Genetic linkage studies place a gene causing early onset familial Alzheimer's disease (FAD) on chromosome 14q24.3 (refs 1-4). Five mutations within the S182 (Presenilin 1: PS-1) gene, which maps to this region, have recently been reported in several early onset FAD kindreds. We have localized the PS-1 gene to a 75 kb region and present the structure of this gene, evidence for alternative splicing and describe six novel mutations in early onset FAD pedigrees all of which alter residues conserved in the STM2 (Presenilin 2: PS-2) gene.

HIV-infected patients have a higher risk of developing cutaneous reactions than the general population, which has a significant impact on patients' current and future care options. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. HIV-infected patients just at the beginning of antiretroviral treatment can frequently show a wide variety of adverse drug effects such as drug rashes, hyperpigmentation, hair loss, hypersensitivity reactions, injection site reaction, urticarial reaction, erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome. The early detection and treatment of cutaneous adverse drug reactions, plus identification of the causative agent, are essential to prevent the progression of the reaction, preventing additional exposures and ensuring the appropriate use of medications for the current condition and keeping in mind others, such as patient age. This article emphasizes the most common features of an antiretroviral drug-induced cutaneous reaction from protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors, fusion inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors and inhibitors of the CCR5 chemokine receptor, paying special attention to the newest drugs approved for the treatment of HIV infection, such as tipranavir, darunavir, etravirine, enfuvirtide, raltegravir and maraviroc.

Arithmetic problems share many surface-level features with typical sentences. They assert information about the world, and readers can evaluate this information for sensibility by consulting their memories as the statement unfolds. When people encounter the solution to the problem 3 × 4, the brain elicits a robust ERP effect as a function of answer expectancy (12 being the expected completion; 15 being unexpected). Initially, this was labeled an N400 effect, implying that semantic memory had been accessed. Subsequent work suggested instead that the effect was driven by a target P300 to the correct solutions. The current study manipulates operand format to differentially promote access to language-based semantic representations of arithmetic. Operands were presented either as spoken number words or as sequential Arabic numerals. The critical solution was always an Arabic numeral. In Experiment 1, the correctness of solutions preceded by spoken operands modulated N400 amplitude, whereas solutions preceded by Arabic numerals elicited a P300 for correct problems. In Experiment 2, using only spoken operands, the delay between the second operand and the Arabic numeral solution was manipulated to determine if additional processing time would result in a P300. With a longer delay, an earlier N400 and no distinct P300 were observed. In brief, highly familiar digit operands promoted target detection, whereas spoken numbers promoted semantic level processing-even when solution format itself was held constant. This provides evidence that the brain can process arithmetic fact information at different levels of representational meaningfulness as a function of symbolic format.

This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.