The Src kinase Lyn is a negative regulator of mast cell proliferation

Previous investigators have reported that deletion of the protein tyrosine kinase Lyn alters mast cell (MC) signaling responses but does not affect or reduces the cytokine-mediated proliferation of mouse bone marrow-derived MC (BMMC) precursors and of mature MC. We observed that Lyn-deficient mice have more peritoneal MC than wild-type (WT) mice. Studies to explore this unexpected result showed that Lyn(-/-) BM cells expand faster than WT cells in response to interleukin (IL)-3 and stem-cell factor over the 4-5 weeks required to produce a >95% pure population of granular, receptor with high affinity for immunoglobulin E-positive BMMC. Furthermore, differentiated Lyn(-/-) BMMC continue to proliferate more rapidly than WT BMMC and undergo less apoptosis in response to cytokine withdrawal. Additionally, Lyn(-/-) BMMC support greater IL-3-mediated phosphorylation of the prosurvival kinase, Akt, and the proliferative kinase, extracellular-regulated kinase 1/2. These results identify Lyn as a negative regulator of murine MC survival and proliferation.     

Genetic diversity of the outer surface protein C gene of southern Borrelia isolates and its possible epidemiological,clinical, and pathogenetic implications

The ospC genes of 20 southern Borrelia strains were sequenced. The strains consisted of B. burgdorferi sensu stricto, B. andersonii, B. bissettii, one undescribed genospecies, MI-8, and one probably new Borrelia species, TXW-1. A high degree of similarity exists between B. burgdorferi sensu stricto and B. bissettii and between B. bissettii and B. andersonii. Lateral transfers of the ospC gene probably occurred between B. burgdorferi sensu stricto and B. bissettii and between B. bissettii and B. andersonii. Internal gene recombination appears to occur among them. The highest degree of genetic diversity among them was observed in the two variable domains (V1 and V2), semivariable domain (SV), and the species-specific epitopes (between amino acids 28 and 31). Differences in ospC sequences among southern strains reflect diversity at the strain and genospecies levels. MI-8, which was recognized as an undescribed genospecies in our previous reports, remains distinguishable in our current analysis of ospC genes and is distinct from B. burgdorferi sensu stricto. Interestingly, another undescribed southern isolate, TXW-1, was not amplified under various PCR conditions. Compared to European B. burgdorferi sensu stricto strains, American B. burgdorferi sensu stricto strains show greater genetic heterogeneity. Southern B. burgdorferi sensu stricto, B. andersonii, and B. bissettii isolates were intermixed with each other in the phylogenetic trees. In the derived trees in our work, at least one southeastern strain of B. burgdorferi, MI-2, most closely aligns with a so-called invasive cluster that possesses many proven human-invasive strains. Transmission experiments show that MI-2 and the strains in this group of southern spirochetes are able to infect mice and hamsters and that the typical vector of Lyme disease, Ixodes scapularis, can acquire the spirochetes from infected mammals. Currently, strain MI-2 appears to be the only southern isolate among the 20 we analyzed that clusters with an OspC invasive group and thus might be invasive for humans.     

Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury.

Tumor necrosis factor (TNF) and interleukin-(IL)-18 are important mediators of neuroinflammation after closed head injury (CHI). Both mediators have been previously found to be significantly elevated in the intracranial compartment after brain injury, both in patients as well as in experimental model systems. However, the interrelation and regulation of these crucial cytokines within the injured brain has not yet been investigated. The present study was designed to assess a potential regulation of intracranial IL-18 levels by TNF based on a clinical study in head-injured patients and an experimental model in mice. In the first part, we investigated the interrelationship between the daily TNF and IL-18 cerebrospinal fluid levels in 10 patients with severe CHI for up to 14 days after trauma. In the second part of the study, the potential TNF-dependent regulation of intracerebral IL-18 levels was further characterized in an experimental set-up in mice: (1) in a standardized model of CHI in TNF/lymphotoxin-alpha gene-deficient mice and wild-type (WT) littermates, and (2) by intracerebro-ventricular injection of mouse recombinant TNF in WT C57BL/6 mice. The results demonstrate an inverse correlation of intrathecal TNF and IL-18 levels in head-injured patients and a TNF-dependent inhibition of IL-18 after intracerebral injection in mice. These findings imply a potential new anti-inflammatory mechanism of TNF by attenuation of IL-18, thus confirming the proposed "dual" function of this cytokine in the pathophysiology of traumatic brain injury.     

