Role of law enforcement response and microbial forensics in investigation of bioterrorism

The risk and threat of bioterrorism and biocrime have become a large concern and challenge for governments and society to enhance biosecurity. Law enforcement plays an important role in assessing and investigating activities involved in an event of bioterrorism or biocrime. Key to a successful biosecurity program is increased awareness and early detection of threats facilitated by an integrated network of responsibilities and capabilities from government, academic, private, and public assets. To support an investigation, microbial forensic sciences are employed to analyze and characterize forensic evidence with the goal of attribution or crime scene reconstruction. Two different molecular biology-based assays – real time polymerase chain reaction (PCR) and repetitive element PCR – are described and demonstrate how molecular biology tools may be utilized to aid in the investigative process. Technologies relied on by microbial forensic scientists need to be properly validated so that the methods used are understood and so that interpretation of results is carried out within the limitations of the assays. The three types of validation are preliminary, developmental, and internal. The first is necessary for rapid response when a threat is imminent or an attack has recently occurred. The latter two apply to implementation of routinely used procedures.     

Assessing the function of human UNC-93B in Toll-like receptor signaling and major histocompatibility complex II response

The high sequence identity observed between UNC-93B of mouse and human imply common evolutionary ancestors and a conserved function. A nonconservative point mutation in the mouse Unc93b1 gene has been associated with defective Toll-like receptor (TLR) signaling and impaired major histocompatibility complex (MHC) I and II restricted antigen responses. Like murine UNC-93B, the human homologue is predicted to form 12 transmembrane domains, and it localizes to the endoplasmic reticulum. In human beings its expression is highest in professional antigen-presenting cells such as dendritic cells and macrophages. Interestingly, UNC-93B itself is specifically induced by TLR3 signaling in monocyte-derived dendritic cells and macrophages. To study the effect of UNC-93B deficiency in TLR signaling and antigen-presentation in human beings, UNC-93B message was knocked down in monocyte-derived dendritic cells and a reduced TNFalpha production in response to TLR3 agonists was observed. In the same experiment, the achieved knockdown had no effect on an MHC II-dependent antigen response, suggesting that the reduced quantity of human UNC-93B was still capable of supporting class II antigen presentation or that UNC-93B is not required for class II antigen presentation in human antigen-presenting cells.     

IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys

BACKGROUND: Airway inflammation is a hallmark feature of asthma and a driver of airway hyperresponsiveness. IL-13 is a key inducer of airway inflammation in rodent models of respiratory disease, but a role for IL-13 has not been demonstrated in primates. OBJECTIVE: We sought to test the efficacy of a neutralizing antibody to human IL-13 in a cynomolgus monkey model of lung inflammation. METHODS: Using cynomolgus monkeys (Macaca fascicularis) that are sensitized to Ascaris suum through natural exposure, we developed a reproducible model of acute airway inflammation after segmental A suum antigen challenge. This model was used to test the in vivo efficacy of mAb13.2, a mouse mAb directed against human IL-13, and IMA-638, the humanized counterpart of mAb13.2. Bronchoalveolar lavage (BAL) cells and BAL fluid were collected before and after antigen challenge and assayed for cellular content by means of differential count. RESULTS: Total BAL cell count, eosinophil number, and neutrophil number were all reduced in animals treated with mAb13.2 or IMA-638 compared with values in control animals that were untreated, given saline, or treated with human IgG of irrelevant specificity. In addition, levels of eotaxin and RANTES in BAL fluid were reduced in anti-IL-13-treated animals compared with levels seen in control animals. CONCLUSION: These findings support a role for IL-13 in maintaining lung inflammation in response to allergen challenge in nonhuman primates. CLINICAL IMPLICATIONS: IL-13 neutralization with a specific antibody could be a useful therapeutic strategy for asthma.     

Reliability of cardiovascular reactivity to stress: internal consistency

Research on the reliability of cardiovascular reactivity has focused on temporal stability and intertask consistency with only modest results. The present study evaluated the internal consistency reliability of cardiovascular reactivity in three large samples of adolescents and young adults (N=326, 136, and 142). Impedance cardiographic and blood pressure measures were recorded at rest and during standard laboratory stress tasks (math, video game, cold pressor). The reliability of cardiovascular reactivity within tasks, as assessed by Cronbach's alpha coefficient of internal consistency, ranged from alpha=.83 to .96 for 4-min to 5-min math tasks, and alpha=.65 to .94 for 3-min video game and cold pressor tasks. Although highly reliable within tasks, cardiovascular reactivity was less reliable across tasks, even within a single testing session. Possible reasons for the discrepancy between internal consistency and intertask consistency are discussed.     

Factors associated with retaliatory attitudes among African American adolescents who have been assaulted

OBJECTIVES: (a) To describe attitudes regarding retaliation among adolescents who have been assaulted. (b) To examine assault/event characteristics, personal, parental, and environmental factors associated with the retaliatory attitudes of adolescents who have been assaulted. METHODS: African American youth aged 10-15 years presenting to two large urban hospitals with peer assault injury and a parent/caregiver completed interviews in their home after their emergency department visit. RESULTS: Multivariate analyses revealed that lower SES, older age, and adolescents' perceptions that their parents support fighting were related to endorsing retaliatory attitudes. Girls who were aggressive were more likely to endorse retaliatory attitudes. However, level of aggression did not impact boys' retaliatory attitudes. Affiliating with aggressive peers influenced the retaliatory attitudes of boys, but did not influence girls' retaliatory attitudes. Overall, youths' perceptions of their parents' attitudes toward fighting had the greatest impact on retaliatory attitudes. CONCLUSIONS: Adolescents' perceptions of their parents' attitudes toward fighting may be a factor in subsequent re-injury among youth. Violence prevention and intervention efforts need to involve components that assess parental attitudes and incorporate strategies to engage parents in violence prevention efforts. In addition, interventions for youth who have been assaulted may need to incorporate some gender-specific components in order to address the unique needs of girls and boys.     

The reliability of lymphoma diagnosis in small tissue samples is heavily influenced by lymphoma subtype

A specific pathologic diagnosis is important in malignant lymphoma because the diverse disease subtypes require tailored approaches to clinical management. Reliance on small samples obtained with cutting needles has been advocated as a less invasive alternative to using larger, excised samples. Although published studies have demonstrated the safety and apparent sufficiency of this approach in informing clinical care, none have systematically determined the accuracy of pathologic lymphoma subtyping based on very small samples. We used a tissue microarray representing 67 cases of malignant lymphoma and 17 samples of nonneoplastic lymphoid tissue to model lymphoma diagnosis in small samples. Overall, 73.8% of the cases were diagnosed with a level of confidence deemed sufficient for directing clinical management; 85.9% of these diagnoses were accurate. Small cell lymphomas with highly distinctive immunophenotypes, including small lymphocytic, mantle cell, and T-lymphoblastic lymphoma, were recognized most consistently and accurately in the small samples. In contrast, follicular lymphoma and marginal zone lymphoma were especially difficult. Our results indicate that the reliability of lymphoma diagnoses based on small samples is heavily influenced by lymphoma subtype.