Cocaine and amphetamine regulated transcript (CART) mediates sex differences in binge drinking through central taste circuits.

The neuropeptide cocaine- and amphetamine-regulated transcript (CART) has been implicated in alcohol consumption and reward behaviours, yet mechanisms mediating these effects have yet to be identified. Using a transgenic CART knockout (KO) mouse line we uncovered a sexually dimorphic effect of CART in binge drinking, with male CART KO mice increasing intake, whilst female CART KO mice decreased their alcohol intake compared to controls. Female CART KO mice show greater sensitivity to bitter solutions that can be overshadowed through addition of a sweetener, implicating taste as a factor. Further we identify that this is not driven through peripherally circulating sex hormones, but the central nucleus of the amygdala (CeA) is a locus where CART contributes to the regulation of alcohol consumption, with CeA CART neutralisation specifically reducing plain alcohol, but not sweetened alcohol consumption in female mice. These findings may have implications for the development of sex-specific treatment options for alcohol use disorders through targeting the CART system.

Optogenetic recruitment of hypothalamic corticotrophin-releasing-hormone (CRH) neurons reduces motivational drive.

Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in animals. Whilst there is a clear relationship between stress and motivational drive, the mechanisms underpinning this association remain unclear. One hypothesis is that the endocrine system, via corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN; PVNCRH), initiates a hormonal cascade resulting in glucocorticoid release, and that excessive glucocorticoids change brain circuit function to produce depression-related symptoms. Another mostly unexplored hypothesis is that the direct activity of PVNCRH neurons and their input to other stress- and reward-related brain regions drives these behaviors. To further understand the direct involvement of PVNCRH neurons in motivation, we used optogenetic stimulation to activate these neurons 1 h/day for 5 consecutive days and showed increased acute stress-related behaviors and long-lasting deficits in the motivational drive for sucrose. This was associated with increased Fos-protein expression in the lateral hypothalamus (LH). Direct stimulation of the PVNCRH inputs in the LH produced a similar pattern of effects on sucrose motivation. Together, these data suggest that PVNCRH neuronal activity may be directly responsible for changes in motivational drive and that these behavioral changes may, in part, be driven by PVNCRH synaptic projections to the LH.

Disposable versus non-disposable tonometer prisms: a UK national survey.

PURPOSE: To determine the prevalence of disposable tonometer versus non-disposable tonometer use in the UK and to determine methods of decontamination and frequency of replacement of prisms.A total of 137 ophthalmology departments were interviewed by telephone using a structured questionnaire. The main outcome measured were:types of tonometer prisms used in clinic (disposable, non-disposable and/or other)average disposable prisms used per clinic sessionaverage lifespan of non-disposable prismsprism preference by glaucoma and other teams within department.A cost and benefit analysis was then performed on the data acquired. RESULTS: One hundred and fifty-five departments were identified for the survey. Of these, 137 (88.3%) responded. Eighty-one departments (59.1%) used Tonosafe prisms alone, whereas 22 departments (16.1%) used Goldmann non-disposable prisms exclusively. Thirty-five departments (64%) on average have a change rate of 26.5% per year (range: 0-100, median: 20) attributed to damage, loss or theft. Sixteen departments (29%) reported that prisms were used until damaged or lost. Four departments (7%) were uncertain of their prism usage and could not provide further information. CONCLUSIONS: Majority of eye departments in the UK opt for disposable prisms. This survey shows the perceived cost-effectiveness of disposable prisms is overestimated when the true cost of disinfection and damage is taken into account. Significant cost savings coupled with the low risk of infectivity (if decontaminated properly) should prompt clinicians and ophthalmic departments worldwide to reconsider the use of non-disposable prisms.

Embedding comprehensive geriatric assessment in the emergency assessment unit: the impact of the COPE zone.

We introduced a geographically embedded frailty unit, the comprehensive older person's evaluation 'COPE' zone within our emergency assessment unit (EAU). We collated data for all medical patients over 75 years admitted non-electively for one month before and after this service change. Significantly more patients were seen by a geriatrician on the EAU earlier in their admission in 2014 (33.4 vs 19.3%, p<0.001; 11 vs 20 h, p<0.001). More patients had documented comprehensive geriatric assessment and discussion in a geriatrician multidisciplinary team meeting (relative risk (RR) 3.3, 95% confidence interval (CI) 2.35-4.73, p<0.001; RR 3.6, 95% CI 2.26-5.57, p<0.001, respectively). More patients with markers of frailty were discharged directly from EAU (42.2 vs 29.0%, p = 0.006) without increasing readmissions. Mean length of stay was reduced (9.5 vs 6.8 days, p = 0.02). The introduction of the COPE zone has improved service delivery at the point of access for older people admitted to hospital.