Two samples of adequately detoxified hospital-treated alcohol abusers were neuropsychologically assessed for alcohol-related cognitive impairment. Both groups manifested the commonly found impairments on the Wechsler Adult Intelligence Scale (N = 50) and the Revised Wechsler Adult Intelligence Scale (N = 44). In addition, an almost identical pattern of substantial impairment was found when both groups were examined by Russell's (1975, 1988) version of the logical memory and visual reproduction subtests of the Wechsler Memory Scale. A clear pattern of memory impairment for both verbal and non-verbal memory was found.

Background Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood–brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. Methods Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target’s natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis. Results Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis. Conclusion ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.

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Dear Editor, The molecular determinants that drive breast cancer progression to metastasis are complex and partly controlled by nucleic acid epi-modifications [1]. Although DNA-methyl modifications in breast cancer metastasis have been well described, there is limited understanding of the role of RNA methylation in advanced disease [2]. This study aimed to provide an understanding on the role of the epitranscriptome in estrogen receptor-positive (ER+) breast cancer progression to metastasis.Numerous RNA modifications have been described to date, of which N 6 -methyladenosine (m 6 A) modifications are the most common [3]. Here, we mapped dynamic global m 6 A-specific methylated RNA immunoprecipitation sequencing (MeRIPseq), with corresponding RNA-sequencing (RNA-seq) and mass spectrometry, in cell models of disease progression to metastasis: endocrine-sensitive (MCF7/luminal A), endocrineresistant (LY2/luminal B) and endocrine-resistant brain metastatic (T347/patient-derived luminal B metastatic) (Figure 1A). The relevance of this model system was verified using comparative analysis of patient-matched brain metastatic samples [4] with RNA-seq data from our cells (LY2 vs. MCF7 and T347 vs. MCF7) [4] (Supplementary Table S1). Consistent differential gene expression in key oncogenic pathways such as Kirsten rat sarcoma virus (KRAS), nuclear factor-κB (NF-κB

A group of recently abstinent alcohol abusers were examined using selected subtests of the WAIS-R and the WMS-R. The pattern of performance on the WAIS-R was similar to that well established for its predecessor. A clear nonmodality-specific memory deficit was evident on the WMS-R subtests. The theoretical and clinical implications of the results are briefly discussed.