Superior Hypogastric Plexus Neurolysis to Manage Metastatic Pelvic Pain in a Forty-Five-Year-Old Spina Bifida Patient: A Case Report.

A 45-year-old patient with spina bifida and adenocarcinoma of the rectum was treated with a superior hypogastric plexus (SHP) ablation for pain control. The procedure enabled her to reduce opioid consumption, being more clear-headed and functional to be discharged to her residence. The case is presented to highlight the options of neurolytic interventions to manage pain in terminally ill cancer patients. We discuss the options of SHP ablation and justify our choice of approach and the use of a neurolytic agent.

A Functional Chopart's Amputation With Tendon Transfers.

Generally, forefoot osteomyelitis is treated with a reliable level of amputation such as at the transmetatarsal level. However, when osteomyelitis extends proximal to the midfoot and presents with significant peripheral arterial disease, it is generally thought that the next best functional level of amputation is a transtibial amputation. This is mostly in part due to the high failure rate of Chopart's amputations which can be attributed to poor biomechanical and tendon balancing. We present a new technique of tendon balancing with a Chopart's amputation that results in optimized ambulatory function, durable soft tissue envelope of amputation, and successful limb salvage.

MAJIQ-SPEL: web-tool to interrogate classical and complex splicing variations from RNA-Seq data.

SUMMARY: Analysis of RNA sequencing (RNA-Seq) data have highlighted the fact that most genes undergo alternative splicing (AS) and that these patterns are tightly regulated. Many of these events are complex, resulting in numerous possible isoforms that quickly become difficult to visualize, interpret and experimentally validate. To address these challenges we developed MAJIQ-SPEL, a web-tool that takes as input local splicing variations (LSVs) quantified from RNA-Seq data and provides users with visualization and quantification of gene isoforms associated with those. Importantly, MAJIQ-SPEL is able to handle both classical (binary) and complex, non-binary, splicing variations. Using a matching primer design algorithm it also suggests to users possible primers for experimental validation by RT-PCR and displays those, along with the matching protein domains affected by the LSV, on UCSC Genome Browser for further downstream analysis. AVAILABILITY AND IMPLEMENTATION: Program and code will be available at http://majiq.biociphers.org/majiq-spel. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PRiMeUM: A Model for Predicting Risk of Metastasis in Uveal Melanoma.

Purpose: To create an interactive web-based tool for the Prediction of Risk of Metastasis in Uveal Melanoma (PRiMeUM) that can provide a personalized risk estimate of developing metastases within 48 months of primary uveal melanoma (UM) treatment. The model utilizes routinely collected clinical and tumor characteristics on 1227 UM, with the option of including chromosome information when available. Methods: Using a cohort of 1227 UM cases, Cox proportional hazard modeling was used to assess significant predictors of metastasis including clinical and chromosomal characteristics. A multivariate model to predict risk of metastasis was evaluated using machine learning methods including logistic regression, decision trees, survival random forest, and survival-based regression models. Based on cross-validation results, a logistic regression classifier was developed to compute an individualized risk of metastasis based on clinical and chromosomal information. Results: The PRiMeUM model provides prognostic information for personalized risk of metastasis in UM. The accuracy of the risk prediction ranged between 80% (using chromosomal features only), 83% using clinical features only (age, sex, tumor location, and size), and 85% (clinical and chromosomal information). Kaplan-Meier analysis showed these risk scores to be highly predictive of metastasis (P < 0.0001). Conclusions: PRiMeUM provides a tool for predicting an individual's personal risk of metastasis based on their individual and tumor characteristics. It will aid physicians with decisions concerning frequency of systemic surveillance and can be used as a criterion for entering clinical trials for adjuvant therapies.

Role of IGF-I, IGF-II and IGFBP-3 in lung function of males: the Caerphilly Prospective Study.

Insulin-like growth factors are peptide hormones that have an endocrine role in the development, growth and repair of human tissues including the respiratory tract. To date, only one population study exists which found positive cross-sectional associations with IGF-I and higher lung volumes. We hypothesised that higher IGF-I, IGF-II, IGFBP-3 and IGF molar ratio would be associated with better cross-sectional and longitudinal lung function. We examined cross-sectional (n=843) and prospective associations (n=717) between IGF-I, IGF-II, IGFBP-3 and IGF molar ratio with lung function in the Caerphilly Prospective Study (CaPS) from blood samples obtained around 1986, with spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)) performed in the same year and around 2003. Higher IGF molar ratio was associated with improved FEV1/FEV ratio cross-sectionally in both simple (0.007, 95% CI 0.001-0.013, P=0.02) and fully adjusted (0.001, 95% CI 0.001-0.012, P=0.03) models. With the exception of IGFBP-3 and FEV1/FVC in the simple model (0.009, 95% CI 0.001-0.018, P=0.04) all prospective associations between IGF and spirometric measures were consistent with chance. In this study of men, higher IGF molar ratio was associated with improved cross-sectional lung function, although these findings were not replicated prospectively. Further work is required with repeat IGF sampling during follow up to see if IGF levels play any role in predicting future lung function through the life course.

The role of IGF-I, IGF-II, and IGFBP-3 in male cognitive aging and dementia risk: the Caerphilly Prospective Study.

