Pesticides in urban runoff are a major source of pollutants in aquatic ecosystems. Fipronil, a phenylpyrazole insecticide, found in structural pest control products, turf grass control, and home pet flea medication, has recently increased in use and is commonly detected in urban runoff. However, little is known about the effects of fipronil on aquatic organisms at early developmental stages. Here, we evaluated toxicity of fipronil to embryos of Japanese Medaka (Oryzias latipes, Qurt stain) using a high-throughput 96-well plate toxicity test. Male and female embryos (< 6 h post fertilization) were exposed to concentrations of fipronil ranging from 0.1–910 μg L−1 for 14 days or until hatching. Embryos were subjected to gross and microscopic examinations of developmental adverse effects as well as transcriptome analysis using RNA-seq. Results indicated a positive dose-response in reduced hatching success, increased gross deformity (tail curvature) at a lowest-observed-effect concentration (LOEC) of 200 μg L−1 and delayed hatching (~1 day at the highest concentration, LOEC = 600 μg L−1). The transcriptome analysis indicated that fipronil exposure enhanced expression of titin and telethonin, which are responsible for muscle development. It is therefore possible that the formation of a tail curvature is due to asymmetrical overgrowth of muscle. Our results indicate that sub-lethal effects occur in embryonic stages of an aquatic vertebrate following exposure to high concentrations of fipronil, although no adverse effects at the highest published environmentally relevant concentration (6.3 μg L−1) were observed.

Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host.

Fungal infections of the central nervous system (FI-CNS) are life-threatening infections that most commonly affect immunocompromised individuals, but immunocompetent individuals may also be infected. Although FI-CNS are relatively rare, the prevalence of FI-CNS is on the rise because of the increasing number of transplant recipients, human immunodeficiency virus-infected individuals, and use of immunosuppressive therapies. Most cases of FI-CNS originate from outside the central nervous system. The etiologic fungi can be classified into 3 fungal groups: molds, dimorphic fungi, and yeasts. The clinical presentation of FI-CNS is highly variable and may be difficult to diagnose premortem. We present a case series of 3 patients, each infected by 1 representative species from each of the 3 fungal groups (Aspergillus species, Blastomyces species, Candida species) to illustrate different neuropathologic phenotypes of FI-CNS. All 3 patients had no history of immunodeficiency and were not suspected to have FI-CNS until they were diagnosed at autopsy. Fungal infections of the central nervous system are often fatal due to delayed diagnosis and diagnostic testing. Awareness of such poly-phenotypic manifestations of FI-CNS will be helpful in reducing delayed diagnosis. It is important for clinicians to include FI-CNS on the differential diagnosis when radiographic findings are nonspecific.

Colloid cysts are rare lesions that account for up to 2% of all intracranial tumors. They are commonly found posterior to the foramen of Monro in the third ventricle and classified as benign lesions due to their slow-growing nature. Diagnosis of colloid cysts are often incidental finds on diagnostic imaging or at autopsy. The strategic location of these cysts primary causes gradual or acute hydrocephalus, as evidenced by flattened gyri and deepened sulci on MRI, nausea, vomiting, and papilledema. Enlargement of the cyst itself can cause a mass effect, which commonly presents with symptoms of ataxia, memory loss, and rapid neurologic deterioration. Microsurgery, endoscopic removal, and stereotactic aspiration are cited to be the most commonly employed treatments in the management of colloid cysts. However, there is no one procedure better than another; the benefits and limitations of several procedures are discussed. Treatment of choice is weighed by clinical judgment and surgical experience that vary between neurosurgeons. Although benign, colloid cysts rarely but can lead to sudden death. Therefore, it is important to consider colloid cysts and other intracranial tumors on the differential diagnosis when presented with acute hydrocephalus and papilledema. We report a case of sudden death in a 22-year-old black female due to obstructive hydrocephalus by a colloid cyst in the third ventricle.

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