The estimation of patient-specific cardiac diastolic functions from clinical measurements

An unresolved issue in patients with diastolic dysfunction is that the estimation of myocardial stiffness cannot be decoupled from diastolic residual active tension (AT) because of the impaired ventricular relaxation during diastole. To address this problem, this paper presents a method for estimating diastolic mechanical parameters of the left ventricle (LV) from cine and tagged MRI measurements and LV cavity pressure recordings, separating the passive myocardial constitutive properties and diastolic residual AT. Dynamic C₁-continuous meshes are automatically built from the anatomy and deformation captured from dynamic MRI sequences. Diastolic deformation is simulated using a mechanical model that combines passive and active material properties. The problem of non-uniqueness of constitutive parameter estimation using the well known Guccione law is characterized by reformulation of this law. Using this reformulated form, and by constraining the constitutive parameters to be constant across time points during diastole, we separate the effects of passive constitutive properties and the residual AT during diastolic relaxation. Finally, the method is applied to two clinical cases and one control, demonstrating that increased residual AT during diastole provides a potential novel index for delineating healthy and pathological cases.     

Evaluating a low‐intensity cognitive behavioural program for young people in regional Australia

NewAccess is a low‐intensity cognitive behavioural program which was recently trialled for the first time in Australia for clients aged under 18. Given that accessing support earlier tends to result in better outcomes for people with mild‐to‐moderate mental health issues, having NewAccess available for young people has the potential to reduce the likelihood of mild‐to‐moderate mental health concerns developing into more serious, or chronic mental illness over time for some clients, while also freeing up resources for those with more severe support needs. This mixed methods approach presents the findings of an independent evaluation of the program delivered out of two regional headspace centres in 2017‐2019. From an initial sample of 165 young participants aged between 12 and 25, 109 completed the program. Of those who completed the program 60 were under the age of 18. The standardised assessment and outcome measures indicated a very good response to the program, with the majority showing significant improvements in their depression, anxiety and psychological distress scores. The overall ‘reliable improvement’ and ‘recovery rates’ were 64.2% and 72.3% respectively. Overall, the results indicated this program was an acceptable and efficacious intervention for young people in rural settings, when delivered in a ‘youth‐friendly’ service environment.     

Parental occupation, family affluence and adolescent health behaviour in 28 countries

Objectives:  We explored the association between socioeconomic position and four different aspects of adolescent health behavior in a wide range of European countries, the US, Canada and Israel. Methods:  Data were collected from the Health Behaviour in School-aged Children (HBSC) study in 2002. Representative samples of 13 and 15 year olds completed a standardised questionnaire during school hours in each country. Logistic regression analyses were used to investigate the independent effect of parental occupation and family affluence on tobacco and alcohol use, vegetable consumption and TV viewing. Results:  Family affluence showed no significant association with regular smoking in most countries, whereas an increase in smoking with decreasing occupational status was found in half of the countries. For alcohol consumption a positive association was found with family affluence in half of the countries, while no relationship with parental occupation was observed. Both measures of socioeconomic position were strong independent predictors for vegetable consumption and television viewing in almost all countries. Conclusions:  The findings suggest that health behaviours that begin to develop in adolescence are less strongly influenced by parental socioeconomic position. Preventive intervention strategies should take the different socioeconomic patterns of health behaviour into account. Submitted: 20 February 2008; revised: 11 October 2008; accepted: 20 October 2008     

Resting-state functional connectivity abnormalities in limbic and salience networks in social anxiety disorder without comorbidity

The neurobiology of social anxiety disorder (SAD) is not yet fully understood. Structural and functional neuroimaging studies in SAD have identified abnormalities in various brain areas, particularly the amygdala and elements of the salience network. This study is the first to examine resting-state functional brain connectivity in a drug-naive sample of SAD patients without psychiatric comorbidity and healthy controls, using seed regions of interest in bilateral amygdala, in bilateral dorsal anterior cingulate cortex for the salience network, and in bilateral posterior cingulate cortex for the default mode network. Twelve drug-naive SAD patients and pair-wise matched healthy controls, all drawn from the Netherlands Study of Depression and Anxiety sample, underwent resting-state fMRI. Group differences were assessed with voxel-wise gray matter density as nuisance regressor. All results were cluster corrected for multiple comparisons (Z>2.3, p<.05). Relative to control subjects, drug-naive SAD patients demonstrated increased negative right amygdala connectivity with the left middle temporal gyrus, left supramarginal gyrus and left lateral occipital cortex. In the salience network patients showed increased positive bilateral dorsal anterior cingulate connectivity with the left precuneus and left lateral occipital cortex. Default mode network connectivity was not different between groups. These data demonstrate that drug-naive SAD patients without comorbidity show differences in functional connectivity of the amygdala, and of areas involved in self-awareness, some of which have not been implicated in SAD before.     

