Gene expression profiles separate endometriosis lesion subtypes and indicate a sensitivity of endometrioma to estrogen suppressive treatments through elevated ESR2 expression.

BACKGROUND: Endometriosis is a common, gynaecological disease characterised by the presence of endometrial-like cells growing outside the uterus. Lesions appear at multiple locations, present with variation in appearance, size and depth of invasion. Despite hormones being the recommended first-line treatment, their efficacy, success and side effects vary widely amongst study populations. Current, hormonal medication for endometriosis is designed to suppress systemic oestrogen. Whether these hormones can influence the lesions themselves is not yet clear. Evidence of hormone receptor expression in endometriotic lesions and their ability to respond is conflicting. A variation in their expression, activation of transcriptional co-regulators and the potential to respond may contribute to their variation in patient outcomes. Identifying patients who would benefit from hormonal treatments remain an important goal in endometriosis research. METHODS: Using gene expression data from endometriosis lesions including endometrioma (OMA, n = 28), superficial peritoneal lesions (SUP, n = 72) and deeply infiltrating lesions (DIE, n = 78), we performed principal component analysis, differential gene expression and gene correlation analyses to assess the impact of menstrual stage, lesion subtype and hormonal treatment on the gene expression. RESULTS: The gene expression profiles did not vary based on menstrual stage, but could distinguish lesion subtypes with OMA significantly differentiating from both SUP and DIE. Additionally, the effect of oestrogen suppression medication altered the gene expression profile in OMA, while such effect was not observed in SUP or DIE. Analysis of the target receptors for hormonal medication indicated ESR2 was differentially expressed in OMA and that genes that correlated with ESR2 varied significantly between medicated and non-medicated OMA samples. CONCLUSIONS: Our results demonstrate of the different lesion types OMA present with strongest response to hormonal treatment directly through ESR2. The data suggests that there may be the potential to target treatment options to individual patients based on pre-surgical diagnoses.

BRADSHAW: a system for automated molecular design.

This paper introduces BRADSHAW (Biological Response Analysis and Design System using an Heterogenous, Automated Workflow), a system for automated molecular design which integrates methods for chemical structure generation, experimental design, active learning and cheminformatics tools. The simple user interface is designed to facilitate access to large scale automated design whilst minimising software development required to introduce new algorithms, a critical requirement in what is a very fast moving field. The system embodies a philosophy of automation, best practice, experimental design and the use of both traditional cheminformatics and modern machine learning algorithms.

Correction to: BRADSHAW: a system for automated molecular design.

The original version of this article unfortunately contained some mistakes in the references.

Towards appropriate imaging: Tips for practice.

BACKGROUND: The best use of diagnostic imaging is a challenge for many health professionals and the health system. Potential hazards of inappropriate imaging include exposure to ionising radiation, false positive and negative results, unexpected incidental findings, overdiagnosis and cost. OBJECTIVE: Using a fictional case, we aim to illuminate and discuss some of the challenges to appropriate diagnostic imaging and offer some solutions. DISCUSSION: While normal imaging results can reassure a patient, abnormal incidental findings can sometimes cause harm. When serious disease is very unlikely, verbal reassurance may be more appropriate than imaging. We remind doctors of the risks of ionising radiation, including how to access resources to estimate these risks and the need to ensure that the potential benefit of the test outweighs the risk - the process of justification. We point readers to imaging guidelines to help guide decision-making, such as the 'Diagnostic imaging pathways' resource. We look forward to relationships between radiologists and general practitioners characterised by collaboration and consultation, rather than just ordering and reporting.

Alternative splicing and genome complexity.

Alternative splicing of mRNA allows many gene products with different functions to be produced from a single coding sequence. It has recently been proposed as a mechanism by which higher-order diversity is generated. Here we show, using large-scale expressed sequence tag (EST) analysis, that among seven different eukaryotes the amount of alternative splicing is comparable, with no large differences between humans and other animals.

Multifunctional fully biobased aerogels for water remediation: Applications for dye and heavy metal adsorption and oil/water separation.

