Broad and Region-Specific Impacts of the Synthetic Cannabinoid CP 55,940 in Adolescent and Adult Female Mouse Brains

Relative to Δ9-tetrahydrocannabinol (THC), the synthetic cannabinoid CP 55,940 (CP) is significantly more potent and efficacious at cannabinoid receptors, the primary targets for endogenous cannabinoids (eCBs). eCBs belong to a large, interconnected lipidome of bioactive signaling molecules with a myriad of effects in optimal and pathological function. Recreational use of highly potent and efficacious synthetic cannabinoids is common amongst adolescents, potentially impacting brain development. Knowledge of the molecular outcomes of synthetic cannabinoid use will be important to develop more targeted therapies for synthetic cannabinoid intoxication and to prevent long-term disruption to the CNS. Here, we test the hypothesis that CP has age and region-dependent effects on the brain lipidome. Adolescent [post-natal day (PND) 35 and PND 50] and young adult female mice were given either an acute dose of CP or vehicle and brains were collected 2 h later. Eight brain regions were dissected and levels of ∼80 lipids were screened from each region using HPLC/MS/MS. CP had widespread effects on the brain lipidome in all age groups. Interestingly, more changes were observed in the PND 35 mice and more were reductions in a lipid’s concentration, including region-dependent lowering of eCB levels. CP levels were highest in the cortex at PND 35, the hippocampus at PND 50, and in the cerebellum in the adult. These data provide novel insights into how high-potency, synthetic cannabinoids drive different, age-dependent, cellular signaling effects in the brain

Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD

Are attitudes towards medication adherence associated with medication adherence behaviours among patients with psychosis? A systematic review and meta analysis

Background Studies have shown patient attitudes to be an important predictor for health related behaviours including medication adherence. It is less clear whether patient attitudes are also associated with medication adherence among patients with psychoses. Method We conducted a systematic review and meta analysis of the data of studies that tested the association of attitude measures with medication adherence among patients with psychoses. 14 studies conducted between 1980 and 2010 were included. Results Results show a small to moderate mean weighted effect size (r + = 0.25 and 0.26 for Pearson and Spearman correlations, respectively). Conclusions Theory based interventions that target potentially modifiable attitude components are needed to assess the relationship between positive patient attitudes and adherence behaviours among patients with psychoses

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses

Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection

A randomised clinical trial on cardiotocography plus fetal blood sampling versus cardiotocography plus ST-analysis of the fetal electrocardiogram (STAN®) for intrapartum monitoring

<p>Abstract</p> <p>Background</p> <p>Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis.</p> <p>Methods/Design</p> <p>We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options.</p> <p>Women in labour with a gestational age ≥ 36 weeks and an indication for CTG-monitoring can be included in the trial.</p> <p>Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG.</p> <p>The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bd_ecf> 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals.</p> <p>The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied.</p> <p>Discussion</p> <p>This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed.</p> <p>Trial Registration Number</p> <p>ISRCTN95732366</p

Reporting of ethical approval and informed consent in clinical research published in leading nursing journals : a retrospective observational study

Background: Ethical considerations play a prominent role in the protection of human subjects in clinical research. To date the disclosure of ethical protection in clinical research published in the international nursing journals has not been explored. Our research objective was to investigate the reporting of ethical approval and informed consent in clinical research published in leading international nursing journals. Methods: This is a retrospective observational study. All clinical research published in the five leading international nursing journals from the SCI Journal Citation Reports between 2015 and 2017 were retrieved to evaluate for evidence of ethical review. Results: A total of 2041 citations have been identified from the contents of all the five leading nursing journals that were published between 2015 and 2017. Out of these, 1284 clinical studies have been included and text relating to ethical review has been extracted. From these, most of prospective clinical studies (87.5%) discussed informed consent. Only half of those (52.9%) reported that written informed consent had been obtained; few (3.6%) reported oral consent, and few (6.8%) used other methods such as online consent or completion and return of data collection (such as surveys) to denote assent. Notably, 36.2% of those did not describe the method used to obtain informed consent and merely described that “consent was obtained from participants or participants agreed to join in the research”. Furthermore, whilst most of clinical studies (93.7%) mentioned ethical approval; 92.5% of those stated the name of ethical committee and interestingly, only 37.1% of those mentioned the ethical approval reference. The rates of reporting ethical approval were different between different study type, country, and whether financial support was received (all P<0.05). Conclusion: The reporting of ethics in leading international nursing journals demonstrates progress, but improvement of the transparency and the standard of ethical reporting in nursing clinical research is required

