Excessive palmitic acid disturbs macrophage α-ketoglutarate/succinate metabolism and causes adipose tissue insulin resistance associated with gestational diabetes mellitus.

Abnormal polarization of adipose tissue macrophages (ATMs) results in low-grade systemic inflammation and insulin resistance (IR), potentially contributing to the development of diabetes. However, the underlying mechanisms that regulate the polarization of ATMs associated with gestational diabetes mellitus (GDM) remain unclear. Thus, we aimed to determine the effects of abnormal fatty acids on macrophage polarization and development of insulin resistance in GDM. Levels of fatty acids and inflammation were assessed in the serum samples and adipose tissues of patients with GDM. An in vitro cell model treated with palmitic acid was established, and the mechanisms of palmitic acid in regulating macrophage polarization was clarified. The effects of excessive palmitic acid on the regulation of histone methylations and IR were also explored in the high-fat diet induced GDM mice model. We found that pregnancies with GDM were associated with increased levels of serum fatty acids, and inflammation and IR in adipose tissues. Increased palmitic acid could induce mitochondrial dysfunction and excessive ROS levels in macrophages, leading to abnormal cytoplasmic and nuclear metabolism of succinate and α-ketoglutarate (αKG). Specifically, a decreased nuclear αKG/succinate ratio could attenuate the enrichment of H3K27me3 at the promoters of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, leading to cytokine secretion. Importantly, GDM mice treated with GSK-J4, an inhibitor of histone lysine demethylase, were protected from abnormal pro-inflammatory macrophage polarization and excessive production of pro-inflammatory cytokines. Our findings highlight the importance of the metabolism of αKG and succinate as transcriptional modulators in regulating the polarization of ATMs and the insulin sensitivity of adipose tissue, ensuring a normal pregnancy. This novel insight sheds new light on gestational fatty acid metabolism and epigenetic alterations associated with GDM.

Evaluating the Accuracy of ChatGPT in Common Patient Questions Regarding HPV+ Oropharyngeal Carcinoma.

OBJECTIVES: Large language model (LLM)-based chatbots such as ChatGPT have been publicly available and increasingly utilized by the general public since late 2022. This study sought to investigate ChatGPT responses to common patient questions regarding Human Papilloma Virus (HPV) positive oropharyngeal cancer (OPC). METHODS: This was a prospective, multi-institutional study, with data collected from high volume institutions that perform >50 transoral robotic surgery cases per year. The 100 most recent discussion threads including the term "HPV" on the American Cancer Society's Cancer Survivors Network's Head and Neck Cancer public discussion board were reviewed. The 11 most common questions were serially queried to ChatGPT 3.5; answers were recorded. A survey was distributed to fellowship trained head and neck oncologic surgeons at 3 institutions to evaluate the responses. RESULTS: A total of 8 surgeons participated in the study. For questions regarding HPV contraction and transmission, ChatGPT answers were scored as clinically accurate and aligned with consensus in the head and neck surgical oncology community 84.4% and 90.6% of the time, respectively. For questions involving treatment of HPV+ OPC, ChatGPT was clinically accurate and aligned with consensus 87.5% and 91.7% of the time, respectively. For questions regarding the HPV vaccine, ChatGPT was clinically accurate and aligned with consensus 62.5% and 75% of the time, respectively. When asked about circulating tumor DNA testing, only 12.5% of surgeons thought responses were accurate or consistent with consensus. CONCLUSION: ChatGPT 3.5 performed poorly with questions involving evolving therapies and diagnostics-thus, caution should be used when using a platform like ChatGPT 3.5 to assess use of advanced technology. Patients should be counseled on the importance of consulting their surgeons to receive accurate and up to date recommendations, and use LLM's to augment their understanding of these important health-related topics.

Effects of simulated long-term exposure to bottled, neutral pH electrolyzed oxidizing water on the properties of denture base resins.

