Aversive drug cues reduce cigarette craving and increase prefrontal cortex activation during processing of cigarette cues in quitting motivated smokers

Aversive drug cues can be used to support smoking cessation and create awareness of negative health consequences of smoking. Better understanding of the effects of aversive drug cues on craving and the processing of appetitive drug cues in abstinence motivated smokers is important to further improve their use in cessation therapy and smoking-related public health measures. In this study, 38 quitting motivated smokers underwent functional magnetic resonance imaging (fMRI) scanning while performing a novel extended cue-reactivity paradigm. Pictures of cigarettes served as appetitive drug cues, which were preceded by either aversive drug cues (e.g., smokers' leg) or other cues (neutral or alternative reward cues). Participants were instructed to rate their craving for cigarettes after presentation of drug cues. When aversive drug cues preceded the presentation of appetitive drug cues, behavioural craving was reduced and activations in prefrontal (dorsolateral prefrontal cortex) and paralimbic (dorsal anterior cingulate cortex [dACC] and anterior insulae) areas were enhanced. A positive association between behavioural craving reduction and neurofunctional activation changes was shown for the right dACC. Our results suggest that aversive drug cues have an impact on the processing of appetitive drug cues, both on a neurofunctional and a behavioural level. A proposed model states that aversive drug-related cues activate control-associated brain areas (e.g., dACC), leading to increased inhibitory control on reward-associated brain areas (e.g., putamen) and a reduction in subjective cravings

Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir

Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines

Understanding and breaking the intergenerational cycle of abuse in families enrolled in routine mental health services: study protocol for a randomized controlled trial and two non-interventional trials investigating mechanisms of change within the UBICA II consortium

Background!#!Parents' mental illness (MI) and parental history of early life maltreatment (ELM) are known to be significant risk factors for poor parenting while poor parenting is a crucial mediator of the intergenerational continuity of child maltreatment. Hence, maltreatment prevention programs for families with an MI parent, which pay particular attention to experiences of ELM in the parent, are urgently needed. Parental mentalizing was previously found to mediate successful parenting. Interventions aimed at improving the parental mentalizing capacity reduced maltreatment risk in parents. The aim of the present study is to investigate the effectiveness of a mentalization-based parenting-counseling in acutely mentally ill parents currently treated at a psychiatric hospital.!##!Methods!#!Mentalization-based parenting-counseling (MB-PC) vs. enhanced standard clinical care (SCC+) will be administered in a cluster-randomized-controlled trial (RCT). Patients treated at psychiatric hospitals with children between 1.5 and 15 years will be included in the trial. MB-PC will be administered as a 12-h combined individual and group program enriched by social counseling (over a course of 5 weeks) as add-on to standard clinical care, while the control condition will be standard clinical care plus a 90-min psychoeducation workshop on positive parenting. Primary efficacy endpoint is self-reported parenting practices at follow-up. Embedded within the RCT will be two sub-studies investigating social cognition and dyadic synchrony as biobehavioral mechanisms of change.!##!Discussion!#!The main goal of the present study is to investigate ways to break the intergenerational continuity of maltreatment by assessing the benefits of a prevention program which aims at improving parenting in vulnerable mothers and fathers. MB-PC is a short, low-cost intervention which can be delivered by nurses and social workers and is applicable to MI patients with children with a broad range of diagnoses. If it is shown to be effective, it can be directly implemented into standard psychiatric hospital care thereby providing help to prevent child maltreatment.!##!Trial registration!#!German Clinical Trials Register DRKS00017398 . Registered on 5 July 2019

Nasal wash cell counts in the presence or absence of oseltamivir treatment.

<p>A, prophylactic oseltamivir regimen from 2; B, therapeutic oseltamivir regimen from 6 hr post-infection. • (red) high dose (10⁶ pfu); ▴ (blue) low dose (10² pfu); ★ mock infected animals; open symbols represent oseltamivir-treated animals. Means from 5 ferrets (A) or 3–9 ferrets per group (B).</p

Effect of virus dose on parameters of infection with influenza A/California/04/09.

1<p>Mean clinical score is calculated as described in Materials and Methods, and expressed as mean score per ferret per day ± standard error of the mean.</p>2<p>Day of onset refers to median onset of respiratory signs and inactivity from four studies.</p><p>ND, not done.</p

Viral RNA loads in ferret respiratory tract tissues.

<p>Ferrets were infected intra-nasally with 10⁶ or 10² pfu Cal/04 and, where indicated, treated with oseltamivir from 6 hr post-infection. Circles show RNA loads for individual animals. Horizontal lines show group means. Filled circles, no treatment; open circles, oseltamivir treated. A, nasal turbinate; B, trachea; C, lung. High, 10⁶ pfu inoculum; Low, 10² pfu inoculum. Samples were taken from 2 ferrets on days 1 to 4, and 3 ferrets on day 5. The sensitivity of the assay was approximately 10³ copies/mg.</p

Summary of severity of pathological changes in untreated or oseltamivir treated ferret tissues.

<p>A. Nasal cavity, B. lung. In each case, changes were scored as minimal (min), mild, moderate (mod), or marked, and were summed for each group of ferrets on each day post-infection. Group size was 2 ferrets, except day 5 which was groups of 3 ferrets. The day 5 summed frequencies have been normalised to facilitate comparison to the other days.</p

Effect of decreasing infectious dose on virus shedding.

<p>Ferrets were infected intra-nasally, and nasal washes were collected at the intervals shown for virus plaque assay. Markers show geometric mean nasal wash titre from groups of 5 or 8 ferrets; error bars show standard deviation. For days 10 and 14 post-infection, 2 ferrets per group were used. • (red) high dose (10⁶ pfu), ▪ (green) medium dose (104 pfu), ▴ (blue) low dose (102 pfu) inoculum. The lower limit of detection was 10 pfu/ml.</p