Biomarkers of Neuroinflammation in Traumatic Brain Injury.

Traumatic brain injury (TBI) is characterized by neuroinflammation and structural damage leading to symptoms and altered brain function. Biomarkers are useful in understanding neuroinflammation and correlations with TBI sequalae. The purpose of this paper is to identify and discuss biomarkers of neuroinflammation used to study TBI and its sequalae. A systematic review was conducted using PubMed, CINAHL, Embase, and Web of Science. A total of 350 articles met criteria; 70 used biomarkers. PRISMA criteria were used for Quality Assessment. Articles included reviews (n = 17), case-control (n = 25), cross-sectional (n = 25) studies, and randomized controlled trials (n = 3). Twenty-seven biomarkers were identified, including inflammasomes, cytokines, neuropeptides, complement complexes, miRNA and exosomes, and glial cell-specific proteins. Biomarkers aid in predicting morbidity and mortality and advance our understanding of neuroinflammation in TBI. This systematic review advances our understanding of the neuroinflammatory response to better enable nurses and clinicians to provide informed care of TBI patients.

Case Report: Double Intrastromal Corneal Ring Segment and Posterior Chamber Phakic Intraocular Lens Implantation.

SIGNIFICANCE: Keratoconus can manifest asymmetrically, affecting binocularity and becoming a refractive problem that is sometimes complex to solve. We propose a therapeutic approach for correction of keratoconus based on parallel implantation of a second intrastromal corneal ring segment (ICRS). PURPOSE: This study aimed to improve the refractive status of a patient affected with advanced bilateral keratoconus using implantation of a second ICRS and a phakic intraocular lens. CASE REPORT: A 44-year-old man came to our clinic requesting a refractive solution for his visual impairment. He had been diagnosed with bilateral severe keratoconus categorized by the Amsler-Krumeich classification scale as grade III (right eye) and grade II (left eye). He had previously undergone corneal cross-linking and implantation of ICRS (Intacs) in both eyes. Significant anisometropia was present between the eyes, and the patient also complained of poor quality of vision. We decided to implant a posterior chamber phakic collamer lens in his right eye and to insert a new ICRS (Keraring) deep and parallel to the previous one in his left eye. We aimed to prevent anisometropia in his right eye and to further regularize the affected cornea in his left eye. Refractive symmetry was achieved, and vision was optimized after surgery. CONCLUSIONS: In a patient with keratoconus, refractive surgery should be performed from a bilateral perspective. Specific cases of keratoconus can be managed by parallel implantation of a second ICRS.

The use of European shag pellets as indicators of microplastic fibers in the marine environment.

Microplastic particles are abundant marine pollutants that are ingested by many seabirds. Some seabirds regurgitate non-digestible materials in the form of pellets and their analysis may be useful to study the abundance of plastic debris at the local scale. Here, we aimed to provide baseline data for the presence of microplastics in pellets regurgitated by European shags (Phalacrocorax aristotelis) (n = 41) in the Iberia peninsula (NW Spain). We found microplastic fibers in 63% of pellets, suggesting that this type of plastic pollution is prevalent in the study area. According to Fourier Transform Infrared spectrometry, nylon fibers were the most abundant, followed by polyester. We also found that the presence of microplastics was higher in pellets containing remains of benthic fishes. Our results suggest that shag pellets may be useful to monitor microplastic pollution in coastal waters.

Herpes simplex virus type 1 induces nuclear accumulation of hyperphosphorylated tau in neuronal cells.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that remains latent in host neurons. Viral DNA replication is a highly structured process in which the redistribution of nuclear proteins plays an important role. Although tau is most widely known as a microtubule-associated protein found in a hyperphosphorylated state in the brains of patients with Alzheimer's disease (AD), this protein has also been detected at other sites such as the nucleolus. Here, we establish that HSV-1 infection gives rise to an increase in tau phosphorylation and that hyperphosphorylated tau accumulates in the nucleus, forming defined structures in HSV-1-infected neuronal cells reminiscent of the common sites of viral DNA replication. When tau expression in human neuroblastoma cells was specifically inhibited using an adenoviral vector expressing a short hairpin RNA to tau, viral DNA replication was not affected, indicating that tau is not required for HSV-1 growth in neuronal cells. Given that HSV-1 is considered a risk factor for AD, our results suggest a new way in which to understand the relationships between HSV-1 infection and the pathogenic mechanisms leading to AD.