STATEMENT OF PROBLEM: Denture stomatitis can pose serious health risks, especially to older people. Chemical denture cleaning agents must be effective, yet not adversely affect the longevity of removable dentures. Ready-to-use (RTU) neutral pH electrolyzed oxidizing water (EOW) is an effective biocide against Candida albicans biofilms on denture resins, but the effects of daily disinfection with EOW on the physical and mechanical properties of resins have not been established. PURPOSE: The purpose of this in vitro study was to investigate the effects of simulated long-term exposure to RTU EOW on the color, surface characteristics, and flexural strength of denture base resins. MATERIAL AND METHODS: Heat-polymerized (HP), 3D printed (3D) and computer-aided design and computer-aided manufacture (CAD-CAM)-milled (CC) denture resin specimens (square: 20×20×3.3 mm; beam: 64×10×3.3 mm) were immersed in tap water (TW), RTU EOW (Neutral Anolyte ANK; Envirolyte; EOW), or a commercial denture cleaning tablet solution (Polident 3-Minute; Glaxo SmithKline; PD), mimicking a 5-minute once daily disinfection routine performed up to 3.0 years. Color and surface roughness were recorded (n=3, squares), and changes in color (∆E00) and surface roughness (∆Ra) were calculated. Flexural strength (n=12, beams) and surface hardness (n=18, beams) were measured with a universal testing machine. The fractured surfaces of specimens were examined by scanning electron microscopy and energy dispersive spectroscopy. Data were assessed by performing the Shapiro-Wilk or D'Agostino and Pearson normality tests. Two-way ANOVA or the Kruskal-Wallis test with a post hoc Tukey HSD or Dunn multiple comparisons (α=.05) was used for statistical analyses. RESULTS: No significant changes were found in either color or surface roughness for HP, 3D, and CC resins after 1.5-year and 3.0-year immersion in any of the agents (P>.05). The surface hardness of 3D resins reduced by 14% with TW and by 23% with EOW and PD at 3.0 years. The flexural strengths of all 3 resins were unaffected by 3.0-year immersion (P>.05). CONCLUSIONS: Simulated long-term immersion disinfection with RTU neutral pH EOW did not adversely affect the physical and mechanical properties of HP or CC denture resins.

Early ambulation after fibular free flap surgery is associated with reduced length of stay, increased mobility independence, and discharge to home.

BACKGROUND: Fibula free flaps (FFF) are one of the most common bony flaps utilized. This paper describes a quality improvement project aimed at increasing early ambulation. METHODS: A review of FFF patients at an academic hospital was completed (2014-2023). In 2018, an institutional change to encourage early ambulation without placement of a boot was made. Changes in hospital disposition and physical therapy outcomes were evaluated. RESULTS: A total of 168 patients underwent FFF reconstruction. There was a statistically significant lower length of stay in Group 2 (early ambulation, no boot) (8.1 vs. 9.4; p = 0.04). A higher rate of discharge to a skilled nursing facility was noted in Group 1 (delayed ambulation with boot) (21.3% vs. 11.9%; p = 0.009). A higher proportion of patients in Group 2 demonstrated independence during bed mobility, transfers, and gait (p < 0.05). CONCLUSIONS: Early ambulation without boot placement after FFF is associated with decreased length of hospital stay, improved disposition to home and physical therapy outcomes.

Adaptive Nanoparticle-Mediated Modulation of Mitochondrial Homeostasis and Inflammation to Enhance Infected Bone Defect Healing.

Infected bone defects (IBDs) exhibit impaired healing due to excessive inflammation triggered by pathogen-associated molecular patterns (PAMPs) from bacteria. As a vital factor in orchestrating immune responses, mitochondrial homeostasis maintenance is central to inflammation blockade. This research developed a chameleon-like nanoplatform by covering hydroxyapatite nanoparticles with a cerium ion coordinated tannic acid supramolecular network (HA@Ce-TA), which adaptively functions to regulate mitochondrial homeostasis based on intra- and extracellular environments. Extracellularly, acidic conditions activate HA@Ce-TA's peroxidase/oxidase-mimicking activity to produce reactive oxygen species (ROS), and external near-infrared (NIR) irradiation excites nanoscale Ce-TA to produce hyperthermia, which is found and explained by chemical computation. ROS production with photothermal therapy can eliminate bacteria effectively and reduce mitochondrial stress. Intracellularly, HA@Ce-TA remodels mitochondrial dynamics by upregulating mitochondrial fusion genes and eliminates excessive ROS by mimicking superoxidase/catalase. Consequently, this comprehensive modulation of mitochondrial homeostasis inhibits inflammasome overactivation. In vitro and in vivo studies showed HA@Ce-TA can modulate the mitochondria-centered inflammatory cascade to enhance IBD treatment, highlighting the potential of engineering nanotherapeutics to recalibrate mitochondrial homeostasis as an infected disease-modifying intervention.

The genetic background determines material-induced bone formation through the macrophage-osteoclast axis.

Osteoinductive materials are characterized by their ability to induce bone formation in ectopic sites. Thus, osteoinductive materials hold promising potential for repairing bone defects. However, the mechanism of material-induced bone formation remains unknown, which limits the design of highly potent osteoinductive materials. Here, we demonstrated a genetic background link among macrophage polarization, osteoclastogenesis and material-induced bone formation. The intramuscular implantation of an osteoinductive material in FVB/NCrl (FVB) mice resulted in more M2 macrophages at week 1, more osteoclasts at week 2 and increased bone formation after week 4 compared with the results obtained in C57BL/6JOlaHsd (C57) mice. Similarly, in vitro, with a greater potential to form M2 macrophages, monocytes derived from FVB mice formed more osteoclasts than those derived from C57 mice. A transcriptomic analysis identified Csf1, Cxcr4 and Tgfbr2 as the main genes controlling macrophage-osteoclast coupling, which were further confirmed by related inhibitors. With such coupling, macrophage polarization and osteoclast formation of monocytes in vitro successfully predicted in vivo bone formation in four other mouse strains. Considering material-induced bone formation as an example of acquired heterotopic bone formation, the current findings shed a light on precision medicine for both bone regeneration and the treatment of pathological heterotopic bone formation.

Electrolysed oxidising water as a multi-purpose biocide in dental healthcare-A scoping review.

OBJECTIVES: The objective of this scoping review was to map evidence of electrolysed oxidising water (EOW) as a biocide for dental applications of relevance to older people and identify research gaps. BACKGROUND: EOW is an emerging, "green," and cost-effective biocide. There are no reviews on the landscape of EOW research as either an antiseptic or disinfectant in dental healthcare or its suitability for the oral healthcare of older people. MATERIALS AND METHODS: The review follows the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. Database searches (Google Scholar, PubMed, Web of Science, Ovid, Scopus and Science Direct) were undertaken using MESH terms and Boolean operators with no date restrictions, to identify full-text, original reports published in English-language peer-reviewed journals. RESULTS: The search yielded 114 papers that met the inclusion/exclusion criteria. Dental applications of EOW include its use as an endodontic irrigant (39%); mouth rinse/surgical irrigant (21%); disinfectant for dental unit water lines (19%) and dental biomaterials (17%); and for antimicrobial efficacy, effects on oral tissues and on dental material properties. Most studies (83%) evaluated a single EOW formulation (acidic, moderately acidic or neutral) that was either generated at 'point-of-use' (POU; 72%), bottled ('ready-to-use', RTU; 24%) or from unspecified (3%) sources. Six reports evaluated storage-related parameters and 25 evaluated clinical applications; 89 were in vitro studies and one investigated the cost-effectiveness of POU EOW. CONCLUSIONS: Neutral-pH, EOW is effective as an antimicrobial agent without deleterious effects on oral tissues. However, research on the impact of storage conditions, anti-Candida biofilm efficacy and mechanism of action against yeasts, long-term effects on denture materials and cost-effectiveness is required to establish the suitability of EOW as a multipurpose biocide for dental healthcare, including infection-control requirements relating to older people.

