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.     

Isolation and sequence analysis of a canine distemper virus from a raccoon dog in Jilin Province,China

Canine distemper virus (CDV) is a major pathogen not only in raccoon dogs but also in a variety of carnivorous animals, including domesticated animals, particularly if they have not been vaccinated. In this study, a wild-type strain of CDV was isolated from lung tissue from a raccoon dog kept at a fur farm in Jilin Province, China. Cytopathic effects typical of CDV infection were observed after three blind passages in Vero cells, yielding a virus titer of 10^4.6 TCID₅₀/mL. Virus identification was carried out by RT-PCR, immunofluorescence, electron microscopy, and genome sequencing. The results showed that the isolated virus, termed the SY strain, corresponded to the Asia-1 genotype of CDV and has a genome of 15,690 nucleotides. This represents the first complete nucleotide sequence of a CDV strain circulating in raccoon dogs in China.     

Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia

Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-κB by upregulating sirtuin 1 and 5′-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47^phox phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor-erythroid 2-related factor 2 to the antioxidant response element in LPS-stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia.     

Attachment,Sexual Assertiveness,and Sexual Outcomes in Women with Provoked Vestibulodynia and Their Partners: A Mediation Model

Provoked vestibulodynia (PVD) is a prevalent women’s sexual pain disorder, which is associated with sexual function difficulties. Attachment theory has been used to understand adult sexual outcomes, providing a useful framework for examining sexual adaptation in couples confronted with PVD. Research to date indicates that anxious and avoidant attachment dimensions correlate with worse sexual outcomes in community and clinical samples. The present study examined the association between attachment, pain, sexual function, and sexual satisfaction in a sample of 101 couples in which the women presented with PVD. The actor–partner interdependence model was used in order to investigate both actor and partner effects. This study also examined the role of sexual assertiveness as a mediator of these associations via structural equation modeling. Women completed measures of pain intensity and both members of the couple completed measures of romantic attachment, sexual assertiveness, sexual function, and satisfaction. Results indicated that attachment dimensions did not predict pain intensity. Both anxious and avoidant attachment were associated with lower sexual satisfaction. Only attachment avoidance predicted lower sexual function in women. Partner effects indicated that higher sexual assertiveness in women predicted higher sexual satisfaction in men. Finally, women’s sexual assertiveness was found to be a significant mediator of the relationship between their attachment dimensions, sexual function, and satisfaction. Findings highlight the importance of examining how anxious and avoidant attachment may lead to difficulties in sexual assertiveness and to less satisfying sexual interactions in couples where women suffer from PVD.     

Dying is the Most Grown-Up Thing We Ever Do: But Do Health Care Professionals Prevent Us from Taking It Seriously?

This paper takes a somewhat slant perspective on flourishing and care in the context of suffering, death and dying, arguing that care in this context consists principally of ‘acts of work and courage that enable flourishing’. Starting with the perception that individuals, society and health care professionals have become dulled to death and the process of dying in Western advanced health systems, it suggests that for flourishing to occur, both of these aspects of life need to be faced more directly. The last days of life need to be ‘undulled’. Reflections upon the experiences of the author as carer and daughter in the face of her mother’s experience of death are used as basis for making suggestions about how care systems and professionals might better assist people in dealing with ‘the most grown up thing’ humans ever do, which is to die.     

Treatment Fidelity of a Nurse-Led Motivational Interviewing-Based Pre-Treatment in Pain Rehabilitation

Treatment fidelity and proficiency of a nurse-led motivational interviewing (MI)-based pre-treatment and control condition was evaluated. A random sample was scored by means of the Motivational Interviewing Treatment Integrity (MITI) scale, and a second rater was in charge. MI fidelity was satisfactory for three out of five ratings. Most mean ratings were higher in the MI-based intervention, but differences were not statistically significant. The threshold for beginning MI proficiency was only exceeded for one score and one additional measure. In general, higher levels of fidelity in the intervention condition confirmed that MI was partially applied there. Although the quality of MI delivery as well as mixed inter-rater reliabilities of the fidelity scores leaves room for improvement, robust findings between the two raters were found. These results suggest the need for rigor selection of MI counselors on beforehand, and continuous supervision. Furthermore, fidelity check in studies using MI is needed.