Expression of CCL18 and interleukin-6 in the plasma of breast cancer patients as compared with benign tumor patients and healthy controls

A growing body of laboratory research has shown that pro-inflammatory cytokines can facilitate tumor growth and metastasis. Our goal was to quantify the expression of CCL18 and IL-6 in patients with breast cancer compared with benign breast tumors patients and healthy women, in order to evaluate if these cytokines could serve for breast cancer diagnosis and evaluation. We also correlated the cytokines level of expression with some clinical and pathological characteristics known as prognostic markers for breast cancer. Plasma samples were obtained before treatment from 58 breast cancers, 41 benign breast tumors and 30 healthy women. The quantitative dosage was performed using ELISA. Wilcoxon test was used to compare groups. IL-6 and CCL18 were dramatically upregulated in breast cancers in comparison with healthy controls, but in comparison with benign tumors only CCL18÷PARC was overexpressed at borderline significance in cancers (p=0.05). The plasma from benign breast tumor patients exhibited also significant higher levels of the two cytokines than normal controls. The cytokines profile was not linked to patient age, tumor size, histopathological type, lymph node status or histological grade. IL-6 was significantly upregulated in ER-positive and metastasized cancers. CCL18÷PARC presented a significantly higher expression in advanced stage and highly proliferative carcinomas. In summary, IL-6 and CCL18 could clearly distinguish between women with breast cancers and healthy controls. High expression of IL-6 seems to confer a poor prognosis for ER-positive cancers. CCL18 was associated with worse prognosis parameters like high Ki67.     

When the self is contested ground

“When the Self Is Contested Ground”: letters from Tommaso Bruni and Ilina Singh about “Anorexia Nervosa and the Language of Authenticity” (Nov‐Dec 2011); and “Strings Attached”: a letter from John A. Robertson about “Conceived and Deceived: The Medical Interests of Donor Conceived Individuals” (Jan‐Feb 2012), with a reply from Vardit Ravitsky.     

Evidence for functional atypical nicotinic receptors that activate K+-dependent Cl- secretion in mouse tracheal epithelium

The present study focused on the influence of nicotinic acetylcholine receptors (nAChR) on ion transport processes in mouse tracheal epithelium. RT-PCR experiments revealed expression of the α3, α4, α5, α7, α9, α10, β2, and β4 nAChR subunits in mouse tracheal epithelium. In Ussing chamber recordings of mouse tracheae, apically applied nicotine (100 μM) induced a dose-dependent increase of the transepithelial short-circuit current (EC(50): 14.6 μM). The nicotine-induced effect (I(NIC)) was attenuated by mecamylamine (25 μM, apical) and methyllycaconitine (1 μM, apical). The nAChR agonist 1.1-dimethyl-4-phenylpiperatinium iodide (DMPP) (100 μM) revealed apical and basolateral location of the receptors. I(NIC) was not affected by the sodium channel inhibitor amiloride (10 μM, apical) or the cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172 (20 μM, apical) but was reduced by the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 μM, apical), the Na(+)/K(+)/2Cl(-) cotransporter inhibitor bumetanide (200 μM, basolateral), the potassium channel inhibitor Ba(2+) (5 mM, basolateral), and 4.4'-diisothiocyanatostilbene-2.2'-disulfonate (100 μM, apical), indicating a contribution of Ca(2+)-activated chloride channels and potassium channels. Removal of extracellular Na(+) (apical) or Ca(2+) (apical) did not influence I(NIC) but reduced the DMPP effect. Experiments with the Ca(2+)-ionophore A23187, a mix of 3-isobutyl-1-methylxanthine and forskolin, or the inositol-1,4,5-triphospate (IP(3)) receptor inhibitor 2-aminoethyl-diphenyl-borinate (75 μM, apical) decreased I(NIC), indicating a nicotine-mediated increase of intracellular Ca(2+) and cAMP levels involving the IP(3) signaling pathway. These findings indicate the activity of Ca(2+)-permeable nAChRs and alternative metabotropic pathways by nAChR activation that mediate Cl(-) and K(+) transport in tracheal epithelium.     

