An evaluation of sampling methods used to produce insect growth models for postmortem interval estimation.

Many authors produced carrion insect development data for predicting the age of an insect from a corpse. Under some circumstances, this age value is a minimum postmortem interval. There are no standard protocols for such experiments, and the literature includes a variety of sampling methods. To our knowledge, there has been no investigation of how the choice of sampling method can be expected to influence the performance of the resulting predictive model. We calculated 95 % inverse prediction confidence limits for growth curves of the forensically important carrion flies Chrysomya megacephala and Sarconesia chlorogaster (Calliphoridae) at a constant temperature. Confidence limits constructed on data for entire age cohorts were considered to be the most realistic and were used to judge the effect of various subsampling schemes from the literature. Random subsamples yielded predictive models very similar to those of the complete data. Because taking genuinely random subsamples would require a great deal of effort, we imagine that it would be worthwhile only if the larval measurement technique were especially slow and/or expensive. However, although some authors claimed to use random samples, their published methods suggest otherwise. Subsampling the largest larvae produced a predictive model that performed poorly, with confidence intervals about an estimate of age being unjustifiably narrow and unlikely to contain the true age. We believe these results indicate that most forensic insect development studies should involve the measurement of entire age cohorts rather than subsamples of one or more cohorts.

Modulation of gut-specific mechanisms by chronic δ(9)-tetrahydrocannabinol administration in male rhesus macaques infected with simian immunodeficiency virus: a systems biology analysis.

Our studies have demonstrated that chronic Δ(9)-tetrahydrocannabinol (THC) administration results in a generalized attenuation of viral load and tissue inflammation in simian immunodeficiency virus (SIV)-infected male rhesus macaques. Gut-associated lymphoid tissue is an important site for HIV replication and inflammation that can impact disease progression. We used a systems approach to examine the duodenal immune environment in 4- to 6-year-old male rhesus monkeys inoculated intravenously with SIVMAC251 after 17 months of chronic THC administration (0.18-0.32 mg/kg, intramuscularly, twice daily). Duodenal tissue samples excised from chronic THC- (N=4) and vehicle (VEH)-treated (N=4) subjects at ∼5 months postinoculation showed lower viral load, increased duodenal integrin beta 7(+)(ß7) CD4(+) and CD8(+) central memory T cells, and a significant preferential increase in Th2 cytokine expression. Gene array analysis identified six genes that were differentially expressed in intestinal samples of the THC/SIV animals when compared to those differentially expressed between VEH/SIV and uninfected controls. These genes were identified as having significant participation in (1) apoptosis, (2) cell survival, proliferation, and morphogenesis, and (3) energy and substrate metabolic processes. Additional analysis comparing the duodenal gene expression in THC/SIV vs. VEH/SIV animals identified 93 differentially expressed genes that participate in processes involved in muscle contraction, protein folding, cytoskeleton remodeling, cell adhesion, and cell signaling. Immunohistochemical staining showed attenuated apoptosis in epithelial crypt cells of THC/SIV subjects. Our results indicate that chronic THC administration modulated duodenal T cell populations, favored a pro-Th2 cytokine balance, and decreased intestinal apoptosis. These findings reveal novel mechanisms that may potentially contribute to cannabinoid-mediated disease modulation.

Social engagement and health in younger, older, and oldest-old adults in the Louisiana Healthy Aging Study.

Social support has been shown to influence health outcomes in later life. In this study, we focus on social engagement as an umbrella construct that covers select social behaviors in a life span sample that included oldest-old adults, a segment of the adult population for whom very little data currently exist. We examined relationships among social engagement, positive health behaviors, and physical health to provide new evidence that addresses gaps in the extant literature concerning social engagement and healthy aging in very old adults. Participants were younger (21-59 years), older (60-89 years), and oldest-old (90-97 years) adults (N = 364) in the Louisiana Healthy Aging Study (LHAS). Linear regression analyses indicated that age, gender, and hours spent outside of the house were significantly associated with self-reported health. The number of clubs and hours outside of home were more important factors in the analyses of objective health status than positive health behaviors, after considering age group and education level. These data strongly suggest that social engagement remains an important determinant of physical health into very late adulthood. The discussion focuses on practical applications of these results including social support interventions to maintain or improve late-life health.

Cannabinoid administration attenuates the progression of simian immunodeficiency virus.

Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ(9)-THC use may impact HIV disease progression. We examined the impact of chronic Δ(9)-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIV(mac251); 100 TCID(50)/ml, iv), on immune and metabolic indicators of disease during the initial 6 month asymptomatic phase of infection in rhesus macaques. SIV(mac251) inoculation resulted in measurable viral load, decreased lymphocyte CD4(+)/CD8(+) ratio, and increased CD8(+) proliferation. Δ(9)-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ(9)-THC administration decreased early mortality from SIV infection (p = 0.039), and this was associated with attenuation of plasma and CSF viral load and retention of body mass (p = NS). In vitro, Δ(9)-THC (10 µm) decreased SIV (10 TCID(50)) viral replication in MT4-R5 cells. These results indicate that chronic Δ(9)-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression. We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for Δ(9)-THC-mediated modulation of disease progression that warrant further study.

Acute alcohol intoxication impairs the hematopoietic precursor cell response to pneumococcal pneumonia.

BACKGROUND: Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated. METHODS: Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae. RESULTS: Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection. CONCLUSIONS: Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.