Imaging characteristics of gubernaculum tracts in patients with cleidocranial dysplasia: a computed tomography study.

OBJECTIVES: To elucidate the imaging characteristics of the gubernaculum tract (GT) in patients with cleidocranial dysplasia (CCD) as visualized with computed tomography (CT). STUDY DESIGN: This was a retrospective analysis of the presence and shape of GTs of unerupted permanent teeth and supernumerary teeth on CT in 9 patients with CCD. RESULTS: The overall GT detection rate for unerupted permanent teeth was 83.5% (81/97), with no significant difference between permanent teeth without and with adjacent supernumerary teeth (P = .414). The overall GT detection rate for unerupted supernumerary teeth was 83.1% (49/59). Of the 156 total unerupted teeth analyzed, 83.3% (130/156) were judged to have GTs. No significant difference in detection rate of GTs was found between permanent and supernumerary teeth (P > 0.999). A composite morphology consisted of a single GT for a permanent unerupted tooth with 1 or 2 supernumerary teeth in which the dental follicles of the permanent and supernumerary teeth were confluent. In total, 44 groups consisted of 1 permanent and 1 or 2 supernumerary teeth; 79.5% (35/44) had GTs. CONCLUSIONS: A specific composite structure of GTs and dental follicles may signify that 2 or 3 teeth are derived from a single dental lamina in patients with CCD. In such cases, tooth eruption may fail due to the presence of only 1 GT for multiple teeth.

Imaging Characteristics of Embedded Tooth-Associated Cemento-Osseous Dysplasia by Retrospective Study.

BACKGROUND: Since there are many differential diagnoses for cemento-osseous dysplasia (COD), it is very difficult for dentists to avoid misdiagnosis. In particular, if COD is related to an embedded tooth, differential diagnosis is difficult. However, there have been no reports on the characteristics of the imaging findings of COD associated with embedded teeth. The aim of the present study was to investigate the occurrence and imaging characteristics of cemento-osseous dysplasia (COD) associated with embedded teeth, in order to appropriately diagnose COD with embedded teeth. METHODS: The radiographs with or without histological findings of 225 patients with COD were retrospectively analyzed. A retrospective search through the picture archiving and communication system (PACS) of the Division of Oral and Maxillofacial Radiology of Kyushu Dental University Hospital was performed to identify patients with COD between 2011 and 2022. RESULTS: Fifteen COD-associated embedded mandibular third molars were identified in 13 patients. All 13 patients were asymptomatic. On imaging, COD associated with embedded mandibular third molars appeared as masses that included calcifications around the apex of the tooth. On panoramic tomography, COD showed inconspicuous internal calcification similar to that of odontogenic cysts or simple bone cysts, especially in patients with COD only around the mandibular third molar region. Those with prominent calcification resembled cemento-ossifying fibroma, calcifying epithelial odontogenic tumor, calcifying odontogenic cyst, adenomatoid odontogenic tumor, and so on, as categories of masses that include calcifications on panoramic tomography and computed tomography. CONCLUSIONS: The current investigation is the first to report and analyze the imaging characteristics of COD associated with embedded teeth. It is important to consider the differences between COD and other cystic lesions on panoramic tomography, and the differences between COD and masses that include calcifications on CT.

Comparison of the distribution of the Bartholin and/or Rivinus salivary ducts assessed with magnetic resonance-sialography in patients with ranula and in healthy subjects.

