Mouth Closure and Airflow in Patients With Obstructive Sleep Apnea: A Nonrandomized Clinical Trial.

Importance: Mouth breathing is associated with increased airway resistance, pharyngeal collapsibility, and obstructive sleep apnea (OSA) severity. The common belief is that closing the mouth can mitigate the negative effects of mouth breathing during sleep. However, mouth breathing may serve as an essential route to bypassing obstruction along the nasal route (eg, the velopharynx). Objective: To investigate the role of mouth breathing as an essential route in some patients with OSA and its association with upper airway anatomical factors. Design, Setting, and Participants: This nonrandomized clinical trial included participants diagnosed with OSA who underwent drug-induced sleep endoscopy. Patients were stratified into 3 quantiles based on oral-breathing level (quantile 1: oral airflow < 0.05 L/min; quantile 2: oral airflow 0.05-2.2 L/min; quantile 3: oral airflow > 2.2 L/min). Interventions: Closing the mouth during sleep during alternating breaths by applying pressure to the mentum until teeth are in occlusion. Main Outcomes and Measures: The primary outcome was total inspiratory flow defined as the change in airflow in the transition from mouth relaxed to mouth closed, analyzed overall and by 3 oral-breathing quantiles. The association of velopharyngeal obstruction on the change in total inspiratory airflow was also investigated. Results: Of 66 enrolled patients with OSA, 12 were excluded due to insufficient baseline airflow. The analytic cohort consisted of 54 patients (39 [72%] male; median [IQR] age, 55 [46-64] years; apnea-hypopnea index, 26.9 [17.6-39.9] events/h; and body mass index calculated as weight in kilograms divided by height in meters squared, 28.9 [27.1-31.6]). Mouth closure increased total inspiratory flow by 27.8 percentage points overall (ß, 1.0 [95% CI, 0.4-1.9] L/min). However, outcomes varied based on the degree of baseline oral breathing. No association was found for 10 patients with near-zero mouth breathing (0.9 [95% CI, -0.2 to 2.1] L/min). Airflow improved with mouth closure in 32 patients with moderate levels of mouth breathing (2.0 [95% CI, 1.3-2.7] L/min), whereas it worsened in patients with high levels of mouth breathing (-1.9 [95% CI, -3.1 to -0.6] L/min). Velopharyngeal obstruction was associated with increased mouth breathing (0.6 [95% CI, 0.1-3.0] L/min) and reduced airflow with mouth closure (-1.9 [95% CI, -3.1 to -0.7] L/min). Conclusion and Relevance: Although mouth closure increased inspiratory airflow in the overall cohort of this nonrandomized clinical trial, the outcomes were heterogeneous. In patients who breathe primarily through their mouth during sleep and have velopharyngeal obstruction, airflow worsens with mouth closure. Hence, personalized approaches to treating mouth breathing should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT06547658.

METTL3-Mediated N 6 -Methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis.

Background: Chemical modifications on RNA profoundly affect RNA function and regulation. m6A, the most abundant RNA modification in eukaryotes, plays a pivotal role in diverse cellular processes and disease mechanisms. However, its importance is understudied in human CKD samples regarding its influence on pathological mechanisms. Methods: Liquid chromatography­tandem mass spectrometry and methylated RNA immunoprecipitation sequencing were used to examine alterations in m6A levels and patterns in CKD samples. Overexpression of the m6A writer METTL3 in cultured kidney tubular cells was performed to confirm the effect of m6A in tubular cells and explore the biological functions of m6A modification on target genes. In addition, tubule-specific deletion of Mettl3 (Ksp-Cre Mettl3f/f) mice and antisense oligonucleotides inhibiting Mettl3 expression were used to reduce m6A modification in an animal kidney disease model. Results: By examining 127 human CKD samples, we observed a significant increase in m6A modification and METTL3 expression in diseased kidneys. Epitranscriptomic analysis unveiled an enrichment of m6A modifications in transcripts associated with the activation of inflammatory signaling pathways, particularly the cyclic guanosine monophosphate­AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway. m6A hypermethylation increased mRNA stability in cGAS and STING1 as well as elevated the expression of key proteins within the cGAS-STING pathway. Both the tubule-specific deletion of Mettl3 and the use of antisense oligonucleotides to inhibit Mettl3 expression protected mice from inflammation, reduced cytokine expression, decreased immune cell recruitment, and attenuated kidney fibrosis. Conclusions: Our research revealed heightened METTL3-mediated m6A modification in fibrotic kidneys, particularly enriching the cGAS-STING pathway. This hypermethylation increased mRNA stability for cGAS and STING1, leading to sterile inflammation and fibrosis.

