Dynamic formation of a posterior-to-anterior peak-alpha-frequency gradient driven by two distinct processes.

Peak-alpha frequency varies across individuals and mental states, but it also forms a negative gradient from posterior to anterior regions in association with increases in cortical thickness and connectivity, reflecting a cortical hierarchy in temporal integration. Tracking the spatial standard deviation of peak-alpha frequency in scalp EEG, we observed that a posterior-to-anterior gradient dynamically formed and dissolved. Periods of high spatial standard deviation yielded robustly negative posterior-to-anterior gradients-the "gradient state"-while periods of low spatial standard deviation yielded globally converged peak-alpha frequency-the "uniform state." The state variations were characterized by a combination of slow (0.3 Hz-0.5 Hz) oscillations and random-walk-like fluctuations. They were relatively independently correlated with peak-alpha frequency variations in anterior regions and peak-alpha power variations in central regions driven by posterior regions (together accounting for ∼50% of the state variations), suggesting that two distinct mechanisms modulate the state variations: an anterior mechanism that directly adjusts peak-alpha frequencies and a posterior-central mechanism that indirectly adjusts them by influencing synchronization. The state variations likely reflect general operations as their spatiotemporal characteristics remained unchanged while participants engaged in a variety of tasks (breath focus, vigilance, working memory, mental arithmetic, and generative thinking) with their eyes closed, or watched a silent nature video. The ongoing state variations may dynamically balance two global processing modes, one that facilitates greater temporal integration (and potentially also information influx) toward anterior regions in the gradient state, and the other that facilitates flexible global communication (via phase locking) in the uniform state.Significance Statement Alpha-band oscillations (8-12 Hz) are implicated in a variety of sensory, attentional, and cognitive processes. Our EEG study reveals that the spatial pattern of alpha-oscillation frequency dynamically varies between forming a negative posterior-to-anterior gradient (i.e., the "gradient state") and converging globally (i.e., the "uniform state"). The gradient state may facilitate temporal integration (and potentially also information influx) toward anterior regions, whereas the uniform state may promote flexible global communication via phase locking. Our results further suggest that the variations between the gradient and uniform states are controlled by two distinct mechanisms: an anterior mechanism that directly adjusts alpha-oscillation frequencies and a posterior mechanism that indirectly adjusts them by increasing or decreasing global oscillatory entrainment in the upper alpha band.

Effect of environmental factors on conjugative transfer of antibiotic resistance genes in aquatic settings.

Antimicrobial-resistance genes (ARGs) are spread among bacteria by horizontal gene transfer, however, the effect of environmental factors on the dynamics of the ARG in water environments has not been very well understood. In this systematic review, we employed the regression tree algorithm to identify the environmental factors that facilitate/inhibit the transfer of ARGs via conjugation in planktonic/biofilm-formed bacterial cells based on the results of past relevant research. Escherichia coli strains were the most studied genus for conjugation experiments as donor/recipient in the intra-genera category. Conversely, Pseudomonas spp., Acinetobacter spp., and Salmonella spp. were studied primarily as recipients across inter-genera bacteria. The conjugation efficiency (ce) was found to be highly dependent on the incubation period. Some antibiotics, such as nitrofurantoin (at ≥0.2 µg ml-1) and kanamycin (at ≥9.5 mg l-1) as well as metallic compounds like mercury (II) chloride (HgCl2, ≥3 µmol l-1), and vanadium (III) chloride (VCl3, ≥50 µmol l-1) had enhancing effect on conjugation. The highest ce value (-0.90 log10) was achieved at 15°C-19°C, with linoleic acid concentrations <8 mg l-1, a recognized conjugation inhibitor. Identifying critical environmental factors affecting ARG dissemination in aquatic environments will accelerate strategies to control their proliferation and combat antibiotic resistance.

Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

CONTEXT: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age can speculate on the mechanism. OBJECTIVE: We examined whether overweight in children and adolescents are associated with thyroid nodule development by sex and age. DESIGN: Approximately 300,000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial two examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. SETTING: A population-based prospective cohort study. PARTICIPANTS: The first and second thyroid examinations involved 299,939 and 237,691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184,519 participants were finalized for analysis. MAIN OUTCOME MEASURES: Multivariable-adjusted odds ratios of new detected thyroid nodules for overweight participants compared with normal-weight participants. RESULTS: New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% confidence interval) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable-adjusted odds ratios for males and females with overweight were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75. CONCLUSIONS: Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.

Cellulolytic enzymes in Microbulbifer sp. Strain GL-2, a marine fish intestinal bacterium, with emphasis on endo-1,4-ß-glucanases Cel5A and Cel8.

Cellulose is an abundant biomass on the planet. Various cellulases from environmental microbes have been explored for industrial use of cellulose. Marine fish intestine is of interest as one source of new enzymes. Here, we report the discovery of genes encoding two ß-glucosidases (Bgl3A and Bgl3B) and four endo-1,4-ß-glucanases (Cel5A, Cel8, Cel5B, and Cel9) as part of the genome sequence of a cellulolytic marine bacterium, Microbulbifer sp. Strain GL-2. Five of these six enzymes (excepting Cel5B) are presumed to localize to the periplasm or outer membrane. Transcriptional analysis demonstrated that all six genes were highly expressed in stationary phase. The transcription was induced by cello-oligosaccharides rather than by glucose, suggesting that the cellulases are produced primarily for nutrient acquisition following initial growth, facilitating the secondary growth phase. We cloned the genes encoding two of the endo-1,4-ß-glucanases, Cel5A and Cel8, and purified the corresponding recombinant enzymes following expression in Escherichia coli. The activity of Cel5A was observed across a wide range of temperatures (10-40 ˚C) and pHs (6-8). This pattern differed from those of Cel8 and the commercial cellulase Enthiron, both of which exhibit decreased activities below 30 ˚C and at alkaline pHs. These characteristics suggest that Cel5A might find use in industrial applications. Overall, our results reinforce the hypothesis that marine bacteria remain a possible source of novel cellulolytic activities.

Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Left Ventricular Hypertrophy (ESES-LVH) Study: A Multicenter, Open-Label, Prospective, Interventional Study.

INTRODUCTION: In contrast to the antihypertensive effect of esaxerenone, there is little evidence of its cardioprotective effect. We investigated the efficacy and safety of esaxerenone in patients with uncontrolled hypertension and left ventricular hypertrophy taking a renin-angiotensin system inhibitor (RASi) or calcium-channel blocker (CCB). METHODS: This was a multicenter, open-label, exploratory study with a 24-week treatment period. Esaxerenone was orally administered at an initial dose of 2.5 mg/day (maximum dose: 5 mg/day). The primary endpoints were the change in morning home systolic blood pressure (BP)/diastolic BP and change and percentage change in left ventricular mass index (LVMI) from baseline to end of treatment (EOT). Key secondary endpoints included change from baseline in bedtime home and office BP, achievement rate of target BP, and safety. RESULTS: In total, 60 patients were enrolled. Morning home systolic/diastolic BP was significantly decreased from baseline to EOT in the total population (- 11.5/ - 4.7 mmHg, p < 0.001) and in both the RASi and CCB subcohorts (all p < 0.01). Significant reductions in bedtime home and office BP were shown in the total population and both subcohorts. LVMI was also significantly decreased from baseline to EOT in the total population (- 9.9 g/m2, - 8.5%, both p < 0.001) and both subcohorts (all p < 0.05). The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 35.0% and 3.3%, respectively; most were mild or moderate. No new safety concerns were identified. CONCLUSION: Esaxerenone showed favorable antihypertensive and cardioprotective effects and safety in hypertensive patients with cardiac hypertrophy. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs071190043).

A phase-shifting anterior-posterior network organizes global phase relations.