Background: The distribution and drainage of the sublingual gland ducts have various patterns that might be related to sublingual gland-related diseases, including ranula. This study aimed to elucidate the characteristics of the distribution of Bartholin and/or Rivinus ducts in patients with ranula using magnetic resonance (MR) sialography. Methods: In this retrospective cross-sectional study, the distributions and drainage patterns of sublingual gland ducts on MR sialography were classified in 74 subjects without sublingual gland-related disease as confirmed by both medical history and clinical examination and 15 patients with ranula, respectively. All patients had visited Kyushu Dental University Hospital from July 2015 to June 2022 to undergo MR imaging. Data on the distributions and drainage patterns of the sublingual gland ducts, including the characteristics of the Bartholin and/or Rivinus ducts, were then statistically compared between subjects without sublingual gland-related disease and patients with ranula. The images were assessed by an experienced oral and maxillofacial radiology specialist certified by the Japanese Society for Oral and Maxillofacial Radiology. The distributions (five groups) and drainage patterns (three patterns) of the sublingual gland ducts on MR sialography were classified in reference to previous studies, with some modifications in all subjects without sublingual gland-related disease and patients with ranula. Results: A significant difference in the distribution of the ducts (P<0.001), with a low number of patients exposing an undetected canal or Rivinius duct, was found in the group of patients with ranula (P<0.05). Regarding drainage patterns, no patient with ranula presented a Rivinius duct only. A significant difference in the drainage patterns of the sublingual gland ducts on MR sialography was observed between subjects without sublingual gland-related disease and patients with ranula (P=0.001). Conclusions: The present results suggest that the distribution of the sublingual gland ducts, mainly, the Bartholin duct, may be related to ranula formation. These findings also demonstrate that MR sialography contributes well to preoperative evaluation and is effective for assessing the complex excretory distribution of the sublingual gland ducts.

Correlation between the presence of tonsilloliths and the bone defects by periodontitis on imaging analysis: a pilot study.

BACKGROUND: Very recently, a significant relationship between tonsilloliths and dental plaque-related pathologies was reported using digital panoramic radiographs. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase that functions to remove foreign matter. The aim of the study was to evaluate the relationship between the occurrence of tonsilloliths and the extent of periodontitis. METHODS: A total of 608 patients who underwent both CT and panoramic radiographs were included in the study. Both of two imaging were retrospectively and independently assessed with respect to the presence of tonsilloliths detected on CT and panoramic radiographs, and bone defects caused by periodontitis detected on panoramic radiographs. The type of retrospective study is case-control. Then, the differences between age groups were evaluated with respect to the degree of bone resorption and its correlation with the presence of tonsilloliths. The relationships between categorical variables were assessed using Pearson's correlation coefficient or Spearman's correlation coefficient. RESULTS: There was a significant relationship between tonsilloliths on CT and the extent of the bone defect on panoramic radiographs (Spearman's correlation coefficient, r = 0.648, p = 0.043). In addition, there was a significant difference in the extent of the bone defect caused by periodontitis between subjects with and without tonsilloliths in the 60 to 69-year-old group (Mann-Whitney U test, p = 0.025), 70 to 79-year-old group (Mann-Whitney U test, p = 0.002), and 80 to 89-year-old group (Mann-Whitney U test, p = 0.022), but not in other age groups (Mann-Whitney U test: under 9-year-old group, p = 1.000; 10 to 19-year-old group, p = 1.000; 20 to 29-year-old group, p = 0.854; 30 to 39-year-old group, p = 0.191, 40 to 49-year-old group, p = 0.749; 50 to 59-year-old group, p = 0.627; ≥90-year-old group, p = 1.000). CONCLUSIONS: The presence of tonsilloliths was related to the extent of periodontitis because the structures were responding dynamically.

Lit-LAMP-DNA-vaccine for shrimp allergy prevents anaphylactic symptoms in a murine model.

Allergen-specific immunotherapy (AIT) is a promising therapeutic approach to food allergy but requires optimization in terms of both efficacy and safety due to the risk of undesired anaphylactic reactions. Here, we investigated the potential of a single DNA plasmid vaccine (Lit-LAMP-DNA-vaccine) encoding multivalent shrimp antigens (Lit v (Litopenaeus vannamei; Whiteleg shrimp) 1, Lit v4, and Lit v3) and a lysosomal-associated membrane protein (LAMP) as the next generation of AIT for patients with allergy. We first confirmed the expression of the LAMP-1-Lit v1-Lit v4-Lit v3 fusion protein in human cells transfected with the Lit-LAMP-DNA-vaccine, and the induction of anti-Lit v1, Lit v3, and Lit v4 IgG2a antibody production as well as Th1 response in Lit-LAMP-DNA-vaccine-treated mice. Next, we established an anaphylaxis model in mice epicutaneously sensitized with a crude shrimp protein extract (SPE) and investigated both the efficacy of Lit-LAMP-DNA-vaccine, and the difference in the mechanism of action (MOA) from oral immunotherapy (OIT). In the mouse shrimp allergy model, Lit-LAMP-DNA-vaccine potently suppressed anaphylactic reactions and mast cell activation with robust antigen-specific IgG2a production. The IgG1:IgG2a ratio was significantly lower than that of OIT. This suppressive effect was also confirmed by plasma transfer from mice previously vaccinated with the Lit-LAMP-DNA-vaccine. These results suggest that this Lit-LAMP-DNA-vaccine may represent a promising therapeutic strategy for human shrimp allergy which acts via the efficient induction of antigen-specific IgG with antagonism.

