The musculoskeletal system, which comprises muscles, tendons, and bones, is an efficient tissue complex that coordinates body movement and maintains structural stability. The process of its ...construction into a single functional and complex organization is unclear. SRY-box containing gene 9 (Sox9) is expressed initially in pluripotent cells and subsequently in ectodermal, endodermal, and mesodermal derivatives. This study investigated how Sox9 controls the development of each component of the musculoskeletal system. Sox9 was expressed in MTJ, tendon, and bone progenitor cells at E13 and in bone at E16. We detected Sox9 expression in muscle progenitor cells using double-transgenic mice and myoblastic cell lines. However, we found no Sox9 expression in developed muscle. A decrease in Sox9 expression in muscle-associated connective tissues, tendons, and bones led to hypoplasia of the cartilage and its attachment to tendons and muscle. These results showed that switching on Sox9 expression in each component (muscle, tendon, and bone) is essential for the development of the musculoskeletal system. Sox9 is expressed in not only tendon and bone progenitor cells but also muscle progenitor cells, and it controls musculoskeletal system development.
Fish bones are common foreign bodies in the upper aero-digestive tract, but their clinical features in relation to fish species have not been confirmed. We aimed to clarify the clinical ...characteristics of fish-bone foreign bodies and their location and removal methods depending on the fish species.
Retrospective, observational, monocentric study.
From October 2015 to May 2020, 368 patients visited the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital complaining of dysphagia, sore throat, or pharyngeal discomfort after eating fish. We analyzed the patients' sex and age distribution, foreign-body location, type of the fish, and the techniques used for removing the foreign body.
Fish bones were confirmed in the upper aero-digestive tract in 270 cases (73.4%), of which 236 (87.4%) involved fish-bone foreign bodies in the mesopharynx. The most frequently involved site was the palatine tonsil (n = 170). Eel was the most frequently observed fish species (n = 39), followed by mackerel (n = 33), salmon (n = 33), horse mackerel (n = 30), and flounder (n = 30). Among the 240 cases in which the bones did not spontaneously dislocate, 109 (45.4%) were treated by endoscopic removal (103 cases) or surgery (6 cases). In pediatric cases (<12 years old), almost all fish bones were found in the mesopharynx (138/139, 99.3%), and 31 cases (22.3%) required endoscopic removal. Flounder fish bones were often lodged in the hypopharynx and esophagus (9/30, 30%), hindering spontaneous dislocation and frequently necessitating endoscopic or surgical removal (19/29, 65.5%).
The characteristics of fish-bone foreign bodies differed depending on the fish species. Flounder bones were often stuck in the hypopharynx and esophagus and were likely to require more invasive removal methods. Confirming the species of the fish could facilitate appropriate diagnosis and treatment of fish-bone foreign bodies.
Swallowing dysfunction and the risk of aspiration pneumonia are frequent clinical problems in the treatment of head and neck squamous cell carcinomas (HNSCCs). Breathing-swallowing coordination is an ...important factor in evaluating the risk of aspiration pneumonia. To investigate breathing-swallowing discoordination after chemoradiotherapy (CRT), we monitored respiration and swallowing activity before and after CRT in patients with HNSCCs. Non-invasive swallowing monitoring was prospectively performed in 25 patients with HNSCCs treated with CRT and grade 1 or lower radiation-induced dermatitis. Videoendoscopy, videofluoroscopy, Food Intake LEVEL Scale, and patient-reported swallowing difficulties were assessed. Of the 25 patients selected for this study, four dropped out due to radiation-induced dermatitis. The remaining 21 patients were analyzed using a monitoring system before and after CRT. For each of the 21 patients, 405 swallows were analyzed. Swallowing latency and pause duration after the CRT were significantly extended compared to those before the CRT. In the analysis of each swallowing pattern, swallowing immediately followed by inspiration (SW-I pattern), reflecting breathing-swallowing discoordination, was observed more frequently after CRT (p = 0.0001). In 11 patients, the SW-I pattern was observed more frequently compared to that before the CRT (p = 0.00139). One patient developed aspiration pneumonia at 12 and 23 months after the CRT. The results of this preliminary study indicate that breathing-swallowing discoordination tends to increase after CRT and could be involved in aspiration pneumonia. This non-invasive method may be useful for screening swallowing dysfunction and its potential risks.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world’s largest public health concern. This study ...evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.
Radiation-induced oral mucositis is one of the most common adverse events in radiation therapy for head and neck cancers, but treatments for oral mucositis are limited to palliative and supportive ...care. New approaches are required to prevent radiation-induced mucositis and to improve treatments. The Keap1-Nrf2 system regulates cytoprotection against oxidative and electrophilic stresses. Nrf2 also regulates keratin layer thickness in mouse tongues. Therefore, we hypothesized that Nrf2 may protect the tongue epithelium against radiation-induced mucositis via elimination of reactive oxygen species and induction of keratin layer thickening. To test this hypothesis, we prepared a system for γ-ray exposure of restricted areas and irradiated the tongues of model mice with Nrf2 and Keap1 loss-of-function. We discovered that loss of Nrf2 expression indeed sensitized the tongue epithelium to radiation-induced ulcer formation with inflammation. Constitutive Nrf2 activation by genetic Keap1 knockdown alleviated radiation-induced DNA damage by increasing antioxidation. In agreement with the genetic Nrf2 activation model, the Nrf2 inducer CDDO-Im prevented irradiation damage to the tongue epithelium. These results demonstrate that Nrf2 activation has the potential to prevent the development of radiation-induced mucositis and that Nrf2 inducers are an important therapeutic drug for protection of the upper aerodigestive tract from radiation-induced mucositis.