Probiotic Escherichia coli Nissle 1917-derived outer membrane vesicles modulate the intestinal microbiome and host gut-liver metabolome in obese and diabetic mice.

Introduction: Obesity and diabetes are common chronic metabolic disorders which can cause an imbalance of the intestinal flora and gut-liver metabolism. Several studies have shown that probiotics, including Escherichia coli Nissle 1917 (EcN), promote microbial balance and metabolic health. However, there are no studies on how EcN outer membrane vesicles (EcN-OMVs) influence the intestinal microflora and affect the metabolic disorders of obesity and diabetes. Methods: In this study, we evaluated the effects of EcN-OMVs on high-fat diet (HFD)-induced obesity and HFD + streptozotocin (STZ)-induced diabetes. Results: EcN-OMVs could reduce body weight, decrease blood glucose, and increase plasma insulin in obese mice. Similarly, EcN-OMVs treatment could modify the ratio of Firmicutes/Bacteroidetes in the gut, elevate intestinal short-chain fatty acid (SCFA)-producing flora, and influence the SCFA content of the intestine. Furthermore, the intestinal metabolites ornithine and fumaric acid, hepatic ω-6 unsaturated fatty acids, and SCFAs were significantly increased after administering EcN-OMVs. Discussion: Overall, this study showed that EcN-OMVs might act as post-biotic agents that could modulate gut-liver metabolism and ameliorate the pathophysiology of obesity and diabetes.

Dual Photo-Enhanced Interpenetrating Network Hydrogel with Biophysical and Biochemical Signals for Infected Bone Defect Healing.

The healing of infected bone defects (IBD) is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, vascularization, and osteogenesis. Based on the theory that bone healing is regulated by both biochemical and biophysical signals, in this study, a copper doped bioglass (CuBGs)/methacryloyl-modified gelatin nanoparticle (MA-GNPs)/methacrylated silk fibroin (SilMA) hybrid hydrogel is developed to promote IBD healing. This hybrid hydrogel demonstrates a dual-photocrosslinked interpenetrating network mechanism, wherein the photocrosslinked SilMA as the main network ensures structural integrity, and the photocrosslinked MA-GNPs colloidal network increases strength and dissipates loading forces. In an IBD model, the hydrogel exhibits excellent biophysical characteristics, such as adhesion, adaptation to irregular defect shapes, and in situ physical reinforcement. At the same time, by sequentially releasing bioactive ions such as Cu2+ , Ca2+ , and Si2+ ions from CuBGs on demand, the hydrogel spatiotemporally coordinates antibacterial, immunomodulatory and bone remodeling events, efficiently removing infection and accelerating bone repair without the use of antibiotics or exogenous recombinant proteins. Therefore, the hybrid hydrogel can be used as a simple and effective method for the treatment of IBD.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

The effect of surface roughening of orthodontic elastomers on hydrophobicity and in vitro adherence of Streptococcus gordonii.

OBJECTIVES: Biofilm formation around orthodontic appliances causes gingivitis, enamel decalcification and caries. Bacteria adhere less readily to superhydrophobic surfaces. The aim of this study was to determine whether a superhydrophobic surface could be generated on orthodontic elastomers by surface modification in order to reduce bacterial adhesion. MATERIALS AND METHODS: Orthodontic elastomers were modified with sandpapers of various grit sizes (80-600 grit). Surface roughness of the modified and unmodified surfaces was assessed qualitatively with scanning electron microscopy and quantitatively with confocal microscopy. Water contact angles were measured with a goniometer to quantify hydrophobicity. Measurements were performed on unextended elastomers (100% original length) and elastomers extended to 150%, and 200% of the original length. Adhesion of Streptococcus gordonii to saliva coated elastomers was measured by counting colony forming units on agar plates. RESULTS: Abrasion with different sandpapers produced elastomers with surface roughness (Ra) ranging from 2 to 12 µm. Contact angles followed a quadratic trend with a maximum contact angle of 104° at an Ra of 7-9 µm. Average water contact angles, when viewed perpendicular to the direction of extension, decreased from 99° to 90° when the extension was increased from 100% to 200% and increased from 100° to 103° when viewed parallel to the direction of extension. Bacterial adhesion increased as roughness increased and this effect was more pronounced with elastomer extension. CONCLUSION: The surface roughness of orthodontic elastomers influences both their hydrophobicity and bacterial adhesion. Superhydrophobicity of elastomers could not be achieved with sandpaper abrasion.

Vascular permeability in HPV+ oropharyngeal cancers aids in fluorescent image-guided transoral robotic surgery using indocyanine green.

BACKGROUND: Indocyanine green (ICG) fluorescent image (FI)-guided surgery has demonstrated success in improving intraoperative visualization and tumor resections. The objectives were to evaluate the use of IGC in FI-guided transoral robotic surgery (TORS) and the underlying molecular mechanism. METHODS: HPV+ oropharyngeal squamous cell carcinoma (OPSCCa) patient (n = 10) undergoing TORS were enrolled in this prospective study. Participants received intravenous ICG. Excised tissues were evaluated for ICG accumulation, tumor demarcation, and pathological characteristics using In-vivo imaging system (IVIS), histology, and RNA sequencing. RESULTS: ICG accumulation was significantly increased in primary tumor and pathological lymph nodes compared with normal tissues (p < 0.001). IVIS was 91.3% accurate in identifying OPSCCa in excised tissues; the correlation between IVIS- and histologically determined tumor tissues was significant (R2 = 0.8301; p = 0.001). Genes associated with vascular and angiogenic signaling pathways were significantly upregulated in OPSCCa tissues. CONCLUSION: ICG effectively demarcates tumor margins in OPSCCa, due to the increased upregulation of genes associated with vascular permeability.

The nano-windmill exerts superior anti-inflammatory effects via reducing choline uptake to inhibit macrophage activation.

Macrophages' activation plays a central role during the development and progression of inflammation, while the regulation of metabolic reprogramming of macrophages has been recently identified as a novel strategy for anti-inflammatory therapies. Our previous studies have found that tetrahedral framework nucleic acid (tFNA) plays a mild anti-inflammatory effect by inhibiting macrophage activation, but the specific mechanism remains unclear. Here, by metabolomics and RNA sequencing, choline uptake is identified to be significantly repressed by decreased slc44a1 expression in tFNA-treated activated macrophages. Inspired by this result, combined with the excellent delivery capacities of tFNA, siR-slc44a1 is loaded into the tFNA to develop a new tFNA-based small interfering RNA (siRNA) delivery system named 'nano-windmill,' which exhibits a synergetic role by targeting slc44a1, finally blowing up the anti-inflammatory effects of tFNA to inhibit macrophages activation via reducing choline uptake. By confirming its anti-inflammatory effects in chronic (periodontitis) and acute (sepsis) inflammatory disease, the tFNA-based nanomedicine developed for inflammatory diseases may provide broad prospects for tFNA upgrading and various biological applications such as anti-inflammatory.

An All-in-One "4A Hydrogel": through First-Aid Hemostatic, Antibacterial, Antioxidant, and Angiogenic to Promoting Infected Wound Healing.

Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu2+ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.

Effect of the Rho-Kinase/ROCK Signaling Pathway on Cytoskeleton Components.

The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate filaments and microtubules. These cellular structures confer both cell shape and mechanical properties. The architecture of the networks formed by the cytoskeleton is regulated by several pathways, a key one being the Rho-kinase/ROCK signaling pathway. This review describes the role of ROCK (Rho-associated coiled-coil forming kinase) and how it mediates effects on the key components of the cytoskeleton that are critical for cell behaviour.

A Mechanically Reinforced Super Bone Glue Makes a Leap in Hard Tissue Strong Adhesion and Augmented Bone Regeneration.

Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting-edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L-DPZ) that integrates poly(vinyl alcohol), L-dopa amino acid, and zeolitic imidazolate framework-8 characterized by catechol-metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio-Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L-DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio-Oss and sustained osteogenesis of L-DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation.