Visualization of Peripheral Blood Vessels on the Lingual Aspect of the Mandible Using a Balanced Steady-State Free-Precession Sequence with a Time-Spatial Labeling Inversion Pulse: Usefulness for Prevention of Severe Complications of Dental Implantation.

The aim of this study was to evaluate whether a balanced steady-state free-precession (SSFP) sequence with a time-spatial labeling inversion pulse (time-SLIP) without contrast medium could elucidate branches of the lingual and facial arteries on the lingual aspect of the mandible as a potential technique for preventing severe complications in dental implantation surgery. In this study, magnetic resonance angiography (MRA) using SSFP with a time-SLIP was evaluated in 40 subjects. The outline and course of branches of the lingual and facial arteries near the mandible were assessed clinically in the same subjects against contrast-enhanced computed tomography (CT) images as the gold standard. The submental, sublingual, and deep lingual arteries could be visualized via MRA in 16, 20, and 16 of the 40 subjects, respectively. The major axes of the respective arteries were approximately 24, 24, and 16 mm. The outline and course of all visualized arteries coincided with those on CT. MRA using SSFP with a time-SLIP appears to have potential as a non-contrast technique for visualizing branches of the lingual and facial arteries on the lingual aspect of the mandible. Information regarding the outline and course of these arteries as obtained using this MRA technique could assist in preventing severe complications in dental implantation surgery.

Imaging characteristics of the gubernaculum tracts in successional teeth related to deciduous fused teeth on computed tomography.

The purpose of this study was to elucidate the imaging characteristics of the gubernaculum tracts in successional teeth related to fused deciduous teeth on computed tomography. The imaging findings of 15 gubernaculum tracts in successional teeth related to fused deciduous teeth were retrospectively analyzed using cone-beam computed tomography or multidetector computed tomography. In cases without a congenitally defected successor, the two gubernaculum tracts of two successional teeth related to fused deciduous teeth were fused into one. Gubernaculum tracts (GTs) in mesial successors were vertical, but in distal successors they were inclined to mesial. The major abnormalities of the successional teeth related to fused deciduous teeth were delayed eruption and delayed formation. No inclined mesial successors were found, whereas most of the distal successors were inclined to mesial along with the inclined GT. The gubernaculum tracts of successors with a congenital defect of the other successors were vertical, and such successors had no abnormalities. The present study showed the imaging characteristics of gubernaculum tracts in successional teeth related to fused deciduous teeth. The abnormal eruption of successional teeth related to fused deciduous teeth may be associated with the characteristics of their gubernaculum tracts.

PGE2-EP2/EP4 signaling elicits immunosuppression by driving the mregDC-Treg axis in inflammatory tumor microenvironment.

Active inflammation generally promotes immune activation. However, in the tumor microenvironment (TME), active inflammation occurs in parallel with immunosuppression, and both contribute to tumor growth. Why inflammation does not lead to immune activation in TME remains unclear. In this study, using the immune checkpoint inhibitor-insensitive mouse cancer model and single-cell RNA sequencing, we show that PGE2-EP2/EP4 signaling simultaneously promotes active inflammation by inducing expression of the NF-κB genes in myeloid cells and elicits immunosuppression by driving the mregDC (mature DC enriched in immunoregulatory molecules)-Treg (regulatory T cell) axis for Treg recruitment and activation in the tumor. Importantly, the EP2/EP4 expression level is strongly correlated with the gene signatures of both active inflammation and the mregDC-Treg axis and has significant prognosis value in various human cancers. Thus, PGE2-EP2/EP4 signaling functions as the key regulatory node linking active inflammation and immunosuppression in TME, which can be targeted by EP2 and EP4 antagonists for cancer therapeutics.

Overview of Radiological Studies on Visualization of Gubernaculum Tracts of Permanent Teeth.

