Epiglottic retraction is useful in diagnosis of exercise-induced laryngeal obstruction.

Background: Exercise-induced laryngeal obstruction (EILO) is distinguished as upper airway obstruction accompanied by inspiratory dyspnoea and stridor during highly intensive exercises. Epiglottic retraction in the diagnosis of EILO has not been sufficiently explored. Aims/objectives: We highlight the importance of epiglottic retraction in patients with EILO by evaluation by several diagnostic methods for EILO. Consideration of epiglottic retraction may be important for accurate diagnosis of EILO. Results: Epiglottic retraction could be observed in three patients by laryngoscopy during heavy breathing and in two patients by continuous laryngoscopy during exercise. Stridor occurred by the forward prolapse of the arytenoids, but not by epiglottic retraction. In comparison with three athletes from other sports, lung volume was significantly greater in four swimmers although it was not different related to depending on the existence of epiglottic retraction. Conclusions and significance: Laryngoscopy during heavy breathing is suggested to be useful to detect the epiglottic retraction, which might be overlooked if only continuous laryngoscopy during exercise is used. Epiglottic retraction was not rare in Japanese swimmers' exercise-induced laryngeal obstruction in our cohort and it might be related to the greater lung volume.

Pneumolysin contributes to dysfunction of nasal epithelial barrier for promotion of pneumococcal dissemination into brain tissue.

Streptococcus pneumoniae is one of the major pathogens responsible for bacterial meningitis and neurological sequelae. The present study was conducted to identify a non-hematogenous route used by S. pneumoniae to gain access to brain tissue without causing bacteremia or pneumonia, as well as bacterial and host factors involved in this process. To investigate the molecular mechanisms and dissemination pathways of pneumococcal infection in brain tissue, mice were intranasally inoculated with S. pneumoniae strain EF3030, a clinical isolate from a patient with otitis media. Pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum, with neither bacteremia nor pneumonia observed in the present model. Immunostaining imaging revealed the presence of S. pneumoniae organisms in olfactory nerve fibers. Knockout of the ply gene encoding pneumolysin (PLY) markedly compromised the ability of the bacterial organisms to disseminate into brain tissue, whereas the dissemination efficiency of the complemented strain was restored to nearly the same level as the wild type. Notably, distinct upregulation of Gli1 and Snail1, which are involved in the transcriptional repression of junctional proteins, along with downregulation of E-cadherin, was detected in nasal lavage samples from mice infected with the wild-type or complemented strain, but not in those from mice infected with the ply mutant. Taken together, the present findings indicate that PLY induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, thus allowing pneumococcal dissemination to brain tissue that occurs in a non-hematogenous manner.IMPORTANCEBacterial meningitis, considered to be caused by bacteremia, can lead to blood-brain barrier disruption and bacterial dissemination into the central nervous system. Despite the availability of intravenously administered antibiotics with cerebrospinal fluid transferability, bacterial meningitis remains associated with high rates of morbidity and mortality. Here, we utilized Streptococcus pneumoniae strain EF3030, clinically isolated from otitis media, for the construction of a murine infection model to investigate the molecular mechanisms by which nasally colonized pneumococci disseminate into brain tissue. The obtained findings indicate that pneumolysin (PLY) induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, which facilitates pneumococcal dissemination to brain tissue in a non-hematogenous manner. Our results support the existence of an alternative route by which S. pneumoniae can reach the central nervous system and indicate the need for the development of novel therapeutic strategies, which would be an important contribution to the clinical management of bacterial meningitis.

Inhibition of transient receptor potential vanilloid 1 reduces shedding and transmission during Streptococcus pneumoniae co-infection with influenza.

Transmission is the first step for a microorganism to establish colonization in the respiratory tract and subsequent development of infectious disease. Streptococcus pneumoniae is a leading pathogen that colonizes the mucosal surfaces of the human upper respiratory tract and causes subsequent transmission and invasive infections especially in co-infection with influenza A virus. Host factors contributing to respiratory contagion are poorly understood. Transient receptor potential vanilloid (TRPV) channels have various roles in response to microoorganism. Inhibition of TRPV exacerbates invasive infection by Streptococcus pneumoniae, but it is unclear how TRPV channels influence pneumococcal transmission. Here, we describe the effect of inhibition of TRPV1 on pneumococcal transmission. We adopted a TRPV1-deficient infant mouse model of pneumococcal transmission during co-infection with influenza A virus. We also analyzed the expression of nasal mucin or pro-inflammatory cytokines. TRPV1 deficiency attenuated pneumococcal transmission and shedding during co-infection with influenza A virus. TRPV1 deficiency suppressed the expression of nasal mucin. In addition, there were increases in the expression of tumor necrosis factor-α and type I interferon, followed by the suppressed replication of influenza A virus in TRPV1-deficient mice. Inhibition of TRPV1 was shown to attenuate pneumococcal transmission by reducing shedding through the suppression of nasal mucin during co-infection with influenza A virus. Inhibition of TRPV1 suppressed nasal mucin by modulation of pro-inflammatory responses and regulation of replication of influenza A virus. TRPV1 could be a new target in preventive strategy against pneumococcal transmission.

