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Objectives This retrospective study examined how a pharmacist-involved education program in a multidisciplinary team (PEMT) for oral mucositis (OM) affected head-and-neck cancer (HNC) patients receiving concurrent chemoradiotherapy (CCRT). Materials and methods Total samples data of 53 patients during the stipulated timeframe were retrospectively collected from electronic medical records from February 2017 to January 2019. We compared the presence/absence of OM (OM: yes/no) between patients with and without PEMT (PEMT: yes/no) as the primary endpoint and OM severity as the secondary endpoint. The following information was surveyed: age, gender, weight loss, steroid or immunosuppressant use, hematological values (albumin, white blood cell count, blood platelets, and neutrophils), cancer grade, primary cancer site, type and use of mouthwash and moisturizer, opioid use (yes/no, days until the start of opioid use, and dose, switch to tape), and length of hospital day (LOD). The two groups were compared using Fisher’s exact test for qualitative data and the Mann-Whitney U test for quantitative data, and a significance level of p.05 was set. Results The group managed by PEMT had significantly lower weight loss and a significantly lower incidence of local anesthetic and opioid use and switch to tape compared with the group not managed by PEMT (p.05). The two groups showed no significant difference in OM (yes/no) or OM severity. The PEMT group had significantly shorter LOD at 57 (53–64) days compared with the non-PEMT group at 63.5 (57–68) days (p.05). Conclusions Our results showed that PEMT did not improve OM (yes/no) or OM severity in HNC patients undergoing CCRT. However, the PEMT group had a lower incidence of grades 3 and 4 OM than the non-PEMT group, although not significantly. In addition, PEMT contributed to oral pain relief and the lowering of the risk for OM by reduction in weight loss.

Introduction According to the guidelines, the dosage for mandibular wisdom tooth extraction (MWTE) varies within the administration period. There is a 24-fold difference between the minimum and maximum doses. If an appropriate antimicrobial can be administered without increasing incidence of surgical site infection (SSI), it may lead to a global action plan on antimicrobial resistance (AMR). Therefore, we prospectively surveyed incidence of SSI post-operatively and use of oral antibiotics (OA) for MWTE. Methods Subjects were patients who underwent MWTE in our dental outpatient clinic from May 2019 to April 2020. Two groups were formed depending on type of administration period they received: 24 h and 48 h after surgery. The following information was collected: (1) patient factors (age, gender, body mass index, presence/absence of preoperative medication, diagnosis, impacted wisdom tooth status; (2) surgical factors (operative time, presence/absence of closure, presence/absence of hemostat, doctor career, type and frequency of painkiller); (3) relationship between administration period of OA and SSI occurrence; and (4) details of SSI. Results Three hundred forty subjects were analyzed, all of which used amoxicillin. There were 106 cases in 24 h group and 234 cases in 48 h group. The total incidence of SSI was 1.1% (4/340 cases), with 0.9% (1/106 cases) in 24 h group and 1.3% (3/234 cases) in 48 h group; there was no difference between the two groups. Conclusion Our study suggests that amoxicillin (250 mg/dose every 8 h x 3 doses beginning 1 h before surgery) might be sufficient in preventing SSI in Japanese dental patients without SSI risk factors.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to β-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with β-lactamase inhibitor showed low MIC90 values.

The mandible is a crucial organ in both clinical and biological fields due to the high frequency of congenital anomalies and the significant morphological changes during evolution. Primary cilia play a critical role in many biological processes, including the determination of left/right axis patterning, the regulation of signaling pathways, and the formation of bone and cartilage. Perturbations in the function of primary cilia are known to cause a wide spectrum of human diseases: the ciliopathies. Craniofacial dysmorphologies, including mandibular deformity, are often seen in patients with ciliopathies. Mandibular development is characterized by chondrogenesis and osteogenesis; however, the role of primary cilia in mandibular development is not fully understood. To address this question, we generated mice with mesenchymal deletions of the ciliary protein, Ift88 (Ift88 (fl/fl) ;Wnt1Cre). Ift88 (fl/fl) ;Wnt1Cre mice showed ectopic mandibular bone formation, whereas Ift88 mutant mandible was slightly shortened. Meckel's cartilage was modestly expanded in Ift88 (fl/fl) ;Wnt1Cre mice. The downregulation of Hh signaling was found in most of the mesenchyme of Ift88 mutant mandible. However, mice with a mesenchymal deletion of an essential molecule for Hh signaling activity, Smo (Smo (fl/fl) ;Wnt1Cre), showed only ectopic mandibular formation, whereas Smo mutant mandible was significantly shortened. Ift88 is thus involved in chondrogenesis and osteogenesis during mandibular development, partially through regulating Sonic hedgehog (Shh) signaling.