The eruption pathway from the dental follicle to the gingiva for permanent teeth is known as the gubernaculum tract (GT), a physiologic structure thought to play a role in tooth eruption. Cone beam computed tomography and multi-detector computed tomography have recently been used to visualize the GT, with the results indicating that this structure might be related to the normal eruption of teeth. By contrast, curved and/or constricted GTs may lead to abnormal tooth eruption. In addition, complex odontomas have been reported from within the GT or dental sac of unerupted permanent teeth. If an odontoma occurs within the GT, the tooth will not erupt normally. Moreover, the imaging characteristics of the GT from the top of the odontogenic mass to the alveolar crest are extremely useful for making a differential pathological diagnosis and for differentiating between odontogenic and non-odontogenic masses. Therefore, radiological studies on the GT have been attracting increasing attention. Given this background, the present review aims to clarify the imaging characteristics and review recent studies on the GT considering the importance of the research.

Imaging peculiarities of gubernaculum tracts in molars as accessional teeth on CT.

OBJECTIVES: The shapes of gubernaculum tracts (GTs) in molars as accessional teeth remain unidentified. To elucidate imaging peculiarities of GTs in molars with aging on multidetector-row computed tomography (MDCT). MATERIAL AND METHODS: This retrospective study was conducted using CT images, including maxillary and mandibular molars, with no abnormal findings from 239 patients. Shapes of alveolar bone, GTs, and dental sacs of the maxillary and mandibular molars were analyzed multi-sectionally. Correlations between 2- and 3-dimensional imaging figures of GTs in molars and chronological age or stage of molar formation were analyzed. RESULTS: Some forms of GTs in maxillary and mandibular third molars were observed. In the early stage, GTs were visualized as bone defect lines on the dentition and grooves on the mesial alveolar crest continuous with the dental sac to mesial tooth bud. GTs of the third molar formed a J-shape in maxillary teeth and Y-shape in mandibular teeth in the middle stage, as alveolar bone around the GT developed. In the mature stage, the course of the GT changed to straight and perpendicular. Some GT forms were also identified in first and second molars. Significant correlations were found between GT alterations and chronological age or stage of molar formation. Moreover, tracts continuing from the distal side of mandibular third molars were detected. CONCLUSIONS: This paper describes the peculiarities and process of progression for GTs in molars, and the existence of tracts continuing from the distal side of mandibular third molars, unlikely dentition with deciduous predecessors. These preliminary data should prove beneficial for studies focusing on GTs in molars.

Changes in tonsillolith characteristics detected in a follow-up CT study.

BACKGROUND: Tonsilloliths are related clinically to halitosis and tonsillar abscess. However, the dynamics of tonsilloliths over time are unknown. The aim of the study was to evaluate change in the characteristics of tonsilloliths in a time-dependent fashion by follow-up computed tomography (CT). METHODS: Tonsilloliths were analyzed in 326 CT scan pair sets of initial and at least two follow-up CT examinations of patients with whole palatine tonsils and various diseases of the oral and maxillofacial regions. RESULTS: Over the follow-up period, 12.1% of tonsilloliths disappeared. Approximately 26.1% of tonsilloliths changed in size during follow-up, mostly increasing in size. In tonsilloliths that showed enlargement, the mean (± standard deviation) growth rate was 0.61 ± 0.41 mm per year. Approximately 37.3% of tonsilloliths changed position during the follow-up period; of these, movement was toward the respiratory tract in 92% at a mean rate of - 1.38 ± 1.59 mm per year. The calcification levels of almost all tonsilloliths showed dynamic change: HU number increased in 84.3% and decreased in 12.7% of tonsilloliths over the follow-up period. The mean rate of HU increase was 63.8 ± 96.3 HU/year, and the mean rate of HU decrease was - 38.4 ± 66.8 HU/year. CONCLUSIONS: The calcification levels of all tonsilloliths showed dynamic fluctuation, and a tendency for excretion of tonsilloliths from the body. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase which functions to remove foreign matter.

First Report of Sublingual Gland Ducts: Visualization by Dynamic MR Sialography and Its Clinical Application.