Expressing miR-282 mitigates Aß42-induced neurodegeneration in Alzheimer's model in Drosophila.

Alzheimer's disease is a complex neurodegenerative condition characterized by the accumulation of amyloid beta plaques, leading to memory loss, cognitive decline, and impaired autonomous behavior. Despite extensive research, an effective treatment remains elusive. The buildup of amyloid beta plaques (Aß42) in the brain causes oxidative stress and disrupts normal molecular signaling, adversely affecting neuron function. Previous research has identified factors that can either exacerbate or mitigate neurodegenerative diseases. Our study aimed to uncover new factors involved in the pathogenesis of Alzheimer's disease. Using Drosophila as a model organism, we employed the Gal4/UAS system to express human Aß42 in the flies' retinal neurons which led to neurodegenerative changes in their compound eyes. To identify genetic modifiers, we conducted a screen by co-expressing microRNAs and found that miR-282 acts as a suppressor. Overexpressing miR-282 in the GMR > Aß42 background reduced Aß42-induced neurodegeneration. Further analysis using prediction tools and RNA interference experiments identified three potential downstream targets of miR-282: calpain-B, knot, and scabrous. Downregulating these genes via RNA interference in the GMR > Aß42 background mitigated neurodegeneration. Our research highlights miR-282 as a novel molecule that may influence the progression of Alzheimer's disease, offering potential avenues for future therapeutic or diagnostic developments.

Energy Consumption Minimization with SNR Constraint for Wireless Powered Communication Networks.

The article addresses the energy consumption minimization problem in wireless powered communication networks (WPCNs) and proposes a time allocation scheme, named DaTA, which is based on the Different Target Simultaneous Wireless Information and Power Transfer (DT-SWIPT) scheme such that the wireless station can share the remaining energy after transmission to the Hybrid Access Point (HAP) to those who have not transmitted to the HAP to minimize the energy consumption of the WPCN. In addition to proposing a new frame structure, the article also considers the Signal-to-Noise (SNR) constraint to guarantee that the HAP can successfully receive data from wireless stations. In the article, the problem of minimization of energy consumption is formulated as a nonlinear programming model. We employ the SQP (Sequential Quadratic Programming) algorithm to figure out the optimal solution. Moreover, a heuristic method is proposed as well to obtain a near-optimal solution in a shorter time. The simulation results showed that the proposed scheme outperforms the related work in terms of energy consumption and energy efficiency.

Selective Protein Degradation through Tetrazine Ligation of Genetically Incorporated Unnatural Amino Acids.

Small molecule-responsive tags for targeted protein degradation are valuable tools for fundamental research and drug target validation. Here, we show that genetically incorporated unnatural amino acids bearing a strained alkene or alkyne functionality can act as a minimalist tag for targeted protein degradation. Specifically, we observed the degradation of strained alkene- or alkyne-containing kinases and E2 ubiquitin-conjugating enzymes upon treatment with hydrophobic tetrazine conjugates. The extent of the induced protein degradation depends on the identity of the target protein, unnatural amino acid, and tetrazine conjugate, as well as the site of the unnatural amino acid in the target protein. Mechanistic studies revealed proteins undergo proteasomal degradation after tetrazine tethering, and the identity of tetrazine conjugates influences the dependence of ubiquitination on protein degradation. This work provides an alternative approach for targeted protein degradation and mechanistic insight, facilitating the future development of more effective targeted protein degradation strategies.

Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells.

Purpose: Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM), yet their role in ocular hypertension remains unclear. We used a human TM cell line that spontaneously forms fluorescently-labeled CLANs (GTM3L) to explore the origin of CLANs, developed techniques to increase CLAN incidence in GMT3L cells, and computationally studied the biomechanical properties of CLAN-containing cells. Methods: GTM3L cells were fluorescently sorted for viral copy number analysis. CLAN incidence was increased by (i) differential sorting of cells by adhesion, (ii) cell deswelling, and (iii) cell selection based on cell stiffness. GTM3L cells were also cultured on glass or soft hydrogel to determine substrate stiffness effects on CLAN incidence. Computational models were constructed to mimic and study the biomechanical properties of CLANs. Results: All GTM3L cells had an average of 1 viral copy per cell. LifeAct-GFP expression level did not affect CLAN incidence rate, but CLAN rate was increased from ~0.28% to ~50% by a combination of adhesion selection, cell deswelling, and cell stiffness-based sorting. Further, GTM3L cells formed more CLANs on a stiff vs. a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus. Conclusions: It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the effect of CLANs on TM biomechanics and mechanobiology as well as the etiology of CLAN formation in the TM.

