Symptoms of somatization as a rapid screening tool for mitochondrial dysfunction in depression

<p>Abstract</p> <p>Aims</p> <p>Somatic symptomatology is common in depression, and is often attributed to the Freudian-inspired concept of "somatization". While the same somatic symptoms and depression are common in mitochondrial disease, in cases with concurrent mood symptoms the diagnosis of a mitochondrial disorder and related therapy are typically delayed for many years. A short screening tool that can identify patients with depression at high risk for having underlying mitochondrial dysfunction is presented.</p> <p>Methods</p> <p>Six items of the Karolinska Scales of Personality (KSP) were found to differentiate among 21 chronically-depressed Swedish subjects with low versus normal muscle ATP production rates. A screening tool consisting of the six KSP questions was validated in the relatives of American genetics clinic patients, including in 24 matrilineal relatives in families with maternally inherited mitochondrial disease and in 30 control relatives.</p> <p>Results</p> <p>Among the depressed Swedish patients, the screening tool was positive in 13/14 with low and 1/7 with normal mitochondrial function (P = 0.0003). Applied to the American relatives of patients, the screening tool was positive in 13/24 matrilineal relatives and in 1/30 control relatives (P = 2 × 10^-5).</p> <p>Conclusion</p> <p>Our preliminary data suggest that a small number of specific somatic-related questions can be constructed into a valid screening tool for cases at high risk for having a component of energy metabolism in their pathogenesis.</p

Epidemiology of Nontuberculous Mycobacteria Infection in Children and Young People With Cystic Fibrosis: Analysis of UK Cystic Fibrosis Registry

Background Infection with nontuberculous mycobacteria (NTM) is of growing clinical concern in people with cystic fibrosis (CF). The epidemiology of infection in children and young people remains poorly understood. Our goal was to investigate the epidemiology of NTM infection in the pediatric age group using data from the UK CF Registry. Methods Data from 2010–2015 for individuals aged <16 years (23200 observations from 5333 unique individuals) were obtained. Univariate analysis of unique individuals comparing all key clinical factors and health outcomes to NTM status was performed. The significant factors that were identified were used to generate a multivariate logistic regression model that, following step-wise removal, generated a final parsimonious model. Results The prevalence of individuals with a NTM-positive respiratory culture increased every year from 2010 (45 [1.3%]) to 2015 (156 [3.8%]). Allergic bronchopulmonary aspergillosis (odds ratio [OR], 2.66; P = 5.0 × 10−8), age (OR, 1.08; P = 3.4 × 10−10), and intermittent Pseudomonas aeruginosa infection (OR, 1.51; P = .004) were significantly associated with NTM infection. Conclusions NTM infection is of increasing prevalence in the UK pediatric CF population. This study highlights the urgent need for work to establish effective treatment and prevention strategies for NTM infection in young people with CF

Which patients with heart failure should receive specialist palliative care?

AIMS: We investigated which patients with heart failure (HF) should receive specialist palliative care (SPC) by first creating a definition of need for SPC in patients hospitalised with HF using patient-reported outcome measures (PROMs) and then testing this definition using the outcome of days alive and out of hospital (DAOH). We also evaluated which baseline variables predicted need for SPC and whether those with this need received SPC. METHODS AND RESULTS: PROMs assessing quality of life (QoL), symptoms, and mood were administered at baseline and every 4 months. SPC need was defined as persistently severe impairment of any PROM without improvement (or severe impairment immediately preceding death). We then tested whether need for SPC, so defined, was reflected in DAOH, a measure which combines length of stay, days of hospital re-admission, and days lost due to death. Of 272 patients recruited, 74 (27%) met the definition of SPC needs. These patients lived one third fewer DAOH than those without SPC need (and less than a quarter of QoL-adjusted DAOH). A Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score of <29 identified patients who subsequently had SPC needs (area under receiver operating characteristic curve 0.78). Twenty-four per cent of patients with SPC needs actually received SPC (n = 18). CONCLUSIONS: A quarter of patients hospitalised with HF had a need for SPC and were identified by a low KCCQ score on admission. Those with SPC need spent many fewer DAOH and their DAOH were of significantly worse quality. Very few patients with SPC needs accessed SPC services

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

&lt;b&gt;Background&lt;/b&gt;: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. &lt;b&gt;Methods/design&lt;/b&gt;: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Risk measures for direct real estate investments with non-normal or unknown return distributions

The volatility of returns is probably the most widely used risk measure for real estate. This is rather surprising since a number of studies have cast doubts on the view that volatility can capture the manifold risks attached to properties and corresponds to the risk attitude of investors. A central issue in this discussion is the statistical properties of real estate returns—in contrast to neoclassical capital market theory they are mostly non-normal and often unknown, which render many statistical measures useless. Based on a literature review and an analysis of data from Germany we provide evidence that volatility alone is inappropriate for measuring the risk of direct real estate. We use a unique data sample by IPD, which includes the total returns of 939 properties across different usage types (56% office, 20% retail, 8% others and 16% residential properties) from 1996 to 2009, the German IPD Index, and the German Property Index. The analysis of the distributional characteristics shows that German real estate returns in this period were not normally distributed and that a logistic distribution would have been a better fit. This is in line with most of the current literature on this subject and leads to the question which indicators are more appropriate to measure real estate risks. We suggest that a combination of quantitative and qualitative risk measures more adequately captures real estate risks and conforms better with investor attitudes to risk. Furthermore, we present criteria for the purpose of risk classification

SNOntology: Myriads of novel snornas or just a mirage?

<p>Abstract</p> <p>Background</p> <p>Small nucleolar RNAs (snoRNAs) are a large group of non-coding RNAs (ncRNAs) that mainly guide 2'-O-methylation (C/D RNAs) and pseudouridylation (H/ACA RNAs) of ribosomal RNAs. The pattern of rRNA modifications and the set of snoRNAs that guide these modifications are conserved in vertebrates. Nearly all snoRNA genes in vertebrates are localized in introns of other genes and are processed from pre-mRNAs. Thus, the same promoter is used for the transcription of snoRNAs and host genes.</p> <p>Results</p> <p>The series of studies by Dahai Zhu and coworkers on snoRNAs and their genes were critically considered. We present evidence that dozens of species-specific snoRNAs that they described in vertebrates are experimental artifacts resulting from the improper use of Northern hybridization. The snoRNA genes with putative intrinsic promoters that were supposed to be transcribed independently proved to contain numerous substitutions and are, most likely, pseudogenes. In some cases, they are localized within introns of overlooked host genes. Finally, an increased number of snoRNA genes in mammalian genomes described by Zhu and coworkers is also an artifact resulting from two mistakes. First, numerous mammalian snoRNA pseudogenes were considered as genes, whereas most of them are localized outside of host genes and contain substitutions that question their functionality. Second, Zhu and coworkers failed to identify many snoRNA genes in non-mammalian species. As an illustration, we present 1352 C/D snoRNA genes that we have identified and annotated in vertebrates.</p> <p>Conclusions</p> <p>Our results demonstrate that conclusions based only on databases with automatically annotated ncRNAs can be erroneous. Special investigations aimed to distinguish true RNA genes from their pseudogenes should be done. Zhu and coworkers, as well as most other groups studying vertebrate snoRNAs, give new names to newly described homologs of human snoRNAs, which significantly complicates comparison between different species. It seems necessary to develop a uniform nomenclature for homologs of human snoRNAs in other vertebrates, e.g., human gene names prefixed with several-letter code denoting the vertebrate species.</p