Background The timing, location, and level of gene expression are crucial for normal organ development, because morphogenesis requires strict genetic control. MicroRNAs (miRNAs) are noncoding small single-stranded RNAs that play a critical role in regulating gene expression level. Although miRNAs are known to be involved in many biological events, the role of miRNAs in organogenesis is not fully understood. Mammalian eyelids fuse and separate during development and growth. In mice, failure of this process results in the eye-open at birth (EOB) phenotype. Results It has been shown that conditional deletion of mesenchymal Dicer (an essential protein for miRNA processing; Dicer fl/fl ;Wnt1Cre) leads to the EOB phenotype with full penetrance. Here, we identified that the up-regulation of Wnt signaling resulted in the EOB phenotype in Dicer mutants. Down-regulation of Fgf signaling observed in Dicer mutants was caused by an inverse relationship between Fgf and Wnt signaling. Shh and Bmp signaling were down-regulated as the secondary effects in Dicer fl/fl ;Wnt1Cre mice. Wnt, Shh, and Fgf signaling were also found to mediate the epithelial-mesenchymal interactions in eyelid development. Conclusions miRNAs control eyelid development through Wnt. Developmental Dynamics 248:201-210, 2019. © 2019 Wiley Periodicals, Inc.

Rodent incisors maintain the ability to grow continuously and their labial dentin is covered with enamel. Bcl11b zinc-finger transcription factor is expressed in ameloblast progenitors in mouse incisors and its absence in Bcl11bKO/KO mice results in a defect in embryonic tooth development. However, the role of Bcl11b in incisor maintenance in adult tissue was not studied because of death at birth in Bcl11bKO/KO mice. Here, we examined compound heterozygous Bcl11bS826G/KO mice, one allele of which has an amino acid substitution of serine at position 826 for glycine, that exhibited hypoplastic maxillary incisors with lower concentrations of minerals at the enamel and the dentin, accompanying the maxillary bone hypoplasia. Histological examinations revealed hypoplasia of the labial cervical loop in incisors, shortening of the ameloblast progenitor region, and impairment in differentiation and proliferation of ameloblast-lineage cells. Interestingly, however, juvenile mice at 5 days after birth did not show marked change in these phenotypes. These results suggest that attenuated Bcl11b activity impairs ameloblast progenitors and incisor maintenance. The number of BrdU label-retaining cells, putative stem cells, was lower in Bcl11bS826G/KO incisors, which suggests the incisor hypoplasia may be in part a result of the decreased number of stem cells. Interestingly, the level of Shh and FGF3 expressions, which are assumed to play key roles in the development and maintenance of ameloblasts and odontoblasts, was not decreased, though the expressed areas were more restricted in ameloblast progenitor and mesenchyme regions of Bcl11bS826G/KO incisors, respectively. Those data suggest that the incisor maintenance by Bcl11b is not directly related to the FGF epithelial–mesenchymal signaling loop including Shh but is intrinsic to ameloblast progenitors and possibly stem cells.

Members of the Sox gene family play critical roles in many biological processes including organogenesis. We carried out comparative in situ hybridisation analysis of seventeen Sox genes (Sox1-14, 17, 18 and 21) during murine palatogenesis from initiation to fusion of the palatal shelves above the dorsal side of the tongue. At palatal shelf initiation (E12.5), the localized expression of six Sox genes (Sox2, 5, 6, 9, 12 and 13) was observed in the shelves, whereas Sox4 and Sox11 showed ubiquitious expression. During the down-growth of palatal shelves (E13.5), Sox4, Sox5, and Sox9 exhibited restricted expression to the interior side of the palatal shelves facing the tongue. Following elevation of the palatal shelves (E14.5), Sox2, Sox11 and Sox21 expression was present in the midline epithelial seam. We thus identify dynamic spatio-temporal expression of Sox gene family during the process of palatogenesis.

