Real-Time Imaging Assessment of Stress-Induced Vascular Inflammation Using Heartbeat-Synchronized Motion Compensation.

BACKGROUND: Chronic mental stress accelerates atherosclerosis through complicated neuroimmune pathways, needing for advanced imaging techniques to delineate underlying cellular mechanisms. While histopathology, ex vivo imaging, and snapshots of in vivo images offer promising evidence, they lack the ability to capture real-time visualization of blood cell dynamics within pulsatile arteries in longitudinal studies. METHODS: An electrically tunable lens was implemented in intravital optical microscopy, synchronizing the focal plane with heartbeats to follow artery movements. ApoE-/- mice underwent 2 weeks of restraint stress before baseline imaging followed by 2 weeks of stress exposure in the longitudinal imaging, while nonstressed mice remained undisturbed. The progression of vascular inflammation was assessed in the carotid arteries through intravital imaging and histological analyses. RESULTS: A 4-fold reduction of motion artifact, assessed by interframe SD, and an effective temporal resolution of 25.2 Hz were achieved in beating murine carotid arteries. Longitudinal intravital imaging showed chronic stress led to a 6.09-fold (P=0.017) increase in myeloid cell infiltration compared with nonstressed mice. After 3 weeks, we observed that chronic stress intensified vascular inflammation, increasing adhered myeloid cells by 2.45-fold (P=0.031), while no significant changes were noted in nonstressed mice. Microcirculation imaging revealed increased circulating, rolling, and adhered cells in stressed mice's venules. Histological analysis of the carotid arteries confirmed the in vivo findings that stress augmented plaque area, myeloid cell and macrophage accumulation, and necrotic core volume while reducing fibrous cap thickness indicating accelerated plaque formation. We visualized the 3-dimensional structure of the carotid artery and 4-dimensional dynamics of the venules in the cremaster muscle. CONCLUSIONS: Dynamic focusing motion compensation intravital microscopy enabled subcellular resolution in vivo imaging of blood cell dynamics in beating arteries under chronic restraint stress in real time. This novel technique emphasizes the importance of advanced in vivo imaging for understanding cardiovascular disease.

Detoxification of ars genotypes by arsenite-oxidizing bacteria through arsenic biotransformation.

The detoxification process of transforming arsenite (As(III)) to arsenate (As(V)) through bacterial oxidation presents a potent approach for bioremediation of arsenic-polluted soils in abandoned mines. In this study, twelve indigenous arsenic-oxidizing bacteria (AOB) were isolated from arsenic-contaminated soils. Among these, Paenibacillus xylanexedens EBC-SK As2 (MF928871) and Ochrobactrum anthropi EBC-SK As11 (MF928880) were identified as the most effective arsenic-oxidizing isolates. Evaluations for bacterial arsenic resistance demonstrated that P. xylanexedens EBC-SK As2 (MF928871) could resist As(III) up to 40 mM, while O. anthropi EBC-SK As11 (MF928880) could resist As(III) up to 25 mM. From these bacterial strains, genotypes of arsenic resistance system (ars) were detected, encompassing ars leader genes (arsR and arsD), membrane genes (arsB and arsJ), and aox genes known to be crucial for arsenic detoxification. These ars genotypes in the isolated AOBs might play an instrumental role in arsenic-contaminated soils with potential to reduce arsenic contamination.

An integrative single-cell atlas for exploring the cellular and temporal specificity of genes related to neurological disorders during human brain development.

Single-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expression under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of the developing human brain, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including those associated with autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages that diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder-related genes. Lineages of nonneuronal cells determined by molecular profiles also showed temporal-specific expression, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types associated with neuronal disorders indicative of the prenatal stage's influence on disease determination. Our findings facilitate unbiased comparisons of cell type‒disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders.

Increased antimicrobial resistance of acid-adapted pathogenic Escherichia coli, and transcriptomic analysis of polymyxin-resistant strain.

