Adrenocortical oncocytic carcinoma with recurrent metastases: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional pathological entity, since only 22 cases have been documented in the literature so far.</p> <p>Case presentation</p> <p>Our case concerns a 54-year-old man with past medical history of right adrenal excision with partial hepatectomy, due to an adrenocortical carcinoma. The patient was admitted in our hospital to undergo surgical resection of a left lung mass newly detected on chest Computed Tomography scan. The histological and immunohistochemical study revealed a metastatic AOC. Although the patient was given mitotane orally in adjuvant basis, he experienced relapse with multiple metastases in the thorax twice in the next year and was treated with consecutive resections. Two and a half years later, a right hip joint metastasis was found and concurrent chemoradiation was given. Finally, approximately five years post disease onset, the patient died due to massive metastatic disease. A thorough review of AOC and particularly all diagnostic difficulties are extensively stated.</p> <p>Conclusion</p> <p>Histological classification of adrenocortical oncocytic tumours has been so far a matter of debate. There is no officially established histological scoring system regarding these rare neoplasms and therefore many diagnostic difficulties occur for pathologists.</p

Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment

Using the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver. Two established ASOs are tested. Nicotinamide N-methyltransferase (NNMT)-ASO prevents diet- induced obesity in mice. Apolipoprotein B (ApoB)-ASO is an FDA approved drug for treating familial hypercholesterolemia. NNMT-ASO and ApoB-ASO are chemically conjugated with T3 using a non- cleavable sulfo-SMCC linker. Both NNMT-ASO-T3 (NAT3) and ApoB-ASO-T3 (AAT3) enhance thyroid hormone receptor activity. Treating obese mice with NAT3 or AAT3 decreases adiposity and increases lean mass. ASO-T3 enhances white fat browning, decreases genes for fatty acid synthesis in liver, and shows limited effects on T3 target genes in heart and muscle. Furthermore, AAT3 augments LDL cholesterol-lowering effects of ApoB-ASO. Therefore, ASO and hormone/drug conjugation may provide a novel strategy for obesity and hyperlipidemia treatment

Interaction between drug and placebo effects: a cross-over balanced placebo design trial

<p>Abstract</p> <p>Background</p> <p>The total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.</p> <p>Methods</p> <p>180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.</p> <p>Results</p> <p>The placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P = 0.007).</p> <p>Conclusions</p> <p>Drug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identification number - NCT00426010.</p

Fluorescent RNA cytosine analogue - an internal probe for detailed structure and dynamics investigations

The bright fluorescent cytosine analogue tCO stands out among fluorescent bases due to its virtually unquenched fluorescence emission in duplex DNA. However, like most reported base analogues, it has not been thoroughly characterized in RNA. We here report on the first synthesis and RNA-incorporation of tCO, and characterize its base-mimicking and fluorescence properties in RNA. As in DNA, we find a high quantum yield inside RNA duplexes (&lt;?F&gt; = 0.22) that is virtually unaffected by the neighbouring bases (?F = 0.20-0.25), resulting in an average brightness of 1900 M-1 cm-1. The average fluorescence lifetime in RNA duplexes is 4.3 ns and generally two lifetimes are required to fit the exponential decays. Fluorescence properties in ssRNA are defined by a small increase in average quantum yield (&lt;?F &gt; = 0.24) compared to dsRNA, with a broader distribution (?F = 0.17-0.34) and slightly shorter average lifetimes. Using circular dichroism, we find that the tCO-modified RNA duplexes form regular A-form helices and in UV-melting experiments the stability of the duplexes is only slightly higher than that of the corresponding natural RNA (&lt;?T m&gt; = + 2.3 °C). These properties make tCO a highly interesting fluorescent RNA base analogue for detailed FRET-based structural measurements, as a bright internal label in microscopy, and for fluorescence anisotropy measurements of RNA dynamics

Why do you drink caffeine? The development of the Motives for Caffeine Consumption Questionnaire (MCCQ) and its relationship with gender, age and the types of caffeinated beverages

Caffeine is the most popular psychoactive substance that is consumed worldwide. As motives influence behavior, investigation of the motivational background of caffeine consumption should help provide a better understanding of the popularity of caffeinated products. The present study aimed (i) to explore and operationalize the motives of caffeine consumption and (ii) to reveal possible differences in the motives regarding gender, age and the type of caffeinated products consumed. Motives for caffeine consumption were collected from regular caffeine consumers (N = 26) and were informed by a review of the relevant literature. Following this, a cross-sectional study was conducted on a convenience sample of Hungarian university students and working adults (N = 598). The participants completed the Motives for Caffeine Consumption Questionnaire and the Caffeine Consumption Questionnaire. Six motivational factors were identified: Alertness, Habit, Mood, Social, Taste and Symptom Management. Women had higher scores on Habit, Social, Taste and Symptom Management. Younger participants had higher scores on Alertness than the older group, and the older group had higher scores on Habit and Symptom Management. Five types of caffeine users were identified. Those who consumed (i) coffee, (ii) tea, (iii) energy drinks, (iv) coffee and tea and (v) mixed drinks. Several differences between the five groups were revealed across all motives except for Taste. The present study developed a robust psychometric instrument for assessing caffeine consumption motives. The factors varied in importance in relation to gender, age and caffeine consumption habits

Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control

Controlling the mosquito Aedes aegypti is of public health importance because, at present, it is the only means to stop dengue virus transmission. Implementing successful mosquito control programs requires understanding what factors regulate population abundance, as well as anticipating how mosquitoes may adapt to control measures. In some species of mosquitoes, females choose egg-laying sites to improve the survival and growth of their offspring, a behavior that ultimately influences population distribution and abundance. In the current study, we tested whether Ae. aegypti actively choose the containers in which they lay their eggs and determined what cues are most relevant to that process. We also explored whether females select containers that provide the most food for their larval progeny. Surprisingly, egg-laying females were most attracted to sites containing other immature Ae. aegypti, rather than to sites containing the most food. We propose that this behavior may contribute to density-dependent competition for food among larvae and play a larger role than previously thought in regulating Ae. aegypti populations. We recommend that accounting for, and even taking advantage of, this natural behavior will lead to more effective strategies for dengue prevention

The potential of antisense oligonucleotide therapies for inherited childhood lung diseases.

Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient's genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism