Efficacy of perioperative oral care management in the prevention of surgical complications in 503 patients after pancreaticoduodenectomy for resectable malignant tumor: A multicenter retrospective analysis using propensity score matching.

BACKGROUND: Pancreaticoduodenectomy has been associated with a high mortality rate and significant postoperative morbidity. Recently, perioperative oral care management has been reported to be effective in preventing postoperative pneumonia and surgical site infection. In this study, we examined the effect of perioperative oral care management in reducing complications after pancreaticoduodenectomy, including surgical site infection. METHODS: This retrospective multicenter study included 503 patients who underwent pancreaticoduodenectomy at 8 facilities between January 2014 and December 2016. Among these, 144 received perioperative oral management by dentists and dental hygienists (oral management group), whereas the remaining 359 did not (control group). The oral care management program included oral health instructions, removal of dental calculus, professional mechanical tooth cleaning, removal of tongue coating, denture cleaning, instructions for gargling, and tooth extraction. The participants were matched using propensity scores to reduce background bias. Various factors were examined for correlation with the development of complications. RESULTS: The incidence of organ/space surgical site infection was significantly lower in the oral management group than in the control group (8.0% vs 19.6%, P = .005). Multivariable logistic regression analysis revealed that hypertension and lack of perioperative oral management were independent risk factors for organ/space surgical site infection. Lack of perioperative oral management had an odds ratio of 2.847 (95% confidence interval 1.335-6.071, P = .007). CONCLUSION: Perioperative oral care management reduces the occurrence of surgical site infections after pancreaticoduodenectomy and should be recommended as a strategy to prevent infections in addition to antibiotic use.

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state.

ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes: canonical BAF (cBAF), polybromo BAF (PBAF), and a newly described non-canonical BAF (ncBAF). While cBAF and PBAF regulate fates of multiple cell types, roles for ncBAF in hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery of disrupted expression of BRD9, an essential component of ncBAF, in multiple cancers, including clonal hematopoietic disorders, we evaluate here the role of BRD9 in normal and malignant HSCs. BRD9 loss enhances chromatin accessibility, promoting myeloid lineage skewing while impairing B cell development. BRD9 significantly colocalizes with CTCF, whose chromatin recruitment is augmented by BRD9 loss, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. These data uncover ncBAF as critical for cell fate specification in HSCs via three-dimensional regulation of gene expression and illuminate roles for ncBAF in normal and malignant hematopoiesis.

Isomerism tunes the diradical character of difluorenopyrroles at constant Hückel-level anti-aromaticity.

A new diradical based on diindenocarbazole or difluorenopyrrole was synthesized and experimentally characterized by optical, electrochemical, and magnetic techniques, as well as quantum chemical calculations. The isomerism of these structures tunes the diradical character and the associated properties, representing a unique case of such important modulation. A full study of the electronic structure was carried out considering the perturbative interactions between different canonical forms as well as the anti-aromatic character of the molecular cores. Such a study reveals how we can tune diradical character simply by reorganizing the bonding patterns at constant chemical costs (composition).

Purification and characterization of 3-(5-oxo-2-thioxoimidazolidin-4-yl) propionic acid desulfhydrase involved in ergothioneine utilization in Burkholderia sp. HME13.

Recombinant 3-(5-oxo-2-thioxoimidazolidin-4-yl) propionic acid desulfhydrase (ErtC) derived from Burkholderia sp. HME13 was purified to homogeneity. Here, ErtC's kinetic parameters, optimum reaction temperature and pH, and stability at varying temperatures and pH and the effects of various additives on ErtC activity were determined. Real-time polymerase chain reaction and enzyme assays suggested that ergothioneine induced the expression of ertC.

A series of boron difluoride complexes of azinylcarbazoles: synthesis and structure-property relationships.