This study investigated the acid adaptation and antimicrobial resistance of seven pathogenic Escherichia coli strains and one commensal strain under nutrient-rich acidic conditions. After acid adaptation, three pathogenic E. coli survived during 100 h incubation in tryptic soy broth at pH 3.25. Acid-adapted (AA) strains showed increased resistance to antimicrobials including ampicillin, ciprofloxacin and especially polymyxins (colistin and polymyxin B), the last resort antimicrobial for multidrug-resistant Gram-negative bacteria. Enterotoxigenic E. coli strain (NCCP 13717) showed significantly increased resistance to acids and polymyxins. Transcriptome analysis of the AA NCCP 13717 revealed upregulation of genes related to the acid fitness island and the arn operon, which reduces lipopolysaccharide binding affinity at the polymyxin site of action. Genes such as eptA, tolC, and ompCF were also upregulated to alter the structure of the cell membrane, reducing the outer membrane permeability compared to the control, which is likely to be another mechanism for polymyxin resistance. This study highlights the emergence of antimicrobial resistance in AA pathogenic E. coli strains, particularly polymyxin resistance, and the mechanisms behind the increased antimicrobial resistance, providing important insights for the development of risk management strategies to effectively control the antimicrobial resistant foodborne pathogens.

Targeted precision cryotherapy for acne vulgaris.

BACKGROUND: Acne vulgaris poses a significant dermatological challenge, necessitating alternative treatments due to limitations and side effects associated with current therapies. This pilot clinical trial investigated the feasibility and efficacy of precision cryotherapy for acne vulgaris. METHODS: A total of 20 volunteers underwent targeted precision cryotherapy using a carbon dioxide-based device. Treatment outcomes were assessed using various parameters, including Investigator Global Assessment (IGA) score, acne lesion count, erythema index (EI), global evaluation score, and participant satisfaction. Safety monitoring included adverse event reporting and physical examination. RESULTS: Precision cryotherapy demonstrated a significant reduction (90.25%) in the acne lesion count by week 4, with clinical improvement indicated by IGA score reduction (p < 0.001). The EI showed notable improvements at weeks 1, 2, and 4. The global evaluation score demonstrated a 75%-100% clinical improvement at Visit 4. Participants reported high satisfaction (6.75 ± 0.79) with the procedure. No adverse event or discomfort was reported. CONCLUSION: Precision cryotherapy effectively improved acne lesions, which was safe and satisfactory for participants. These findings suggest its potential as an alternative therapeutic modality, especially for populations with limited treatment options. Further research is needed to validate the results and explore underlying mechanisms.

Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets.

Background: Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms. Methods: We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets. Results: We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063). Conclusions: Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

Co-occurrence between key HAB species and particle-attached bacteria and substrate specificity of attached bacteria in the coastal ecosystem.

The ecological dynamics of particle-attached bacteria (PAB) were observed through changes in the core phytoplankton phycosphere, and were associated with the dynamics of free-living bacteria (FLB) using metabarcoding and microscopic analyses over 210 days (with weekly sampling intervals) in the Jangmok coastal ecosystem, South Korea. Cluster analysis and non-metric multidimensional scaling classified the phytoplankton community into six groups comprising core phytoplankton species, including the harmful algal species Akashiwo sanguinea (dinoflagellate) in late autumn, Teleaulax amphioxeia (cryptomonads) in early winter and spring, Skeletonema marinoi-dohrnii complex (diatom) in winter, Pseudo-nitzschia delicatissima (diatom) in early spring, and diatom complexes such as Chaetoceros curvisetus and Leptocylindrus danicus in late spring. We identified 59 and 32 indicators in PAB and FLB, respectively, which rapidly changed with the succession of the six core phytoplankton species. The characteristics of PAB were mainly divided into "Random encounters" or "Attraction of motivation by chemotaxis." When Akashiwo sanguinea bloomed, bacteria of the genera Kordiimonas and Polaribacter, which are commonly observed in PAB and FLB, indicated "Random encounter" characteristics. In addition, Sedimenticola of PAB was uniquely presented in Akashiwo sanguinea, exhibiting characteristics of "Attraction of motivation by chemotaxis." In contrast, FLB followed the strategy of "Random encounters" because it was not affected by specific habitats and energy sources. Thus, many common bacteria were PAB and FLB, thereby dictating the bacteria's strategy of "Random encounters." "Attraction of motivation by chemotaxis" has characteristics of the species-specific interactions between PAB and specific harmful algal species, and is potentially influenced by organic matter of core phytoplankton cell surface and/or EPS released from phytoplankton.

Determining ecological interactions of key dinoflagellate species using an intensive metabarcoding approach in a semi-closed coastal ecosystem of South Korea.

