Detection of distant metastasis to skeletal muscle by 18F-FDG-PET in a case of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma is a rare malignancy that originates from the epithelial cells of the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma can metastasize in lymphatic chains, including the hepatoduodenal ligament, and it often invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenal glands, and brain. However, distant skeletal muscle metastasis is very rare. Moreover, a metastatic skeletal muscle tumor rarely shows specific symptoms, making it difficult to identify in a routine examination. A 45-year-old man with a chief complaint of right upper quadrant abdominal pain was admitted to our hospital. Abdominal ultrasound and computed tomography with contrast enhancement showed a malignant mass in the right hepatic lobe, and 2-[18F] fluoro-2-deoxy-D-glucose positron-emission tomography revealed distant skeletal muscle metastases in the thorax and buttock. The patient underwent an ultrasound-guided percutaneous needle biopsy for the metastatic low-echo masses in the skeletal muscle

Genomewide Analyses Define Different Modes of Transcriptional Regulation by Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ)

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with essential functions in lipid, glucose and energy homeostasis, cell differentiation, inflammation and metabolic disorders, and represent important drug targets. PPARs heterodimerize with retinoid X receptors (RXRs) and can form transcriptional activator or repressor complexes at specific DNA elements (PPREs). It is believed that the decision between repression and activation is generally governed by a ligand-mediated switch. We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. Chromatin immunoprecipitation sequencing (ChIP-Seq) of PPARβ/δ, H3K4me3 and RNA polymerase II enrichment sites combined with transcriptional profiling enabled the definition of 112 bona fide PPARβ/δ target genes showing either of three distinct types of transcriptional response: (I) ligand-independent repression by PPARβ/δ; (II) ligand-induced activation and/or derepression by PPARβ/δ; and (III) ligand-independent activation by PPARβ/δ. These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. Our results also suggest that the type of transcriptional response by a given target gene is connected to the structure of its associated PPRE(s) and the biological function of its encoded protein. These observations have important implications for understanding the regulatory PPAR network and PPARβ/δ ligand-based drugs

Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Previous cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB. We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening. METHODS: Using data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990-2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates. RESULTS: During just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons). CONCLUSIONS: Diabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.This article presents independent research supported by a National Institute for Health Research (NIHR) In Practice Fellowship to LP (grant number NIHR/IPF/11/05). DAJM received Wellcome Trust funding (grant number 092691/Z/10/Z). LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science

The importance of alternative host plants as reservoirs of the cotton leaf hopper, Amrasca devastans, and its natural enemies

Many agricultural pests can be harboured by alternative host plants but these can also harbour the pests’ natural enemies. We evaluated the capacity of non-cotton plant species (both naturally growing and cultivated) to function as alternative hosts for the cotton leaf hopper Amrasca devastans (Homoptera: Ciccadellidae) and its natural enemies. Forty-eight species harboured A. devastans. Twenty-four species were true breeding hosts, bearing both nymphal and adult A. devastans, the rest were incidental hosts. The crop Ricinus communis and the vegetables Abelmoschus esculentus and Solanum melongena had the highest potential for harbouring A. devastans and carrying it over into the seedling cotton crop. Natural enemies found on true alternative host plants were spiders, predatory insects (Chrysoperla carnea, Coccinellids, Orius spp. and Geocoris spp.) and two species of egg parasitoids (Arescon enocki and Anagrus sp.). Predators were found on 23 species of alternative host plants, especially R. communis. Parasitoids emerged from one crop species (R. communis) and three vegetable species; with 39 % of A. devastans parasitised. We conclude that the presence of alternative host plants provides both advantages and disadvantages to the cotton agro-ecosystem because they are a source of both natural enemy and pest species. To reduce damage by A. devastans, we recommend that weeds that harbour the pest should be removed, that cotton cultivation with R. communis, A. esculentus, and S. melongena should be avoided, that pesticides should be applied sparingly to cultivate alternative host plants and that cotton crops should be sown earlier

Electronic structure, linear, nonlinear optical susceptibilities and birefringence of CuInX2 (X = S, Se, Te) chalcopyrite-structure compounds

The electronic structure, linear and nonlinear optical properties have been calculated for CuInX2 (X=S, Se, Te) chalcopyrite-structure single crystals using the state-of-the-art full potential linear augmented plane wave (FP-LAPW) method. We present results for band structure, density of states, and imaginary part of the frequency-dependent linear and nonlinear optical susceptibilities. We find that these crystals are semiconductors with direct band gaps. We have calculated the birefringence of these crystals. The birefringence is negative for CuInS2 and CuInSe2 while it is positive for CuInTe2 in agreement with the experimental data. Calculations are reported for the frequency-dependent complex second-order non-linear optical susceptibilities . The intra-band and inter-band contributions to the second harmonic generation increase when we replace S by Se and decrease when we replace Se by Te. We find that smaller energy band gap compounds have larger values of in agreement with the experimental data and previous theoretical calculations.Comment: 17 pages, 6 figure

A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes.

Understanding the dynamics of endogenous protein-protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity. Using the qPLEX-RIME method, we delineate the temporal changes of the Estrogen Receptor alpha (ERα) interactome in breast cancer cells treated with 4-hydroxytamoxifen. Furthermore, we identify endogenous ERα-associated proteins in human Patient-Derived Xenograft tumours and in primary human breast cancer clinical tissue. Our results demonstrate that the combination of RIME with isobaric labelling offers a powerful tool for the in-depth and quantitative characterisation of protein interactome dynamics, which is applicable to clinical samples

Periodontitis and diabetes: a two-way relationship

Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10–15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA1c reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management