Impact of Educational Films on Antibiotic Prescription among Physicians: A Web-Based Survey in Japan.

Although antibiotics are most frequently prescribed for respiratory tract infections, effective interventions for their proper use by physicians have not been fully established. We assessed the impact of educational films on the rates of antibiotic prescriptions for respiratory tract infections using fictitious scenarios. In this nationwide web-based survey prospective study, a total of 1100 physicians were included. The physicians were required to view educational short films and determine the need for prescribing antibiotics in 10 fictitious scenarios involving adults diagnosed with different acute respiratory tract infectious diseases. The antibiotic prescription rates for each scenario were compared before and after viewing the educational short film. The rates of antibiotic prescription significantly decreased after viewing the educational film, especially in cases with a narrowly defined common cold (from 51% to 15%), mild pharyngolaryngitis (from 71% to 25%), and acute bronchitis without chronic respiratory underlying diseases (from 63% to 23%). Alternatively, a slight decrease in rates was observed in cases with moderate or severe rhinosinusitis (from 94% to 79%), moderate or severe acute pharyngitis (from 88% to 69%), and acute bronchitis with chronic lung disease (from 70% to 58%), for which antibiotics are recommended. Educational short films may encourage the proper use of antibiotics for respiratory tract infections; however, the possibility of undertreatment in patients requiring antibiotics must be considered.

A rapid simultaneous antigen detection of Haemophilus influenzae and Streptococcus pneumoniae for predicting the prognosis of acute otitis media.

BACKGROUND: Rapid identification of causative bacteria in treatment of acute otitis media (AOM) is of paramount importance for appropriate antibiotic use. MATERIALS AND METHODS: This prospective observational study was conducted in 15 hospitals and clinics in Japan between 2018 and 2020. A new rapid antigen test kit (AOS-116), which simultaneously detects antigens for Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi), was applied for middle ear fluids (MEFs) and nasopharyngeal secretions (NPSs) in patients with moderate to severe AOM. We investigated relationship between the results of rapid test, severity at initial visit, and clinical course. RESULTS: Regarding performance accuracy based on culture results, AOS-116 showed 1) high (>80%) sensitivity, specificity, and negative predictive value (NPV) in MEFs for both antigens, 2) high sensitivity, specificity, and positive predictive value (PPV) in NPSs for Hi antigen, and 3) high specificity, and PPV in NPSs for Sp antigen. Regarding predictive value of nasopharyngeal culture and antigen detection for causative middle ear pathogens, similar results were observed between AOS-116 and culture, which was characterized with high sensitivity and NPV for both pathogens. MEFs/NPSs positive for Hi antigen were significantly associated with eardrum findings, and severity. MEFs/NPSs positive for pneumococcal antigen were significantly associated with severity of otalgia, fever, and otorrhea. Among patients with prior antimicrobial treatment, improvement tended to be slower in cases positive for Hi than in cases negative. CONCLUSION: The rapid antigen detection test is useful as a decision-making tool for prescribing antimicrobial agents and may play an important role in promoting appropriate antimicrobial use.

Traditional Japanese herbal medicine Hochuekkito protects development of sepsis after nasal colonization in mice.