The diagnosis of orofacial pain associated with temporomandibular disorders after repeated temporomandibular joint (TMJ) surgeries can be quite difficult. This case report describes a 52-year-old woman who had previously undergone five TMJ surgeries and developed divergent pain caused by a trigger point in the left preauricular area. Computed tomography and magnetic resonance imaging could not be used to identify a lesion because of metallic artifacts from a TMJ prosthesis. However, sonography indicated the location of the suspected lesion. Moreover, a neurological examination performed with local anesthesia was clinically effective in ruling out other diagnoses of orofacial pain. Ultimately, a histopathological examination of a biopsy specimen from the painful site confirmed the lesion to be a traumatic neuroma. This case report suggests the value of including traumatic neuroma in the differential diagnosis of patients with a history of previous TMJ surgery who present with orofacial pain in the region of the TMJ.

[Purpose] This study examines using ultrasonography and unenhanced computed tomography (CT) to determine the location of the internal maxillary artery (IMA) before orthognathic surgery.[Patients and Methods] From January 2008 to February 2011, 15 patients (30 sides as bilateral) with jaw deformities agreed to participate in this study after informed consent was obtained. IMAs were visualized through the acoustic window formed by the zygomatic arch and mandibular notch using power Doppler ultrasonography. Ultrasonographic findings were classified into 2 patterns as follows: 1) clear pattern, indicating continuous or string-like structure; 2) unclear pattern, indicating discontinuous dot-like structure or no apparent blood flow. Each unenhanced CT image of the IMA location was categorized referring to the ultrasonographic image as predictable or unpredictable.In addition, each predictable image was subclassified as lateral (located external to the lateral pterygoid muscle) or medial (other than the former).[Results] The ultrasonography had 24 (80.0%) IMAs classified as clear and 6 (20.0%) as unclear. For the 24 clear patterns, the mean distance from the mandibular notch to the IMA was 2.77 mm (1.0-6.0 mm). The IMA location was detectable in all patients using unenhanced CT plus ultrasonographic imaging. Of the 26 (86.7%) IMAs located lateral to the lateral pterygoid muscle, the ultrasonographic artery findings were classified as clear for 24 and unclear for 2. Of the 4 (13.3%) IMAs located medial to the lateral pterygoid muscle, the ultrasonography findings were classified as unclear.[Discussion] Paying attention to unclear-pattern images classified as lateral was necessary because they may indicate that the IMA is located in proximity to the ramus medially, and to clear-pattern images classified as lateral that approach the mandibular notch. We assume that the risk for hemorrhage during orthognathic surgery will increase if the IMA route is located in the surgery area.[Conclusion] A combination of ultrasonography and unenhanced CT for determining the IMA route may provide safer orthognathic surgery.

Progressive hemifacial atrophy (PHA) is a self-limited atrophy of subcutaneous tissues (and less frequently of hard tissues) on one side of the face. It is a sporadic, slowly progressing disease whose pathogenesis is still unknown. As a rule the asymmetry caused by PHA (usually of soft tissue) is treated by volume augmentation that involves free tissue grafting or a pedicled flap transfer. We describe a rare case of hard tissue PHA. The atrophic changes occurred in the left molar tooth, maxilla and mandible and were associated with moderate soft tissue atrophy. The left side of the patient's mouth was higher on the right side, and the occlusal plane was severely inclined in spite of normal occlusion. After no alteration and no progression of the atrophy were established, the patient was treated with orthodontic surgery. To correct the inclined occlusal plane and asymmetry profile, we performed a Le Fort I and intraoral vertical ramus osteotomy. In the 3-year follow-up, there were good occlusal balance and improved symmetrical profile without relapse or recurrence of the atrophy. Thus, orthodontic surgery was effective as a first procedure to treat hard tissue atrophy that appeared with moderate soft tissue atrophy.

