. However, to date only dominant forms of the disease have been described. We report here a consanguineous patient with a severe recessive form of presynaptic CMS and denervation atrophy caused by the homozygous mutation c.1191delG, p.Arg397Serfs*37 in SYT2. The affected 2‐year‐old girl had profound weakness and areflexia with moderate bulbar deficit. Repetitive nerve stimulation revealed an extreme reduction of compound muscle action potential amplitudes at rest, with a striking facilitation followed by a progressive decline at fast stimulation rates. These findings were reminiscent, but not identical to those seen in the Lambert–Eaton myasthenic syndrome. 3,4 diaminopyridine and pyridostigmine were effective to ameliorate muscle fatigue, but albuterol was ineffective. Modeling of the mutation using the rat Syt1 C2B x‐ray structure revealed that Arg397Serfs*37 disrupts a highly conserved amino acid sequence at the bottom face of the C2B domain not directly involved in calcium binding, but crucial for synaptotagmin‐SNARE interaction and exocytosis. Thus, this report describes a recessive form of synaptotagmin 2‐CMS and highlights the importance of the synaptotagmin C‐terminal on synaptic vesicle fusion and exocytosis.     

Design and development of a digital stethoscope encapsulation for simultaneous acquisition of phonocardiography and electrocardiography signals: the SmartHeart case study

Abstract

The stethoscope is a major symbol of modern medicine. It is used for diagnosis of different conditions and enables physicians to listen to internal body sounds. Electrocardiography was only introduced in medicine in the beginning of the twentieth century. Today measuring heart’s electrical activity is also fundamental cardiac diseases diagnosis. Although performed with independent devices, requiring physician and patient presence in the same physical space, in combination they enhance cardiovascular assessment. In this paper, a digital stethoscope encapsulation was designed, adding new functionality to this advanced medical device. Today wired and wireless communications enable different medical devices to share data and information, over long distances. Using low-cost hardware technologies, the encapsulation will add the ability to acquire and transmit via Bluetooth the Electrocardiographic activity, determined in the same cardiac focus and synchronised with the Phonocardiographic sound recordings. Several encapsulation concepts were developed and prototyped using 3D printing. They were easily fitted to the digital stethoscope and tested in a hospital environment for ergonomics, acoustic and electric signals acquisition. The best concept was chosen with the help of a physician’s opinion and the final prototype performance was very satisfactory.