Characteristics and Prevalence of Vancomycin-variable Enterococcus faecium bacteremia in southern Taiwan.

BACKGROUND: Vancomycin-variable enterococci (VVE) are vanA-carrying Enterococcus faecium that are phenotypically susceptible to vancomycin and can only be detected using molecular methods, leading to the possibility of treatment failure and posing threats to infection control. This study aimed to determine the prevalence of VVE and its associated clinical risk factors. METHODS: This retrospective study was conducted in two hospitals in southern Taiwan. Patients with phenotypically vancomycin-susceptible E. faecium bacteremia were enrolled between 2017 and 2021. VVEs were defined as isolates harboring the vanA gene that were phenotypically susceptible to vancomycin. Vancomycin-susceptible E. faecium (VSE) isolates were phenotypically susceptible to vancomycin and lacked vanA or vanB genes. RESULTS: Of the 142 enrolled patients, 121 (85.2%) had VSE and 21 (14.8%) had VVE. Resistance rates to penicillin, tetracycline, and fosfomycin were higher in VVE isolates. Malignancy (adjusted odds ratio [aOR] = 4.87; 95% confidence interval [CI] 1.54-15.41, p = 0.007) and central venous catheter usage (aOR = 4.69; 95% CI 1.49-14.78, p = 0.008) were the independent risk factors associated with VVE bacteremia. Being male (aOR = 0.12, CI 0.03-0.44, p = 0.002) was less likely to be associated with VVE bacteremia. Although VVE was not associated with 30-day mortality (38.1% [VVE] vs. 35.5% [VSE], p = 0.822), one case of subsequent vancomycin-resistant enterococci infection in the VVE group with vancomycin treatment (4.8%, 1/21) was identified, which led to subsequent mortality. CONCLUSIONS: The prevalence of VVE was high among E. faecium isolates with vancomycin-susceptible phenotypes in southern Taiwan. Although the current study revealed that VVE bacteremia was not associated with poor clinical outcome, further multicenter surveillance survey is recommended to evaluate the possible impact of VVE on public health in Taiwan.

Hepsin as a potential therapeutic target for alleviating acetaminophen-induced hepatotoxicity via gap-junction regulation and oxidative stress modulation.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver damage, highlighting the limitations of current emergency treatments that primarily involve administering the glutathione precursor N-acetylcysteine and supportive therapy. This study highlights the essential protective role of the type II transmembrane serine protease (TTSP), hepsin, in mitigating acetaminophen-induced liver injury, particularly through its regulation of gap junction (GJ) abundance in response to reactive oxygen stress in the liver. We previously reported that reduced levels of activated hepatocyte growth factor and the c-Met receptor tyrosine kinase-both of which are vital for maintaining cellular redox balance-combined with increased expression of GJ proteins in hepsin-deficient mice. Here, we show that hepsin deficiency in mice exacerbates acetaminophen toxicity compared to wild-type mice, leading to more severe liver pathology, elevated oxidative stress, and greater mortality within 6 h after exposure. Administering hepsin had a protective effect in both mouse models, reducing hepatotoxicity by modulating GJ abundance. Additionally, transcriptome analysis and a functional GJ inhibitor have highlighted hepsin's mechanism for managing oxidative stress. Combining hepsin with relatively low doses of N-acetylcysteine had a synergistic effect that was more efficacious than high-dose N-acetylcysteine alone. Our results illustrate the crucial role of hepsin in modulating the abundance of hepatic GJs and reducing oxidative stress, thereby offering early protection against acetaminophen-induced hepatotoxicity and a new, combination approach. Emerging as a promising therapeutic target, hepsin holds potential for combination therapy with N-acetylcysteine, paving the way for novel approaches in managing drug-induced liver injury.

PIAS1 S510G variant acts as a genetic modifier of spinocerebellar ataxia type 3 by selectively impairing mutant ataxin-3 proteostasis.