Pyruvate protection against beta-amyloid-induced neuronal death: role of mitochondrial redox state.

The mechanism by which beta-amyloid protein (A beta) causes degeneration in cultured neurons is not completely understood, but several lines of evidence suggest that A beta-mediated neuronal death is associated with an enhanced production of reactive oxygen species (ROS) and oxidative damage. In the present study, we address whether supplementation of glucose-containing culture media with energy substrates, pyruvate plus malate (P/M), protects rat primary neurons from A beta-induced degeneration and death. We found that P/M addition attenuated cell death evoked by beta-amyloid peptides (A beta(25-35) and A beta(1-40)) after 24 hr treatment and that this effect was blocked by alpha-ciano-3-hydroxycinnamate (CIN), suggesting that it requires mitochondrial pyruvate uptake. P/M supply to control and A beta-treated neuronal cultures increases cellular reducing power, as indicated by the ability to reduce the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The early increases in ROS levels, measured by dichlorofluorescein (DCF) fluorescence, and caspase-3 activity that follow exposure to A beta were notably reduced in the presence of P/M. These results place activation of caspase-3 most likely downstream of oxidative damage to the mitochondria and indicate that mitochondrial NAD(P) redox status plays a central role in the neuroprotective effect of pyruvate. Inhibition of respiratory chain complexes and mitochondrial uncoupling did not block the early increase in ROS levels, suggesting that A beta could initiate oxidative stress by activating a source of ROS that is not accesible to the antioxidant defenses fueled by mitochondrial substrates.

Nodular onchocercosis of red deer in central Spain.

The presence of nodular onchocercosis was investigated post-mortem in 142 red deer (11 calves, 35 yearlings and 96 adults) shot from February 1998 to January 1999, and July-November 1999 in "Quintos de Mora" (Toledo, central Spain), a game property belonging to the National Wildlife Reserves. Between 6 and 13 animals were analysed monthly by inspection for subcutaneous nodules of Onchocerca spp. Subcutaneous nodules of Onchocerca sp. were detected in 24% of the animals. Anatomical locations for nodules were the back and flanks. Infection ranged from 1 to 29 nodules per animal. Adult worms collected from nodules were identified as O. flexuosa. No apparent seasonal trend was observed either in prevalence or in mean intensity of infection, which fluctuated between 48% (5+/-8 nodules) in winter 1998 and 5% (1+/-0 nodules) in summer 1999. Prevalence of infection was significantly higher in adult (30%) than in young animals (9% in calves, 11% in yearlings), although no age effect on intensity was observed. The size of the nodules was measured to evaluate the age of infection. Small (recent) nodules (5-6mm of diameter) were collected in late spring, summer and fall; medium-sized nodules (12-15 mm) were in second half of summer, fall and winter, and large (mature) nodules (20-25 mm) in fall, winter and part of spring. Significant differences were found among host age groups.

Regulation of tau phosphorylation and protection against beta-amyloid-induced neurodegeneration by lithium. Possible implications for Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of the beta-amyloid peptide and the hyperphosphorylation of the tau protein, among other features. The most widely accepted hypothesis on the etiopathogenesis of this disease proposes that the aggregates of the beta-amyloid peptide are the main triggers of tau hyperphosphorylation and the subsequent degeneration of affected neurons. In support of this view, fibrillar aggregates of synthetic beta-amyloid peptide induce tau hyperphosphorylation and cell death in cultured neurons. We have previously reported that lithium inhibits tau hyperphosphorylation and also significantly protects cultured neurons from cell death triggered by beta-amyloid peptide. As lithium is a relatively specific inhibitor of glycogen synthase kinase-3 (in comparison with other protein kinases), and other studies also point to a relevant role of this enzyme, we favor the view that glycogen synthase kinase-3 is a crucial element in the pathogenesis of Alzheimer's disease. In our opinion, the possibility of using lithium, or other inhibitors of glycogen synthase kinase-3, in experimental trials aimed to ameliorate neurodegeneration in Alzheimer's disease should be considered.