In a double-blind trial lasting 4 months in 42 mentally handicapped patients, the effect of lithium on aggression was assessed in comparison with placebo. In the lithium-treated group, 73% of patients showed a reduction in aggression during treatment. There were significant differences in mean weekly aggression scores and in the frequency of aggressive episodes between the lithium and placebo groups. Side-effects were noted in 36% of the lithium group (and 20% of the placebo group), but were mainly transitory. There were no episodes of toxicity, and no patients had to be withdrawn from the trial. Lithium appears to be worth a 2-month trial in such patients, where repeated aggression has not been relieved by more appropriate placement, occupation or company.

CRISPR-Cas systems have emerged as a powerful tool to generate genetic models for studying normal and diseased central nervous system (CNS). Targeted gene disruption at specific loci has been demonstrated successfully in non-dividing neurons. Despite its simplicity, high specificity and low cost, the efficiency of CRISPR-mediated knockout in vivo can be substantially impacted by many parameters. Here, we used CRISPR-Cas9 to disrupt the neuronal-specific gene, NeuN, and optimized key parameters to achieve effective gene knockout broadly in the CNS in postnatal mice. Three cell lines and two primary neuron cultures were used to validate the disruption of NeuN by single-guide RNAs (sgRNA) harboring distinct spacers and scaffold sequences. This triage identified an optimal sgRNA design with the highest NeuN disruption in in vitro and in vivo systems. To enhance CRISPR efficiency, AAV-PHP.B, a vector with superior neuronal transduction, was used to deliver this sgRNA in Cas9 mice via neonatal intracerebroventricular (ICV) injection. This approach resulted in 99.4% biallelic indels rate in the transduced cells, leading to greater than 70% reduction of total NeuN proteins in the cortex, hippocampus and spinal cord. This work contributes to the optimization of CRISPR-mediated knockout and will be beneficial for fundamental and preclinical research.

Highlights d TBI elevates distinct phenotypes of microglia, macrophages, and dendritic cells d Ccr2 deficiency alters cell proportions and reduces ISG expression in microglia d TBI induces crosstalk between microglia and circulating monocytes d Preclinical translational studies to target human CCR2 after TBI improves outcomes

Traditionally the sexuality of mentally handicapped people was feared by those who made the rules governing Western societies. Where sexual needs were admitted at all, rigid rules were laid down in order to prevent thementally handicapped members of a society from procreating. Thus arose the segregated and isolated colonies for defectives, prohibitions on marriages (Berg and Nyland, unpublished; Grunewald and Limier, 1979) and laws permitting sterilization of the mentally incompetent which became widespread, particularly intheUSA. The reasons forsterilization were summed up in the much quoted judgement of Justice Oliver Wendell Holmes: It is 1?etterfor all the world, if, instead of waiting to execute degenerate offspring for crimes, or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind. The principle that sustains compulsory vaccination is broad enough to cover cutting the fallopian tubes. .. three generations of imbeciles are enough. (Buck v Bell, 274 US 200(1927)). Sterilizations continued, even though evidence to demonstrate theireffectiveness in preventing the birth of mentally handicapped children was lacking (Grunewald, 1979). More recently people have viewed the mentally handicapped asa sexually oppressed group(Kempton, 1977a). Although the ‘¿ normal' socio-sexual model is to finda mate,marry and have children, when a retarded person expresses, or worse, acts out these desires, many perceive it as excessive or shocking (Hall, 1975). A review of the literature shows up the conflict in viewpoints between parents, professionals, and mentally handicapped people themselves. In addition, there is literature concerned with helping mentally handicapped people to develop their potential for loving relationships in ways which are socially acceptable (see for example Lee and Katz, 1974). Let us start with the parental viewpoint.

Health promotion activity in community pharmacies was studied along with pharmacists' perceptions of the barriers and constraints to increasing health promotion activity within community pharmacy. A stratified sample (of 30 pharmacists) was investigated using a structured interview in the spring of 1993. Health promotion activities were undertaken by all study pharmacies. The number of times advice was given and/or a query dealt with was estimated to be around 1400 per week for the sample. It was found that the activity was 2.5 times more likely to be reactive rather than proactive. In general pharmacists felt isolated and excluded from formal activity: five pharmacists felt that they had enough support from local health promotion units and only one pharmacist had any liaison with a unit. There was evidence to suggest that these community pharmacies were an under-utilised resource for health promotion.