Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorderprimarily affecting motor neurons. The etiology of the majorityof cases remains unknown. Recent findings from several laboratoriessuggest a role for neurofilaments in the development of motorneuron disorders. The C-terminal region of the human neurofilamentheavy subunit (NEFH) contains a unique functional domain consistingof 43 repeat motifs of the amino acids Lys-Ser-Pro (KSP). ThisC-terminal region of NEFH forms the sidearm projections whichcross-link the neurofilaments. Previously, we have demonstratedpolymorphism in the C-terminal region of the human NEFH: anallelic variant of a slightly larger molecular size, containingan additional KSP phosphorylation motif. Novel mutations inthis region were found in five ALS patients. We propose thatchanges in the KSP-repeat domain may affect the cross-linkingproperties of the heavy neurofilament subunit and perhaps contributeto the development of neurofilamentous swellings in motor neurons,a hallmark of ALS.     

Experience in the medical management of potential laboratory exposures to agents of bioterrorism on the basis of risk assessment at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID)

Experience in managing laboratory exposures to potential agents of bioterrorism is limited. The United States Army Medical Research Institute of Infectious Diseases reviewed laboratory exposures involving these agents (1989 to 2002) to assess the effectiveness of medical management. The evaluation of 234 persons (78% vaccinated) for exposure to 289 infectious agents revealed 5 confirmed infections (glanders, Q fever, vaccinia, chikungunya, and Venezuelan equine encephalitis). Postexposure antibiotic prophylaxis was given for most moderate- or high-risk bacterial exposures (41/46; 89%); most unvaccinated minimal-risk (7/10; 70%), and subsets of vaccinated minimal-risk exposures (18/53; 34%) but generally not negligible-risk exposures (6/38; 16%). Vaccine "breakthroughs" were not unexpected (enzootic Venezuelan equine encephalitis, localized vaccinia) or presented with mild symptoms (Q fever). A multifaceted policy of personal protective measures, vaccination, early assessment, and postexposure antibiotic prophylaxis was effective in minimizing morbidity and mortality in at-risk laboratory workers.     

An outbreak of Campylobacter jejuni gastroenteritis linked to meltwater contamination of a municipal well

A large outbreak of Campylobacter jujuni gastroenteritis attributed to contamination of an unchlorinated municipal water system was investigated. Unlike most previous summer outbreaks, this one began in early spring and was attributed to meltwater entering one or more municipal wells. 241 suspected cases were documented, but retrospective information from local health care workers suggested a much larger outbreak. 45 laboratory-confirmed cases participated in a case-control study which showed a significant association between infection and amount of town water consumed. Stool specimens from 29 patients were studied with detailed serotyping by the method of Lior, with eight known serotypes and one previously unknown one identified. It is concluded that intensive surveillance of water quality during periods of spring runoff is essential, and that timely reporting of disease outbreak patterns in emergency department settings is necessary to protect the public's health.     

Accuracy of ultrasound in counting and measuring gallstones

A prospective study of accuracy of ultrasound in measuring and counting gallstones was undertaken in 30 patients undergoing cholecystectomy. Stones were correctly counted (up to five) in 27 of 30 patients. Ninety-three of 106 stones (88%) examined were measured accurately (with a 2 mm error margin). The size of the smaller stones tended to be overestimated, whereas the size of the larger stones tended to be underestimated. When nonoperative treatment of gallstones is considered, ultrasound can be used as the first examination to identify patients who will not be eligible for one or another protocol on the basis of size or number of stones.     

Recent drug use and suicidal behaviour among young offenders

Patterns of psychoactive substance use were examined among 216 young offenders in South Australian secure care facilities. Compared to four student samples (n = 1525), young offenders reported recent use of most substances considerably more often than did student peers. Almost one-half used a substance at the time of committing their last offence. A subgroup of offenders (n = 126) was questioned about suicide attempts, mood, recent suicidal ideation and deliberate self-injury. Past suicide attempts and deliberate self-injury were found to be associated with increased substance use. Drawing on evidence from other studies it is argued that impulsiveness often underlies these behaviours and contributes to their covariation. Substance use can further increase impulsiveness and thereby exacerbate offending and suicide risk. Not only should substance use be considered in all assessments of antisocial and self-destructive behaviour but innovative approaches to developing effective interventions for the reduction of substance misuse need to be encouraged.     

Neural correlates of long-term object memory in the mouse anterior cingulate cortex

Damage to the hippocampal formation results in a profound temporally graded retrograde amnesia, implying that it is necessary for memory acquisition but not its long-term storage. It is therefore thought that memories are transferred from the hippocampus to the cortex for long-term storage in a process called systems consolidation (Dudai and Morris, 2000). Where in the cortex this occurs remains an open question. Recent work (Frankland et al., 2005; Vetere et al., 2011) suggests the anterior cingulate cortex (ACC) as a likely candidate area, but there is little direct electrophysiological evidence to support this claim. Previously, we demonstrated object-associated firing correlates in caudal ACC during tests of recognition memory and described evidence of neuronal responses to where an object had been following a brief delay. However, long-term memory requires evidence of more durable representations. Here we examined the activity of ACC neurons while testing for long-term memory of an absent object. Mice explored two objects in an arena and then were returned 6 h later with one of the objects removed. Mice continued to explore where the object had been, demonstrating memory for that object. Remarkably, some ACC neurons continued to respond where the object had been, while others developed new responses in the absent object's location. The incidence of absent-object responses by ACC neurons was greatly increased with increased familiarization to the objects, and such responses were still evident 1 month later. These data strongly suggest that the ACC contains neural correlates of consolidated object/place association memory.