BioMed Central - Latest Articles

Mycobacterium abscessus isolated from municipal water - a potential source of human infection

Rachel Thomson — 2013-05-25T00:00:00Z

Background: Mycobacterium abscessus is a rapidly growing mycobacterium responsible for progressive pulmonary disease, soft tissue and wound infections. The incidence of disease due to M. abscessus has been increasing in Queensland. In a study of Brisbane drinking water, M. abscessus was isolated from ten different locations.The aim of this study was to compare genotypically the M. abscessus isolates obtained from water to those obtained from human clinical specimens. Methods: Between 2007 and 2009, eleven isolates confirmed as M. abscessus were recovered from potable water, one strain was isolated from a rainwater tank and another from a swimming pool and two from domestic taps. Seventy-four clinical isolates referred during the same time period were available for comparison using rep-PCR strain typing (Diversilab). Results: The drinking water isolates formed two clusters with >=97% genetic similarity (Water patterns 1 and 2). The tankwater isolate (WP4), one municipal water isolate (WP3) and the pool isolate (WP5) were distinctly different. Patient isolates formed clusters with all of the water isolates except for WP3. Further patient isolates were unrelated to the water isolates. Conclusion: The high degree of similarity between strains of M. abscessus from potable water and strains causing infection in humans from the same geographical area, strengthens the possibility that drinking water may be the source of infection in these patients.

Forecasting future prevalence of type 2 diabetes mellitus in Syria

Radwan Al Ali — 2013-05-25T00:00:00Z

Background: Type 2 diabetes mellitus (T2DM) is increasingly becoming a major public health problem worldwide. Estimating the future burden of diabetes is instrumental to guide the public health response to the epidemic. This study aims to project the prevalence of T2DM among adults in Syria over the period 2003--2022 by applying a modelling approach to the country's own data. Methods: Future prevalence of T2DM in Syria was estimated among adults aged 25 years and older for the period 2003--2022 using the IMPACT Diabetes Model (a discrete-state Markov model). Results: According to our model, the prevalence of T2DM in Syria is projected to double in the period between 2003 and 2022 (from 10% to 21%). The projected increase in T2DM prevalence is higher in men (148%) than in women (93%). The increase in prevalence of T2DM is expected to be most marked in people younger than 55 years especially the 25--34 years age group. Conclusions: The future projections of T2DM in Syria put it amongst countries with the highest levels of T2DM worldwide. It is estimated that by 2022 approximately a fifth of the Syrian population aged 25 years and older will have T2DM.

HbA1c versus oral glucose tolerance test as a method to diagnose diabetes mellitus in vascular surgery patients

Irene D Hjellestad — 2013-05-25T00:00:00Z

Background: The diagnosis of diabetes mellitus (DM) is based on either fasting plasma glucose levels or an oral glucose tolerance test (OGTT). Recently, an HbA1c value of >= 48 mmol/mol (6.5%) has been included as an additional test to diagnose DM. The purpose of this study was to validate HbA1c versus OGTT as a method to diagnose DM in vascular surgery patients. Methods: The study population consisted of 345 patients admitted consecutively due to peripheral arterial disease. Sixty-seven patients were previously diagnosed with DM. Glucose levels of OGTT and HbA1c values were analyzed in 275 patients. The OGTT results were categorized into three groups according to the World Health Organization 1999 criteria: 1) DM defined as fasting plasma glucose (FPG) >= 7.0 mmol/L and/or two-hour value (2-h-value) >= 11.1 mmol/L; 2) intermediate hyperglycaemia, which consists of IGT (FPG < 7.0 mmol/L and a 2-h-value between 7.8 mmol/L and 11.1 mmol/L), and IFG (fasting glucose value between 6.1 mmol/L and 7.0 mmol/L with a normal 2-h-value); and 3) normal glucose metabolism defined as FPG < 6.1 mmol/L and a 2-h-value < 7.8 mmol/L. Results: Of the 275 patients on whom OGTT was performed, 33 were diagnosed with DM, 90 with intermediate hyperglycaemia and 152 had normal glucose metabolism. An HbA1c value of >= 48 mmol/mol (6.5%) detected DM with a 45.5% sensitivity and a 90% specificity compared with the OGTT results. Combining the measurements of the HbA1c value with the fasting plasma glucose level (>=7.0 mmol/L) increased the sensitivity to 64%. The total prevalence of DM and intermediate hyperglycaemia was 85% based on HbA1c values and 45% based on the OGTT. Conclusions: Compared with the OGTT the HbA1c cut-off value of >= 48 mmol/mol (6.5%) had a 45.5% sensitivity to diagnose DM in patients with peripheral arterial disease. OGTT and HbA1c categorized different individuals with DM and intermediate hyperglycaemia. The total prevalence of pathologic glucose metabolism was substantially higher based on HbA1c values than based on OGTT. The high prevalence of DM and intermediate hyperglycaemia when using HbA1c in this study may reflect a high chronic glycaemic burden in patients with peripheral arterial disease. Further studies on vascular surgery patients are needed to identify which method, OGTT or HbA1c, is the better in predicting DM and future clinical development of vascular disease.Trial registration: REK vest 14109

Using latent class analysis to model prescription medications in the measurement of falling among a community elderly population

Patrick C Hardigan — 2013-05-25T00:00:00Z

Background: Falls among the elderly are a major public health concern. Therefore, the possibility of a modeling technique which could better estimate fall probability is both timely and needed. Using biomedical, pharmacological and demographic variables as predictors, latent class analysis (LCA) is demonstrated as a tool for the prediction of falls among community dwelling elderly. Methods: Using a retrospective data-set a two-step LCA modeling approach was employed. First, we looked for the optimal number of latent classes for the seven medical indicators, along with the patients' prescription medication and three covariates (age, gender, and number of medications). Second, the appropriate latent class structure, with the covariates, were modeled on the distal outcome (fall/no fall). The default estimator was maximum likelihood with robust standard errors. The Pearson chi-square, likelihood ratio chi-square, BIC, Lo-Mendell-Rubin Adjusted Likelihood Ratio test and the bootstrap likelihood ratio test were used for model comparisons. Results: A review of the model fit indices with covariates shows that a six-class solution was preferred. The predictive probability for latent classes ranged from 84% to 97%. Entropy, a measure of classification accuracy, was good at 90%. Specific prescription medications were found to strongly influence group membership. Conclusions: In conclusion the LCA method was effective at finding relevant subgroups within a heterogenous at-risk population for falling. This study demonstrated that LCA offers researchers a valuable tool to model medical data.