Dysregulated protein homeostasis, characterized by abnormal protein accumulation and aggregation, is a key contributor to the progression of neurodegenerative disorders such as Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Previous studies have identified PIAS1 gene variants in patients with late-onset SCA3 and Huntington's disease. This study aims to elucidate the role of PIAS1 and its S510G variant in modulating the pathogenic mechanisms of SCA3. Through in vitro biochemical analyses and in vivo assays, we demonstrate that PIAS1 stabilizes both wild-type and mutant ataxin-3 (ATXN3). The PIAS1 S510G variant, however, selectively reduces the stability and SUMOylation of mutant ATXN3, thereby decreasing its aggregation and toxicity while maintaining the stability of wild-type ATXN3. This effect is mediated by a weakened interaction with the SUMO-conjugating enzyme UBC9 in the presence of mutant ATXN3. In Drosophila models, downregulation of dPIAS1 resulted in reduced levels of mutant ATXN3 and alleviated associated phenotypes, including retinal degeneration and motor dysfunction. Our findings suggest that the PIAS1 S510G variant acts as a genetic modifier of SCA3, highlighting the potential of targeting SUMOylation as a therapeutic strategy for this disease.

Single-Molecule Sequencing of the C9orf72 Repeat Expansion in Patient iPSCs.

A hexanucleotide GGGGCC repeat expansion in the C9orf72 gene is the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). C9orf72 repeat expansions are currently identified with long-range PCR or Southern blot for clinical and research purposes, but these methods lack accuracy and sensitivity. The GC-rich and repetitive content of the region cannot be amplified by PCR, which leads traditional sequencing approaches to fail. We turned instead to PacBio single-molecule sequencing to detect and size the C9orf72 repeat expansion without amplification. We isolated high molecular weight genomic DNA from patient-derived iPSCs of varying repeat lengths and then excised the region containing the C9orf72 repeat expansion from naked DNA with a CRISPR/Cas9 system. We added adapters to the cut ends, capturing the target region for sequencing on PacBio's Sequel, Sequel II, or Sequel IIe. This approach enriches the C9orf72 repeat region without amplification and allows the repeat expansion to be consistently and accurately sized, even for repeats in the thousands. Key features • This protocol is adapted from PacBio's previous "no-amp targeted sequencing utilizing the CRISPR-Cas9 system." • Optimized for sizing C9orf72 repeat expansions in patient-derived iPSCs and applicable to DNA from any cell type, blood, or tissue. • Requires high molecular weight naked DNA. • Compatible with Sequel I and II but not Revio.

Paclitaxel-resistance facilitates glycolytic metabolism via Hexokinase-2-regulated ABC and SLC transporter genes in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) frequently develops resistance to platinum-based therapies, which is regarded as an aggressive subtype. However, metabolic changes in paclitaxel resistance remain unclear. Herein, we present the metabolic alternations of paclitaxel resistance in bioenergetic profiling in OCCC. Paclitaxel-resistant OCCC cells were developed and metabolically active with oxygen consumption rates (OCR) compared to parental cells. Metabolite profiling analysis revealed that paclitaxel-resistant OCCC cells reduced intracellular ATP and GTP influx rates, increasing the NADH/NAD+ ratio. We further demonstrated that paclitaxel-resistant OCCC cells led to characteristic alternations of metabolite levels in energy-requiring and energy-releasing steps of glycolysis and their corresponding glycolytic enzymes. Copy number alterations and RNA sequencing analysis demonstrated that ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporter genes involved in glycolysis metabolism and molecular transport were enriched in paclitaxel-resistant OCCC cells. We first identified that Hexokinase 2 (HK2) expression is upregulated in paclitaxel-resistant OCCC cells to determine the quantity of glucose entering glycolysis. Utilizing proteolysis-targeting chimera (PROTAC) HK2 degraders, we also found that paclitaxel sensitivity, viability, and oxygen consumption rates under paclitaxel treatment were restored by HK2 degraders treatment, and decreased downstream expression of the ABC and SLC transporters was shown in OCCC cells. Taken together, these findings highlight the paclitaxel resistance in OCCC elucidates metabolic alternation, including ABC- and SLC- drug transporters, thereby affecting glycolysis metabolism in response to paclitaxel resistance, and HK2 may become a novel potential therapeutic target for paclitaxel resistance.

The risk of geriatric syndromes in older COVID-19 survivors among the nonvaccinated population: a real world retrospective cohort study.