This study was done to determine whether the sublingual gland ducts could be visualized and/or their function assessed by MR sialography and dynamic MR sialography and to elucidate the clinical significance of the visualization and/or evaluation of the function of sublingual gland ducts by clinical application of these techniques. In 20 adult volunteers, 19 elderly volunteers, and 7 patients with sublingual gland disease, morphological and functional evaluations were done by MR sialography and dynamic MR sialography. Next, four parameters, including the time-dependent changes (change ratio) in the maximum area of the detectable sublingual gland ducts in dynamic MR sialographic images and data were analyzed. Sublingual gland ducts could be accurately visualized in 16 adult volunteers, 12 elderly volunteers, and 5 patients. No significant differences in the four parameters in detectable duct areas of sublingual glands were found among the three groups. In one patient with a ranula, the lesion could be correctly diagnosed as a ranula by MR sialography because the mass was clearly derived from sublingual gland ducts. This is the first report of successful visualization of sublingual gland ducts. In addition, the present study suggests that MR sialography can be more useful in the diagnosis of patients with lesions of sublingual gland ducts.

Real-time evaluation of swallowing in patients with oral cancers by using cine-magnetic resonance imaging based on T2-weighted sequences.

OBJECTIVE: The aim of this study was to evaluate whether a new cine-magnetic resonance imaging (CMRI) technique might be useful for evaluating swallowing function in patients with different types of oral cancers by assessing 12 CMRI-related parameters. STUDY DESIGN: In total, 111 patients with oral cancers were evaluated. We examined whether visualization of fluid flow and determination of flow direction to the trachea or the esophagus were possible with CMRI. We evaluated the correlations between CMRI-related parameters and self-reported dysphagia scores as the status of dysphagia, T classification groups as tumor staging for preoperative patients, alterations in CMRI-related parameters between pre- and postoperative patients, and the degree of invasiveness of oral cancer surgery. RESULTS: We could judge the flow direction to the esophagus on CMRI in all 111 patients. Six CMRI-related parameters showed significant correlations with dysphagia status. Increases in CMRI-related parameters were significantly related to deterioration of swallowing status, as shown by a decrease in self-reported dysphagia scores, advances in the T classification, and degree of invasiveness of oral cancer surgery. CONCLUSIONS: The results of the present study suggest that CMRI can be used to directly visualize swallowing dynamics and objectively evaluate the swallowing complaints of patients with oral cancer.

Can the lower rate of CT- or MRI-related adverse drug reactions to contrast media due to stricter limitations on patients undergoing contrast-enhanced CT or MRI?

OBJECTIVE: The aim of this study was to examine whether a decreased occurrence rate of adverse drug reactions (ADRs) to contrast media in contrast-enhanced CT and MRI was attributable to appropriate criteria for patients with some diseases. A secondary aim was to elucidate safety profiles for contrast media and factors influencing the occurrence of ADRs. METHODS: Clinical data of patients who underwent contrast-enhanced CT (5576 cases) or MRI (3357 cases) were retrospectively analyzed to evaluate rates of ADRs to contrast media, symptoms of ADRs, treatments for ADRs, and differences in medical history, blood test results, and other factors between patients with and without ADRs in a dental hospital. RESULTS: The rate of ADRs to contrast media was 0.54% for CT and 0.09% for MRI. The most frequent ADRs in contrast-enhanced CT or MRI were nausea and vomiting as physiologic reactions. Two serious reactions were seen for CT, but none for MRI. Significant differences between patients with and without ADRs were seen in liver function according to blood tests for CT, and in digestive disorders elicited from medical interviews for MRI. CONCLUSION: The lower occurrence rate of ADRs to contrast media in dental hospitals could be due to the adoption of appropriate criteria for patients with some diseases undergoing enhanced CT or MRI. Complete suppression of ADRs to contrast media for CT or MRI is unrealistic, so attention is warranted for patients with decreased liver function when performing enhanced CT, and for patients with digestive disorders when performing enhanced MRI.

Advocacy of diagnostic criteria for maxillary incisive canal cysts based on alteration of normal maxillary incisive canals according to aging in Japanese populations.

