Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit all?

In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes.

Human immunodeficiency virus type-1 (HIV-1) is responsible for significant mortality and morbidity worldwide. Despite complete control of viral replication with antiretrovirals, cells with integrated HIV-1 provirus can produce viral transcripts. In a cross-sectional study of 84 HIV+ individuals of whom 43 were followed longitudinally, we found that HIV-1 RNAs are present in extracellular vesicles (EVs) derived from cerebrospinal fluid and serum of all individuals. We used seven digital droplet polymerase chain reaction assays to evaluate the transcriptional status of the latent reservoir. EV-associated viral RNA was more abundant in the CSF and correlated with neurocognitive dysfunction in both, the cross-sectional and longitudinal studies. Sequencing studies suggested compartmentalization of defective viral transcripts in the serum and CSF. These findings suggest previous studies have underestimated the viral burden and there is a significant relationship between latent viral transcription and CNS complications of long-term disease despite the adequate use of antiretrovirals.

Autophagy Deregulation in HIV-1-Infected Cells Increases Extracellular Vesicle Release and Contributes to TLR3 Activation.

Human immunodeficiency virus type 1 (HIV-1) infection can result in HIV-associated neurocognitive disorder (HAND), a spectrum of disorders characterized by neurological impairment and chronic inflammation. Combined antiretroviral therapy (cART) has elicited a marked reduction in the number of individuals diagnosed with HAND. However, there is continual, low-level viral transcription due to the lack of a transcription inhibitor in cART regimens, which results in the accumulation of viral products within infected cells. To alleviate stress, infected cells can release accumulated products, such as TAR RNA, in extracellular vesicles (EVs), which can contribute to pathogenesis in neighboring cells. Here, we demonstrate that cART can contribute to autophagy deregulation in infected cells and increased EV release. The impact of EVs released from HIV-1 infected myeloid cells was found to contribute to CNS pathogenesis, potentially through EV-mediated TLR3 (Toll-like receptor 3) activation, suggesting the need for therapeutics to target this mechanism. Three HIV-1 TAR-binding compounds, 103FA, 111FA, and Ral HCl, were identified that recognize TAR RNA and reduce TLR activation. These data indicate that packaging of viral products into EVs, potentially exacerbated by antiretroviral therapeutics, may induce chronic inflammation of the CNS observed in cART-treated patients, and novel therapeutic strategies may be exploited to mitigate morbidity.

A Novel, Possibly Pathogenic, COL4A1 Gene Variant (c.3698G>A) in a Family With Childhood Epilepsy and Leukoencephalopathy.

This case report explores the clinical presentation and genetic findings of a 44-year-old male with a history of pediatric epilepsy. The patient's daughter, recently diagnosed with autism, underwent genetic testing, revealing a variant of uncertain significance (VUS) in the type IV collagen alpha 1 (COL4A1) gene. The male patient reported a spectrum of neurological symptoms, including chronic migraines, exertional weakness, and sensory disturbances. Detailed neurological examination findings were within normal limits, but a brain MRI unveiled confluent deep white matter T2/fluid-attenuated inversion recovery (FLAIR) signal abnormalities with basal ganglia involvement. Genetic testing identified a novel COL4A1 gene variant, c.3698G>A (p.Gly1233Glu), in the patient, which was also carried by his daughter. The nature and clinical implications of this VUS in the context of the family's clinical history are discussed in this case report, emphasizing the potential significance of this genetic variant in understanding the etiology of the patient's neurologic symptoms. Further research and correlation with clinical findings are needed to elucidate whether this is a pathogenic variant.