BACKGROUND: We aimed to analyse the differences in the risk of geriatric syndromes between older adults with and without coronavirus disease 2019 (COVID-19). METHODS: We conducted a retrospective cohort study of patients from the US Collaborative Network in the TriNetX between January 1, 2020, and December 31, 2022. We included individuals aged older than 65 years with at least 2 health care visits who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests during the study period. We excluded those with SARS-CoV-2 vaccination, diagnosis with neoplasm and geriatric syndromes before the index date, and death within 30 days after the index date. The index date was defined as the first date of the PCR test for SARS-CoV-2 during the study period. Hazard ratios (HRs) and 95% confidence intervals (CIs) for eight geriatric syndromes were estimated for propensity score-matched older adults with and without COVID-19. Subgroup analyses of sex and age were also performed. RESULTS: After propensity score matching, 315 826 patients were included (mean [standard deviation] age, 73.5 [6.4] years; 46.7% males and 51.7% females). The three greatest relative increases in the risk of geriatric syndromes in the COVID-19 cohort were cognitive impairment (HR: 3.13; 95% CI: 2.96-3.31), depressive disorder (HR: 2.72; 95% CI: 2.62-2.82) and pressure injury (HR: 2.52; 95% CI: 2.34-2.71). CONCLUSIONS: The risk of developing geriatric syndromes is much higher in the COVID-19 cohort. It is imperative that clinicians endeavour to prevent or minimise the development of these syndromes in the post-COVID-19 era.

Glaucoma: Current and New Therapeutic Approaches.

Glaucoma is identified by the loss of retinal ganglion cells (RGCs). The primary approach to managing glaucoma is to control intraocular pressure (IOP). Lately, there has been an increasing focus on neuroprotective therapies for glaucoma because of the limited effectiveness of standard methods in reducing IOP and preventing ongoing vision deterioration in certain glaucoma patients. Various drug-based techniques with neuroprotective properties have demonstrated the ability to decrease the mortality of retinal ganglion cells. This study will analyze the currently recommended drug-based techniques for neuroprotection in the prospective treatment of glaucoma.

Enhancing Organizing Pneumonia Diagnosis: A Novel Super-token Transformer Approach for Masson Body Segmentation.

BACKGROUND/AIM: In this study, we introduce an innovative deep-learning model architecture aimed at enhancing the accuracy of detecting and classifying organizing pneumonia (OP), a condition characterized by the presence of Masson bodies within the alveolar spaces due to lung injury. The variable morphology of Masson bodies and their resemblance to adjacent pulmonary structures pose significant diagnostic challenges, necessitating a model capable of discerning subtle textural and structural differences. Our model incorporates a novel architecture that integrates advancements in three key areas: Semantic segmentation, texture analysis, and structural feature recognition. MATERIALS AND METHODS: We employed a dataset of whole slide imaging from 20 patients, totaling 100 slides of OP, segmented into training, validation, and testing sets to reflect real-world application scenarios. Our approach utilizes a modified multi-head self-attention mechanism combined with ResUNet for semantic segmentation, enhanced by superpixel concepts. This method facilitates the generation of representative token features through iterative super-token blocks, creating high-resolution token maps that leverage local and high-level feature information for improved accuracy. RESULTS: Benefiting from token features and distribution for enhanced texture alignment with fewer false-positives, the super-token transformer (STT) model achieved a mean intersection over union (mIOU) of 72.42%, with a sensitivity of 47.81%, specificity of 99.83%, positive predictive value of 64.03%, and negative predictive value of 99.94%, highlighting superior efficacy in Masson body segmentation in complex cross-tissue analyses. CONCLUSION: Our team developed an iterative learning model based on the STT approach, emphasizing token features of super token, including texture and distribution, that enable enhanced alignment with the unique textures of Masson bodies to improve sensitivity and mIOU, The development of this STT model presents a significant advancement in the field of medical image analysis for OP that offers a promising avenue for improving diagnostic precision and patient outcomes in pulmonary pathology.

Feasibility of Early Surgical Treatment for Adolescent Patients with Prolactinoma: A Case Report and Literature Review.

Background and Objectives: Prolactinomas are the most common pituitary adenomas, comprising 30-50% of such tumors. These adenomas cause hyperprolactinemia, leading to decreased fertility, reduced energy and libido, and galactorrhea. Diagnosing and treating prolactinomas in adolescents present unique challenges, as symptoms may be confused with age-related developmental variations. This case report explores the outcomes of early surgical intervention in an adolescent with a prolactinoma. Materials and Methods: A 14-year-old female presented delayed menarche and absent pubertal development. Initial evaluation revealed hyperprolactinemia (228.37 ng/mL) with normal estradiol levels. Initial management through observation was adopted, but persistent amenorrhea and severe headaches prompted further investigation. Magnetic resonance imaging revealed a cystic pituitary mass with apoplexy. Due to concerns regarding delayed puberty and the need for rapid normalization of prolactin levels, the patient underwent transsphenoidal surgery. Results: After operation, prolactin levels normalized, menarche occurred within three months, and secondary sexual characteristics developed within eight months. Pathology confirmed a pituitary adenoma with a high Ki-67 index (15%). Conclusions: Early surgical intervention for prolactinomas in adolescents can achieve successful biochemical remission and resolution of endocrine symptoms. Adolescents, particularly those with a high Ki-67 index and potential resistance to dopamine agonists, may benefit from prompt surgical management, resulting in improved clinical outcomes and complete tumor resection.