BACKGROUND: The increasing incidence of cognitive impairment and dementia in an aging population poses a significant burden on healthcare. Consequently, identifying modifiable physiological factors which may influence the onset of cognitive decline are becoming increasingly important. Previous studies have suggested an association between levels of insulin-like growth factors and cognitive function. OBJECTIVE: To investigate whether low IGF-I, IGF-II, and IGF molar ratio is associated with greater cognitive decline and increased risk of dementia. METHODS: We examined prospective associations between IGF-I, IGF-II, and IGFBP-3 and cognitive function in the Caerphilly Prospective Study (CaPS) (n = 746 men) from samples obtained around 1986, with assessment in around 2003 for clinical diagnosis of cognitive impairment but no dementia (CIND) or dementia, as well as with CAMCOG scores at three phases. RESULTS: A one standard deviation increase in IGF-II was associated with a reduced odds ratio for CIND (0.76, 95% CI 0.60, 0.96) which hardly altered after further adjustment for confounders. A one standard deviation increase in IGFBP-3 among participants without dementia or CIND was associated with greater decline in cognition (p = 0.002) equivalent to 2.4 years difference in age. All the associations between IGF-I and our outcomes were consistent with chance. CONCLUSION: In this study of men, we found that both IGF-II and IGFBP-3 are associated with normal age-related cognitive decline and clinical pathology associated with CIND, but we failed to replicate previous associations with IGF-I. Assuming these findings are replicated, they may provide new insights into potential biological mechanisms that underlie age-related cognitive changes and development of dementia.

Enrichment and cultivation of prokaryotes associated with the sulphate-methane transition zone of diffusion-controlled sediments of Aarhus Bay, Denmark, under heterotrophic conditions.

The prokaryotic activity, diversity and culturability of diffusion-controlled Aarhus Bay sediments, including the sulphate-methane transition zone (SMTZ), were determined using a combination of geochemical, molecular (16S rRNA and mcrA genes) and cultivation techniques. The SMTZ had elevated sulphate reduction and anaerobic oxidation of methane, and enhanced cell numbers, but no active methanogenesis. The prokaryotic population was similar to that in other SMTZs, with Deltaproteobacteria, Gammaproteobacteria, JS1, Planctomycetes, Chloroflexi, ANME-1, MBG-D and MCG. Many of these groups were maintained in a heterotrophic (10 mM glucose, acetate), sediment slurry with periodic low sulphate and acetate additions (~2 mM). Other prokaryotes were also enriched including methanogens, Firmicutes, Bacteroidetes, Synergistetes and TM6. This slurry was then inoculated into a matrix of substrate and sulphate concentrations for further selective enrichment. The results demonstrated that important SMTZ bacteria can be maintained in a long-term, anaerobic culture under specific conditions. For example, JS1 grew in a mixed culture with acetate or acetate/glucose plus sulphate. Chloroflexi occurred in a mixed culture, including in the presence of acetate, which had previously not been shown to be a Chloroflexi subphylum I substrate, and was more dominant in a medium with seawater salt concentrations. In contrast, archaeal diversity was reduced and limited to the orders Methanosarcinales and Methanomicrobiales. These results provide information about the physiology of a range of SMTZ prokaryotes and shows that many can be maintained and enriched under heterotrophic conditions, including those with few or no cultivated representatives.

Non-resonant two-photon photochemistry of a Barton ester, N-phenylacetyloxy-2-pyridinethione.

N-Acetyloxy-2-pyridinethiones, otherwise known as Barton esters, are a class of molecules that can be easily photolysed via single-photon excitation to facilitate the controlled release of carbon or oxygen-centred radicals. In the present work, we investigate the two-photon chemistry of a simple Barton ester, and show that this material can be photolysed via two-photon excitation, with a two-photon bleaching cross section value of 0.13 +/- 0.01 GM.

Nanodroplet real-time PCR system with laser assisted heating.

We report the successful application of low-power (approximately 30 mW) laser radiation as an optical heating source for high-speed real-time polymerase chain reaction (PCR) amplification of DNA in nanoliter droplets dispersed in an oil phase. Light provides the heating, temperature measurement, and Taqman real-time readout in nanoliter droplets on a disposable plastic substrate. A selective heating scheme using an infrared laser appears ideal for driving PCR because it heats only the droplet, not the oil or plastic substrate, providing fast heating and completing the 40 cycles of PCR in 370 seconds. No microheaters or microfluidic circuitry were deposited on the substrate, and PCR was performed in one droplet without affecting neighboring droplets. The assay performance was quantitative and its amplification efficiency was comparable to that of a commercial instrument.

Regulation of transcription of the human prepronociceptin gene by Sp1.

Nociceptin/orphanin FQ is a recently discovered neuropeptide and the endogenous ligand for opioid receptor-like-1. The promoter region of the precursor protein prepronociceptin (ppN/OFQ) has been cloned and sequenced. We have previously shown that a stretch of 110 bases immediately 5' to the first intron 23 bp upstream of the ATG start codon is responsible for significant enhancement of transcription of the human ppN/OFQ gene. We performed electromobility shift assays (EMSAs) using oligonucleotides spanning portions of the promoter region close to the intron to determine which DNA elements were important for transcriptional regulation. EMSAs using Sp1 antibody revealed a cis-acting regulatory element from bases 35-67 that appeared to bind Sp1 transcription factor and cause a shift to higher molecular weight. Deletion of this 30-bp region of DNA from the 1.2 kb promoter caused a significant loss of transcription as measured by luciferase reporter assays. Mutation of four bases at the Sp1 binding site also induced a significant loss of transcription compared to wildtype constructs. Finally, an Sp1- but not Etf-binding consensus oligonucleotide was able to compete with the interaction of the oligo with the NS20Y nuclear extract. Combined with the data from the supershift EMSAs, it appears that Sp1 is the transcription factor binding to the GC region close to the intron to regulate transcription of the human ppN/OFQ gene.