Pseudomonas aeruginosa displays intrinsic resistance to many antibiotics and known to acquire actively genetic mutations for further resistance. In this study, we attempted to understand genomic and ...transcriptomic landscapes of P. aeruginosa clinical isolates that are highly resistant to multiple antibiotics. We also aimed to reveal a mode of antibiotic resistance by elucidating transcriptional response of genes conferring antibiotic resistance. To this end, we sequenced the whole genomes and profiled genome-wide RNA transcripts of three different multi-drug resistant (MDR) clinical isolates that are phylogenetically distant from one another. Multi-layered genome comparisons with genomes of antibiotic-susceptible P. aeruginosa strains and 70 other antibiotic-resistance strains revealed both well-characterized conserved gene mutations and distinct distribution of antibiotic-resistant genes (ARGs) among strains. Transcriptions of genes involved in quorum sensing and type VI secretion systems were invariably downregulated in the MDR strains. Virulence-associated phenotypes were further examined and results indicate that our MDR strains are clearly avirulent. Transcriptions of 64 genes, logically selected to be related with antibiotic resistance in MDR strains, were active under normal growth conditions and remained unchanged during antibiotic treatment. These results propose that antibiotic resistance is achieved by a "constitutive" response scheme, where ARGs are actively expressed even in the absence of antibiotic stress, rather than a "reactive" response. Bacterial responses explored at the transcriptomic level in conjunction with their genome repertoires provided novel insights into (i) the virulence-associated phenotypes and (ii) a mode of antibiotic resistance in MDR P. aeruginosa strains.
The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and ...signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.
Temporomandibular joint disorders (TMDs) are closely related to the masticatory muscles, but objective and quantitative methods to evaluate muscle are lacking. IDEAL-IQ, a type of chemical ...shift-encoded magnetic resonance imaging (CSE-MRI), can quantify the fat fraction (FF). The purpose of this study was to develop an MR IDEAL-IQ-based method for quantitative muscle diagnosis in TMD patients. A total of 65 patients who underwent 3 T MRI scans, including CSE-MRI sequences, were retrospectively included. MRI diagnoses and clinical data were reviewed. There were 19 patients in the normal group and 46 patients in the TMD group with unilateral disc displacement. The TMD group was subdivided into those with and without clenching. The right and left FF values of the masseter, medial, and lateral pterygoid muscles were measured twice by two oral radiologists on CSE-MRI, and the average value was used. FF measurements using CSE-MRI showed excellent intra- and inter-observer agreement (ICC > 0.889 for both). There were no statistically significant differences between the right and left FF values in the masseter, medial pterygoid, and lateral pterygoid of the normal group (p > 0.05). A statistically significant difference was found in the TMD group without clenching, in which the masseter muscle had a statistically significantly lower FF value on the disc displacement side (3.94 ± 1.61) than on the normal side (4.52 ± 2.24) (p < 0.05). CSE-MRI, which can reproducibly quantify muscle FF values, is expected to be a biomarker for objective muscle evaluation in TMD patients. The masseter muscle is expected to be particularly useful compared to other masticatory muscles, but further research is needed.
Objective The purpose of this study was to evaluate the effects of miniscrew insertion angle and vertical facial type on the interradicular miniscrew-root distance available for molar distalization. ...Materials and methods Cone-beam computed tomography images of 60 adults with skeletal Class I occlusion exhibiting hyperdivergent (n = 20), normodivergent (n = 20), and hypodivergent (n = 20) facial types were used. Placement of a 6-mm long, 1.5-mm diameter, tapered miniscrew was simulated at a site 4 mm apical to the cementoenamel junction, with insertion angles of 0#176;, 30#176;, 45#176;, and 60#176; relative to the transverse occlusal plane. The shortest linear distance between the miniscrew and anterior root at four interradicular sites was measured: maxillary second premolar and first molar (Mx 5-6), maxillary first and second molars (Mx 6-7), mandibular second premolar and first molar (Mn 5-6), and mandibular first and second molars (Mn 6-7). Results Miniscrew-root distance significantly increased as the insertion angle increased from 0#176; to 60#176;. In the mandible, the distances significantly differed among vertical facial types, increasing in the following order: hyperdivergent, normodivergent, and hypodivergent. The minimum mean distance was found in the Mx 6-7 (30#176;; 0.86#177;0.35 mm), and the maximum mean distance was found in the Mn 5-6 (60#176;; 2.64#177;0.56 mm). The rates of miniscrews located buccally outside the root distalization path were up to 70% and 55% when the miniscrews were placed at 60#176; insertion angles in the Mx 5-6 and Mn 5-6 regions, respectively. Conclusions Miniscrew-root distance increased significantly with the increased insertion angle, and the amount of increase was affected by the miniscrew placement site and vertical facial type. To ensure adequate distalization of the posterior segment, the miniscrew should be inserted at an angle in the interradicular area between the second premolar and first molar.
