The Kidney Clock Contributes to Timekeeping by the Master Circadian Clock

The kidney harbors one of the strongest circadian clocks in the body. Kidney failure has long been known to cause circadian sleep disturbances. Using an adenine-induced model of chronic kidney disease (CKD) in mice, we probe the possibility that such sleep disturbances originate from aberrant circadian rhythms in kidney. Under the CKD condition, mice developed unstable behavioral circadian rhythms. When observed in isolation in vitro, the pacing of the master clock, the suprachiasmatic nucleus (SCN), remained uncompromised, while the kidney clock became a less robust circadian oscillator with a longer period. We find this analogous to the silencing of a strong slave clock in the brain, the choroid plexus, which alters the pacing of the SCN. We propose that the kidney also contributes to overall circadian timekeeping at the whole-body level, through bottom-up feedback in the hierarchical structure of the mammalian circadian clocks

Characterization and Genome Analysis of Staphylococcus aureus Podovirus CSA13 and Its Anti-Biofilm Capacity

Staphylococcus aureus is one of the notable human pathogens that can be easily encountered in both dietary and clinical surroundings. Among various countermeasures, bacteriophage therapy is recognized as an alternative method for resolving the issue of antibiotic resistance. In the current study, bacteriophage CSA13 was isolated from a chicken, and subsequently, its morphology, physiology, and genomics were characterized. This Podoviridae phage displayed an extended host inhibition effect of up to 23 hours of persistence. Its broad host spectrum included methicillin susceptible S. aureus (MSSA), methicillin resistant S. aureus (MRSA), local S. aureus isolates, as well as non-aureus staphylococci strains. Moreover, phage CSA13 could successfully remove over 78% and 93% of MSSA and MRSA biofilms in an experimental setting, respectively. Genomic analysis revealed a 17,034 bp chromosome containing 18 predicted open reading frames (ORFs) without tRNAs, representing a typical chromosomal structure of the staphylococcal Podoviridae family. The results presented here suggest that phage CSA13 can be applicable as an effective biocontrol agent against S. aureus

Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea

Abstract Background Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively. Methods Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD. Results Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD. Conclusions Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality

Emerging role of vascular burden in AT(N) classification in individuals with Alzheimers and concomitant cerebrovascular burdens.

OBJECTIVES: Alzheimers disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimers pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p&lt;0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimers pathological changes (A-T+, A-N+; p=0.002) and Alzheimers pathological changes (p&lt;0.001) categories. CONCLUSION: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system