A series of boron difluoride (BF2) complexes of azinylcarbazoles 1b-1h were synthesized, and the effects of the structure of azine moieties on the photophysical and electrochemical properties of the BF2 complexes were clarified. UV-vis analysis of 1b with quinoline, 1c with isoquinoline, and fully fused 1d revealed that fusion with a benzene ring to a pyridylcarbazole BF2 complex (1a) resulted in red shifts of longest-maximum absorption wavelengths (λmax). UV-vis analysis of 1e and 1f with pyrimidine, 1g with pyridazine, and 1h with pyrazine revealed that substitution of a carbon atom to a nitrogen atom in 1a also resulted in red shifts of λmax. The fluorescence quantum yields (Φf) decreased from 1a to 1b-1h, and especially, the fluorescence of 1e, 1g, and 1h was quenched in solution. At 77 K, the emission intensities of 1b-1h were significantly increased compared with those at ambient temperature, and they also exhibited phosphorescence with relatively narrow energy gaps between the singlet and triplet excited states. These results on the emission at 77 K indicate that the quench of fluorescence from 1e, 1g, and 1h at ambient temperature originates from both internal conversions and intersystem crossing. In the solid state, all of the complexes including 1e, 1g, and 1h exhibited emission. Distinctive aggregation-induced emission properties were observed for 1e-1h. Electrochemical measurements revealed that the replacement of the pyridine moiety in 1a with azine moieties reduced electrochemical gaps mainly due to a decrease in the LUMO levels. The effects of azine moieties on electronic structures were also discussed based on theoretical calculations.

Dynamic vocal cord behavior and stridor during emergence from general anesthesia in small children with supraglottic airway.

PURPOSE: Stridor during emergence from anesthesia is not rare in children managed with supraglottic airway (SGA). However, we know little about the mechanisms of stridor and behavior of the vocal cords (VC). This study aimed to clarify patterns of VC movement and laryngeal airway maintenance function during recovery from anesthesia in children with SGA. METHODS: This is a secondary analysis of data collected from an observational study involving 27 anesthetized children. Using a multi-panel recording system, endoscopic VC image, vital sign monitor, multi-channel tracings of respiratory variables and respiratory sound and patient's view were simultaneously captured in one monitor. Inspiratory and expiratory VC angles formed by lines connecting anterior and posterior commissures were measured at the first spontaneous breath and the breath one minute after the first breath. VC narrowing and dilation were assessed by differences of VC angles. RESULTS: Inspiratory VC narrowing (median (IQR): 5.3 (2.7, 9.1) degree at the first breath) and dilation (- 2.7 (- 3.8, - 1.7) degree at the first breath) were observed in 15 and 12 out of 27 children, respectively. The former group achieved greater tidal volume compared to the latter in one minute. Five children (19%) temporarily developed stridor-like sound from outside with inspiratory VC narrowing. The stridor-like sound was captured by microphones attached to the neck and anesthesia circuit, but was not evident from the chest. CONCLUSION: Laryngeal narrowing occurs in half of the children with SGA during emergence from anesthesia, and temporal stridor-like sound is relatively common. CLINICAL TRIAL REGISTRATION: UMIN (University Hospital Information Network) Clinical Registry: UMIN000025058 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028697 ).

Site-selective radical reactions of kinetically stable open-shell singlet diradicaloid difluorenoheteroles with tributyltin hydride and azo-based radical initiators.

We have demonstrated site-selective radical reactions of the kinetically stable open-shell singlet diradicaloids difluoreno[3,4-b:4',3'-d]thiophene (DFTh) and difluoreno[3,4-b:4',3'-d]furan (DFFu) with tributyltin hydride (HSn(n-Bu)3) and azo-based radical initiators. Treatment of these diradicaloids with HSn(n-Bu)3 induces hydrogenation at the ipso-carbon in the five-membered rings, while treatment with 2,2'-azobis(isobutyronitrile) (AIBN) induces substitution at the carbon atoms in the peripheral six-membered rings. We have also developed one-pot substitution/hydrogenation reactions of DFTh/DFFu with various azo-based radical initiators and HSn(n-Bu)3. The resulting products can be converted into substituted DFTh/DFFu derivatives via dehydrogenation. Theoretical calculations unveiled a detailed mechanism of the radical reactions of DFTh/DFFu with HSn(n-Bu)3 and with AIBN, and that the site-selectivity of these radical reactions is controlled by the balance of the spin density and the steric hindrance in DFTh/DFFu.

Characterization of hydantoin-5-propionic acid amidohydrolase involved in ergothioneine utilization in Burkholderia sp. HME13.