We report a case of mandibular asymmetry suggested to have delayed growth as a late effect after orthodontic surgery.Postoperative delayed growth often causes occlusal instability and a poor profile as a late effect. It is difficult to predict such changes because the causes differ from those of general relapse, and development is accidental. Although occlusal instability caused by delayed growth after orthodontic surgery is rare and poorly understood, investigating the details of such changes is of great value for postoperative orthodontics or planning reoperation.Our findings suggested that changes in mandibular elongation caused by delayed growth differed between the right and left sides. The differences were greatest at the ramus and condyle on the displaced side, showing vertical elongation.In patients undergoing orthodontic surgery for mandibular asymmetry, the possibility of puberal growth spurts should be considered and patients should be followed up carefully since asymmetry can recur.

Susceptibility to gamma-ray induction of thymic lymphomas in mouse strains is controlled by low-penetrance genetic variant alleles. Our previous genome-wide scan of a mouse backcross between BALB/c and MSM strains suggested the existence of a BALB/c resistance locus near D5Mit5 on chromosome 5. To confirm this resistance, we produced congenic mice carrying a 28.4 cM region between D5Mit4 and D5Mit315 from the MSM parental strain on the BALB/c background. Lymphomas were induced in their progeny by gamma-ray irradiation or administration of N-methyl-N-nitrosourea (MNU), an alkylating agent. The incidence of radiogenic lymphomas was 87.5% in mice of the M/M genotype at D5Mit7, significantly higher than the 46% incidence in mice of the C/M genotype, indicating highly significant linkage between the locus and the resistance (P = 0.000054). In contrast, the frequencies of MNU-induced thymic lymphomas were similar between the two genotypes (P = 0.35 in chi2 test). These results confirm the presence of a resistance allele for gamma-ray induction of thymic lymphomas near the D5Mit7 locus and strongly suggest that this locus modifies carcinogenic risk from exposure to radiation but not to alkylating agents.

Trp53-deficient mice exhibit increased incidences of developmental anomalies when irradiated, probably due to lack of Trp53-dependent apoptosis. A/J strain-derived CL/Fr mice develop clefts of the lip with or without the palate (CL/P) in approximately one-fifth of the embryos. We produced Trp53-deficient CL/Fr mice and examined the susceptibility to spontaneous development of CL/P and clefts of palate only (CPO), which differ in their developmental mechanisms, CL/P resulting from clefts of the primary palate and CPO from clefts of the secondary palate. The effect of radiation on the two phenotypes was also studied. Unexpectedly, no increase in the frequency of CL/P was observed under either condition, indicating that Trp53 deficiency does not contribute to genesis of CL/P. On the other hand, radiation enhanced the incidence of CPO in Trp53(+/+) embryos but not in Trp53(+/-) and Trp53(-/-/) embryos, suggesting that the absence or presence of only one allele of Trp53 is insufficient to hinder differentiation and proliferation of cells involved in the secondary palate formation. These results indicate that Trp53 function adversely affects the development of CPO when certain damaging agents such as radiation are given.

Low-penetrance genes control different susceptibilities to gamma-ray-induced thymic lymphomas in mouse strains. Our previous genetic analyses with backcross mice between BALB/c and MSM strains and congenic lines localized one such gene near the D4Mit12 locus on chromosome 4. N-Methyl-N-nitrosourea (MNU) is a guanine base-alkylating agent and differs from gamma-radiation in its mechanism of mutagenic action. Accordingly, in this study, we examined whether or not the locus also provides susceptibility to MNU-induced thymic lymphomas using 84 offsprings derived from congenic mice for D4Mit12. Association analysis provided a suggestive linkage at D4Mit12 (P = 0.0075) and the linkage was sustained by the peak of likelihood ratio statistical values being at the same position as that for the gamma-ray-induced lymphomas. The results strongly suggest that the BALB/c allele near D4Mit12 is associated with susceptibility to lymphomas induced by two carcinogenic agents having different mechanisms of mutagenic action.