Water ecosystem contamination from industrial pollutants is an emerging threat to both humans and native species, making it a point of global concern. In this work, fully biobased aerogels (FBAs) were developed by using low-cost cellulose filament (CF), chitosan (CS), citric acid (CA), and a simple and scalable approach, for water remediation applications. The FBAs displayed superior mechanical properties (up to ∼65 kPa m3 kg-1 specific Young's modulus and ∼111 kJ/m3 energy absorption) due to CA acting as a covalent crosslinker in addition to the natural hydrogen bonding and electrostatic interactions between CF and CS. The addition of CS and CA increased the variety of functional groups (carboxylic acid, hydroxyl and amines) on the materials' surface, resulting in super-high dye and heavy metal adsorption capacities (619 mg/g and 206 mg/g for methylene blue and copper, respectively). Further modification of FBAs with a simple approach using methyltrimethoxysilane endowed aerogel oleophilic and hydrophobic properties. The developed FBAs showed a fast performance in water and oil/organic solvents separation with more than 96% efficiency. Besides, the FBA sorbents could be regenerated and reused for multiple cycles without any significant impact on their performance. Moreover, thanks to the presence of amine groups by addition of CS, FBAs also displayed antibacterial properties by preventing the growth of Escherichia coli on their surface. This work demonstrates the preparation of FBAs from abundant, sustainable, and inexpensive natural resources for applications in wastewater purification.

Clinical implications of interleukins-31, 32, and 33 in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality. AIM: To determine whether interleukin (IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients. METHODS: Tissue array (n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA. RESULTS: We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues (P < 0.05). IL-33 in peripheral blood of GC patients was significantly lower than that of healthy individuals (1.50 ± 1.11 vs 9.61 ± 8.00 ng/mL, P <0.05). Decreased IL-31, IL-32, and IL-33 in GC were observed in younger patients (< 60 years), and IL-32 and IL-33 were lower in female patients (P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people (P < 0.05). CONCLUSION: Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.

Novel insights into bicuspid aortic valve (BAV) aortopathy: Long non-coding RNAs TUG1 and MIAT are differentially expressed in BAV ascending aortas.

BACKGROUND: Whilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood. METHODS: Utilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ΔΔCT, with fold-change calculated as RQ=2-ΔΔCT. RESULTS: When comparing samples from BAV patients (n=29, males n=25; median age 58 years, Q1-Q3 51-65, maximum aortic dimension 50±5 mm) with healthy controls (n=7; males n=4, P=.12; median age 39 years, Q1-Q3 18-47, P=.001), there were two differentially expressed lncRNA: TUG1 expression was significantly lower in BAV aortic tissue (RQ 0.59, 95% CI 0.50-0.69, P=.02), whilst MIAT expression was significantly higher (RQ 2.87, 95% CI 1.96-4.20, P=.01). Sensitivity analysis including only patients with normal BAV function showed similar trends of differential expression of TUG1 (RQ 0.69, 95% CI 0.50-0.90, P=.29) and MIAT (RQ 2.55, 95% CI 1.21-5.36, P=.29) compared to controls. CONCLUSIONS: LncRNA TUG1 and MIAT are differentially expressed in BAV aortopathy compared to healthy controls, independent of BAV hemodynamics. Aberrant lncRNA expression may be involved in the pathogenesis of BAV aortopathy.

Coherence training in children with attention-deficit hyperactivity disorder: cognitive functions and behavioral changes.

Attention-deficit hyperactivity disorder (ADHD) is the most prevalent behavioral diagnosis in children, with an estimated 500 000 children affected in the United Kingdom alone. The need for an appropriate and effective intervention for children with ADHD is a growing concern for educators and childcare agencies. This randomized controlled clinical trial evaluated the impact of the HeartMath self-regulation skills and coherence training program (Institute of HeartMath, Boulder Creek, California) on a population of 38 children with ADHD in academic year groups 6, 7, and 8. Learning of the skills was supported with heart rhythm coherence monitoring and feedback technology designed to facilitate self-induced shifts in cardiac coherence. The cognitive drug research system was used to assess cognitive functioning as the primary outcome measure. Secondary outcome measures assessed teacher and student reposted changes in behavior. Participants demonstrated significant improvements in various aspects of cognitive functioning such as delayed word recall, immediate word recall, word recognition, and episodic secondary memory. Significant improvements in behavior were also found. The results suggest that the intervention offers a physiologically based program to improve cognitive functioning in children with ADHD and improve behaviors that is appropriate to implement in a school environment.