INTRODUCTION: Streptococcus pneumoniae, a commensal in the nasopharynx, can cause invasive pneumococcal diseases (IPDs). To prevent the aggravation of IPDs, it is important to enhance host immune defense against S. pneumoniae. Hochuekkito (HET) is expected to have an immunostimulatory effect against infections. METHODS: HET was administrated by gavage to adult BALB/cA mice before and after intranasal inoculation of S. pneumoniae. We evaluated the effect of HET on pneumococcal nasal colonization and subsequent development of lethal pneumococcal infections. RESULTS: No effect on nasal colonization was observed, but HET significantly reduced bacterial count in the blood, decreased the incidence of bacteremia, and improved survival. HET also reduced nasal tissue damage 3 days after intranasal infection. Neutrophils from HET-treated mice showed significantly higher bactericidal activity against S. pneumoniae in the presence of the serum from the HET group compared with from the control group. CONCLUSIONS: The non-specific immunostimulatory effect of HET is suggested by this study to be effective in preventing the progression in IPDs and provided insights into novel strategy in the post-pneumococcal vaccine era.

Contrast-Enhanced MRI Is Useful for Prognostic Prediction on Idiopathic Bilateral Simultaneous Facial Nerve Palsy: A Case Report and Literature Review.

Idiopathic bilateral facial nerve palsy is a rare condition and presents a diagnostic and prognostic challenge. Specifically, when bilateral nerves are damaged, it is difficult to predict the prognosis. We showcase the usefulness of contrast-enhanced magnetic resonance imaging (MRI) by providing information about localization and severity of degeneration of facial nerve. A 70-year-old Japanese man presented with bilateral simultaneous facial nerve palsy of House-Brackmann Grade VI on both sides. Contrast-enhanced MRI revealed bilateral intensity enhancement of intratemporal facial nerves. The signal intensity was higher on the left side than on the right side. Facial nerve decompression was performed on the left side. The left facial nerve palsy was finally improved eight months after the onset, while the right side was improved just under two months after the onset. Contrast-enhanced MRI for facial nerve palsy can provide valuable information for the evaluation of damaged facial nerves. In our patient's case, it was useful as a prognostic predictor of bilateral facial nerve palsy.

Factors affecting the antimicrobial changes during treatment for acute otitis media in Japan: A retrospective cohort study using classification and regression trees (CART) analysis.

OBJECTIVES: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use. METHODS: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis. RESULTS: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes. CONCLUSIONS: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment.

Direct toxicity of cigarette smoke extract on cardiac function mediated by mitochondrial dysfunction in Sprague-Dawley rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes.

Cigarette smoke has been recognized as a major risk factor for cardiovascular disease. However, its direct effects on rodent and human cardiomyocytes and its cellular mechanisms are not fully understood. In this study, we examined the direct effects of cigarette smoke extract (CSE) on contractile functions, intracellular Ca2+ dynamics, and mitochondrial function using cultured or freshly isolated rat ventricular myocytes and human induced pluripotent stem cell (iPS)-derived cardiomyocytes. In rat cardiomyocytes, CSE (≥0.1%) resulted in a time- and concentration-dependent cessation of spontaneous beating of cultured cardiomyocytes, eventually leading to cell death, which indicates direct toxicity. In addition, 1% CSE reduced contractile function of freshly isolated ventricular myocytes. Similar contractile dysfunction (declined spontaneous beating rate and contractility) was also observed in human iPS-derived cardiomyocytes. Regarding intracellular Ca2+ dynamics, 1% CSE increased the Ca2+ transient amplitude by greatly increasing systolic Ca2+ levels and slightly increasing diastolic Ca2+ levels. CSE also accelerated the decay of Ca2+ transients, and triggered spike-shaped Ca2+ transients in some cells. These results indicate that CSE causes abnormal Ca2+ dynamics in cardiomyocytes. Furthermore, CSE induced a cascade of mitochondrial dysfunctions, including increased mitochondrial reactive oxygen species, opening of mitochondrial permeability transition pore, reduction of mitochondrial membrane potential, and release of cytochrome c from mitochondria. These results suggest that CSE-induced contractile dysfunction and myocardial cell death is caused by abnormal Ca2+ dynamics and subsequent mitochondrial dysregulation, which would result in reduced bioenergetics and activation of cell death pathways.

Nucleic acid sensing Toll-like receptors 3 and 9 play complementary roles in the development of bacteremia after nasal colonization associated with influenza co-infection.

