Associations of actigraphy derived rest activity patterns and circadian phase with clinical symptoms and polysomnographic parameters in chronic insomnia disorders.

We explored the associations of actigraphy-derived rest-activity patterns and circadian phase parameters with clinical symptoms and level 1 polysomnography (PSG) results in patients with chronic insomnia to evaluate the clinical implications of actigraphy-derived parameters for PSG interpretation. Seventy-five participants underwent actigraphy assessments and level 1 PSG. Exploratory correlation analyses between parameters derived from actigraphy, PSG, and clinical assessments were performed. First, participants were classified into two groups based on rest-activity pattern variables; group differences were investigated following covariate adjustment. Participants with poorer rest-activity patterns on actigraphy (low inter-day stability and high intra-daily variability) exhibited higher insomnia severity index scores than participants with better rest-activity patterns. No between-group differences in PSG parameters were observed. Second, participants were classified into two groups based on circadian phase variables. Late-phase participants (least active 5-h and most active 10-h onset times) exhibited higher insomnia severity scores, longer sleep and rapid eye movement latency, and lower apnea-hypopnea index than early-phase participants. These associations remained significant even after adjusting for potential covariates. Some actigraphy-derived rest-activity patterns and circadian phase parameters were significantly associated with clinical symptoms and PSG results, suggesting their possible adjunctive role in deriving plans for PSG lights-off time and assessing the possible insomnia pathophysiology.

Associations of rest-activity patterns with amyloid burden, medial temporal lobe atrophy, and cognitive impairment.

BACKGROUND: We sought to investigate the possible associations of rest-activity patterns with cortical amyloid burden, medial temporal lobe (MTL) neurodegeneration, and cognitive function in patients in the early stage of cognitive impairment. METHODS: Rest-activity patterns were assessed in 100 participants (70 with mild cognitive impairment and 30 with mild dementia) using wrist actigraphy. All participants underwent 18F-flutemetamol positron emission tomography (PET) imaging to quantify cortical amyloid burden, structural brain magnetic resonance imaging (MRI) to quantify MTL grey matter volume, neuropsychological testing, and clinical diagnosis. We used multiple linear regression models adjusted for covariates, including demographics, diabetes, hypertension, depressive symptom, psychotropic medication, sleep medication, weekend effect, and apolipoprotein-ε allele status. FINDINGS: After adjusting for possible confounders, we found that the midline estimation of statistic of rhythm (MESOR) associated positively with frontal/executive function (estimate = 1.17, standard error [SE] = 0.37, p = 0.002). The least active 5-h (L5) onset time associated positively with MTL grey matter volume and memory function (estimate = 1.24, SE = 0.33, p = 0.001, and estimate = 3.77, SE = 1.22, p = 0.003, respectively), particularly in amyloid-negative participants. Additional path analysis revealed that MTL grey matter volume partially mediated the association between L5 onset time and memory function in amyloid-negative participants. INTERPRETATION: Decreased MESOR and advanced L5 onset time may be useful as early signs of cognitive decline or MTL neurodegeneration. Furthermore, amyloid pathology may act as a moderator of the relationships between rest-activity patterns, neurodegeneration, and cognitive function. FUNDING: Korea Centres for Disease Control and Prevention (#4845-303); National Research Foundation of Korea (2019M3C7A1031905, 2019R1A5A2026045).

Risk Evaluation of Azithromycin-Induced QT Prolongation in Real-World Practice.

BACKGROUND: Azithromycin exposure has been reported to increase the risk of QT prolongation and cardiovascular death. However, findings on the association between azithromycin and cardiovascular death are controversial, and azithromycin is still used in actual practice. Additionally, quantitative assessments of risk have not been performed, including the risk of QT prolongation when patients are exposed to azithromycin in a real-world clinical setting. Therefore, in this study, we aimed to evaluate the risk of exposure to azithromycin on QT prolongation in a real-world clinical setting using a 21-year medical history database of a tertiary medical institution. METHODS: We analyzed the electrocardiogram results and relevant electronic health records of 402,607 subjects in a tertiary teaching hospital in Korea from 1996 to 2015. To evaluate the risk of QT prolongation of azithromycin, we conducted a case-control analysis using amoxicillin for comparison. Multiple logistic regression analysis was performed to correct for age, sex, accompanying drugs, and disease. RESULTS: The odds ratio (OR) for QT prolongation (QTc>450 ms in male and >460 ms in female) on azithromycin exposure was 1.40 (95% confidence interval [CI], 1.23-1.59), and the OR for severe QT prolongation (QTc>500 ms) was 1.43 (95% CI, 1.13-1.82). On the other hand, the ORs on exposure to amoxicillin were 1.06 (95% CI, 0.97-1.15) and 0.88 (95% CI, 0.70-1.09). In a subgroup analysis, the risk of QT prolongation in patients aged between 60 and 80 years was significantly higher when they are exposed to azithromycin. CONCLUSIONS: The risk of QT prolongation was increased when patients, particularly the elderly aged 60-79 years, were exposed to azithromycin. Therefore, clinicians should pay exercise caution using azithromycin or consider using other antibiotics, such as amoxicillin, instead of azithromycin.