A disorder of anger and aggression: children's perspectives on attention deficit/hyperactivity disorder in the UK

This article investigates the social and moral dimensions of Attention Deficit/Hyperactivity Disorder (ADHD) diagnosis, asking what ADHD means in UK children's everyday lives, and what children do with this diagnosis. Drawing on interviews with over 150 children, the analysis examines the influence of a UK state school-based culture of aggression on the form and intensity of diagnosed children's difficulties with behavioral self-control. Diagnosed children's mobilization of ADHD behaviors and their exploitation of the diagnosis shows how children's active moral agency can support and compromise cognitive, behavioral and social resilience. The findings support a proposal for a complex sociological model of ADHD diagnosis and demonstrate the relevance of this model for national policy initiatives related to mental health and wellbeing in children.     

Hepatitis B Virus Genetic Typing Using Mass-Spectrometry

Mini-sequencing with subsequent result registration using MALDI-ToF mass-spectrometry was employed for hepatitis B virus genetic typing in Russian population. This approach was employed for hepatitis B virus genetic typing in HBsAg-positive patients with chronic hepatitis B, hepatitis of combined etiology and hepatic cirrhosis and allowed to show the prevalence of D genotype (83.3%) in all groups of patients. Other hepatitis B virus genotypes: genotype A (5.9%), genotype C (3.6%), and mixed infection with D and C (7.2%) were also found in patients with chronic hepatitis B and hepatic cirrhosis. All genotypes were found in patients with chronic hepatitis B and hepatic cirrhosis. Chronic hepatitis of combined etiology was noted only in patients with genotype D. Possibility of detection of mixed infection with hepatitis B viruses of various genotypes is a distinct advantage of mini-sequencing approach over direct nucleotide sequence evaluation for hepatitis B virus genetic typing. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 2, pp. 181-186, February, 2009     

Automatic adjustment of biphasic pulse duration in transthoracic defibrillation

Many studies have proven that biphasic defibrillation pulses are more efficient than the damped sinusoid monopolar waveform. Transthoracic resistance was shown to change during the two phases. On the other hand, it was proven that transthoracic resistance plays an important role in the defibrillation process, yielding the current for selected energy or voltage. Pre-shock measurement of the resistance may lead to improved selection. Stabilized current defibrillators are of low stored-to-delivered energy ratio. Therefore, automatic dynamic adjustment of some defibrillator parameters with respect to transthoracic resistance changes seems rational. An approach is known for modifying the pulse duration, in order to deliver a selected energy. A method is proposed here and an experimental defibrillator is developed for dynamic pulse duration adjustment with the purpose of obtaining a desired optimal timecourse of the cardiac cell transmembrane potential.     

The ethics of global psychiatric genomics: Multilayered challenges to integrating genomics in global mental health and disability—A position paper of the Oxford Global Initiative in Neuropsychiatric GenEthics (NeuroGenE)

Psychiatric genomics has the potential to radically improve the prevention and early intervention of serious mental and neurodevelopmental disorders worldwide. However, little work has been done on the ethics of psychiatric genomics—an oversight that could result in poor local uptake, reduced practical/clinical application, and ethical violations in this rapidly developing area of scientific research. As part of the Global Project of the Stanley Center for Psychiatric Research, the Global Initiative in Neuropsychiatric GenEthics (NeuroGenE) based at the University of Oxford aims to embed ethical inquiry within scientific investigation and engage with fundamental ethical questions around a psychiatric genomics approach to mental and neurodevelopmental disorder. This position paper sets out the core aims of the NeuroGenE research programme and explores the importance of a crosscutting research orientation in this field based on multidisciplinary methodologies which can ensure that efforts to translate and apply global psychiatric genomics in public policy and clinical practice are ethically grounded strategies, respectful of different cultures and contexts.