BACKGROUND: The purpose of the present study was to describe the CT imaging findings of normal incisive canals and incisive canal cysts and propose cut-off values to differentiate between them. METHODS: A total of 220 normal subjects and 40 patients with incisive canal cysts on multi-detector row computed tomography (MDCT) were retrospectively analyzed. The shapes, sizes, anatomic variations, Hounsfield scale values, and so on of maxillary incisive canals and the sizes and Hounsfield scale values of maxillary incisive canal cysts were analyzed. RESULTS: A significant difference in sizes of maxillary incisive canals in normal subjects was found between males and females. The sizes of maxillary incisive canals were significantly wider during aging, but shapes, anatomic variations, and Hounsfield scale values in the maxillary incisive canals were not significantly different with aging. A significant difference in sizes but not Hounsfield scale values was found between normal maxillary incisive canals and maxillary incisive canal cysts. Based on a cut-off of over 6 mm in the width of incisive canals, maxillary incisive canal cysts could not be appropriately diagnosed for subjects over 60 years of age. Over 60 years of age, maxillary incisive canal cysts could be appropriately diagnosed based on a cut-off of over 7.1 mm in width of incisive canals. When maxillary incisive canals of the hourglass types were seen on sagittal sections, significantly more patients had maxillary incisive canal cysts than other types. CONCLUSION: In coincidentally diagnosing asymptomatic incisive canal cysts on imaging, we should apply different cut-offs for the size of the maxillary incisive canal for patients over and under 60 years of age. Specifically, the cut-offs for the long axis of maxillary incisive canal cysts were 7.1 mm for patients over 60 years of age and 6.0 mm for those under 60 years of age. In addition, we should pay attention to wider canals with hourglass shapes as indicative of cystic change of maxillary incisive canals.

[Antimicrobial profile and clinical evidence of fidaxomicin (Dafclir®), a therapeutic agent for Clostridioides (Clostridium) difficile infection].

Fidaxomicin (Dafclir® Tablets 200 mg) is a member of a novel class of oral, 18-membered macrocyclic antibiotic agents used for the treatment of patients with Clostridioides (Clostridium) difficile (C. difficile) infection (CDI), approved in Japan in July 2018. Preclinical studies demonstrated that fidaxomicin inhibits RNA synthesis by bacterial DNA-dependent RNA polymerase derived from C. difficile, shows antibacterial activities against C. difficile clinically isolated in Japan, and is bactericidal against C. difficile. Fidaxomicin was less likely to disrupt gut microflora due to its narrow antimicrobial spectrum, showing antibacterial activities against limited gram-positive bacteria including C. difficile, but not against gram-negative bacteria, as determined by minimum inhibitory concentration (MIC) measurement against American Type Culture Collection strains. Fidaxomicin inhibited spore production, subsequent spore recovery/outgrowth after removal of fidaxomicin, outgrowth to vegetative cells, and toxin production under fidaxomicin at lower MIC. Additionally, it had protective effects on lethal CDI in animal models. In clinical studies conducted in Europe, US, and Japan, fidaxomicin 200 mg twice daily for 10 days showed higher clinical cure, higher global cure (cure with no recurrence), and lower recurrence rate compared with oral vancomycin 125 mg four times daily for 10 days. Adverse events observed in the fidaxomicin group were similar to those in the vancomycin group, and no clinically important findings regarding safety and tolerability were reported. In conclusion, in vitro, in vivo and clinical evidence indicate that fidaxomicin is an effective treatment for C. difficile, with limited disruption to gut microflora, for adult patients with CDI in Japan.

Antimicrobial susceptibility and molecular characterisation using whole-genome sequencing of Clostridioides difficile collected in 82 hospitals in Japan between 2014 and 2016.