Streptococcus pneumoniae can cause mortality in infant, elderly, and immunocompromised individuals owing to invasion of bacteria to the lungs, the brain, and the blood. In building strategies against invasive infections, it is important to achieve greater understanding of how the pneumococci are able to survive in the host. Toll-like receptors (TLRs), critically important components in the innate immune system, have roles in various stages of the development of infectious diseases. Endosomal TLRs recognize nucleic acids of the pathogen, but the impact on the pneumococcal diseases of immune responses from signaling them remains unclear. To investigate their role in nasal colonization and invasive disease with/without influenza co-infection, we established a mouse model of invasive pneumococcal diseases directly developing from nasal colonization. TLR9 KO mice had bacteremia more frequently than wildtype in the pneumococcal mono-infection model, while the occurrence of bacteremia was higher among TLR3 KO mice after infection with influenza in advance of pneumococcal inoculation. All TLR KO strains showed poorer survival than wildtype after the mice had bacteremia. The specific and protective role of TLR3 and TLR9 was shown in developing bacteremia with/without influenza co-infection respectively, and all nucleic sensing TLRs would contribute equally to protecting sepsis after bacteremia.

Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci.

BACKGROUND: Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques. METHODS: C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia. RESULTS: Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection. CONCLUSIONS: Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.

Leuconostoc mesenteroides subsp. strain NTM048 ameliorated nasal symptoms in patients with Japan cedar pollinosis: Randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Lactobacillales including L mesenteroides have beneficial effects on human health, including improvement of psychological status and alleviation of allergic rhinitis. In mice, L mesenteroides subsp. strain NTM048 (NTM048) increased intestinal s-IgA. In humans, however, the effects of NTM048 on s-IgA secretion have been unclear. STUDY: This 16-week trial was performed using a double-blind, placebo-controlled, parallel group design. We aimed to establish whether Leuconostoc mesenteroides subsp. strain NTM048 increases the secretion of s-IgA in saliva. Forty healthy adults and forty patients with Japanese cedar pollinosis were recruited. Participants took either 2 test capsules including NTM048 (1010 CFU/day), or 2 placebo capsules per day, for 16 weeks. They were asked to collect their saliva and answered POMS2, a questionnaire about psychological status. The patients also answered questions about nasal symptoms. Blood samples were collected from the patients with Japanese Cedar pollinosis. Stool samples were collected at the start and on the last day of the trial. RESULTS: All subjects completed the trial. It was conducted during the season when Japanese cedar pollen is most scattered. Serum concentration of Japanese cedar pollen-specific IgE was > 2.0 UA/mL in patients with Japanese cedar pollinosis. The amount of s-IgA in saliva was not increased by NTM048 in overall subjects, and Japanese cedar pollen-specific IgE was not changed by NTM048 in patients with Japanese cedar pollinosis. The symptom of nasal blockage was improved by NTM048 12 weeks after the start of trial. post hoc analysis indicated a positive correlation between improving psychological status and the increase in occupation ratio of lactobacillus including NTM048. CONCLUSION: The amount of s-IgA in saliva was not increased by NTM048, but nasal blockage was improved by it. Psychological status might be improved if dosage of NTM048 is raised to the degree that NTM048 might be increased in the intestinal tract.

Case Report: Solid variant of papillary thyroid carcinoma in a young adult with Turner syndrome with chronic thyroiditis.

Turner syndrome is associated with an increased risk of developing several neoplasms. In particular, a clinical feature of Turner syndrome with chronic thyroiditis implies a relationship with thyroid malignancies. We report a very rare case of a solid variant of papillary thyroid carcinoma that was identified during a follow-up of chronic thyroiditis in a 22-year-old woman with Turner syndrome. The patient had no notable history of radiation exposure. No genetic mutations relating to the occurrence of the solid variant of papillary thyroid carcinoma, including RET/PTC rearrangements and mutations in the BRAF or RAS, were detected by a gene panel test, namely, the Oncomine™ Dx Target test. To the best of our knowledge, this is the first report of a solid variant of papillary thyroid carcinoma in a young adult with Turner syndrome with chronic thyroiditis. Our case suggests that in patients with Turner syndrome, there may be different pathogeneses from those previously reported, including exposure to radiation or known genetic mutations for the development of a solid variant of papillary thyroid carcinoma.

Case report: Cochlear implantation was effective for progressive bilateral severe hearing loss associated with Kawasaki disease.

Sensorineural hearing loss associated with Kawasaki disease has been increasingly reported, but its etiology remains unclear. Most reported cases of sensorineural hearing loss associated with Kawasaki disease have been mild and reversible during acute or subacute phases. However, bilateral severe hearing loss as a complication of Kawasaki disease can cause delays in cognitive and speech development. A 4-year-old Japanese boy treated for Kawasaki disease had right-side moderate and left-side profound sensorineural hearing loss on the 141st day after onset of Kawasaki disease. Despite systemic steroid pulse treatment, hearing loss remained in both sides. After the recurrence of Kawasaki disease, hearing on the right side progressively worsened, meaning there was now severe hearing loss on both sides. Left cochlear implantation performed on the 1065th day after the onset of Kawasaki disease improved the patient's hearing and his ability to communicate. Sensorineural hearing loss associated with Kawasaki disease may progress over a long period and cause bilateral severe hearing loss, although past reports showed occurrence during acute or subacute phases. The clinical course of our patient suggests that intense inflammation caused by Kawasaki disease could be related to prolonged hearing loss. Cochlear implantation seems to be effective for sensorineural hearing loss associated with Kawasaki disease.

Chondroma Arising from the Temporomandibular Joint: A Case Report.

Periarticular chondromas are common in the humerus and femur but rarely occur in the temporomandibular joint. We report a case of a chondroma in the anterior part of the ear. One year prior to his visit, a 53-year-old man became aware of swelling in the right cheek region which gradually increased in size. In the anterior part of the right ear, there was a palpable 25 mm tumor, elastic and hard, with poor mobility and without tenderness. A contrast-enhanced computed tomography CT showed a mass lesion with diffuse calcification or ossification in the upper pole of the parotid gland and areas of poor contrast within. A magnetic resonance imaging showed a low-signal mass lesion at the parotid gland with some high signals in both T1 and T2. Fine-needle aspiration cytology did not lead to diagnosis. Using a nerve monitoring system, the tumor was resected with normal tissue of the upper pole of the parotid gland in the same way as for a benign parotid tumor. Distinguishing between pleomorphic adenoma, including diffuse microcalcification of the parotid gland and cartilaginous tumors of the temporomandibular joint, may be sometimes difficult. In such cases, surgical resection may be a beneficial treatment option.

Maternal immunization with pneumococcal surface protein A provides the immune memories of offspring against pneumococcal infection.

Introduction: Streptococcus pneumoniae (S. pneumoniae) is one of the most widespread pathogens in the world and one of the largest infectious causes of infant mortality. Although current vaccines have various benefits, antibiotic resistance and the inability to vaccinate infants less than one year old demands the development of new protective strategies. One strategy, 'maternal immunization', is to protect infants by passive immunity from an immunized mother, although its mechanism is still not fully understood. Materials and methods: The current study aimed to acquire immunity against S. pneumoniae in infants by maternal immunization with pneumococcal common antigen, pneumococcal surface protein A (PspA). Four-week-old female mice were immunized with recombinant PspA intranasally twice a week for three weeks. Females were mated with age-matched males after immunization, and delivered offspring. Results: The week-old offspring derived from and fostered by immunized mothers had more anti-PspA-specific antibody producing cells in the spleen than those derived from sham-immunized mothers. The offspring were raised up to four weeks old and were subcutaneously stimulated with recombinant PspA. The levels of anti-PspA IgG in sera after stimulation were significantly higher in the offspring derived from the immunized mothers and the induced specific antibody to PspA showed protective efficacy against systemic pneumococcal infection. Discussion: Maternal immunization is suggested to be able to provide a sustained immune memory to offspring. The current study would be a milestone in the field of maternal immunization toward a universal pneumococcal vaccine.

The Roles of Transient Receptor Potential Vanilloid 1 and 4 in Olfactory Regeneration.

Olfactory disorders, which are closely related to cognitive deterioration, can be caused by several factors, including infections, such as COVID-19; aging; and environmental chemicals. Injured olfactory receptor neurons (ORNs) regenerate after birth, but it is unclear which receptors and sensors are involved in ORN regeneration. Recently, there has been great focus on the involvement of transient receptor potential vanilloid (TRPV) channels, which are nociceptors expressed on sensory nerves during the healing of damaged tissues. The localization of TRPV in the olfactory nervous system has been reported in the past, but its function there are unclear. Here, we investigated how TRPV1 and TRPV4 channels are involved in ORN regeneration. TRPV1 knockout (KO), TRPV4 KO, and wild-type (WT) mice were used to model methimazole-induced olfactory dysfunction. The regeneration of ORNs was evaluated using olfactory behavior, histologic examination, and measurement of growth factors. Both TRPV1 and TRPV4 were found to be expressed in the olfactory epithelium (OE). TRPV1, in particular, existed near ORN axons. TRPV4 was marginally expressed in the basal layer of the OE. The proliferation of ORN progenitor cells was reduced in TRPV1 KO mice, which delayed ORN regeneration and the improvement of olfactory behavior. Postinjury OE thickness improved faster in TRPV4 KO mice than WT mice but without acceleration of ORN maturation. The nerve growth factor and transforming growth factor ß levels in TRPV1 KO mice were similar to those in WT mice, and the transforming growth factor ß level was higher than TRPV4 KO mice. TRPV1 was involved in stimulating the proliferation of progenitor cells. TRPV4 modulated their proliferation and maturation. ORN regeneration was regulated by the interaction between TRPV1 and TRPV4. However, in this study, TRPV4 involvement was limited compared with TRPV1. To our knowledge, this is the first study to demonstrate the involvement of TRPV1 and TRPV4 in OE regeneration.

Improvement of Surgical View and Working Space at the Lower Pole by Three-Dimensional Exoscope-Assisted Coblation Tonsillectomy: A Case Series.

Advantages of hot devices for tonsillectomy, represented by coblation, have been highlighted in recent years. During hot technique tonsillectomy it is important to identify and coagulate the vessels of the tonsillar capsule, especially at the lower pole of the tonsil. Hot technique tonsillectomy under microscope or endoscope has therefore been recommended to achieve accurate identification of the microstructure of the surgical field. We have applied ORBEYE, a three-dimensional surgical exoscope system, to coblation tonsillectomy. Advantages of using ORBEYE include high definition and high magnification images, and flexibility of camera position and angle. This means there is an improved surgical view and working space, particularly at the lower pole during performance of coblation tonsillectomy. Here, we demonstrate that ORBEYE can be an effective surgical instrument in coblation tonsillectomy.

Bactericidal effect of lascufloxacin on HEp-2 cell-internalized group A Streptococcus.

INTRODUCTION: Although amoxicillin (AMPC) is recommended as first-line therapy for acute pharyngotonsillitis caused by group A streptococci (GAS), it often fails to eradicate infections. Internalization and subsequent intracellular survival of GAS are considered major mechanisms for penicillin therapeutic failure. It is, therefore, desirable to administer drugs that exert bactericidal effects on extracellular and intracellular GAS. In this study, we aim to investigate the bactericidal effects of lascufloxacin (LSFX) on internalized GAS in HEp-2 cells. MATERIALS AND METHODS: The GAS strain M1 and clinical isolate strain #2 were used in this study. Following treatment of GAS-infected human pharyngeal carcinoma epithelial HEp-2 cells with LSFX or AMPC, internalized GAS cells were recovered. The concentrations of LSFX and AMPC were equivalent to 1 × and 2 × MIC for strain M1. Culture medium was used as a control. Time-lapse and fluorescence images of GAS invading HEp-2 cell were obtained. LIVE/DEAD fluorescence staining was used to confirm the viability of internalized GAS. RESULTS: LSFX significantly reduced the number of cell-internalized M1 and #2 GAS strains compared to the control (p < 0.01) in a dose-dependent manner. However, AMPC did not reduce this in both strains. Both live and dead intracellular GAS were confirmed in HEp-2 cells exposed to LSFX. In contrast, intracellular GAS survived in HEp-2 cells exposed to AMPC and in the control. CONCLUSION: LSFX elicits significant bactericidal effects on cell-internalized GAS, hence it may represent a potent therapeutic option for patients with acute pharyngotonsillitis in whom AMPC treatment has failed.

A rare case of Pseudomonas aeruginosa enteritis induced by pembrolizumab.

A 72-year-old male had pseudomonal enteritis related to pembrolizumab. Chemotherapy for hypopharyngeal carcinoma with lung metastasis comprised cisplatin, 5-FU, and pembrolizumab. On day 14 of chemotherapy treatment he had a sudden prominent abdominal bulge, decreased consciousness, and drop in blood pressure in septic shock. CT scan showed marked intestinal gas through to intrahepatic bile ducts. Pseudomonas aeruginosa was simultaneously detected in both blood and stool cultures. Intestinal endoscopy revealed ulcerative lesions from the transverse colon to the rectum. Pathological investigations indicated apoptosis of the villus. The patient was diagnosed with pseudomonal enteritis induced by immune-related adverse events from the use of pembrolizumab. Treatment by corticosteroid and meropenem were subsequently switched to cefepime and metronidazole, and this successfully improved his colitis. In this new era of biological-targeted drugs and as clinical experience grows, we recommend a high level of alertness for potential diagnosis of infectious complications.