Sensitivity to Experiencing Alcohol Hangovers: Reconsideration of the 0.11% Blood Alcohol Concentration (BAC) Threshold for Having a Hangover

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their “normal” drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their “regular” drinking level, considerably higher alcohol intake—irrespective of the absolute amount—may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned

Kinematic analysis of the daily activity of drinking from a glass in a population with cervical spinal cord injury

Background Three-dimensional kinematic analysis equipment is a valuable instrument for studying the execution of movement during functional activities of the upper limbs. The aim of this study was to analyze the kinematic differences in the execution of a daily activity such as drinking from a glass between two groups of patients with tetraplegia and a control group. Methods A total of 24 people were separated into three groups for analysis: 8 subjects with metameric level C6 tetraplegia, 8 subjects with metameric level C7 tetraplegia and 8 control subjects (CG). A set of active markers that emit infrared light were positioned on the upper limb. Two scanning units were used to record the sessions. The activity of drinking from a glass was broken down into a series of clearly identifiable phases to facilitate analysis. Movement times, velocities, and the joint angles of the shoulder, elbow and wrist in the three spatial planes were the variables analyzed. Results The most relevant differences between the three groups were in the wrist. Wrist palmar flexion during the back transport phase was greater in the patients with C6 and C7 tetraplegia than in the CG, whereas the highest wrist dorsal flexion values were in forward transport in the subjects with C6 or C7 tetraplegia, who required complete activation of the tenodesis effect to complete grasping. Conclusions A detailed description was made of the three-dimensional kinematic analysis of the task of drinking from a glass in healthy subjects and in two groups of patients with tetraplegia. This was a useful application of kinematic analysis of upper limb movement in a clinical setting. Better knowledge of the execution of this movement in each of these groups allows therapeutic recommendations to be specifically adapted to the functional deficit present. This information can be useful in designing wearable robots to compensate the performance of AVD, such as drinking, in people with cervical SCI

A qualitative analysis exploring preferred methods of peer support to encourage adherence to a Mediterranean diet in a Northern European population at high risk of cardiovascular disease.

BACKGROUND: Epidemiological and randomised controlled trial evidence demonstrates that adherence to a Mediterranean diet (MD) can reduce cardiovascular disease (CVD) risk. However, methods used to support dietary change have been intensive and expensive. Peer support has been suggested as a possible cost-effective method to encourage adherence to a MD in at risk populations, although development of such a programme has not been explored. The purpose of this study was to use mixed-methods to determine the preferred peer support approach to encourage adherence to a MD. METHODS: Qualitative (focus groups) and quantitative methods (questionnaire and preference scoring sheet) were used to determine preferred methods of peer support. Sixty-seven high CVD risk participants took part in 12 focus groups (60% female, mean age 64 years) and completed a questionnaire and preference scoring sheet. Focus group data were transcribed and thematically analysed. RESULTS: The mean preference score (1 being most preferred and 5 being least preferred) for group support was 1.5, compared to 3.4 for peer mentorship, 4.0 for telephone peer support and 4.0 for internet peer support. Three key themes were identified from the transcripts: 1. Components of an effective peer support group: discussions around group peer support were predominantly positive. It was suggested that an effective group develops from people who consider themselves similar to each other meeting face-to-face, leading to the development of a group identity that embraces trust and honesty. 2. Catalysing Motivation: participants discussed that a group peer support model could facilitate interpersonal motivations including encouragement, competitiveness and accountability. 3. Stepping Stones of Change: participants conceptualised change as a process, and discussed that, throughout the process, different models of peer support might be more or less useful. CONCLUSION: A group-based approach was the preferred method of peer support to encourage a population at high risk of CVD to adhere to a MD. This finding should be recognised in the development of interventions to encourage adoption of a MD in a Northern European population