Survival,growth, and accumulation of ingested lead in nestling American Kestrels (Falco sparverius)

One-day old American Kestrel (Falco sparverius) nestlings were dosed orally daily with 5 l/g of corn oil (controls), 25 mg/kg, 125 mg/kg, or 625 mg/kg of metallic lead in corn oil through day 10. Forty percent of the nestlings given 625 mg/kg died after six days. Growth rates became significantly different from controls in the 625 mg/kg group by day 3 and in the 125 mg/kg group by day 4. Crown-rump lengths and brain weights were significantly lower in both treatment groups. Liver and kidney weights were lower in the 625 mg/kg groups. Skeletal examination and measurement of alizarin red-S stained nestlings revealed reduced growth for the humerus, radius-ulna, femur, and tibiotarsus in the 125 mg/kg and 625 mg/kg groups. Skeletons were otherwise normal in appearance. Greater than 2 ppm (wet weight) lead in the liver or 6 ppm in the kidney was associated with suppressed growth, while more than 5 ppm in the liver and 15 ppm in the kidney occurred in survivors in the 625 mg/kg group. The order of accumulation of lead in tissues at the end of 10 days was kidney > liver > brain. These findings suggest that altricial nestlings may be considerably more sensitive to lead exposure than adults and also more sensitive than hatchlings of many precocial species.     

Survival,growth, and histopathological effects of paraquat ingestion in nestling american kestrels(Falco sparverius)

The use of paraquat as a herbicide is becoming more extensive with the increasing popularity of no tillage agriculture, increasing the possibility of exposure for wildlife species. American kestrel(Falco sparverius) nestlings were orally dosed daily with 5 l/g of distilled water (controls), 10 mg/kg, 25 mg/kg, or 60 mg/kg of paraquat dichloride (1,1-dimethyl-4,4-bipyridinium) in distilled water from day 1 through day 10. Forty-four percent of the nestlings given 60 mg/kg died after 4 days. Significant differences in growth rates occurred between controls and all paraquat-dosed groups. Reduced skeletal growth occurred in the humerus and femur in the 25 mg/kg and 60 mg/kg groups, and in the radius-ulna and tibiotarsus in the 60 mg/kg group. Skeletons were otherwise normal in appearance. Histopathological examination revealed localized focal necrosis in the liver of one nestling in the 60 mg/kg group and tubular cell degeneration and focal tubular dilation in the kidneys of another. The brain and lungs were unremarkable histologically. These findings suggest that altricial nestling kestrels are more sensitive to paraquat exposure than young or adult birds of precocial species.     

Surgical management of aortic coarctation associated with ruptured cerebral artery aneurysm

We report two patients with coarctation of the aorta who were admitted to the hospital with ruptured cerebral artery aneurysms. In both patients, we surgically treated the coarctation and later repaired the intracranial lesion. One patient, a 34-year-old woman, is alive and well after 3 years; whereas, the other, a 19-year-old man, did not survive. We discuss the sequence for surgery, which continues to be subjected to debate.     

Moving from Implementation Science to Implementation Practice: The Need to Solve Practical Problems to Improve Behavioral Health Services

It is well recognized that the use of evidence-based practices (EBPs) is critical to improving service outcomes for those receiving behavioral health services. However, EBPs are not easily implemented in behavioral health settings, and there are many challenges to supporting these services over time. Recently, research efforts in implementation science (IS) have greatly expanded our understanding of issues that influence the successful implementation of EBPs. Unfortunately, less effort has been devoted to translating this research theory on a practical level to help individual service entities solve the specific problems of putting programs into place. A process is needed where service organizations and practitioners can build their capacity, informed by IS research, to improve service outcomes. The purpose of this commentary is to describe the IS research base, provide an introduction to implementation practice, describe challenges confronting practitioners, and propose necessary steps in building organizational capacity that enables practitioners to implement the most effective services available.

     

Outbreak of Rabbit Hemorrhagic Disease Virus 2 Infections,Ghana

In September 2019, high mortality in commercial rabbits was reported in the Greater Accra Region of Ghana. Rabbit hemorrhagic disease virus 2 phylogenetically related to isolates from 2015–2017 outbreaks in the Netherlands was confirmed as the causative agent. The virus has not yet been detected in native rabbits in Ghana.