Marine phytoplankton communities are pivotal in biogeochemical cycles and impact global climate change. However, the dynamics of the dinoflagellate community, its co-occurrence relationship with other eukaryotic plankton communities, and environmental factors remain poorly understood. In this study, we aimed to analyze the temporal changes in the eukaryotic plankton community using a 18S rDNA metabarcoding approach. We performed intensive monitoring for 439 days at intervals of three days during the period from November 2018 to June 2020 (n = 260) in Jangmok Bay Time-series Monitoring Site in South Korea. Among the 16,224 amplicon sequence variants (ASVs) obtained, dinoflagellates were the most abundant in the plankton community (38 % of total relative abundance). The dinoflagellate community was divided into 21 groups via cluster analysis, which showed an annually similar distribution of low-temperature periods. Additionally, we selected 11 taxa that had an occurrence mean exceeding 1 % of the total dinoflagellate abundance, accounting for 93 % of the total dinoflagellate community: namely Heterocapsa rotundata, Gymnodinium sp., Akashiwo sanguinea, Amoebophrya sp., Euduboscquella sp., Spiniferites ramosus, Dissodinium pseudolunula, Sinophysis sp., Karlodinium veneficum, and Katodinium glaucum. The key dinoflagellate species were well represented at temporally variable levels over an entire year. Heterocapsa rotundata was not significantly affected by water temperature, whereas its dynamics were largely influenced by strong predation pressure, competition, and/or the supplementation of food sources. The growth of A. sanguinea was associated with dissolved inorganic phosphorus concentrations, while Euduboscquella sp. showed a significant relationship with D. pseudolunula and K. glaucum, largely representing a positive association that implies possible parasitic mechanisms. This study demonstrated interactions between key dinoflagellate species and the environment, as well as parasites, predators, competitors, and feeders.

Visceral adiposity is associated with iron deposition and myelin loss in the brains of aged mice.

Iron deposition and myelin loss are observed in the brain with aging, and iron accumulation is suggested to be involved in myelin damage. However, the exact mechanism of iron deposition with aging remains unclear. This study was aimed to determine whether expanded visceral adipose tissue contributes to iron deposition and myelin loss by inducing hepcidin in the brains of aged male mice. Compared with young adult mice, levels of hepcidin in the brain, epididymal adipose tissue, and circulation were increased in aged mice, which had expanded visceral adipose tissue with inflammation. An increase in expressions of ferritin, an indicator of intracellular iron status, was accompanied by decreased levels of proteins related to myelin sheath in the brains of aged mice. These age-related changes in the brain were improved by visceral fat removal. In addition, IL-6 level, activation of microglia/macrophages, and nuclear translocation of phosphorylated Smad1/5 (pSmad1/5) inducing hepcidin expression were reduced in the brains of aged mice after visceral fat removal, accompanied by decreases of pSmad1/5- and ferritin-positive microglia/macrophages and mature oligodendrocytes. These findings indicate that visceral adiposity contributes to hepcidin-mediated iron deposition and myelin loss with inflammation in the aged brain. Our results support the importance of preventing visceral adiposity for maintaining brain health in older individuals.

Reconsidering Neurogenetic Indication in the Human Brain: Broad Expression of Doublecortin Transcript in the Hippocampal and Cortical Cell Populations.

INTRODUCTION: Neurogenesis in the adult brain may play an important role in memory and cognition; however, knowledge of neurogenic markers in the human brain remains limited. We compared the single-nucleus transcriptome of the hippocampus with that of other cortical regions to identify hippocampus-specific neurogenic markers. METHODS: We analyzed 26,189 nuclei from four human brains collected within 16 h of death. Clustering and annotation were performed to examine differential expression, gene ontology, and intercellular communication. DCX expression was validated by ddPCR. RESULTS: Immature markers such as DCX, CALB2, NES, SOX2, PAX6, DPYSL3, and TUBB3 were expressed in both hippocampus and prefrontal cortex, with higher levels in the prefrontal cortex. ddPCR confirmed higher expression of DCX in the prefrontal cortex. DCX was involved in both neurogenesis and neuroprotection pathways. CONCLUSION: Neurogenic markers are not definitive indicators of adult neurogenesis as their roles are more complex than previously understood.

Enterohemorrhagic Escherichia coli (EHEC) disrupts intestinal barrier integrity in translational canine stem cell-derived monolayers.

This study addresses the gap in translatable in vitro models for investigating Enterohemorrhagic E. coli (EHEC) infections, particularly relevant to both canine and human health. EHEC is known to induce acute colitis in dogs, leading to symptoms like hemorrhagic diarrhea and hemolytic uremic syndrome, similar to those observed in humans. However, understanding the pathophysiology and developing treatment strategies have been challenging due to the lack of effective models that replicate the clinical disease caused by EHEC in both species. Our approach involved the development of colonoid-derived monolayers using intestinal tissues from healthy, client-owned dogs. These monolayers were exposed to EHEC, and the impact of EHEC was assessed through several techniques, including trans-epithelial electrical resistance (TEER) measurement, immunofluorescence staining for junction proteins and mucus, and scanning electron microscopy for morphological analysis. Modified culture with saline, which was intended to prevent bacterial overgrowth, maintained barrier integrity and cell differentiation. EHEC infection led to significant decreases in TEER and ZO-1 expression, but not in E-cadherin levels or mucus production. In addition, EHEC elicited a notable increase in tumor necrosis factor-alpha production, highlighting its distinct impact on canine intestinal epithelial cells compared to non-pathogenic E. coli. These findings closely replicate in vivo observations in dogs and humans with EHEC enteropathy, validating the canine colonoid-derived monolayer system as a translational model to study host-pathogen interactions in EHEC and potentially other clinically significant enteric pathogens. IMPORTANCE: This study develops a new model to better understand Enterohemorrhagic E. coli (EHEC) infections, a serious bacterial disease affecting both dogs and humans, characterized by symptoms such as hemorrhagic diarrhea and hemolytic uremic syndrome. Traditional research models have fallen short of mimicking how this disease manifests in patients. Our research used intestinal tissues from healthy dogs to create layers of cells, known as colonoid-derived monolayers, which we then exposed to EHEC. We assessed the damage caused by the bacteria using several techniques, observing significant changes similar to those seen in actual cases of the disease. The model proved effective in replicating the interaction between the host and the pathogen, marking an important step toward understanding EHEC's effects and developing treatments. This canine colonoid-derived monolayer system not only bridges a crucial gap in current research but also offers a promising platform for studying other enteric pathogens affecting both canine and human health.

Nurses' perspectives about end-of-life care when family presence is restricted during a pandemic: A qualitative study.

BACKGROUND: To prevent the infection from spreading, patients who were dying from COVID-19 were treated in isolation with restricted family access, which differed from existing end-of-life care procedures. This was a significant change that affected the care provided by nurses. OBJECTIVES: This study explored nurses' end-of-life care experiences in a limited family visitation setting during the COVID-19 pandemic. METHODS: A descriptive qualitative study was conducted. Data were collected through individual, in-depth, semistructured interviews with ten critical care nurses who provided end-of-life care to patients with COVID-19 in South Korea. The data were analysed using thematic analysis. The Consolidated Criteria for Reporting Qualitative Research checklist was used to assess the study's rigour. FINDINGS: Three themes were identified: 'Witnessing patients' and families' heartbreak over separation', 'The gaps between the ideals and realities of end-of-life care', and 'Efforts to provide patients with a comfortable final journey'. Nurses realise the importance of their central role in supporting interactions between patients and families during end-of-life care. CONCLUSIONS: Family participation, facilitated by nurses' interest and efforts as mediators connecting patients and families, is essential for achieving high-quality care for inpatients facing end of life. This study is significant as it emphasises that the direction of end-of-life care should be family centric, even in a pandemic situation with limited family participation. To improve interaction between patients and families, creating an environment based on family participation that builds trust and strengthens communication is essential. Additionally, hospital support, such as professional education and counselling, should be provided to strengthen nurses' end-of-life care competency.

The effect of remote ischemic conditioning on mortality after kidney transplantation: the systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes. METHODS: Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1. RESULTS: Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13-75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14-3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23-1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30-1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73-1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61-1.56, P = 0.93). CONCLUSIONS: It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336565.

Multimodal Imaging-Assisted Intravascular Theranostic Photoactivation on Atherosclerotic Plaque.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.

Low-level brain somatic mutations in exonic regions are collectively implicated in autism with germline mutations in autism risk genes.

Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p < 0.05). Patients with damaging mutations in the merged gene set had a greater ASD risk than did controls (odds ratio = 3.92, p = 0.025, 95% confidence interval = 1.12-14.79). The findings of this study suggest that brain somatic SNVs and germline SNVs may collectively contribute to ASD-associated pathophysiology.

Association between Systolic Blood Pressure Variability and Incident Aortic Stenosis.