NEXT-peak: a normal-exponential two-peak model for peak-calling in ChIP-seq data

Nak-Kyeong Kim — 2013-05-25T00:00:00Z

Background: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) can locate transcription factor binding sites on genomic scale. Although many models and programs are available to call peaks, none has dominated its competition in comparison studies. Results: We propose a rigorous statistical model, the normal-exponential two-peak (NEXT-peak) model, which parallels the physical processes generating the empirical data, and which can naturally incorporate mappability information. The model therefore estimates total strength of binding (even if some binding locations do not map uniquely into a reference genome, effectively censoring them); it also assigns an error to an estimated binding location. The comparison study with existing programs on real ChIP-seq datasets (STAT1, NRSF, and ZNF143) demonstrates that the NEXT-peak model performs well both in calling peaks and locating them. The model also provides a goodness-of-fit test, to screen out spurious peaks and to infer multiple binding events in a region. Conclusions: The NEXT-peak program calls peaks on any test dataset about as accurately as any other, but provides unusual accuracy in the estimated location of the peaks it calls. NEXT-peak is based on rigorous statistics, so its model also provides a principled foundation for a more elaborate statistical analysis of ChIP-seq data.

Epigenetics and transgenerational inheritance

Emilie Brasset — 2013-05-24T00:00:00Z

A report on the 'Non-coding RNA, epigenetics and transgenerational inheritance' meeting, Churchill College, Cambridge, UK, 11-12 April 2013.

New gene expression pipelines gush lncRNAs

Jiashi Wang — 2013-05-24T00:00:00Z

Genome-wide techniques provide robust and comprehensive identification of lncRNAs in adult mouse neural stem cells and their derivatives, illuminating the functions of these underappreciated transcripts.

Response to 'TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro'

Jing Ma — 2013-05-24T00:00:00Z

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The Adult Respiratory Distress Syndrome Cognitive Outcomes Study: long-term neuropsychological function in survivors of acute lung injury

Catherine Carlson — 2013-05-24T00:00:00Z

Expanded abstractCitationMikkelsen ME, Christie JD, Lanken PN, Biester RC, Thompson BT, Bellamy SL, Localio AR, Demissie E, Hopkins RO, Angus DC: The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med 2012, 185:1307-1315. Background: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking. Methods: ObjectiveThe objectives were to determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial and to determine the frequency and risk factors for long-term neuropsychological impairment.DesignA prospective, multicenter cohort study of a subset of survivors from the Fluid and Catheter Treatment Trial (FACTT) was conducted.SettingThe FACTT enrolled patients from 38 North American hospitals between June 2000 and October 2005.SubjectsTo be eligible for the ALI Cognitive Outcomes Study (ACOS), subjects had to be enrolled in the FACTT and the EA-PAC (Economic Assessment of the Pulmonary Artery Catheter) trial. The FACTT enrolled mechanically ventilated adults who met the American-European Consensus Conference criteria for ALI.InterventionIn an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, neuropsychological function at 2 and 12 months after hospital discharge was assessed.OutcomesThe primary outcome was the result of a validated telephone battery of standardized neuropsychological tests administered to consenting, English-speaking subjects at 2 and 12 months after hospital discharge. Results: Of 406 eligible survivors, 261 patients were approached to participate and 213 consented. One hundred twenty-two subjects, including 102 subjects at 12 months, were tested at least once. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors, respectively. Long-term cognitive impairment was present in 41 (55%) of the 75 survivors who completed cognitive testing. Depression, post-traumatic stress disorder, and anxiety were present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors, respectively. Enrollment in a conservative fluid management strategy (P <0.005) was associated with cognitive impairment, and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P <0.02) and psychiatric (P <0.02) impairment. Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. A fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation.

Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease

Scott J Webster — 2013-05-24T00:00:00Z

IntroductionDespite the extensive mechanistic and pathological characterization of the APP/PS1 knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD- relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model to other commonly used AD mouse models. Methods: Four different groups of mice ranging across the lifespan of this model (test groups: 7 months, 11 months, 15 months, and 24 months old) were run in a behavioral test battery consisting of tasks to assess motor function (grip strength, rotor-rod, beam walk, open field ambulatory movement), anxiety-related behavior (open field time spent in peripheral zone vs. center zone, elevated plus maze), and cognitive function (novel object recognition, radial arm water maze). Results: There were no differences in motor function or anxiety-related behavior between APP/PS-1 knock-in mice and wild type counterpart mice for any age group. Cognitive deficits in both recognition memory (novel object recognition) and spatial reference memory (radial arm water maze) became apparent for the knock-in animals as the disease progressed. Conclusions: This is the first reported comprehensive behavioral analysis of the APP/PS1 knock-in mouse model of AD. The lack of motor/coordination deficits or abnormal anxiety levels, coupled with the age/disease related cognitive decline and high physiological relevance of this model, make it well suited for utilization in preclinical testing of AD-relevant therapeutics.