In our previous study, ertABC genes encoding ergothionase, thiourocanate hydratase, and 3-(5-oxo-2-thioxoimidazolidin-4-yl) propionic acid desulfhydrase were identified, all of which may be involved in ergothioneine utilization of Burkholderia sp. HME13. In this study, we identify the ertD gene encoding metal-dependent hydantoin-5-propionic acid amidohydrolase in this strain. Mn2+-containing ErtD showed maximum activity at 45 °C and pH 8.5 and was stable at temperatures up to 45 °C. The Km and Vmax values of Mn2+-containing ErtD for hydantoin-5-propionic acid were 2.8 m m and 16 U/mg, respectively. Real-time polymerase chain reaction (PCR) revealed that ertD expression levels in Burkholderia sp. HME13 cells cultivated in ergothioneine medium were 3.3-fold higher than those in cells cultivated in Luria-Bertani (LB) medium. ErtD activity in the crude extract from Burkholderia sp. HME13 cells cultured in ergothioneine medium was 0.018 U/mg, whereas that in LB medium was not detected. Accordingly, we suggest that ErtD is involved in ergothioneine utilization in this strain.

A double-helical S,C-bridged tetraphenyl-para-phenylenediamine and its persistent radical cation.

A structurally constrained, double-helical S,C-bridged tetraphenyl-para-phenylenediamine (TPPD) has been synthesized. The stable radical cation of the S,C-bridged TPPD was generated by chemical oxidation, and the electron spin was found to be delocalized over the entire π-conjugated framework. The excellent conformational stability of the neutral molecule facilitated the separation of its enantiomers.

The cancer epigenome: Non-cell autonomous player in tumor immunity.

Dysregulation of the tumor-intrinsic epigenetic circuit is a key driver event for the development of cancer. Accumulating evidence suggests that epigenetic and/or genetic drivers stimulate intrinsic oncogenic pathways as well as extrinsic factors that modulate the immune system. These modulations indeed shape the tumor microenvironment (TME), allowing pro-oncogenic factors to become oncogenic, thereby contributing to cancer development and progression. Here we review the epigenetic dysregulation arising in cancer cells that disseminates throughout the TME and beyond. Recent CRISPR screening has elucidated key epigenetic drivers that play important roles in the proliferation of cancer cells (intrinsic) and inhibition of antitumor immunity (extrinsic), which lead to the development and progression of cancer. These epigenetic players can serve as promising targets for cancer therapy as a dual (two-in-one)-targeted approach. Considering the interplay between cancer and the immune system as a key determinant of immunotherapy, we discuss a novel lineage-tracing technology that enables longitudinal monitoring of cancer and immune phenotypic heterogeneity and fate paths during cancer development, progression, and therapeutic interventions.

Two cases of parapharyngeal space tumor resected by a double split mandibular osteotomy technique.

Parapharyngeal space tumors have poor subjective symptoms and often grow until diagnosed; therefore, mandibular transection may be needed to obtain a wider field of view during surgery. However, if a median lower lip incision is performed for the mandibular transection, esthetic problems occur after surgery. Here, we report two cases of parapharyngeal space tumors that were removed with a mandibular lateral segment-osteotomy technique without median lower lip incision to avoid esthetic problems. Case 1 was a 49-year-old woman. She was aware of a right tonsillar swelling, and an imaging test revealed a tumor lesion 60 mm in size in the right parapharyngeal space. Case 2 was a 40-year-old woman with an abnormal position of the uvula, and an imaging test showed the left parapharyngeal space tumor lesion 45 mm in size. Both cases were diagnosed as a pleomorphic adenoma, and surgery under general anesthesia was performed jointly with otolaryngology and oral surgery. The incision was performed from the lower part of the right auricle to the anterior part of the submandibular area. After the tumor resection, the mandible was repositioned, fixed by plates, and the intermaxillary fixation was performed with a surgical stent. In both cases, slight paralysis of the mandibular branch of the facial nerve and the mental nerve was observed after the operation, but they were improved immediately. One year after the operation, the plates were removed. There have been no recurrences until now.

Phylogenic analysis of new viral cluster of large phages with unusual DNA genomes containing uracil in place of thymine in gene-sharing network, using phages S6 and PBS1 and relevant uncultured phages derived from sewage metagenomics.

