Learning methods determine the degree of stimulation of engrams encoding information to be memorised. More enriching modes of learning allow more enduring long-term potentiation of the synapses associated with these memories. The additional activity causes a prolonged increase in [Ca2+] in the dendritic spine of the postsynaptic neuron. This allows Ca2+-mediated molecular pathways to bring about cytoskeletal remodeling, posttranslational modifications, and protein trafficking. These processes contribute to early long-term potentiation of the synapses, strengthening the memory they store and lead to improved performance on tests of memory recall.

REFERENCES 1. Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387: 1109-22. 2. Laopaiboon M, Lumbiganon P, Intarut N et al. Advanced maternal age and pregnancy outcomes: a multicountry assessment. BJOG 2014; 121(Suppl 1): 49-56. 3. Olesen AB, Ellingsen AR, Larsen FS et al. Atopic dermatitis may be linked to whether a child is firstor second-born and/or the age of the mother. Acta Derm. Venereol. 1996; 76: 457-60. 4. Dioun AF, Harris SK, Hibberd PL. Is maternal age at delivery related to childhood food allergy? Pediatr. Allergy Immunol. 2003; 14: 307-11. 5. Development Crow JF. There's something curious about paternal-age effects.

Background/Objectives: Disseminated superficial actinic porokeratosis (DSAP) is a porokeratosis variant that is cosmetically disfiguring and may be associated with squamous cell carcinoma. It is an autosomal dominant condition caused by germline mutations in mevalonate pathway genes involved in cholesterol synthesis. Lesions are precipitated by ultraviolet radiation-induced second-hit mutations. Modulation of this pathway by topical simvastatin-cholesterol may lead to improvement.Methods: This open-label, split-body clinical trial was carried out in 2020 at a metropolitan dermatology clinic. Eight patients contributing 13 limb pairs were recruited. Limbs within each pair were randomly allocated to 2% simvastatin/2% cholesterol cream applied twice daily or bland emollients. Lesion number, erythema, scale and patientreported disease activity were measured at baseline and 6 weeks. Data were analysed using Bayesian ordinal logistic regression. Odds ratios compare the odds of a higher score at 6 weeks in treated limbs with the odds in controls. Values less than one indicate improvement.Results: Patients had a median age of 65 years (interquartile range [IQR] 58 to 69 years). The median baseline DLQI was 5 (range 2-21). Odds ratios were 0.12 (95% credible interval [CI] 0.01 to 0.72) for lesion number, 0.25 (95% CI 0.05 to 0.79) for erythema score, 0.18 (95% CI 0.03 to 0.64) for scale score and 0.33 (95% CI 0.09 to 0.89) for patientreported disease activity. Conclusions:Topical simvastatin-cholesterol cream improved lesion number, erythema and scale on treated limbs compared with controls. Patientreported disease activity also improved. These findings warrant confirmation in blinded, vehiclecontrolled trials.

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