The prevalence of temporomandibular joint disorder (TMD) is gradually increasing, and magnetic resonance imaging (MRI) is becoming increasingly common as a modality used to diagnose TMD. Edema and ...osteonecrosis in the bone marrow of the mandibular condyle have been considered to be precursors of osteoarthritis, but these changes are not evaluated accurately and quantitatively on routine MRI. The iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method, as a cutting-edge MRI technique, can separate fat and water using three asymmetric echo times and the three-point Dixon method. The purpose of this study was to analyze the quantitative fat fraction (FF) in the mandibular condyle head using the IDEAL-IQ method. Seventy-nine people who underwent MRI using IDEAL-IQ were investigated and divided into 1) the control group, without TMD symptoms, and 2) the TMD group, with unilateral temporomandibular joint (TMJ) pain. In both groups, the FF of the condyle head in the TMJ was analyzed by two oral and maxillofacial radiologists. In the TMD group, 29 people underwent cone-beam computed tomography (CBCT) and the presence or absence of bony changes in the condylar head was evaluated. The FF measurements of the condyle head using IDEAL-IQ showed excellent inter-observer and intra-observer agreement. The average FF of the TMD group was significantly lower than that of the control group (p < 0.05). In the TMD group, the average FF values of joints with pain and joints with bony changes were significantly lower than those of joints without pain or bony changes, respectively (p < 0.05). The FF using IDEAL-IQ in the TMJ can be helpful for the quantitative diagnosis of TMD.
To address the drug-resistance of bacterial pathogens without imposing a selective survival pressure, virulence and biofilms are highly attractive targets. Here, we show that terrein, which was ...isolated from Aspergillus terreus, reduced virulence factors (elastase, pyocyanin, and rhamnolipid) and biofilm formation via antagonizing quorum sensing (QS) receptors without affecting Pseudomonas aeruginosa cell growth. Additionally, the effects of terrein on the production of QS signaling molecules and expression of QS-related genes were verified. Interestingly, terrein also reduced intracellular 3,5-cyclic diguanylic acid (c-di-GMP) levels by decreasing the activity of a diguanylate cyclase (DGC). Importantly, the inhibition of c-di-GMP levels by terrein was reversed by exogenous QS ligands, suggesting a regulation of c-di-GMP levels by QS; this regulation was confirmed using P. aeruginosa QS mutants. This is the first report to demonstrate a connection between QS signaling and c-di-GMP metabolism in P. aeruginosa, and terrein was identified as the first dual inhibitor of QS and c-di-GMP signaling.
Recent evidence suggests that Fusobacterium nucleatum (Fn) is associated with the development and progression of colorectal cancer. We aimed to delineate the clinical implications of Fn in metastatic ...colon cancer. We performed quantitative polymerase chain reaction (qPCR) using DNA samples from synchronous metastatic colon cancer patients with either formalin-fixed paraffin-embedded (FFPE) archival primary site tumor samples or fresh colon tissues. Progression-free survival (PFS)1 and PFS2 were defined as PFS of first- and second-line palliative settings. qPCR for Fn was successfully performed using 112 samples (FFPE, n = 61; fresh tissue, n = 51). Forty-one and 68 patients had right-sided and left-sided colon cancer, respectively. Patients with Fn enriched right-sided colon cancers had shorter PFS1 (9.7 vs. 11.2 months) than the other subgroups (HR 3.54, 95% confidence interval CI 1.05-11.99; P = 0.04). Fn positive right-sided colon was also associated with shorter PFS2 (3.7 vs. 6.7 months; HR 2.34, 95% CI 0.69-7.91; P = 0.04). In the univariate analysis, PFS1 was affected by differentiation and Fn positive right-sided colon cancer. The multivariate analysis showed that differentiation (HR 2.68, 95% CI 1.40-5.14, P = 0.01) and Fn positive right-sided colon (HR 0.40, 95% CI 0.18-0.88, P = 0.02) were associated with PFS1. Fn enrichment in right sided colon was not associated with overall survival (OS). Fn enrichment has significantly worse prognosis in terms of PFS1 and PFS2 in patients with right-sided metastatic colon cancers.
