Cost-effectiveness of expanded latent TB infection testing and treatment: Lynn City, Massachusetts, USA.

BACKGROUND: Between October 2016 and March 2019, Lynn Community Health Center in Massachusetts implemented a targeted latent TB infection testing and treatment (TTT) program, increasing testing from a baseline of 1,200 patients tested to an average of 3,531 patients tested, or 9% of the population per year.METHODS: We compared pre-implementation TTT, represented by the first two quarters of implementation data, to TTT, represented by 12 quarters of data. Time, diagnostic, and laboratory resources were estimated using micro-costing. Other cost and testing data were obtained from the electronic health record, pharmaceutical claims, and published reimbursement rates. A Markov cohort model estimated future health outcomes and cost-effectiveness from a societal perspective in 2020 US dollars. Monte Carlo simulation generated 95% uncertainty intervals.RESULTS: The TTT program exhibited extended dominance over baseline pre-intervention testing and had an incremental cost-effectiveness ratio (ICER) of US$52,603 (US$22,008â-"US$95,360). When compared to baseline pre-TTT testing, the TTT program averted an estimated additional 7.12 TB cases, 3.49 hospitalizations, and 0.16 deaths per lifetime cohort each year.CONCLUSIONS: TTT was more cost-effective than baseline pre-implementation testing. Lynn Community Health Centerâ-™s experience can help inform other clinics considering expanding latent TB infection testing.

SARS-CoV-2 reinfections with BA.1 (Omicron) variant among fully vaccinated individuals in northeastern Brazil.

BACKGROUND: The first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Rio Grande do Norte, northeastern Brazil, was diagnosed on March 12, 2020; thereafter, multiple surges of infection occurred, similar to what was seen elsewhere. These surges were mostly due to SARS-CoV-2 mutations leading to emergence of variants of concern (VoC). The introduction of new VoCs in a population previously exposed to SARS-CoV-2 or after vaccination has been a challenge to understanding the kinetics of the protective immune response against this virus. The aim of this study was to investigate the outbreak of SARS-CoV-2 reinfections observed in mid-January 2022 in Rio Grande do Norte state, Brazil. It describes the clinical and genomic characteristics of nine cases of reinfection that occurred coincident with the introduction of the omicron variant. METHODOLOGY/PRINCIPAL FINDINGS: Of a total of 172,965 individuals with upper respiratory symptoms tested for SARS-CoV-2, between March 2020 through mid-February 2022, 58,097 tested positive. Of those, 444 had documented a second SARS-CoV-2 infection and nine reinfection cases were selected for sequencing. Genomic analysis revealed that virus lineages diverged between primary infections and the reinfections, with the latter caused by the Omicron (BA.1) variant among individuals fully vaccinated against SARS-CoV-2. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the Omicron variant is able to evade both natural and vaccine-induced immunity, since all nine cases had prior natural infection and, in addition, were fully vaccinated, emphasizing the need to develop effective blocking vaccines.

Development of a one-step RT-qPCR assay for the detection of Grapevine leafroll-associated virus 7.

Grapevine leafroll disease (GLD) is one of the most economically important viral diseases of grapevines. GLD is caused by a complex of several ssRNA (+) viruses referred to as Grapevine leafroll-associated viruses (GLRaVs). To date, five different GLRaV species have been identified. One of those species, GLRaV-7, was first reported from a symptomless white-fruited wine grape cultivar from Albania. Since its discovery, GLRaV-7 has been reported from 14 countries. Although serological assays have been developed to detect GLRaV-7, commercially available antibodies produce high background signals making them unsuitable for regulatory testing. Furthermore, while molecular detection assays have been shown to be more sensitive when compared to the serological assays, published molecular assays, except the one Reverse Transcription-quantitaive Polymerase Chain Reaction (RT-qPCR) assay based on heat shock protein 70 homologue (HSP70h) gene, have been reported to be inadequate in detecting all reported isolates of GLRaV-7. Availability of multiple assays provides flexibility to diagnostic laboratories in cases where the chosen assay fails to detect a strain or an isolate of a pathogen due to variation in its targeted region or where additional confirmation of the results is required. In this study, we developed a sensitive and specific RT-qPCR assay, based on a region of p61 gene of GLRaV-7, which detected all available isolates.

SARS-CoV-2 reinfections with BA.1 (Omicron) variant among fully vaccinated individuals in the northeast of Brazil

BackgroundThe first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Rio Grande do Norte, northeast Brazil, was diagnosed on March 12, 2020; thereafter, the pattern of COVID-19 followed the multiple waves as seen elsewhere. Those waves were mostly due to the SARS-CoV-2 virus mutations leading to emergence of variants of concern (VoC). The introduction of new VoCs in a population context of prior SARS-CoV-2 infections or after vaccination has been a challenge in understanding the kinetics of the protective immune response against SARS-CoV-2. The aim of this study was to investigate the outbreak of SARS-CoV-2 reinfections observed in mid-January 2022 in Rio Grande do Norte state, Brazil when the omicron variant was introduced. Methodology/Principal findingsFrom a total of 172,965 individuals with mild to severe respiratory symptoms, 58,097 tested positive for SARS-CoV-2 between March 2020 through mid-February 2022. Of those previously infected, 444 had documented a second SARS-CoV-2 infection and 9 of these reinfection cases were selected for sequencing. Genomic analysis revealed that virus lineages diverged between primary and the reinfection, with the latter caused by the Omicron (BA.1) variant among individuals fully vaccinated against SARS-CoV-2. Conclusions/SignificanceOnce all subjects whose samples were sequenced had prior SARS-CoV-2 infection and were also fully vaccinated, our data suggest that the Omicron variant evades natural and vaccine-induced immunities, confirming the continuous need to decrease transmission and to develop effective blocking vaccines. Author summaryThe pattern of the COVID-19 pandemic has been characterized by multiple waves of cases with a variety of outcomes from asymptomatic, to moderate or to severe fatal cases. By December 2021, about 75.3% of Rio Grande do Norte population, northeast Brazil, had already been fully vaccinated against SARS-CoV-2 and a decrease in newer detection cases was seen to about 8% of the suspected ones. Nevertheless, with the introduction of the Omicron variant at the end of 2021, the number of new SARS-CoV-2 infections reached its highest peak since the start of the pandemic with 75% of the suspected cases testing positive. From March 2020 to February 2022, we confirmed 444 reinfection cases among the ones tested, of which 62.3% (n=277) occurred during the Omicron outbreak, from December 2021 to early February 2022. Of the reinfection cases, 9 were sequenced and genetic analysis showed that they belong to a BA.1 lineage, which seems to have been introduced multiple times into the region. The primary isolates varied. Thus, our data suggest that the Omicron variant evades immunity provided from either natural infection from any other SARS-CoV-2 variants or from different types of vaccines.

Oral Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Clinicopathologic and Immunohistochemical Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents rapid transmission and significant mortality worldwide. It is responsible for coronavirus disease 2019 (COVID-19). The disease presents diverse clinical symptoms, including fever, cough, dyspnea, and pneumonia. However, other manifestations associated with COVID-19 need to be clarified, leading specialists to an early diagnosis and better prognosis. We describe the spectrum of clinicopathologic COVID-19-related oral lesions that can be the first and/or the unique manifestation of the disease. Fourteen patients with a mean age of 58 years (range: 23 to 88 y) with oral lesions were included. All patients were confirmed to be infected with SARS-CoV-2 by reverse transcription polymerase chain reaction testing. Patients demonstrated mild symptoms, including dysgeusia, anosmia, fever, and headache. The lesions were recognized and classified into 2 groups: (1) lesions caused by ischemia and/or hemorrhage and (2) lesions secondary to inflammatory events associated with viral load. The palate was most affected (n=8), followed by the tongue (n=4), and both the lip and palate (n=2). Histologic analysis demonstrated thrombosis of small arteries and capillaries, associated with areas of hemorrhage and chronic inflammatory infiltrate. Immunohistochemistry showed positive staining for spike protein (SARS-CoV and SARS-CoV-2) and angiotensin-converting enzyme 2 in the surface epithelium, salivary glands, inflammatory cells, and endothelial cells. Although the incidence of oral lesions among patients infected with SARS-CoV-2 appears to be uncommon, these findings suggest that the oral mucosa can also be a target organ for SARS-CoV-2.

A Murine Model of Mycobacterium kansasii Infection Reproducing Necrotic Lung Pathology Reveals Considerable Heterogeneity in Virulence of Clinical Isolates.

Among non-tuberculous mycobacteria, Mycobacterium kansasii is one of the most pathogenic, able to cause pulmonary disease indistinguishable from tuberculosis in immunocompetent susceptible adults. The lack of animal models that reproduce human-like lung disease, associated with the necrotic lung pathology, impairs studies of M. kansasii virulence and pathogenicity. In this study, we examined the ability of the C57BL/6 mice, intratracheally infected with highly virulent M. kansasii strains, to produce a chronic infection and necrotic lung pathology. As a first approach, we evaluated ten M. kansasii strains isolated from Brazilian patients with pulmonary disease and the reference strain M. kansasii ATCC 12478 for virulence-associated features in macrophages infected in vitro; five of these strains differing in virulence were selected for in vivo analysis. Highly virulent isolates induced progressive lung disease in mice, forming large encapsulated caseous granulomas in later stages (120-150 days post-infection), while the low-virulent strain was cleared from the lungs by day 40. Two strains demonstrated increased virulence, causing premature death in the infected animals. These data demonstrate that C57BL/6 mice are an excellent candidate to investigate the virulence of M. kansasii isolates. We observed considerable heterogeneity in the virulence profile of these strains, in which the presence of highly virulent strains allowed us to establish a clinically relevant animal model. Comparing public genomic data between Brazilian isolates and isolates from other geographic regions worldwide demonstrated that at least some of the highly pathogenic strains isolated in Brazil display remarkable genomic similarities with the ATCC strain 12478 isolated in the United States 70 years ago (less than 100 SNPs of difference), as well as with some recent European clinical isolates. These data suggest that few pathogenic clones have been widely spread within M. kansasii population around the world.

Regional, socioeconomic and behavioural- impacts on consumer acceptability of beef in Northern Ireland, Republic of Ireland and Great Britain.

This study was commissioned to assess if there are regional differences in the acceptability of beef between consumers from Northern Ireland (NI), Republic of Ireland (ROI) and Great Britain (GB). Palatability traits were affected by socioeconomic and behavioural factors such as preferred cooking endpoint, animal welfare, value, health aspects of beef product, ease of preparation as well as consumption frequency for specific cuts. "Willingness to pay" (WTP) was influenced by income, preferred cooking endpoint, value of beef product, ease of preparation and consumption frequency for frying steak. Results showed that GB consumers scored higher for the same striploin steak compared to NI and ROI consumers. This may be due to differences in the motivation for beef choice and/or consumption habits. GB consumers were less concerned about the healthiness of beef product and beef origin. In addition, a higher consumption frequency for rump was reported in GB, which may explain the higher sensory scores observed among GB consumers for striploins.

Diagnosing slipped capital femoral epiphysis amongst various medical specialists.

PURPOSE: To evaluate sensitivity, specificity and accuracy of a radiographic slipped capital femoral epiphysis (SCFE)-diagnosis among medical specialists. METHODS: Three paediatricians, three paediatric radiologists and three paediatric orthopaedic surgeons completed two rounds of a survey of anteroposterior and frog-leg lateral radiographs of patients with a diagnosis of SCFE (25), femoroacetabular impingement (four), Legg-Calvé-Perthes (11) or no hip pathology (ten). Intra- and interobserver agreement among specialties regarding the diagnosis of a SCFE were assessed using Cohen's kappa coefficient (κ). Diagnostic accuracy of SCFE relative to the benchmark, a combination of the radiographic diagnosis based on Klein's line, clinical symptoms and surgical treatment, was assessed computing sensitivity, specificity and accuracy. RESULTS: Intraobserver agreement between the surveys was moderate among paediatricians (κ-range, 0.44 to 0.52), moderate to almost perfect among orthopaedic surgeons (κ-range, 0.79 to 0.88) and almost perfect among paediatric radiologists (κ-range, 0.83 to 1.00). Interobserver agreement for survey 1 and 2 was slight among paediatricians (mean κ, 0.19), substantial among orthopaedic surgeons (mean κ, 0.77) and almost perfect among paediatric radiologists (mean κ, 0.86). Sensitivity of SCFE-diagnosis was high among radiologists and orthopaedic surgeons (88% to 100% for both specialties), but lower for paediatricians (24% to 76%). Specificity was high among radiologists and orthopaedic surgeons (72% to 84%), however, variable among paediatricians (56% to 80%). Accuracy of a SCFE-diagnosis was highest in radiologists (84% to 92%), followed by orthopaedic surgeons (80% to 88%) and paediatricians (48% to 78%). CONCLUSION: SCFE can be detected on radiographs by different medical specialties. Intra- and interobserver agreement, specificity, sensitivity and accuracy for radiographic SCFE-diagnosis amongst paediatric radiologists and orthopaedic surgeons are better than that of general paediatricians. LEVEL OF EVIDENCE: II.

Correction: Hypervirulent Mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant C57BL/6 mice.

[This corrects the article DOI: 10.1371/journal.pone.0173715.].

Hypervirulent Mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant C57BL/6 mice.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that in most cases induces irreversible necrosis of lung tissue as a result of excessive inflammatory reactions. The murine model of TB in resistant C57BL/6 mice infected with reference Mtb strains is widely used in TB studies; however, these mice do not show a necrotic pathology, which restricts their use in studies of irreversible tissue damage. Recently, we demonstrated that necrotic lung lesions could be induced in the C57BL/6 mice by highly virulent Mtb strains belonging to the modern Beijing sublineage. However, the pathogenic mechanisms leading to necrosis in this model were not elucidated. In this study, we investigated the dynamics of lung lesions in mice infected with highly virulent Beijing Mtb strain M299, compared with those infected with laboratory Mtb strain H37Rv. The data demonstrate that necrotic lung lesions in mice infected by the strain M299 were associated with enhanced recruitment of myeloid cells, especially neutrophils, and increased levels of proinflammatory cytokines, consistent with exacerbated inflammation. High levels of IFN-γ production contributed to the control of bacterial growth. Further progression to chronic disease was associated with a reduction in the levels of inflammatory mediators in the lungs, the accumulation of foamy macrophages and partial healing of the necrotic tissue by fibrosis. At a late stage of disease, degradation of foamy cells resulted in the liberation of accumulated lipids and persisting bacilli and further activation of inflammation, which promoted lung consolidation. Overall, our studies show that C57BL/6 mice infected with highly virulent Mtb strain may serve as a TB model reproducing an exacerbated inflammatory response in a resistant host to hypervirulent mycobacteria, leading to irreversible necrotic lung lesions.

Evaluating remediation of radionuclide contaminated forest near Iwaki, Japan, using radiometric methods.

Radiometric surveys have been conducted in support of a project investigating the potential of biofuel power generation coupled with remediation of forests contaminated with radionuclides following the Fukushima Daiichi accident. Surveys conducted in 2013 and 2014 were used to determine the distribution and time dependence of radionuclides in a cedar plantation and adjacent deciduous forestry subject to downslope radionuclide migration, and a test area where litter removal was conducted. The radiocaesium results confirmed enhanced deposition levels in the evergreen areas compared with adjacent areas of deciduous forestry, implying significant differences in depositional processes during the initial interception period in 2011. Surveys were conducted both with and without a collimator on both occasions, which modified the angular response of the detector to separate radiation signals from above and below the detector. The combined data have been used to define the influence of radionuclides in the forest canopy on dose rate at 1 m, indicating that, in evergreen areas, the activity retained within the canopy even by 2013 contributed less than 5% of ground level dose rate. The time dependent changes observed allow the effect of remediation by litter removal in reducing radionuclide inventories and dose rates to be appraised relative natural redistribution processes on adjacent control areas. A 15 × 45 m area of cedar forest was remediated in September 2013. The work involved five people in a total of 160 person hours. It incurred a total dose of 40-50 µSv, and generated 2.1 t of waste comprising forest litter and understory. Average dose rates were reduced from 0.31 µSv h-1 to 0.22 µSv h-1, with nuclide specific analyses indicating removal of 30 ± 3% of the local radiocaesium inventory. This compares with annual removal rates of 10-15% where radionuclide migration down-slope over ranges of 10-50 m could be observed within adjacent areas. Local increases were also observed in areas identified as sinks. The results confirm the utility of time-series, collimated, radiometric survey methods to account for the distribution and changes in radionuclide inventory within contaminated forests. The data on litter removal imply that significant activity transfer from canopy to soil had taken place, and provide benchmark results against which such remediation actions can be appraised.

What causes aberrant salience in schizophrenia? A role for impaired short-term habituation and the GRIA1 (GluA1) AMPA receptor subunit.

The GRIA1 locus, encoding the GluA1 (also known as GluRA or GluR1) AMPA glutamate receptor subunit, shows genome-wide association to schizophrenia. As well as extending the evidence that glutamatergic abnormalities have a key role in the disorder, this finding draws attention to the behavioural phenotype of Gria1 knockout mice. These mice show deficits in short-term habituation. Importantly, under some conditions the attention being paid to a recently presented neutral stimulus can actually increase rather than decrease (sensitization). We propose that this mouse phenotype represents a cause of aberrant salience and, in turn, that aberrant salience (and the resulting positive symptoms) in schizophrenia may arise, at least in part, from a glutamatergic genetic predisposition and a deficit in short-term habituation. This proposal links an established risk gene with a psychological process central to psychosis and is supported by findings of comparable deficits in short-term habituation in mice lacking the NMDAR receptor subunit Grin2a (which also shows association to schizophrenia). As aberrant salience is primarily a dopaminergic phenomenon, the model supports the view that the dopaminergic abnormalities can be downstream of a glutamatergic aetiology. Finally, we suggest that, as illustrated here, the real value of genetically modified mice is not as 'models of schizophrenia' but as experimental tools that can link genomic discoveries with psychological processes and help elucidate the underlying neural mechanisms.

Demonstration of lightweight gamma spectrometry systems in urban environments.

Urban areas present highly complex radiation environments; with small scale features resulting from different construction materials, topographic effects and potential anthropogenic inputs from past industrial activity or other sources. Mapping of the radiation fields in urban areas allows a detailed assessment of exposure pathways for the people who live and work there, as well as locating discrete sources of activity that may warrant removal to mitigate dose to the general public. These areas also present access difficulties for radiometric mapping using vehicles or aircraft. A lightweight portable gamma spectrometry system has been used to survey sites in the vicinity of Glasgow to demonstrate the possibilities of radiometric mapping of urban areas, and to investigate the complex radiometric features such areas present. Variations in natural activity due to construction materials have been described, the presence of (137)Cs used to identify relatively undisturbed ground, and a previously unknown NORM feature identified. The effect of topographic enclosure on measurements of activity concentration has been quantified. The portable system is compared with the outputs that might be expected from larger vehicular or airborne systems. For large areas airborne surveys are the most cost effective approach, but provide limited spatial resolution, vehicular surveys can provide sparse exploratory data rapidly or detailed mapping of open areas where off-road access is possible. Backpack systems are ideally suited to detailed surveys of small areas, especially where vehicular access is difficult.

Evaluating airborne and ground based gamma spectrometry methods for detecting particulate radioactivity in the environment: a case study of Irish Sea beaches.

In several places, programmes are in place to locate and recover radioactive particles that have the potential to cause detrimental health effects in any member of the public who may encounter them. A model has been developed to evaluate the use of mobile gamma spectrometry systems within such programmes, with particular emphasis on large volume (16l) NaI(Tl) detectors mounted in low flying helicopters. This model uses a validated Monte Carlo code with assessment of local geochemistry and natural and anthropogenic background radiation concentrations and distributions. The results of the model, applied to the example of particles recovered from beaches in the vicinity of Sellafield, clearly show the ability of rapid airborne surveys conducted at 75 m ground clearance and 120 kph speeds to demonstrate the absence of sources greater than 5 MBq (137)Cs within large areas (10-20 km(2)h(-1)), and identify areas requiring further ground based investigation. Lowering ground clearance for airborne surveys to 15m whilst maintaining speeds covering 1-2 km(2) h(-1) can detect buried (137)Cs sources of 0.5MBq or greater activity. A survey design to detect 100 kBq (137)Cs sources at 10 cm depth has also been defined, requiring surveys at <15m ground clearance and <2 ms(-1) ground speed. The response of airborne systems to the Sellafield particles recovered to date has also been simulated, and the proportion of the existing radiocaesium background in the vicinity of the nuclear site has been established. Finally the rates of area coverage and sensitivities of both airborne and ground based approaches are compared, demonstrating the ability of airborne systems to increase the rate of particle recovery in a cost effective manner. The potential for equipment and methodological developments to improve performance are discussed.

Analgesics improve the gait of lame dairy cattle.

Pain associated with injuries of the hoof and surrounding tissues is an important cause of lameness. The objective was to detect the attributes of impaired gait that are associated with pain. In 3 separate experiments, lactating Holstein cows (n = 20; n = 21; n = 27) diagnosed with varying degrees of gait impairment were injected i.m. (Exp. 1 and 2) or i.v. (Exp. 3) with the analgesic ketoprofen at 0, 0.3, 1.5, or 3.0 mg/kg of BW. Gait was evaluated subjectively using a numerical rating system (NRS; varying from 1 to 5) and 6 specific gait attributes (back arch, tracking up, joint flexion, asymmetric steps, head bob, and reluctance to bear weight). Each experiment was divided into 3 phases each lasting 3 d: before treatment, after treatment, and during treatment with daily injections of ketoprofen. The NRS improved by 0.25 +/- 0.05 with the highest dose of ketoprofen. Although none of the specific gait attributes showed a consistent response to treatment, there was an interaction between dose and experiment for asymmetric steps and reluctance to bear weight; in Exp. 1, but not Exp. 2 and 3, cow steps were more symmetrical (improving by 7.16 +/- 1.02), and cows distributed their weight more evenly (improving by 5.84 +/- 1.13) at the highest doses of ketoprofen. These results indicated that the NRS was more sensitive than the specific gait attributes in assessing differences in gait associated with pain. The results showed that ketoprofen has only a modest effect on gait, indicating either that this drug has little effect on pain due to lameness or that much variation in NRS was due to factors other than pain.

The role of the GluR-A (GluR1) AMPA receptor subunit in learning and memory.

It is widely believed that synaptic plasticity may provide the neural mechanism that underlies certain kinds of learning and memory in the mammalian brain. The expression of long-term potentiation (LTP) in the hippocampus, an experimental model of synaptic plasticity, requires the GluR-A subunit of the AMPA subtype of glutamate receptor. Genetically modified mice lacking the GluR-A subunit show normal acquisition of the standard, fixed-location, hidden-platform watermaze task, a spatial reference memory task that requires the hippocampus. In contrast, these mice are dramatically impaired on hippocampus-dependent, spatial working memory tasks, in which the spatial response of the animal is dependent on information in short-term memory. Taken together, these results argue for two distinct and independent spatial information processing mechanisms: (i) a GluR-A-independent associative learning mechanism through which a particular spatial response is gradually or incrementally strengthened, and which presumably underlies the acquisition of the classic watermaze paradigm and (ii) a GluR-A-dependent, non-associative, short-term memory trace which determines performance on spatial working memory tasks. These results are discussed in terms of Wagner's SOP model (1981).

Age-dependent and -independent behavioral deficits in Tg2576 mice.

The Tg2576 mouse model of excessive cerebral beta-amyloid deposition is now more than a decade old, yet consensus as to its exact characteristics and utility as a model of Alzheimer's disease is still lacking. Four different cohorts of control and Tg2576 mice, aged approximately 3, 9, 13 and 21 months, were therefore subjected to a battery of tests, principally to assess cognitive and species-typical behaviors. A novel test, the paddling Y-maze, demonstrated an age-dependent deficit in 10 and 14, but not 3 month Tg2576 mice, also in aged (21 month) control mice. However, in many other cognitive tests few Tg2576-related deficits could be shown. This frequently seemed attributable to poor performance of control mice. Tests of species-typical behaviors showed that Tg2576 mice had a deficit in burrowing behavior at all ages. An age-independent deficit was also seen in nest construction, but only when mice were group-housed; most individually housed mice in either group made reasonable nests. Overall, the results suggested that these Tg2576 mice are not a simple, suitable or reliable model for routine screening of treatments for Alzheimer's disease. However, this model might perform better behaviorally on a different genetic background.

Supersmart mice: surprising or surprised? Theoretical comment on Singer, Boison, Möhler, Feldon, and Yee (2007).

The glycine transporter (GlyT1) regulates levels of the neurotransmitter glycine, a coagonist of the N-methyl-D-aspartate receptor (NMDAR), and as such may represent a novel site for developing cognition-enhancing drugs. Genetically modified mice with reduced levels of GlyT1 have been generated to test this hypothesis. P. Singer, D. Boison, H. Möhler, J. Feldon, and B. K. Yee now show, through a spontaneous exploration task, that mice in which GlyT1 has been deleted, specifically in neurons in the forebrain, demonstrate enhanced object recognition memory. Whereas both control and mutant mice show a preference for a novel object over a familiar object 2 min after the initial presentation of 1 of the objects, only the mutant mice show a preference for the novel object when tested after a 2-hr delay. The longer-lasting habituation displayed by the GlyT1 mice is consistent with a role for glycine/NMDAR-dependent synaptic plasticity in supporting a nonassociative, short-term memory trace of a recently experienced stimulus. This short-term habituation process may be independent of associative learning mechanisms and may be best described by A. R. Wagner's (1981) sometimes opponent process model.