In vitro and in vivo defensive effect of probiotic LAB against Pseudomonas aeruginosa using Caenorhabditis elegans model.

This study aimed to investigate in vitro and in vivo the probiotic characteristics of lactic acid bacteria (LAB) isolated from Korean traditional fermented foods. Caenorhabditis elegans  (C. elegans) was used for analytical assays of fertility, chemotaxis, life-span, worm-killing and bacterial colonization in the intestinal lumen of the worm. All 35 strains of LAB reduced fertility and slowed development in the worms. The worm-killing assay showed that LAB significantly increased the lifespan (P < 0.05) and reduced the susceptibility to virulent PA14; however, the heat-killed LAB did not. The bacterial colonization assay revealed that LAB proliferated and protected the gut of the worm against infection by Pseudomonas aeruginosa PA14. In addition, specific LAB Pediococcus acidilactici(P. acidilactici DM-9), Pediococcus brevis (L. brevis SDL1411), and Pediococcus pentosaceus (P. pentosaceus SDL1409) strains showed acid resistance (66-91%), resistance to pepsin (64-67%) and viability in simulated intestinal fluid (67-73%) based on in vitro probiotic analyses. Taken together, these results suggest that C. elegans may be a tractable model for screening efficient probiotics.

In vivo screening platform for shiga toxin-producing Escherichia coli (STEC) using Caenorhabditis elegans as a model.

Shiga toxin-producing Escherichia coli (STEC) strains are the main cause of bacillary dysentery, although STEC strains generally induce milder disease symptoms compared to Shigella species. This study aimed to determine the virulence of STEC using the nematode Caenorhabditis elegans as a model host. Worm killing, fertility and bacterial colonisation assays were performed to examine the potential difference in the virulence of STEC strains compared to that of the control E. coli OP50 strains on which worms were fed. A statistically significant difference in the survival rates of C. elegans was observed in that the STEC strains caused death in 8-10 days and the E. coli OP50 strains caused death in 15 days. STEC strains severely reduced the fertility of the worms. The intestinal load of bacteria in the adult stage nematodes harbouring the E. coli OP50 strains was found to be 3.5 log CFU mL-1. In contrast, the STEC strains E15, E18 and E22 harboured 4.1, 4.2 and 4.7 log CFU ml-1 per nematode, respectively. The heat-killed STEC strains significantly increased the longevity of the worms compared to the non-heated STEC strains. In addition, PCR-based genomic profiling of shiga toxin genes, viz., stx1 and stx2, identified in selected STEC strains revealed that these toxins may be associated with the virulence of the STEC strains. This study demonstrated that C. elegans is an effective model to examine and compare the pathogenicity and virulence variation of STEC strains to that of E. coli OP50 strains.

Quantitative Evaluation of the Relationship between T-Wave-Based Features and Serum Potassium Level in Real-World Clinical Practice.

BACKGROUND: Proper management of hyperkalemia that leads to fatal cardiac arrhythmia has become more important because of the increased prevalence of hyperkalemia-prone diseases. Although T-wave changes in hyperkalemia are well known, their usefulness is debatable. We evaluated how well T-wave-based features of electrocardiograms (ECGs) are correlated with estimated serum potassium levels using ECG data from real-world clinical practice. METHODS: We collected ECGs from a local ECG repository (MUSE™) from 1994 to 2017 and extracted the ECG waveforms. Of about 1 million reports, 124,238 were conducted within 5 minutes before or after blood collection for serum potassium estimation. We randomly selected 500 ECGs and two evaluators measured the amplitude (T-amp) and right slope of the T-wave (T-right slope) on five lead waveforms (V3, V4, V5, V6, and II). Linear correlations of T-amp, T-right slope, and their normalized feature (T-norm) with serum potassium levels were evaluated using Pearson correlation coefficient analysis. RESULTS: Pearson correlation coefficients for T-wave-based features with serum potassium between the two evaluators were 0.99 for T-amp and 0.97 for T-right slope. The coefficient for the association between T-amp, T-right slope, and T-norm, and serum potassium ranged from -0.22 to 0.02. In the normal ECG subgroup (normal ECG or otherwise normal ECG), there was no correlation between T-wave-based features and serum potassium level. CONCLUSIONS: T-wave-based features were not correlated with serum potassium level, and their use in real clinical practice is currently limited.