Bacteriophages (phages) are the most diverse and abundant life-form on Earth. Jumbophages are phages with double-stranded DNA genomes longer than 200 kbp. Among these, some jumbophages with uracil in place of thymine as a nucleic acid base, which we have tentatively termed "dU jumbophages" in this study, have been reported. Because the dU jumbophages are considered to be a living fossil from the RNA world, the evolutionary traits of dU jumbophages are of interest. In this study, we examined the phylogeny of dU jumbophages. First, tBLASTx analysis of newly sequenced dU jumbophages such as Bacillus phage PBS1 and previously isolated Staphylococcus phage S6 showed similarity to the other dU jumbophages. Second, we detected the two partial genome sequences of uncultured phages possibly relevant to dU jumbophages, scaffold_002 and scaffold_007, from wastewater metagenomics. Third, according to the gene-sharing network analysis, the dU jumbophages, including phages PBS1 and S6, and uncultured phage scaffold_002 formed a cluster, which suggested a new viral subfamily/family. Finally, analyses of the phylogenetic relationship with other phages showed that the dU jumbophage cluster, which had two clades of phages infecting Gram-negative and Gram-positive bacteria, diverged from the single ancestral phage. These findings together with previous reports may imply that dU jumbophages evolved from the same origin before divergence of Gram-negative and Gram-positive bacteria.

Three-Dimensional Printing of an Apigenin-Loaded Mucoadhesive Film for Tailored Therapy to Oral Leukoplakia and the Chemopreventive Effect on a Rat Model of Oral Carcinogenesis.

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient's quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting.

Medium Diradical Character, Small Hole and Electron Reorganization Energies and Ambipolar Transistors in Difluorenoheteroles.

Four difluorenoheteroles having a central quinoidal core with the heteroring varying as furan, thiophene, its dioxide derivative and pyrrole have shown to be medium character diradicals. Solid-state structures, optical, photophysical, magnetic, and electrochemical properties have been discussed in terms of diradical character, variation of aromatic character and captodative effects (electron affinity). Organic field-effect transistors (OFETs) have been prepared, showing balanced hole and electron mobilities of the order of 10-3  cm2 V-1 s-1 or ambipolar charge transport which is first inferred from their redox amphoterism. Quantum chemical calculations show that the electrical behavior is originated from the medium diradical character which produces similar reorganization energies for hole and electron transports. The vision of a diradical as simultaneously bearing pseudo-hole and pseudo-electron defects might justify the reduced values of reorganization energies for both regimes. Structure-function relationships between diradical and ambipolar electrical behavior are revealed.

Enzymatic determination of carnosine in meat and fish using ß-Ala-Xaa dipeptidase and histidine ammonia-lyase derived from Pseudomonas putida NBRC100650.

Carnosine is a naturally occurring dipeptide and a functional component in foods, while also showing health-promoting effects. Generally, food-derived carnosine is quantified via high-performance liquid chromatography (HPLC). We have developed a method for quantifying carnosine in foods using microbial enzymes, ß-Ala-Xaa dipeptidase (BapA) and histidine ammonia-lyase (HAL). The carnosine concentrations in extracts of chicken, pork, beef, bonito, and tuna were determined via both HPLC and enzymatic determination. The carnosine contents measured via enzymatic determination were in agreement with those determined via conventional HPLC analysis. Relative standard-deviation values of the conventional HPLC method and the enzymatic determination of carnosine in foods were 0.728-5.76% and 0.504-4.58%, respectively. The recovery of carnosine in food extracts via enzymatic determination was 97-103%. Therefore, the developed enzymatic determination technique using BapA and HAL can be used for the determination of carnosine in meats and fishes with comparable accuracy to that of conventional HPLC analysis.

Augmented Self-Association by Electrostatic Forces in Thienopyrrole-Fused Thiadiazoles that Contain an Ester instead of an Ether Linker.

During the self-assembly of π-conjugated molecules, linkers and substituents can potentially add supportive noncovalent intermolecular interactions to π-stacking interactions. Here, we report the self-assembly behavior of thienopyrrole-fused thiadiazole (TPT) fluorescent dyes that possess ester or ether linkers and dodecyloxy side chains in solution and the condensed phase. A comparison of the self-association behavior of the ester- and ether-bridged compounds in solution using detailed UV-vis, fluorescence, and NMR spectroscopic studies revealed that the subtle replacement of the ether linkers by ester linkers leads to a distinct increase in the association constant (ca. 3-4 fold) and the enthalpic contribution (ca. 3 kcal mol-1 ). Theoretical calculations suggest that the ester linkers, which are in close proximity to one another due to the π-stacking interactions, induce attractive electrostatic forces and augment self-association. The self-assembly of TPT dyes into well-defined 1D clusters with high aspect ratios was observed, and their morphologies and crystallinity were investigated using SEM and X-ray diffraction analyses. TPTs with ester linkers exhibit a columnar liquid crystalline mesophase in the condensed phase.