Prior research has identified a variety of task-dependent networks that form through inter-regional phase-locking of oscillatory activity that are neural correlates of specific behaviors. Despite ample knowledge of task-specific functional networks, general rules governing global phase relations have not been investigated. To discover such general rules, we focused on phase modularity, measured as the degree to which global phase relations in EEG comprised distinct synchronized clusters interacting with one another at large phase lags. Synchronized clusters were detected with a standard community-detection algorithm, and the degree of phase modularity was quantified by the index q. Notably, we found that the mechanism controlling phase modularity is remarkably simple. A network comprising anterior-posterior long-distance connectivity coherently shifted phase relations from low-angles (|Δθ| < π/4) in low-modularity states (bottom 5% in q) to high-angles (|Δθ| > 3π/4) in high-modularity states (top 5% in q), accounting for fluctuations in phase modularity. This anterior-posterior network may play a fundamental functional role as (1) it controls phase modularity across a broad range of frequencies (3-50 Hz examined) in different behavioral conditions (resting with the eyes closed or watching a silent nature video) and (2) neural interactions (measured as power correlations) in beta-to-gamma bands were consistently elevated in high-modularity states. These results may motivate future investigations into the functional roles of phase modularity as well as the anterior-posterior network that controls it.

Persistence of Marine Bacterial Plasmid in the House Fly (Musca domestica): Marine-Derived Antimicrobial Resistance Genes Have a Chance of Invading the Human Environment.

The house fly is known to be a vector of antibiotic-resistant bacteria (ARB) in animal farms. It is also possible that the house fly contributes to the spread of ARB and antibiotic resistance genes (ARGs) among various environments. We hypothesized that ARB and ARGs present in marine fish and fishery food may gain access to humans via the house fly. We show herein that pAQU1, a marine bacterial ARG-bearing plasmid, persists in the house fly intestine for 5 days after fly ingestion of marine bacteria. In the case of Escherichia coli bearing the same plasmid, the persistence period exceeded 7 days. This interval is sufficient for transmission to human environments, meaning that the house fly is capable of serving as a vector of marine-derived ARGs. Time course monitoring of the house fly intestinal microflora showed that the initial microflora was occupied abundantly with Enterobacteriaceae. Experimentally ingested bacteria dominated the intestinal environment immediately following ingestion; however, after 72 h, the intestinal microflora recovered to resemble that observed at baseline, when diverse genera of Enterobacteriaceae were seen. Given that pAQU1 in marine bacteria and E. coli were detected in fly excrement (defined here as any combination of feces and regurgitated material) at 7 days post-bacterial ingestion, we hypothesize that the house fly may serve as a vector for transmission of ARGs from marine items and fish to humans via contamination with fly excrement.

Resistomes in freshwater bioaerosols and their impact on drinking and recreational water safety: A perspective.

Antibiotic resistance genes (ARGs) are widespread environmental pollutants of biological origin that pose a significant threat to human, animal, and plant health, as well as to ecosystems. ARGs are found in soil, water, air, and waste, and several pathways for global dissemination in the environment have been described. However, studies on airborne ARG transport through atmospheric particles are limited. The ARGs in microorganisms inhabiting an environment are referred to as the "resistome". A global search was conducted of air-resistome studies by retrieving bioaerosol ARG-related papers published in the last 30 years from PubMed. We found that there is no dedicated methodology for isolating ARGs in bioaerosols; instead, conventional methods for microbial culture and metagenomic analysis are used in combination with standard aerosol sampling techniques. There is a dearth of information on the bioaerosol resistomes of freshwater environments and their impact on freshwater sources used for drinking and recreational activities. More studies of aerobiome freshwater environments are needed to ensure the safe use of water and sanitation. In this review we outline and synthesize the few studies that address the freshwater air microbiome (from tap water, bathroom showers, rivers, lakes, and swimming pools) and their resistomes, as well as the likely impacts on drinking and recreational waters. We also discuss current knowledge gaps for the freshwater airborne resistome. This review will stimulate new investigations of the atmospheric microbiome, particularly in areas where both air and water quality are of public health concern.