In Situ Alignment of Bacterial Cellulose Using Wrinkling.

A scalable method for the assembly of oriented bacterial cellulose (BC) films is presented based on using wrinkled thin silicone substrates of meter-square size as templates during biotechnological syntheses of BC. Control samples, including flat templated and template-free bacterial cellulose, along with the oriented BC, are morphologically characterized using scanning electron microscopy (SEM). Multiple functional properties including wettability, birefringence, mechanical strength, crystallinity, water retention, thermal stability, etc., are being characterized for the BC samples, where the wrinkling-induced in situ BC alignment not only significantly improved material mechanical properties (both strength and toughness) but also endowed unique material surface characteristics such as wettability, crystallinity, and thermal stability. Owing to the enhanced properties observed, potential applications of wrinkle templated BC in printing and cell culture are being demonstrated as a proof of concept, which renders their approach promising for various biomedical and packaging applications.

A Review of Collagen and Collagen-based Wound Dressings.

Collagen is a key component of a healing wound. In this review, a general description of the wound healing process is provided focusing on collagen's unique role. The mode of action (MoA) of collagen-based dressings is also addressed. Due to a number of potential stimuli (local tissue ischemia, bioburden, necrotic tissue, repeated trauma, etc.), wounds can stall in the inflammatory phase contributing to the chronicity of the wound. One key component of chronic wounds is an elevated level of matrix metalloproteinases (MMPs). At elevated levels, MMPs not only degrade nonviable collagen but also viable collagen. In addition, fibroblasts in a chronic wound may not secrete tissue inhibitors of MMPs (TIMPs) at an adequate level to control the activity of MMPs. These events prevent the formation of the scaffold needed for cell migration and ultimately prevent the formation of the extracellular matrix (ECM) and granulation tissue. Collagen based wound dressings are uniquely suited to address the issue of elevated levels of MMPs by acting as a 'sacrificial substrate' in the wound. It has also been demonstrated that collagen breakdown products are chemotactic for a variety of cell types required for the formation of granulation tissue. In addition, collagen based dressings have the ability to absorb wound exudates and maintain a moist wound environment.

EBM journal clubs in general practice.

The context of general practice makes the translation of evidence into clinical practice difficult. General practitioners interested in implementing evidence met at The Royal Australian College of General Practitioners' 2006 Annual Scientific Convention. We discussed evidence based medicine (EBM) journal club as a solution to this problem, including keys to success and barriers to overcome. The aim of this article is to provide suggestions for those wishing to set up their own EBM journal club. This will be supported as a Category 1 CPD activity by The Royal Australian College of General Practitioners in the 2008-2010 triennium.

The Effect of Local Versus Intravenous Corticosteroids on the Likelihood of Dysphagia and Dysphonia Following Anterior Cervical Discectomy and Fusion: A Single-Blinded, Prospective, Randomized Controlled Trial.

BACKGROUND: Dysphagia and dysphonia are the most common postoperative complications following anterior cervical discectomy and fusion (ACDF). Although most postoperative dysphagia is mild and transient, severe dysphagia can have profound effects on overall patient health and on surgical outcomes. The purpose of this study was to compare the efficacy of local to intravenous (IV) steroid administration during ACDF on postoperative dysphagia and dysphonia. METHODS: This was a single-blinded, prospective, randomized clinical trial. Seventy-five patients undergoing ACDF with cervical plating were randomized into 3 groups: control (no steroid), IV steroid (10 mg of IV dexamethasone at the time of closure), or local steroid (40 mg of local triamcinolone). Patient-reported outcome measures (PROMs) were collected for dysphagia, dysphonia, and neck pain postoperatively for 1 year. RESULTS: Patient demographics were similar. Postoperative day 1 PROMs showed significantly lower scores for dysphonia (p = 0.015) and neck pain (p = 0.034) in the local steroid group. At 2 weeks postoperatively, the local steroid cohort showed significantly decreased prevalence of severe dysphagia (Eating Assessment Tool-10 [EAT-10], severe dysphagia, p = 0.027) compared with the control and IV steroid groups. Both steroid groups had significantly less severe dysphagia when compared with the control group at the 6-week and 3-month time points. At 1 year postoperatively, both steroid groups had significantly reduced dysphagia rates (p = 0.014) compared with the control group. CONCLUSIONS: Both local and IV steroid administration after cervical plating in ACDF yielded better PROMs for dysphagia compared with a control group. This finding is particularly evident in the reduced number of patients who reported severe dysphagia symptoms following ACDF with local steroid application within the first 2 postoperative weeks. Future studies should attempt to stratify dysphagia severity when reporting outcomes related to anterior cervical spine surgery. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