Microbial Analysis of Obturators During Maxillofacial Prosthodontic Treatment Over an 8-Year Period.

The aim of the study was to investigate the microbial colonization (by Candida species, anaerobic and facultative anaerobic bacteria) of maxillary obturators used for the restoration of maxillary defects, including during radiotherapy.Retrospective cohort study.Fifteen patients requiring a maxillary obturator prosthesis had swabs of their obturators and adjacent tissues taken at different stages of their treatment over a period of 8 years.Identification of microbial species from the swabs was carried out using randomly amplified polymorphic DNA polymerase chain reaction (RAPD PCR) analysis, checkerboard DNA-DNA hybridization, CHROMagar Candida chromogenic agar, and DNA sequencing.Candida species were detected in all patients and all patients developed mucositis and candidiasis during radiotherapy which was associated with an increase in colonization of surfaces with Candida spp., particularly C albicans. Microbial colonization increased during radiotherapy and as an obturator aged, and decreased following a reline, delivery of a new prosthesis, or antifungal treatment during radiotherapy.Microbial colonization of maxillary obturators was related to the stage of treatment, age of the obturator material, radiotherapy and antifungal medications, and antifungal treatment may be recommended if C albicans colonization of palatal tissues is greater than 105 colony-forming units per cm2 following the first week of radiotherapy.

Adhesion of Yeast and Bacteria to Oral Surfaces.

Colonization of surfaces in the human body by microorganisms is an early, essential, step in the initiation of infectious disease. We have developed in vitro assays to investigate interactions between yeast or bacterial cells and human tissues, fluids, or prostheses. Such assays can be used to identify the adhesins, ligands, and receptors involved in these interactions, for example, by determining which components of the microbe or human tissue/fluid interfere with adherence in the assay. The assays can also be applied to find ways of preventing adhesion, and subsequent disease, by investigating the effects of different conditions and added compounds on adherence in the in vitro assays. Here we describe assays for measuring adhesion of the oral yeast Candida albicans, a common commensal and opportunistic pathogen, or the bacterium Staphylococcus epidermidis, which is not normally pathogenic but is known to form biofilms on medical prostheses. The assays described belong to two approaches to investigating adhesion and biofilm formation: (i) retention at a fixed time point following liquid washes, and (ii) retention against a continuous flow of medium.

Survival outcomes for patients with T3N0M0 squamous cell carcinoma of the glottis treated with definitive radiation alone versus chemoradiation.

BACKGROUND: Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis. METHODS: We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation. RESULTS: A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25-0.37] and 0.48 [0.31-0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%-37.2%] vs. 58.0% [55.8%-60.0%]). In patients <70 with no comorbidities this difference persisted (51.0% [44.5%-57.0%] versus 66.7% [64.0%-69.3%]). CONCLUSION: Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.

The relationship between hair metabolites, air pollution exposure and gestational diabetes mellitus: A longitudinal study from pre-conception to third trimester.

Background: Gestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort. Methods: A total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution was estimated by two methods, namely proximal and land use regression (LUR) models, using air quality data from the air quality monitoring station nearest to the participant's home. Logistic regression and mixed models were applied to investigate associations between the air pollution exposure data and the GDM associated metabolites. Results: Of the 276 hair metabolites identified, the concentrations of fourteen were significantly different between GDM cases and non-GDM controls, including some amino acids and their derivatives, fatty acids, organic acids, and exogenous compounds. Three of the metabolites found in significantly lower concentrations in the hair of women with GDM (2-hydroxybutyric acid, citramalic acid, and myristic acid) were also negatively associated with daily average concentrations of PM2.5, PM10, SO2, NO2, CO and the exposure estimates of PM2.5 and NO2, and positively associated with O3. Conclusions: This study demonstrated that the maternal hair metabolome reflects the longitudinal metabolic changes that occur in response to environmental exposures and the development of GDM.