Background: This study investigated the potential link between blood pressure variability (BPV) and the incidence of aortic stenosis (AS) using Korean National Health Insurance Service data from 2002 to 2019. Methods: We collected annual systolic blood pressure variability (SBPV) measurements consisting of three consecutive blood pressure readings each year over three years. The obtained SBPV data was divided into five quantiles, with the highest quintile representing a high fluctuation of blood pressure. Results: Analyzing 9,341,629 individuals with a mean age of 40.7 years, the study found 3981 new AS diagnoses during an average 8.66-year follow-up. Independent predictors for AS included higher blood pressure levels and elevated systolic blood pressure variability (SBPV). The hazard ratios (HR) for different SBPV quintiles compared to the reference (1st quintile) were as follows: 2nd quintile HR 1.09 (p = 0.18), 3rd quintile HR 1.13 (p = 0.04), 4th quintile HR 1.13 (p = 0.04), and 5th quintile HR 1.39 (p < 0.001). Conclusion: Our findings suggest that both hypertension and high fluctuations in SBP during consecutive visits are associated with an increased risk of incident AS. These results emphasize the importance of blood pressure management and stability in the prevention of AS.

Stress resistance insights of 65 Listeria strains: Acidic, low temperature, and high salt environments.

Genetically, Listeria monocytogenes is closely related to non-L. monocytogenes (L. innocua, L. welshimeri, L. grayi, L. aquatica, and L. fleischimannii). This bacterium is well known for its resistance to harsh conditions including acidity, low temperatures, and high salt concentrations. This study explored the responses of 65 Listeria strains to stress conditions and characterized the prevalence of stress-related genes. The 65 Listeria strains were isolated from different environments and their viability was assessed in four different tests: independent tests for pH 3, 1 °C, and 5 % salt concentration and multiple resistance tests that combined pH 3, 1 °C, 5 % salt. From the data, the 65 strains were categorized into stress-resistant (56) or stress-sensitive groups (9), with approximately 4 log CFU/mL differences. The PCR assay analyzed the prevalence of two virulence genes prfA and inlA, and eight stress-related genes: three acid (gadB, gadC, and atpD), two low temperature (betL and opuCA) and three salt resistance genes (flaA, cysS, and fbp). Two low temperature (bet and opuCA) and salt resistance (fbp) genes were more prevalent in the stress-resistant strains than in the stress-sensitive Listeria group.

Garre's osteomyelitis of the mandible managed by nonsurgical re-endodontic treatment.

Chronic osteomyelitis with proliferative periostitis, known as Garre's osteomyelitis, is a type of osteomyelitis characterized by a distinctive gross thickening of the periosteum of bones. Peripheral reactive bone formation can be caused by mild irritation or infection. Garre's osteomyelitis is usually diagnosed in children and young adults, and the mandible is more affected than the maxilla. The following is a case report of a 12-year-old female patient with Garre's osteomyelitis of the mandible due to an infection of a root canal-treated tooth. Without surgical intervention, the patient's symptoms were relieved through nonsurgical root canal re-treatment with long-term calcium hydroxide placement. A cone-beam computed tomography image obtained 6 months after treatment completion displayed complete healing of the periapical lesion and resolution of the peripheral reactive buccal bone. Due to the clinical features of Garre's osteomyelitis, which is characterized by thickening of the periosteum, it can be mistaken for other diseases such as fibrous dysplasia. It is important to correctly diagnose Garre's osteomyelitis based on its distinctive clinical features to avoid unnecessary surgical intervention, and it can lead to minimally invasive treatment options.

Bioengineered human gut-on-a-chip for advancing non-clinical pharmaco-toxicology.

INTRODUCTION: There is a growing need for alternative models to advance current non-clinical experimental models because they often fail to accurately predict drug responses in human clinical trials. Human organ-on-a-chip models have emerged as promising approaches for advancing the predictability of drug behaviors and responses. AREAS COVERED: We summarize up-to-date human gut-on-a-chip models designed to demonstrate intricate interactions involving the host, microbiome, and pharmaceutical compounds since these models have been reported a decade ago. This overview covers recent advances in gut-on-a-chip models as a bridge technology between non-clinical and clinical assessments of drug toxicity and metabolism. We highlight the promising potential of gut-on-a-chip platforms, offering a reliable and valid framework for investigating reciprocal crosstalk between the host, gut microbiome, and drug compounds. EXPERT OPINION: Gut-on-a-chip platforms can attract multiple end users as predictive, human-relevant, and non-clinical model. Notably, gut-on-a-chip platforms provide a unique opportunity to recreate a human intestinal microenvironment, including dynamic bowel movement, luminal flow, oxygen gradient, host-microbiome interactions, and disease-specific manipulations restricted in animal and in vitro cell culture models. Additionally, given the profound impact of the gut microbiome on pharmacological bioprocess, it is critical to leverage breakthroughs of gut-on-a-chip technology to address knowledge gaps and drive innovations in predictive drug toxicology and metabolism.