A discussion of silver as an antimicrobial agent: alleviating the confusion.

Within the last 3 to 5 years, many silver-based antimicrobial dressings have become available and more are on the way. However, sometimes dressing manufacturers and authors make claims and send messages that conflict with data and conclusions in the literature, creating confusion for clinicians. A literature review of six relevant and frequently discussed topics was conducted. Pre-clinical and clinical study data suggest that: a) bacterial resistance to silver may occur, b) silver dissociation is affected by the test medium used, c) bactericidal activity differences may be a function of the bacterial strain used for testing, d) higher rather than lower levels of silver may be needed because Ag+ binds to proteins and nucleic acids, e) rapid delivery of silver (ie, rate of kill) may be a positive factor when considering prevention of silver resistance and biofilm formation, and f) based on the vast majority of in vivo studies available, silver does not adversely effect viable cells; thus, is not cytototoxic. Continued research into the implications of the data is warranted.

A journey to zero: reduction of post-operative cesarean surgical site infections over a five-year period.

BACKGROUND: Surgical site infections (SSI) are a substantial concern for cesarean deliveries in which a surgical site complication is most unwelcome for a mother with a new infant. Steps taken pre- and post-operatively to reduce the number of complications may be of substantial benefit clinically, economically, and psychologically. METHODS: A risk-based approach to incision management was developed and implemented for all cesarean deliveries at our institution. A number of incremental interventions for low-risk and high-risk patients including pre-operative skin preparations, standardized pre- and post-operative protocols, post-operative nanocrystalline silver anti-microbial barrier dressings, and incisional negative pressure wound therapy (NPWT) were implemented sequentially over a 5-y period. A systematic clinical chart review of 4,942 patients spanning all cesarean deliveries between 2007-2012 was performed to determine what effects the interventions had on the rate of SSI for cesarean deliveries. RESULTS: The percentage of SSI was reduced from 2.13% (2007) to 0.10% (2012) (p<0.0001). There were no substantial changes in the patient population risk factors over this time. As a result of the changes in incision management practice, a total of 92 cesarean post-operative SSIs were avoided: A total cost saving of nearly $5,000,000. CONCLUSION: Applying a clinical algorithm for assessing the risk of surgical site complication and making recommendations on pre-operative and post-operative incision management can result in a substantial and sustainable reduction in cesarean SSI.

Evaluation of annotation strategies using an entire genome sequence.

MOTIVATION: Genome-wide functional annotation either by manual or automatic means has raised considerable concerns regarding the accuracy of assignments and the reproducibility of methodologies. In addition, a performance evaluation of automated systems that attempt to tackle sequence analyses rapidly and reproducibly is generally missing. In order to quantify the accuracy and reproducibility of function assignments on a genome-wide scale, we have re-annotated the entire genome sequence of Chlamydia trachomatis (serovar D), in a collaborative manner. RESULTS: We have encoded all annotations in a structured format to allow further comparison and data exchange and have used a scale that records the different levels of potential annotation errors according to their propensity to propagate in the database due to transitive function assignments. We conclude that genome annotation may entail a considerable amount of errors, ranging from simple typographical errors to complex sequence analysis problems. The most surprising result of this comparative study is that automatic systems might perform as well as the teams of experts annotating genome sequences.