Anatomical structure classification is necessary task in medical field, but the inevitable variability of interpretation among experts makes reliable classification difficult. This study aims to ...introduce cluster analysis, unsupervised machine learning method, for classification of three-dimensional (3D) mandibular canal (MC) courses, and to visualize standard MC courses derived from cluster analysis in the Korean population.
A total of 429 cone-beam computed tomography images were used. Four sites in the mandible were selected for the measurement of the MC course and four parameters, two vertical and two horizontal parameters were measured per site. Cluster analysis was carried out as follows: parameter measurement, parameter normalization, cluster tendency evaluation, optimal number of clusters determination, and k-means cluster analysis. The 3D MC courses were classified into three types with statistically significant mean differences by cluster analysis.
Cluster 1 showed a smooth line running towards the lingual side in the axial view and a steep slope in the sagittal view. Cluster 2 ran in an almost straight line closest to the lingual and inferior border of mandible. Cluster 3 showed the pathway with a bent buccally in the axial view and an increasing slope in the sagittal view in the posterior area. Cluster 2 showed the highest distribution (42.1%), and males were more widely distributed (57.1%) than the females (42.9%). Cluster 3 comprised similar ratio of male and female cases and accounted for 31.9% of the total distribution. Cluster 1 had the least distribution (26.0%) Distributions of the right and left sides did not show a statistically significant difference.
The MC courses were automatically classified as three types through cluster analysis. Cluster analysis enables the unbiased classification of the anatomical structures by reducing observer variability and can present representative standard information for each classified group.
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease, is a widespread liver condition characterized by excessive fat ...buildup in hepatocytes without significant alcohol consumption. Manipulation of the gut microbiome has been considered to prevent and improve the occurrence and progression of MASLD, particularly through the gut-liver axis. This study aimed to investigate the correlation between the gut microbiome and liver function and determine whether the gut microbiome can ameliorate MASLD. We comparatively analyzed the gut microbiome composition between mice fed normal chow and those fed a high-fat diet and observed that the abundance of
Kineothrix alysoides
decreased in the high-fat group. Further analysis showed that treatment with
K. alysoides
in the high-fat diet group led to decreased weight loss, and MASLD attenuation. Importantly,
K. alysoides
treatment attenuated MASLD in mice fed a high-fat, high-fructose diet (HFHF), which can cause advanced liver damage. Furthermore, administration of
K. alysoides
altered the gut microbial composition in the HFHF diet group and improved MASLD. Overall, these findings demonstrate the potential of
K. alysoides
in restoring gut health and facilitating lipid metabolism to prevent and treat MASLD.
This paper presents a reconfigurable wide input power range radio frequency (RF) energy harvester (EH) with alliance for wireless power (A4WP) wireless power receiver (WPR). A reconfigurable RF-DC ...converter for RF EH and maximum power point tracking algorithm are proposed to maintain high efficiency over a wide input power range -20 to +20 dBm. The A4WP WPR is designed and merged with the EH to receive power higher than +20 dBm. In order to improve the power conversion efficiency (PCE), the delay between the ac input voltage and current is compensated by the proposed open-loop delay compensation method. The chip is implemented in 0.18 μm bipolar-CMOS-double-diffused metal-oxide-semiconductor process. The die area of the chip is 4.3 mm × 3.2 mm, including the pads. The proposed EH with WPR achieves a measured peak PCE of 48.19% with respect to the input power of 0 dBm at 900 MHz. It also has a peak PCE of 82.14% with respect to the input power of 30 dBm in an A4WP mode operation at 6.78 MHz.
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