We studied the antimicrobial susceptibility and the molecular characteristics using draft whole-genome sequencing of Clostridioides (Clostridium) difficile strains before and after treatment in adults with C. difficile infection (CDI) enrolled in a Phase III, randomised, nationwide study of fidaxomicin versus vancomycin in Japan (NCT02179658). C. difficile strains were cultured from stool samples collected before and after standard treatment with either fidaxomicin or vancomycin. Overall, 285 C. difficile strains were recovered, with 188 derived from CDI cases at baseline (87 patients received fidaxomicin and 101 received vancomycin). No strains isolated from episodes of CDI at baseline were shown to have reduced susceptibilities to fidaxomicin (MIC ≥1 mg/L), or resistance to vancomycin and metronidazole. Thirty-three sequence types (STs) were identified, the most common being ST17 (n=61; 32.4%), ST8 (n=26; 13.8%) and ST2 (n=21; 11.2%). Core-genome single nucleotide polymorphism analysis showed that outbreaks of C. difficile were unlikely to have occurred at each hospital. The predominant toxin gene profile was tcdA+tcdB+cdtA/cdtB- (n=149; 79.3%). Six of 87 patients who received fidaxomicin harboured C. difficile isolates with reduced fidaxomicin susceptibilities conferred by previously described mutations, Val1143Leu/Gly/Asp in RpoB or Arg89Gly in RpoC or putative mutations, Gln1149Pro in RpoB or Arg326Cys in RpoC. Allelic exchange studies of these putative mutations were not performed. Prior to fidaxomicin use, we found no C. difficile strains with reduced fidaxomicin susceptibilities causing CDI in Japan; however, mutant strains with reduced fidaxomicin susceptibilities were detected after fidaxomicin treatment.

ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity against Aspergillus Species through a Specific Transporter.

Current therapies against invasive pulmonary aspergillosis (IPA) have a limited cure rate. Given that a delay in treatment initiation may be fatal, a new drug with rapid-onset and potent fungicidal activity is needed. The novel cyclic hexapeptide ASP2397 (currently known as VL-2397) exhibited antifungal activity against Aspergillus fumigatus (including azole-sensitive and azole-resistant isolates), A. terreus, and A. flavus at an MIC range of 1 to 4 µg/ml in human serum. Time-kill curve experiments showed that ASP2397 reduced germinated conidia of A. fumigatus by more than 1 log10 CFU within 6 h. In addition, ASP2397 inhibited hyphal elongation from germinated conidia of A. fumigatus, A. terreus, and A. flavus more rapidly than voriconazole. Under conditions of delayed treatment initiation in an IPA mouse model, ASP2397 had efficacy superior to that of posaconazole, with 100% survival and over 1 log10 CFU/g reduction in lung fungal burden. Histopathological investigation of lungs also showed that ASP2397 markedly suppressed disease progression. To clarify its mechanism of action, we generated a UV-induced mutant of A. fumigatus with low susceptibility to ASP2397. The mutant had a point mutation in the siderophore transporter gene sit1, which is absent in mammalian cells. These findings suggest that ASP2397 may improve clinical treatment options for IPA.

Characteristics of diffusion-weighted images and apparent diffusion coefficients of ranulas and other masses in and around the floor of the mouth.

OBJECTIVE: The aim of this study was to evaluate the characteristics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values of ranulas. In addition, to elucidate DWI findings and ADC values of other representative masses in and around the floor of the mouth. STUDY DESIGN: DWI findings and ADC values in 35 patients with ranulas and 33 patients with other masses were retrospectively reviewed with a central focus on cystic masses or lesions that may have cyst-like components in and around the floor of the mouth based on the diagnosis of each respective disease. RESULTS: Ranulas were all well-defined, homogeneous masses with high signal intensity on DWI. The mean ± standard deviation ADC value of the 35 ranulas was 2.59 ± 0.31 × 10-3 mm2/s. There was a significant difference in ADC values between simple and plunging ranulas. On DWI, most other masses were heterogeneous, and most ADC values, except those for thyroglossal duct cysts, hemangiomas, and pleomorphic adenomas, were significantly lower than those for ranulas. CONCLUSIONS: The characteristic DWI and ADC findings of ranulas can be determined accurately, and these data can be significantly useful in the differential diagnosis of many kinds of diseases in and around the oral floor.

Multiple mandibular static bone depressions attached to the three major salivary glands.

A Stafne bone defect is a static bone depression in the mandible that is commonly observed in cortical bone near the mandibular angle. We herein present a rare case in which static bone depressions attached to the three major salivary glands were observed on panoramic radiography and computed tomography (CT). The three static bone depressions in the mandible were visualized on a panoramic radiograph and CT as oval radiolucent masses in a 68-year-old man. The CT numbers in the bone depressions ranged from 10 to 50 HU, and they were close to those of the respective salivary glands. Based on the CT numbers, the areas in the bone depressions were determined to be a normal parotid gland, sublingual gland, and submandibular gland. The patient underwent a follow-up examination and did not request further consultation.