Prevalence and Risk Factors of Intensive Care Unit-acquired Weakness in Patients With COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND: Intensive care unit acquired weakness (ICUAW) is a common neuromuscular complication of critical illness, impacting patients' recovery and long-term outcomes. However, limited evidence is available on pooled prevalence and risk factors of ICUAW specifically in the COVID-19-infected population. METHODS: We searched on PubMed, Embase, Cochrane Library, Web of Science, PEDro, and EBSCOhost/CINAHL up to January 31, 2024. Data synthesis was conducted using the Freeman-Tukey double-arcsine transformation model for the pooled prevalence rate and odds ratios with corresponding 95% confidence intervals was used to identify risk factors. RESULTS: The pooled prevalence of ICUAW in COVID-19 patients was 55% in eight studies on 868 patients. Risk factors for developing ICUAW in these patients were: old age (WMD 4.78, 95% CI, 1.06-8.49), pre-existing hypertension (OR = 1.63, 95% CI, 1.02-2.61), medical intervention of prone position (OR = 5.21, 95% CI, 2.72-9.98), use of neuromuscular blocking agents (NMBA) (OR = 12.04, 95% CI, 6.20-23.39), needed tracheostomy (OR = 18.07, 95% CI, 5.64-57.92) and renal replacement therapy (RRT) (OR = 5.24, 95% CI = 2.36-11.63). CONCLUSIONS: The prevalence of ICUAW in patients with COVID-19 was considered relatively high. Older age, pre-existing hypertension, medical intervention of prone position, NMBA use, needed tracheostomy and RRT were likely risk factors. In the future, interdisciplinary medical team should pay attention to high-risk groups for ICUAW prevention and early treatments.

Peritonitis caused by Listeria monocytogenes and Burkholderia cepacia in a patient on peritoneal dialysis: a case report.

Peritoneal dialysis (PD)-associated peritonitis is a major cause of peritoneal dysfunction and failure. The main issue regarding the treatment is whether to remove the catheter surgically or to treat with antibiotics alone. Notably, PD-associated peritonitis is commonly caused by gram-positive cocci, but rarely by Listeria monocytogenes and Burkholderia cepacia. Here, we report a patient diagnosed with PD-associated peritonitis caused by L. monocytogenes and B. cepacia who presented with a fever, abdominal pain, and turbid dialysate and had been receiving PD for over 20 years. After 2 weeks of antibiotic treatment, the catheter in the patient was surgically removed. Culture and pathology results revealed pathogen growth, foreign body granuloma with chronic inflammation, and inflammatory cells with fibroblast infiltration. The patient was switched to hemodialysis. She eventually recovered and was discharged. The patient presented fair health at the 3-month follow-up. In conclusion, sequential dialysate white blood cell count may help clinicians decide the course of treatment and guide the timing of surgical intervention.

Bactofencin YH, a novel bacteriocin with high inhibitory activity against clinical Streptococcus species.

Strain Lactiplantibacillus plantarum D1 with bacteriocin producing ability was found in the intestine of Gambusia affinis. The bacteriocin was found to have high inhibitory activity against multiple Streptococcus species and several other Gram-positive and Gram-negative bacteria. Bacteriocin was purified from culture supernatant by ion-exchange chromatography, Sep-Pak C18 cartridge, and reverse-phase high-performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectral analysis determined that purified bacteriocin has a molecular mass of 2,731 Da. A partial N-terminal sequence KRKKHKXQIYNNGM was obtained from the Edman analysis. The N-terminal sequence was employed to search against a translation of the draft genome of strain D1. The translated full amino acid sequence of the mature peptide is as follows: NH2- KRKKHKCQIYNNGMPTGQYRWC, which has a molecular weight of 2738 Da. A BLAST search revealed that this bacteriocin was most similar to bactofencin A but differed from it with three amino acid residues. No identical peptide or protein has been previously reported, and this peptide, termed bactofencin YH, was therefore considered to be a new bacteriocin produced by Lactiplantibacillus plantarum D1.