The hyoid bone is located in the middle of the cervical muscles involved in oral masticatory function. The position of the hyoid bone is commonly determined by lateral cephalometric analysis. Although cephalometric radiography is commonly used in orthodontic treatment, the modality remains rare; routine dental care would benefit from precise identification of hyoid bone location using a more common modality, such as panoramic radiography. The purpose of this study was to investigate the usefulness of panoramic radiography compared to lateral cephalometric radiography for evaluating hyoid bone position as a potential screening method for oral hypofunction. The study included 347 patients referred for both a panoramic radiograph and a lateral cephalometric radiograph. The patients were divided into the following five groups according to the appearance of the hyoid bone in the panoramic radiograph: Group 1: hyoid bone could not be observed, or part of the greater horn was observed; Group 2: part of the hyoid body was observed, but not the most supero-anterior point of the hyoid bone; Group 3: the most supero-anterior point of the hyoid bone was observed; Group 4: all of the hyoid body was observed; Group 5: the hyoid body overlapped the mandible. The gold standard for measurement of hyoid bone position is the lateral cephalometric radiograph. Hyoid bone position as revealed by lateral cephalometric radiograph was compared among the groups. Hyoid bones that were observed in higher positions on lateral cephalometric radiograph were also observed in higher positions on panoramic radiograph. Hyoid bone position can be assessed by panoramic radiography, and this modality might be useful as a screening method for oral hypofunction.
The anti-human epidermal growth factor receptor 2 （HER2） antibody （Ab） is a molecularly targeted Ab for cancer therapy. In the field of breast cancer, approximately 20％ overexpress HER2 protein. However, the recurrence rate is 30％ and the metastasis rate is 18％ one year after treatment of anti-HER2 Ab for HER2 positive breast cancer. The resistance to Ab treatment is a major problem for patients. We previously reported that anti-HER2 Ab and Gamma Interferon （IFN-γ） combined therapy show a higher anti-tumor effect than typical therapy in in vitro and in vivo mouse experiments. In this study, we evaluated whether anti-HER2 Ab and IFN-γ combined therapy shows a good synergistic effect against drug-resistant HER2 positive breast cancer cells and a higher antitumor effect than chemotherapy as a conventional clinical treatment. Further, we evaluated a synergy effect with the PD-L1 as a new check point inhibitor. The resistant cell lines were made under the continuous presence of Ab until cell growth was not affected by the drug. The resistant cells were divided into the appropriate number of groups, and then treated with anti-cancer therapy. We evaluated the antitumor effect for both the in vitro study and in vivo mouse xenograft model prepared with the same immunogenicity. The differences of immunofluorescence staining of CD8, Gr-1 and PDL-1 in tissues were investigated, especially in relation to the immune system. The combined therapy showed a significantly higher anti-tumor effect than other groups in in vitro and in vivo experiments. The combined therapy affected anti-tumor immunity in this immunofluorescence experiment. Taken together, we showed the possibility that combined therapy could be an effective treatment option for anti-HER2 Ab resistant breast cancer, thus helping patients suffering from cancer progression after developing treatment resistance.
Hepatitis C virus（HCV）infection can cause chronic liver disease; it has also been associated with lymphoproliferative disorders（LPDs）, such as cryoglobulinemia and B-cell non-Hodgkin’s lymphoma. Our previous studies suggested that cryoglobulinemia, high titer of rheumatoid factor（RF）, and hypocomplementemia are immunological markers of LPDs. In addition, recent therapies with direct-acting antivirals（DAAs）have achieved high rates of sustained virological response（SVR）in patients with chronic hepatitis C（CH-C）. This study analyzed the efficacy of DAA therapy in CH-C patients with cryoglobulinemia, and the association of biochemical and other immune markers for LPDs with persistence of cryoglobulinemia in patients after DAA therapy. Of 226 patients tested, 31（13.7％）had cryoglobulinemia prior to receiving DAAs, and these individuals showed lower complement 4 levels, decreased complement hemolytic activity, and higher IgM than patients without cryoglobulinemia. Of the 24 cryoglobulinemia-positive patients（83％）who could be followed for 24 weeks, 20 became cryoglobulinemia negative after the therapy. The remaining four patients retained the abnormal LPD markers, indicating the possibility of long-term LPD persistence even following successful eradication of HCV in CH-C patients. Thus, long-term follow-up is recommended to avoid exacerbation of extrahepatic manifestations as well as new events.
Anxiety affects respiration, and in turn perturbs the internal environment, although the neuronal systems controlling anxiety-related respiration remain unclear. Recent reports indicate that serotonin（5-HT）neurons in the median raphe nucleus（MRN）enhance anxiety. In the present study, we aimed to clarify the contribution of 5-HT neurons in the MRN to anxiety and respiratory control using mice expressing a channelrhodopsin-2 variant-enhanced yellow fluorescent protein（ChR2 ［C128S］-EYFP; a step-function opsin）in the central 5-HT neurons. We applied an optogenetic method to bigenic mice expressing ChR2［C128S］-EYFP in 5-HT neurons and to monogenic mice without such expression. Photostimulation of free-moving mice was performed using a wireless system through an optical fiber pre-inserted above the MRN, and respiratory variables were measured using whole-body plethysmography. Anxiety was evaluated using an elevated-plus maze test. In the bigenic mice, we confirmed ChR2［C128S］-EYFP expression in tryptophan hydroxylase 2（a brain 5-HT synthase）-positive neurons in the raphe nuclei of the mesopontine, such as the MRN and the dorsal raphe nucleus. Blue light illumination to the MRN of the bigenic mice significantly increased respiratory rate and minute ventilation without affecting tidal volume, and significantly decreased the time spent in the open arms of the elevated plus maze without changing distance traveled, compared with monogenic mice. These results suggest that 5-HT neuron activity in the MRN increases anxiety-like behavior without affecting locomotor activity, enhances respiratory rhythm and minute ventilation without changing tidal volume, and can mimic anxiety-related respiratory responses in humans.
Postoperative atrial fibrillation（AF）is associated with significant morbidity after cardiac surgery. We examined the effects of a prophylactic postoperative amiodarone infusion to prevent postoperative AF. A prospective randomized study was performed in patients with a high risk of postoperative AF between March 2016 and March 2019. High risk of AF was defined as combined valve surgery, aortic valve replacement（age＞70）, or off-pump coronary bypass grafting（age＞65）. Forty-two patients were enrolled and randomly assigned to receive prophylactic amiodarone infusion（amiodarone group, n＝20）or saline infusion（control group, n＝22）. In the amiodarone group, amiodarone was infused intravenously for 48hr postoperatively（initially 125mg/10min, then 288mg/6hr, then maintenance of 1,040mg/42hr）. There were no significant differences between the two groups in age, sex, body height, body weight, surgical procedure, and perioperative use of beta blockers. The occurrence of sustained AF for＞1hr was significantly lower in the amiodarone group（30.0％）than in the control group（63.6％, p＝0.04）. The total duration of AF over one week was also significantly shorter in the amiodarone group（296.8±676.9min）than in the control group（921.4±1641.6min, p＝0.04）, as was the postoperative hospital stay（17.3±6.1 vs. 24.5±11.3 days, respectively, p＝0.01）. There were no major side effects with amiodarone infusion except for one case of bradycardia. These results show the prophylactic use of intravenous amiodarone infusion for the first 48hr of the postoperative period is a safe and effective treatment to prevent postoperative AF after cardiac surgery and to shorten the hospital stay.
This study sought to determine whether antibiotic treatments affect the pathogenesis of allergic diseases. We demonstrated that mice treated with a mixture of four antibiotic agents （ampicillin, neomycine, metronidazole, and vancomycin） showed significantly decreased antigen-specific IgE production compared to control mice, whereas mice treated with the same cocktail without metronidazole showed no change in IgE production compared to controls. Regulatory T cell suppression induced by particular antibody combinations is a possible mechanism of this effect, with an increased frequency of regulatory T cells also observed in the mesenteric lymph nodes （MLN） of mice treated with the mixture of four antibiotics, but not in the second cocktail without metronidazole. Our antibiotic treatments also dramatically decreased the diversity of mouse intestinal microbiota compared to control mice, based on 16SrRNA analysis of the cecum fecal composition. In conclusion, mice treated with antibiotic mixtures containing metronidazole, but not those treated without metronidazole, showed attenuated allergy responses and increased induction of regulatory T cells in the mucosa.
A 28-year-old man had right elbow pain just as he was throwing his usual fastball from the pitcher’s mound while playing a recreational baseball game. He had tenderness and swelling at the site of the olecranon without a history of trauma, previous elbow pain, instability or degenerative change in his elbow. An olecranon stress fracture was diagnosed caused by an impaction force during the throwing motion. Open reduction and internal fixation using tension band wiring was performed. Bone union was achieved and he returned to playing baseball as a pitcher. We report our case along with some discussion of the literature.