Association between dental extraction after radiotherapy and osteoradionecrosis: A multi-centre retrospective study.

OBJECTIVE: Radiotherapy (RT) carries a substantial risk for the development of osteoradionecrosis (ORN) of the jaw. This study was performed to investigate the relationship between dental extractions after RT and the development of ORN. MATERIAL AND METHODS: Thirty-two patients with head and neck cancer who underwent tooth extraction after RT were investigated for correlations between the development of ORN and various factors. RESULTS: Postextraction ORN was diagnosed in 12 (12.1%) teeth of 9 patients. The RT dose against the site of tooth extraction was 62.0 and 37.4 Gy in the ORN and Non-ORN groups, respectively (p < .001). The duration from RT to tooth extraction was 41.2 and 28.2 months in the ORN and Non-ORN groups, respectively (p = .025). Tooth extraction was significantly associated with ORN in patients with a high RT dose against the site (odds ratio = 1.231) and a longer duration of time from RT (odds ratio = 1.084). CONCLUSIONS: Extraction of non-restorable teeth and those with a poor prognosis should not necessarily be postponed even when patients are undergoing RT. However, clinicians should pay special attention to postoperative management after tooth extraction in patients with a high RT dose and longer time from RT.

SOX10 Regulates Melanoma Immunogenicity through an IRF4-IRF1 Axis.

Loss-of-function mutations of JAK1/2 impair cancer cell responsiveness to IFNγ and immunogenicity. Therefore, an understanding of compensatory pathways to activate IFNγ signaling in cancer cells is clinically important for the success of immunotherapy. Here we demonstrate that the transcription factor SOX10 hinders immunogenicity of melanoma cells through the IRF4-IRF1 axis. Genetic and pharmacologic approaches revealed that SOX10 repressed IRF1 transcription via direct induction of a negative regulator, IRF4. The SOX10-IRF4-IRF1 axis regulated PD-L1 expression independently of JAK-STAT pathway activity, and suppression of SOX10 increased the efficacy of combination therapy with an anti-PD-1 antibody and histone deacetylase inhibitor against a clinically relevant melanoma model. Thus, the SOX10-IRF4-IRF1 axis serves as a potential target that can bypass JAK-STAT signaling to immunologically warm up melanoma with a "cold" tumor immune microenvironment. SIGNIFICANCE: This study identifies a novel SOX10/IRF4 pathway that regulates noncanonical induction of IRF1 independent of the JAK-STAT pathway and can be targeted to improve the efficacy of anti-PD-1 therapy in melanoma.

Perioperative management of von Willebrand patients at the time of implant placement: Case report.

In the management of patients with type 1 von Willebrand disease, supplementation with Con Facto F® as well as hemodynamic stabilization with appropriate analgesia and sedation may be important to reduce the risk of bleeding.

S,C,C- and O,C,C-Bridged Triarylamines and Their Persistent Radical Cations.

This work reports the synthesis, crystal structures, and electronic properties of structurally constrained S,C,C- and O,C,C-bridged triarylamine derivatives and their persistent radical cations. O,C,C-Bridged triphenylamines and a dinaphthylphenylamine were obtained through a straightforward synthetic protocol. Similar to a previously reported S,C,C-bridged triphenylamine, the O,C,C-bridged triarylamines were easily oxidized to afford the corresponding radical cations, which were obtained as hexachloroantimonate salts. X-ray crystallographic analyses showed almost planar structures for these O,C,C-bridged triarylamine radical cations, which represent new members of the family of planar triarylamine radical cations without substituents on the aryl rings. Detailed investigations of the electronic properties of the S,C,C- and O,C,C-bridged triarylamine radical cations demonstrated that the spin and positive charge are sufficiently delocalized over the planar triarylamine scaffolds. The results provide the following insights into the effects of the bridging unit (sulfur vs oxygen) and the dibenzo-annulation on the spin delocalization in the bridged triarylamine radical cations: (1) An effective decrease of the spin density on the nitrogen atom is observed for the sulfur bridge relative to the oxygen bridge; and (2) a moderate decrease of the spin density on the oxygen atom rather than the nitrogen atom is induced by the dibenzo-annulation.