Evaluation of Age and Sex Differences in Contemporary versus High-Sensitivity Troponin I Measurement in Hospitalized Patients.

Background: With the transition from the contemporary (cTnI) to high-sensitivity troponin assay (hs-cTnI), concerns have arisen regarding the diagnostic differences between these two assays due to analytical distinctions. This study aims to evaluate the age and sex differences between these two assays, as well as the differences resulting from using two different 99th percentile values of the high-sensitivity troponin assay. Method: A retrospective observational study was conducted at an academic medical center, encompassing a total of 449 lithium heparin plasma samples included in the dataset. Both contemporary and high-sensitivity troponin were simultaneously measured using Siemens ADVIA Centaur analyzers. Two sets of sex-specific 99th percentile URLs from the Siemens study (cutoff-1) and Universal Sample Bank data (cutoff-2) were used for the data analysis. Results: The use of cutoff-1 or cutoff-2 had a negligible impact on troponin classification. Troponin elevation significantly increased in individuals > 50 years old for males and >40 years old for females, with both troponin assays. A receiver operating characteristic analysis did not find significant differences between the two assays. The Kaplan-Meier curves showed no differences in survival in cTnI according to the non-sex-specific 99th URL or hs-cTnI (cutoff-2) but showed a slight difference in survival in hs-cTnI (cutoff-1). Conclusions: Overall, there were no significant differences in age and sex in the diagnostic performance between the contemporary and high-sensitivity troponin assays. Selection criteria for the establishment of the 99th percentile URL should be standardized to avoid the misinterpretation of the troponin results.

Eruptive Lichen Planus Associated With Chronic Hepatitis C Infection Presenting as a Diffuse, Pruritic Rash.

Lichen planus has been associated with several precipitating factors, such as drugs, immunizations, and viral infections, including hepatitis C virus (HCV). Eruptive or disseminated lichen planus is a rare variation that most often presents as an acute, widespread exanthem that progresses rapidly and usually lasts for a shorter duration. This variation has not been well studied, and little is known about the etiologies and treatments of this rare form. Thus far, only a few cases of eruptive lichen planus have been reported to be associated with HCV infection. We report a case a 62-year-old woman who presented with a rapidly progressive, diffuse, pruritic rash of the trunk, upper extremities, and thighs that was determined to be eruptive lichen planus secondary to chronic HCV infection. The patient was treated with topical steroids and oral antihistamines, and her rash spontaneously resolved approximately six months after the initial presentation.

The role of PHOX2B-derived astrocytes in chemosensory control of breathing and sleep homeostasis.

KEY POINTS: The embryonic PHOX2B-progenitor domain generates neuronal and glial cells which together are involved in chemosensory control of breathing and sleep homeostasis. Ablating PHOX2B-derived astrocytes significantly contributes to secondary hypoxic respiratory depression as well as abnormalities in sleep homeostasis. PHOX2B-derived astrocyte ablation results in axonal pathologies in the retrotrapezoid nucleus. ABSTRACT: We identify in mice a population of ∼800 retrotrapezoid nucleus (RTN) astrocytes derived from PHOX2B-positive, OLIG3-negative progenitor cells, that interact with PHOX2B-expressing RTN chemosensory neurons. PHOX2B-derived astrocyte ablation during early life results in adult-onset O2 chemoreflex deficiency. These animals also display changes in sleep homeostasis, including fragmented sleep and disturbances in delta power after sleep deprivation, all without observable changes in anxiety or social behaviours. Ultrastructural evaluation of the RTN demonstrates that PHOX2B-derived astrocyte ablation results in features characteristic of degenerative neuro-axonal dystrophy, including abnormally dilated axon terminals and increased amounts of synapses containing autophagic vacuoles/phagosomes. We conclude that PHOX2B-derived astrocytes are necessary for maintaining a functional O2 chemosensory reflex in the adult, modulate sleep homeostasis, and are key regulators of synaptic integrity in the RTN region, which is necessary for the chemosensory control of breathing. These data also highlight how defects in embryonic development may manifest as neurodegenerative pathology in an adult.

CCNA2 Ablation in Aged Mice Results in Abnormal rRNA Granule Accumulation in Hippocampus.

Mounting evidence in the literature suggests that RNA-RNA binding protein aggregations can disturb neuronal homeostasis and lead to symptoms associated with normal aging as well as dementia. The specific ablation of cyclin A2 in adult neurons results in neuronal polyribosome aggregations and learning and memory deficits. Detailed histologic and ultrastructural assays of aged mice revealed that post-mitotic hippocampal pyramidal neurons maintain cyclin A2 expression and that proliferative cells in the dentate subgranular zone express cyclin A2. Cyclin A2 loss early during neural development inhibited hippocampal development through canonical/cell-cycle mechanisms, including prolonged cell cycle timing in embryonic hippocampal progenitor cells. However, in mature neurons, cyclin A2 colocalized with dendritic rRNA. Cyclin A2 ablation in adult hippocampus resulted in decreased synaptic density in the hippocampus as well as in accumulation of rRNA granules in dendrite shafts. We conclude that cyclin A2 functions in a noncanonical/non-cell cycle regulatory role to maintain adult pyramidal neuron ribostasis.

Cyclin A2 promotes DNA repair in the brain during both development and aging.

Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.