Implication of 5-HT<Subscript>2</Subscript> receptor subtypes in the mechanism of action of antidepressants in the four plates test

Rationale The selective serotonin reuptake inhibitors (SSRIs) and the serotonin and noradrenaline reuptake inhibitors (SNRIs) increase synaptic levels of serotonin, leading to an increased activation of a multitude of specific postsynaptic 5-HT receptors. However, it is not yet known which 5-HT receptor subtypes mediate the therapeutic effects of antidepressants.Methods The effects of the SSRI, paroxetine and the SNRI, venlafaxine were evaluated in the mouse four plates test (FPT).Results Paroxetine administered intraperitoneally (IP) (0.5, 2–8 mg/kg) potently augmented the number of punished passages accepted by mice in this paradigm. The effects of paroxetine (8 mg/kg) were not reversed by the selective 5-HT_2C receptor antagonist, RS 10-2221 (0.1 mg/kg and 1 mg/kg) or the selective 5-HT_2B/2C receptor antagonist SB 206553 (0.1 mg/kg and 1 mg/kg), at doses which lack an effect when administered alone. In contrast, the selective 5-HT_2A receptor antagonist, SR 46349B (0.1 mg/kg and 1 mg/kg) completely abolished the paroxetine-induced increase in punished passages. The acute administration of venlafaxine induced an anxiolytic-like effect in the FPT at the doses of 2–16 mg/kg. This effect was reversed by the 5-HT_2B/2C receptor antagonist as did SR 46349B, for both doses administered. Our results strongly suggest that activation of 5-HT_2A receptors is critically involved in the anxiolytic activity of paroxetine, whereas the 5-HT_2A and 5-HT_2B receptors are involved in the anti-punishment action of venlafaxine in the FPT. The co-administration of selective 5-HT_{2A, 2B, 2C} receptor agonists (DOI, 0.06 mg/kg and 0.25 mg/kg; BW 723C86, 0.5 mg/kg and 2 mg/kg and RO 60-0175, 0.06 mg/kg and 0.25 mg/kg), respectively, was subsequently investigated. The effects of sub-active doses of paroxetine (0.25 mg/kg and 1 mg/kg) were augmented by BW 723C86 and RO 60-0175 receptor agonist challenge. The anti-punishment effects of venlafaxine (0.25 mg/kg and 1 mg/kg) were potentialised only by DOI co-administration.Conclusion These results indicate that the co-administration of 5-HT₂ receptor agonists with paroxetine and venlafaxine may provide a powerful tool for enhancing the clinical efficacy of these antidepressants.     

High rates of alcohol consumption and related harm at schoolies week: a portal study

Objective: To investigate alcohol consumption, substance use and risky and harmful behaviour among young people attending ‘schoolies’ week in Victoria. Methods: Breathalyser tests and brief surveys (n=558) measuring alcohol, energy drink and illicit drug use, and experience of aggressive incidents, alcohol‐related injury and unprotected sex, were undertaken with young people attending schoolies week in Lorne and Torquay. Results: Schoolies reported consuming a mean of 8.8 drinks in the current session, with a mean blood alcohol count (BAC) of 0.05; 18.3% recorded a BAC of greater than 0.08. One in six participants had consumed alcohol with energy drinks; 7.7% reported using illicit substances. Participants who co‐consumed alcohol and energy drinks recorded a higher BAC than alcohol‐only users. One in five participants had experienced alcohol‐related harm at schoolies week, including aggressive incidents, alcohol‐related injury and engagement in unprotected sex. Each alcoholic drink consumed increased the potential for involvement in aggressive incidents by 8% and alcohol‐related accidents/injuries by 5%; illicit drug use was associated with six times the likelihood of engaging in unprotected sex with a non‐partner. Conclusions and implications: Excessive alcohol consumption and experience of related harms are common among young people attending schoolies week. Harm reduction initiatives targeting schoolies week should focus on the consequences of excessive alcohol consumption, illicit drugs and the co‐consumption of alcohol and energy drinks.     

D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning

Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared with vehicle, pretreatment with 30 mg/kg DCS 0.5 h before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species, pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared with either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 h after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse.