[Etiological and epidemiological characteristics of Vibrio cholerae in Beijing, 2015-2021].

Objective: To analyze the etiological and epidemiological characteristics of Vibrio cholerae in Beijing during 2015-2021 and provide evidence for the prevention and control of cholera. Methods: The V. cholerae strains isolated in Beijing during 2015-2021 were analyzed by serotyping and virulence genes detection. Pulsed field gel electrophoresis (PFGE) was performed for the molecular typing of the strains. Based on the collected epidemiological and clinical data of cholera cases,the epidemiological characteristics of cholera were analyzed by descriptive epidemiology method. Results: A total of 76 Vibrio cholerae O1 strains were isolated in Beijing during 2015-2021, including 61 strains from human, 10 strains from environment and 5 strains from seafood. The 76 strains consisted of 68 Ogawa strains and 8 Inaba strains. Six Ogawa strains isolated from sporadic cases carried ctxAB. After NotⅠ digestion, 76 strains were divided into 33 PFGE patterns. From 2015 to 2021, a total of 38 cholera epidemics were reported in Beijing, most of them were sporadic ones, accounting for 92.11% (35/38). A total of 45 cases were reported, and the cases occurred during June-September accounted for 97.78% (44/45). Cholera cases occurred in 9 districts of Beijing, and the cases reported in Chaoyang district accounted for 42.22% (19/45) and in Changping district accounted for 31.11% (14/45). The age of the cholera cases ranged from 19 to 63 years. Except for one case with unknown clinical symptoms, 44 cases had diarrhea symptoms with 84.09% (37/44) of the cases reporting diarrhea (3-9 times/day), followed by yellow watery stool (95.45%, 42/44), abdominal pain (68.18%, 30/44), nausea and vomiting (40.91%, 18/44) and fever (36.36%, 16/44). Conclusion: Vibrio cholerae strains isolated in Beijing during 2015-2021 were mainly O1 serotype Ogawa,most of which were non-toxigenic. The PFGE of the strains varied. Cholera epidemics occurred in 9 districts of Beijing, but most were sporadic ones with incidence peak during June-September.

[Application of two RT-PCR methods for detection of norovirus in market-sold oysters and norovirus genetic characteristic analysis, a survey conducted in Beijing].

Objective: To evaluate the application of real-time RT-PCR and semi-nested RT-PCR in the detection of norovirus in oysters and analyzing the genetic characteristics of the isolates. Methods: Real-time fluorescent RT-PCR and semi-nested RT-PCR were used to detect norovirus GⅠ/GⅡ in fresh oysters collected from the markets in Beijing from November 2014 to October 2015. The detection rate of the parallel test was also analyzed. In addition, the reliability of semi-nested RT-PCR was evaluated by agreement rate and consistency test (Kappa value). The positive products of norovirus GⅠ/GⅡ capsid protein region gene by semi-nested RT-PCR were sequenced. Software BioEdit 7.0.9.0 was used for sequence alignment, and software Mega 6.0 was used to construct the evolutionary tree. Results: In 72 samples, the detection rate of norovirus was 31.94% (23/72) by real-time RT-PCR, 38.89% (28/72) by semi-nested RT-PCR and 48.61% (35/72) by parallel test. The coincidence rate of the two methods was 73.61%, a moderate degree (Kappa value =0.43). A total of 13 norovirus strains were successfully sequenced, and 11 strains (7 GⅡ.17 strains, 2 GⅡ. 4 Sydney_ 2012 strains, 1 GⅡ. 1 strain and 1 GⅡ. 21 strain) were obtained from norovirus positive samples by two RT-PCR methods, two strains (1 GⅡ. 17 strain and 1 GⅡ. 3 strain) were obtained from real-time RT-PCR negative samples which were positive for norovirus by semi-nested RT-PCR. The similarity between these strains and reference strains from diarrhea patients, environmental sewage, and shellfish products were 84.4% - 100.0%. Conclusions: The parallel test of norovirus in oysters by two RT-PCR methods can improve the detection rate and detect more genotypes. Norovirus strains in oysters were highly homologous with reference strains from diarrheal patients, environmental sewage, and shellfish products. Therefore, surveillance, prevention and control for norovirus should be carried out in people who have frequent contacts with oysters and related environments.

[Investigation on Norovirus prevalence in catering companies and train station in Beijing during non-epidemic season in 2019].

Objective: To study the prevalence of Norovirus infection among kitchen workers in Beijing, and the contamination status of Norovirus in catering companies and train station. Methods: A cross-sectional survey was conducted to collect anal swab specimens and environmental specimens from catering companies in 16 districts of Beijing and in 3 big train stations. Norovirus nucleic acid was detected by fluorescence quantitative PCR. The contamination status of Norovirus in the environment and the asymptomatic infection status of kitchen workers was analyzed in this study. Results: A total of 650 catering companies were investigated. 1 302 anal swabs or stool specimens and 2 600 environmental swabs were collected and tested. Among the 644 catering companies out of train stations, 1 290 anal swabs or stool specimens and 2 576 environmental swabs were collected and tested. The asymptomatic infection rate of Norovirus was 0.85% (11/1 290) among kitchen workers of the catering companies out of the train stations, while the positive rate of norovirus contamination in the environment was 0.04% (1/2 576). Norovirus was not detected in the specimens collected from the kitchen workers and the environment of the catering companies in train stations. Conclusion: During the non-epidemic season of Norovirus in 2019, the infection rate of Norovirus among kitchen workers in Beijing is low, and the environment is contaminated by Norovirus.

Differential Regional Responses in Soluble Monomeric Alpha Synuclein Abundance Following Traumatic Brain Injury.

Alpha synuclein (α-synuclein) is a neuronal protein found predominately in presynaptic terminals. While the pathological effect of α-synuclein aggregates has been a topic of intense study in several neurodegenerative conditions, less attention has been placed on changes in monomeric α-synuclein and related physiological consequences on neuronal function. A growing body of evidence supports an important physiological role of α-synuclein in neurotransmission. In the context of traumatic brain injury (TBI), we hypothesized that the regional abundance of soluble monomeric α-synuclein is altered over a chronic time period post-injury. To this end, we evaluated α-synuclein in the cortex, hippocampus, and striatum of adult rats at 6 h, 1 day, 1, 2, 4, and 8 weeks after controlled cortical impact (CCI) injury. Western blot analysis demonstrated decreased levels of monomer α-synuclein protein in the ipsilateral hippocampus at 6 h, 1 day, 1, 2, and 8 weeks, as well as in the ipsilateral cortex at 1 and 2 weeks and in the ipsilateral striatum at 6 h after CCI compared with sham animals. Immunohistochemical analysis revealed lower α-synuclein and a modest reduction in synaptophysin staining in the ipsilateral hippocampus at 1 week after CCI compared with sham animals, with no evidence of intracellular or extracellular α-synuclein aggregates. Collectively, these findings demonstrate that monomeric α-synuclein protein abundance in the hippocampus is reduced over an extensive (acute-to-chronic) post-injury interval. This deficit may contribute to the chronically impaired neurotransmission known to occur after TBI.

[Progress on genotyping of norovirus].

Norovirus are now recognized as one of the main pathogens causing acute gastroenteritis in both developed and developing countries. However, norovirus are easily mutated and recombined, and have many genotypes. In early studies, norovirus were amplified and identified by amino acid sequence of VP1 region. It was found that norovirus were easily mutated and recombined in or near the overlapping regions of polymerase and capsid. A two regions genotyping method was positively proposed internationally. Depending on the 2 times standard deviation standard method for two regions identification, norovirus polymerase regions can be divided into 10 gene groups and 76 genotypes including 2 tentative gene groups and 16 tentative genotypes. The VP1 region can be divided into 12 gene groups and 53 genotypes including 2 tentative gene groups and 5 tentative genotypes. However, the tentative gene groups and genotypes need to be further identified and reclassified. In this article, characteristics of norovirus sequences, principles of different genotyping methods, methods of sequence amplification, on-line genotyping tools and the latest studies in norovirus genotypes are reviewed and introduced.

[Analysis on influencing factors for acute gastroenteritis outbreaks caused by norovirus in Beijing, 2014-2018].

Objective: To analyze the influencing factors of acute gastroenteritis outbreaks caused by norovirus in Beijing from 2014 to 2018. Methods: Data of acute gastroenteritis events caused by norovirus in Beijing from April 2014 to March 2018 were collected. Unconditional logistic regression model was conducted to identify the risk factors of the outbreaks. Results: A total of 765 acute gastroenteritis epidemics caused by norovirus were reported in Beijing, in which 85.88% (657/765) were cluster events and 14.12% (108/765) were outbreaks. Among the outbreaks, 70.37% (76/108) were reported in 2017; 84.26% (91/108) were reported in winter and spring; 88.89% (96/108) were reported in kindergartens, primary or secondary schools; 81.48% (88/108) were through person-to-person transmission; 93.52% (101/108) were caused by norovirus GⅡ infection. The risk of outbreaks in suburban and out suburb area were 1.84 times (95%CI: 1.13-3.02) and 3.78 times (95%CI: 1.62-8.82) as high as that in urban area, respectively. The risks of outbreaks in primary, secondary schools and other institutions were 6.26 times (95%CI: 3.53-11.10), 14.98 times (95%CI: 6.23-36.01) and 8.71 times (95%CI: 3.07-24.71) as high as that in kindergartens, respectively. The risk of outbreak in which patients having lower hospital visiting rate than the median rate of all events was 2.29 times than that in the context of having higher hospital visiting rate (95%CI:1.42-3.68). The risk of foodborne outbreak was 14.55 times as high as that transmitted through person-to-person (95%CI: 3.15-67.07). Conclusion: Measures such as strengthening the prevention and control of norovirus outbreaks in suburbs, primary schools, secondary schools and other institutions, promoting patients to visit the hospital actively, improving the management of foodborne events and kitchen workers should be taken to reduce the incidence of acute gastroenteritis outbreaks caused by norovirus.

[Systematic review on the characteristics of acute gastroenteritis outbreaks caused by sapovirus].

Objective: To understand the epidemiological and etiological characteristics of outbreaks on acute gastroenteritis caused by sapovirus (SaV) worldwide. Methods: Literature about the outbreaks on acute gastroenteritis caused by SaV were retrieved from the databases including WanFang, CNKI, PubMed and Web of Science after evaluation. Time, geography, setting and population distributions of outbreaks, transmission mode, SaV genotype and clinical characteristics of the patients were analyzed. Results: A total of 34 papers about SaV were included, involving 146 outbreaks occurred between October 1976 and April 2016. In these papers, 138 outbreaks were reported on the related months. All these outbreaks occurred in northern hemisphere. SaV outbreaks occurred all year around, but mainly in cold season, the incidence was highest in December (25 outbreaks) and lowest in in August (2 outbreaks). Most outbreaks were reported by Japan, followed by Canada, the United States of America and the Netherlands. There were 141 outbreaks for which the occurring settings were reported, child-care settings were most commonly reported setting (48/141, 34.04%), followed by long-term care facility (41/141, 29.08%) and hospital (16/141, 11.35%). Clinical symptoms of 1 704 cases in 31 outbreaks were reported, with the most common symptom was diarrhea (1 331/1 704, 78.12%), followed by nausea (829/1 198, 69.20%), abdominal pain (840/1 328, 63.25%), vomiting (824/1 704, 48.36%) and fever (529/1 531, 34.53%). Genotypes of SaV were determined for 119 outbreaks. GⅠ(51/119, 42.86%) and GⅣ (45/119, 37.82%) were predominant. The outbreaks of GⅣ SaV increased suddenly in 2007, and the outbreaks of GⅠ SaV mainly occurred in 2008 and during 2011-2013. Conclusions: SaV outbreaks were reported mainly by developed countries, with most outbreaks occurred in cold season, in child-care settings and long term care facility. GⅠ and GⅣ were the most common genotypes of SaV. Prevention and control of SaV outbreak in China seemed relatively weak, and it is necessary to conduct related training and to strengthen the SaV outbreak surveillance in areas where service is in need.

[Application of whole genome sequencing technology in the epidemiology of tuberculosis].

Objective: To delineate the application of whole genome sequencing technology in the epidemiology of tuberculosis. Methods: From 2009 to 2012, nine Mycobacterium tuberculosis that sharing identical variable number of tandem repeats genotype (VNTR) patterns were reported from two TB cases designated hospitals. Both whole-genome sequencing analysis (WGS) and epidemiologic investigations were performed to describe the transmission patterns of these Mycobacterium tuberculosis. Results: By WGS analysis, two genomic clusters including 7 and 2 Mycobacterium tuberculosis were noticed, respectively. The cluster of 2 cases possessed more than 15 single nucleotide polymorphisms (SNPs) when compared to the cluster of 7 cases and suggesting that the transmission route was independent. The transmission chain based on the SNPs difference showed the process of the propagation direction and the accumulation of drug resistance mutations in each cluster. Conclusion: Using a WGS-based genomic epidemiologic approach, we were able to reconstruct the tuberculosis transmission network, tracing the putative source of the transmission and determining the transmission direction or the missing links.

Chemotherapeutic effect of Zerumbone on melanoma cells through mitochondria-mediated pathways.

BACKGROUND: Zerumbone (ZER) is a phytochemical that appears to regulate cell proliferation and apoptosis. It has been reported to have an anti-tumour effect in various malignant cells; however, the effect and the mechanism of ZER on melanoma cells needs to be clarified. AIM: To explore whether ZER has an effect on human melanoma cells and to identify the mechanisms involved. METHODS: We determined the chemotherapeutic action of ZER on the human malignant melanoma (MM) A375 cell line by CCK-8 immunohistochemistry, Hoechst 33342 staining and flow cytometry analysis. We also investigated the signalling pathways by which ZER induces apoptosis in A375 cells, using western blotting, reverse transcription PCR and caspase-3 activity analysis. RESULTS: ZER induced significant cytotoxic action in A375 cells. Hoechst 33342 staining and flow cytometry apoptosis analysis further demonstrated that ZER induced apoptosis in A375 cells. Treatment with ZER downregulated Bcl-2 gene and protein levels, upregulated Bax and Cytochrome c gene and protein levels, and activated Caspase-3. CONCLUSIONS: ZER might have a chemotherapeutic effect on human melanoma cells through mitochondria-mediated pathways.

Associations between matrix metalloproteinase gene polymorphisms and the development of cerebral infarction.

The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke.

The clinical significance of CA19-9 in ovarian mature cystic teratoma.

OBJECTIVE: To evaluate the clinical significance of CA19-9 in patients with ovarian mature cystic teratoma (MCT). MATERIALS AND METHODS: A retrospective study was performed on 65 patients with pathologically-confirmed MCT and 80 patients with benign epithelial ovarian tumors. Serum tumor markers for all patients and tissue CA19-9 for MCTs were measured. The relationships between clinical characteris- tics of MCTs and CA19-9, as well as the correlation between serum and tissue level of CA19-9 in MCTs, were evaluated. RESULTS: The mean serum level of CA19-9 in MCTs was significantly higher than that in benign ovarian epithelial tumors (49.9 ± 73.4 IU/ml vs. 17.08 ± 24.8 IU/ml). CA19-9 was the only tumor marker with a mean serum level above the cut-off value and the elevation rate was 30.76% in MCTs. The positive tissue expression rate of CA19-9 in MCT patients were 50.9% and were higher than that of preoperative serum levels (50.9% vs. 32.7%). CONCLUSION: Serum CA19-9 has the highest positivity rate among other tumor markers in MCT. Elevated serum CA19-9 is not an uncommon finding MCT and could be used as a marker in the differential diagnosis of MCT in patients with pelvic mass.

CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke.

The objective of this study was to explore the relationship between CYP4F2 gene polymorphism and ischemic stroke (IS) in the Han Chinese population. We performed a case-control study to genotype four single nucleotide polymorphisms (SNPs) (rs2108622, rs3093100, rs3093105, rs3093135) in the CYF4F2 gene. The genotype and haplotype distributions were compared between the case and control groups. We found that the GG genotype of rs2108622 in the CYP4F2 gene was associated with risk of IS (P = 0.023). Haplotype analysis indicated that the GGGT haplotype comprising rs2108622-rs3093100-rs3093105-rs3093135 was associated with IS, which suggests that the GGGT haplotype may be a risk factor for IS (P = 0.012). CYP4F2 gene polymorphism might increase the risk of IS in the Chinese population.

Association of the ApoE gene polymorphism and dietary factors with cerebral infarction and circulating lipid concentrations.

The aim of this study was to explore the relationship between the ApoE gene polymorphism and dietary factors with stroke and circulating lipid levels in the Chinese population. We selected 580 patients with stroke and 580 age- and gender-matched healthy controls, and examined their ApoE polymorphism genotype using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We also analyzed the relationship between the ApoE gene polymorphism and dietary factors as well as plasma lipid concentrations in this cohort. We detected six ApoE genotypes in the study populations, and determined that the E4 allele was positively associated with cerebral infarction (CI), whereas allele E2 was negatively associated with total cholesterol (TC) and low-density lipoprotein-cholesterol levels. The dietary habits of the subjects with descending order of average total TC and triglyceride levels were: subjects addicted to oily food > subjects addicted to sweets > subjects addicted to smoking > subjects addicted to alcohol > subjects following a vegetarian diet (P < 0.05). Our results demonstrated that the ApoE gene polymorphism was associated with a risk for CI in a Chinese population.

Serum and tissue level of YKL-40 in endometrial cancer.

OBJECTIVE: Serum YKL-40 level is elevated in patients with several malignancies. This study was designed to assess the correlation between serum YKL-40 and the corresponding tissue expression in endometrial cancer (EC). MATERIALS AND METHODS: Preoperative serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA) from 41 patients with EC, 27 patients with uterine myoma, and 30 healthy women. YKL-40 protein expression in tissue was determined by immunohistochemistry for patients with EC and patients with uterine myoma. RESULTS: Median preoperative serum YKL-40 level was 157.2 microg/l (range 76.0 - 301.2) in EC compared with 86.6 microg/l (range 69.3 - 191.1) in uterine myoma, and 86.2 microg/l (range 52.1 - 201.1) in healthy women (p < 0.05). Of 41 patients with EC, 26 patients with elevated serum YKL-40 level statistically differed from the remaining 15 patients with normal serum YKL-40 level with respect to FIGO Stage, tumor grade, washing cytology, and serum CA125 (p < 0.05). In multivariate analysis, elevated serum YKL-40 significantly correlated with FIGO stage (p < 0.05) and tumor grade (p < 0.01). The percentage of positive YKL-40 tissue staining was higher in EC patients (34.1%, 14/41) than in uterine myoma patients (11.1%, 3/27) (p < 0.05) and was lower than that of elevated serum levels in EC (26/41, 63.4%) (p < 0.05). CONCLUSIONS: The elevated preoperative serum YKL-40 is related to stage and histologic grade of EC. The discordance between serum and tissue level of YKL-40 in EC indicates intrauterine tumor may not be the only source of serum YKL-40.

Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer.

The aim of this study was to study the expression of Syk gene and methylation in its promoter region in the lung cancer and to investigate the relationship between silencing of the Syk gene and DNA methylation of the Syk promoter region in lung cancer cell lines. Real-time PCR and immunohistochemistry were used to examine the Syk expression in specimens from 3 lung cancer cell lines and 16 lung cancer patients (tumor tissues and adjacent normal tissues). MSP was used to analyze the methylation status of the Syk promoter region. We also investigated the role of restoring Syk expression by using a DNA methyltransferase inhibitor, 5-aza-CdR, in suppressing invasion of lung cancer cell lines. No expression of the Syk gene was detected in the 3 lung cancer cell lines. In the 16 lung cancer patient samples, Syk expression was significantly lower in the tumor tissues than that in their adjacent normal tissues (P<0.05). Consistently, immunohistochemistry analysis of Syk protein expression showed that in the lung cancer tissues Syk protein expression was also significantly lower than that in their adjacent normal tissues. In the two lung cancer cell lines (NL9980, YTMLC-9) that lack the endogenous Syk expression, 4uM demethylation agent 5-aza-CdR treatment was able to reactivate the Syk gene expression, but not NCI-H446. In conclusion, hypermethylation leads to silencing of the Syk gene in human lung carcinoma cell lines. Methylation of the Syk promoter and loss of Syk expression in lung cancer cell lines are independent biomarkers. Syk may be a potential tumor suppressor in human lung cancer.

Tyrosine hydroxylase, but not dopamine beta-hydroxylase, is increased in rat frontal cortex after traumatic brain injury.

Chronic frontal lobe functional deficits after traumatic brain injury (TBI) may be associated with altered catecholamine systems in the frontal cortex. To test this, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) levels were examined by immunohistochemistry and Western blot at 1, 7, 14, and 28 days after TBI or sham surgery. No alterations in DBH levels were observed by Western blot at any time point examined, but there was a significant increase in TH expression 28 days after TBI (optical density 334 +/- 68% or 3.3-fold, ipsilateral and 218 +/- 39% or 2.2-fold, contralateral) relative to the sham controls. The increase in TH may reflect a compensatory response of dopaminergic neurons to upregulate their synthesizing capacity and increase the efficiency of dopamine neurotransmission chronically after TBI.

Adenovirus-mediated transfer and expression of beta-gal in injured hippocampus after traumatic brain injury in mice.

In models of focal cerebral ischemia, adenoviral gene transfer is often attenuated or delayed versus naive. After controlled cortical impact (CCI)-induced traumatic brain injury in mice, CA1 and CA3 hippocampus exhibit delayed neuronal death by 3 days, with subsequent near complete loss of hippocampus by 21 days. We hypothesized that adenoviral-mediated expression of the reporter gene beta-Galactosidase (beta-Gal) in hippocampus would be attenuated after CCI in mice. C57BL6 mice (n = 16) were subjected to either CCI to left parietal cortex or sham (burr hole). Adenovirus carrying the beta-Gal gene (AdlacZ; 1 x 10(9) plaque-forming units [pfu]/mL) was then injected into left dorsal hippocampus. At 24 or 72 h, beta-Gal expression was quantified (mU/mg protein). Separate mice (n = 10) were used to study beta-Gal spatial distribution in brain sections. Beta-Gal expression in left hippocampus was similar in shams at 24 h (48.4 +/- 4.1) versus 72 h (68.8 +/- 8.8, not significant). CCI did not reduce beta-Gal expression in left hippocampus (68.8 +/- 8.8 versus 88.1 +/- 7.0 at 72 h, sham versus CCI, not significant). In contrast, CCI reduced beta-Gal expression in right (contralateral) hippocampus versus sham (p < 0.05 at both 24 and 72 h). Beta-Gal was seen in many cell types in ipsilateral hippocampus, including CA3 neurons. Despite eventual loss of ipsilateral hippocampus, adenovirus-mediated gene transfer was surprisingly robust early after CCI providing an opportunity to test novel genes targeting delayed hippocampal neuronal death.

Chronic methylphenidate treatment enhances water maze performance following traumatic brain injury in rats.

Methylphenidate (MPH), a central nervous system stimulant with dopaminergic activity, facilitates neurobehavioral outcome following cortical suction ablation injury, but its potential efficacy following experimental traumatic brain injury (TBI) is unknown. Thus, beginning 24 h after controlled cortical impact injury or sham surgery, male Sprague-Dawley rats were injected (i.p.) once daily for 18 days with either MPH (5 mg/kg) or saline vehicle (VEH) and motor function assessed on post-operative days 1-4, followed by Morris water maze training to find a hidden platform on days 14-18. The MPH treatment regimen was ineffective in accelerating beam-balance or beam-walk recovery, but did significantly decrease swim latencies when compared to VEH-treated controls. The results are consistent with published studies showing improved outcome with MPH therapy. Furthermore, this positive finding with delayed treatment suggests that strategies that enhance catecholamine neurotransmission during the chronic post injury phase may be a useful adjunct in ameliorating some of the neurobehavioral sequelae following TBI in humans.