Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio

Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation.     

Reciprocal Peer Support for Post-partum Patients with Diabetes: A Needs Assessment for the Diabetes Buddy Program

While peer support has been investigated in multiple clinical contexts, its application to the postpartum setting is unknown. The aim was to assess acceptability of a postpartum peer support program for women with diabetes. Observational survey-based needs assessment of forty low-income women with diabetes, receiving care at a major medical institution. Mean age and gravidity were 30.7 years and 3.15 ± 1.67 respectively. 45 % expressed interest in a “buddy.” There was no significant difference between groups desiring and not desiring this program. A majority of respondents desired telephone, text messaging, and in-person contacts (79.2, 72.1, 83.8 %), with 72.5 % of patients desiring diabetes-related activities during clinic waiting time. Many women desire a postpartum diabetes reciprocal peer program for support outside of clinician visits. Patients are receptive to educational services during their wait and outside of clinic time, a potentially valuable opportunity to share important health information.     

Welche Parameter haben Einfluss auf den stationären Verlauf bei Patienten mit Spondylodiszitis?

Die Unfallchirurgie - Die Spondylodiszitis ist eine seltene Erkrankung mit steigender Inzidenz. In dieser retrospektiven Studie wurden 112 Patienten mit operativ versorgter Spondylodiszitis vom...     

The (Re) Production of the Genetically Related Body in Law,Technology and Culture: Mitochondria Replacement Therapy

Advances in medicine in the latter half of the twentieth century have dramatically altered human bodies, expanding choices around what we do with them and how they connect to other bodies. Nowhere is this more so than in the area of reproductive technologies (RTs). Reproductive medicine and the laws surrounding it in the UK have reconfigured traditional boundaries surrounding parenthood and the family. Yet culture and regulation surrounding RTs have combined to try to ensure that while traditional boundaries may be pushed, they are reconstructed in similar ways. This paper looks at the most recent RT to be permitted in the UK, mitochondria (mtDNA) replacement therapy (MRT). Despite controversial media headlines surrounding the technique, MRT is in fact an example of how science and regulation seek to expand models of traditional relatedness in a way that doesn’t challenge the existing order. Yet, like other RTs, while attempts are made to ensure it doesn’t push traditional boundaries too far, fissures and inconsistencies appear in law and culture, which give interesting insights into how genetics, parentage and identity are being mediated in new but familiar ways.     

RGS6 as a Novel Therapeutic Target in CNS Diseases and Cancer

Regulator of G protein signaling (RGS) proteins are gatekeepers regulating the cellular responses induced by G protein-coupled receptor (GPCR)-mediated activation of heterotrimeric G proteins. Specifically, RGS proteins determine the magnitude and duration of GPCR signaling by acting as a GTPase-activating protein for Gα subunits, an activity facilitated by their semiconserved RGS domain. The R7 subfamily of RGS proteins is distinguished by two unique domains, DEP/DHEX and GGL, which mediate membrane targeting and stability of these proteins. RGS6, a member of the R7 subfamily, has been shown to specifically modulate Gα_i/o protein activity which is critically important in the central nervous system (CNS) for neuronal responses to a wide array of neurotransmitters. As such, RGS6 has been implicated in several CNS pathologies associated with altered neurotransmission, including the following: alcoholism, anxiety/depression, and Parkinson’s disease. In addition, unlike other members of the R7 subfamily, RGS6 has been shown to regulate G protein-independent signaling mechanisms which appear to promote both apoptotic and growth-suppressive pathways that are important in its tumor suppressor function in breast and possibly other tissues. Further highlighting the importance of RGS6 as a target in cancer, RGS6 mediates the chemotherapeutic actions of doxorubicin and blocks reticular activating system (Ras)-induced cellular transformation by promoting degradation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) to prevent its silencing of pro-apoptotic and tumor suppressor genes. Together, these findings demonstrate the critical role of RGS6 in regulating both G protein-dependent CNS pathology and G protein-independent cancer pathology implicating RGS6 as a novel therapeutic target.     

Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (?14.7?±?0.6 versus ?14.8?±?0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14?±?0.36 and 5.05?±?0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.