Display omitted
•Nrf2 protects against radiation-induced mucositis.•Constitutive Nrf2 activation mitigates DNA damage via antioxidation.•A thickened keratin layer in Nrf2-activated mouse tongues prevents the occurrence of radiation-induced ulcers.•Pharmacological Nrf2 activation prevents radiation-induced mucositis.
A perfusion defect (PD) in non-enlarged lymph nodes (LNs) of oral squamous cell carcinoma (OSCC) is the most reliable radiological criterion for the diagnosis of metastasis. However, conventional ...contrast-enhanced (CE) T1 weighted images using turbo spin echo (TSE) sequence is limited in detecting PD in non-enlarged LNs due to flow artifacts from cervical blood vessels. Vessel wall (VW) MR imaging with blood vessel flow suppression and high spatial resolution may provide new insights into the detection of PD. However, there are no reports in the literature on the usefulness of VW MR imaging for the diagnosis of LN metastasis. It is demonstrated that PD of non-enlarged LNs in CE VR MR imaging of OSCC patients is useful for the diagnosis of metastatic LNs. VW MR imaging was significantly more sensitive in detecting PD of non-enlarged metastatic LNs than conventional TSE imaging on visual evaluation. Furthermore, it was found that the image contrast between PD and surrounding intranodal tissue in CE VW MR images was higher than that in conventional CE TSE images. In the correlation between imaging and histopathological findings of metastatic LNs, all LNs that exhibited PD on CE VW MR images were at an advanced histopathological metastatic stage. The pathology of PD was necrotic tissue with keratinization. The results indicated that PD in CE VW imaging is useful in diagnosing non-enlarged LNs at an advanced metastasis stage. The addition of VW MR imaging to conventional MR examination achieves higher diagnostic performance for non-enlarged metastatic LNs.
Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as ...well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely,
FREM2
p.Val861Phe,
CLK3
p.Phe376Leu,
DLGAP1
p.Lys294Asn,
NOX1
p.Val165Met, and
PSG9
c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.
Common practices to improve the ability to swallow include modifying physical properties of foods and changing the posture of patients. Here, we quantified the effects of the viscosity of a liquid ...bolus and patient posture on the bolus pathway and pharyngeal residue using a computational fluid dynamics simulation. We developed a computational model of an impaired pharyngeal motion with a low pharyngeal pressure and no pharyngeal adaptation. We varied viscosities from 0.002 to 1 Pa·s and postures from -15° to 30° (from nearly vertical to forward leaning). In the absence of pharyngeal adaptation, a honey-like liquid bolus caused pharyngeal residue, particularly in the case of forward-leaning postures. Although the bolus speed was different among viscosities, the final pathway was only slightly different. The shape, location, and tilting of the epiglottis effectively invited a bolus to two lateral pathways, suggesting a high robustness of the swallowing process.
Thickening agents are often used for patients with dysphagia. An increase in bolus viscosity not only reduces the risk of aspiration but also can cause a residual volume in the pharynx. Because information obtained from videofluoroscopic swallowing studies is only two-dimensional, measurement of pharyngeal residue is experimentally difficult. We successfully quantified the three-dimensional bolus pathway and the pharyngeal residual volume using computational modeling and simulation.
Cells are often exposed to exogenous and endogenous redox disturbances and exert their protective mechanisms in response to stimuli. The KEAP1-NRF2 system plays pivotal roles in counteracting ...oxidative damage. Due to the transient nature of NRF2 activation, the identification of cells in which NRF2 is activated in response to systemic stimuli is sometimes not easy. To examine the electrophilic stress response at a single-cell resolution, we aimed to develop a new reporter mouse in this study. A cell-tracing strategy exploiting Cre recombinase-mediated activation of a reporter gene was chosen for stable detection of reporter expression instead of real-time monitoring of the cellular response. We established a transgenic mouse line expressing the Neh2-Cre recombinase fusion protein. As Neh2 is an amino-terminal domain of NRF2 that serves as a degron and mediates KEAP1-dependent degradation and electrophile-inducible stabilization, Neh2-Cre was expected to be activated in response to electrophiles. The Neh2-Cre transgenic mouse was crossed with the ROSA26-loxP-stop-loxP-tdTomato reporter mouse (ROSA-LSL-tdTomato mouse). The compound mutant reporter mice exhibited accumulation of tdTomato-positive cells in various organs after repeated administration of CDDO-Im, one of the NRF2-inducing electrophiles. The mice were also successfully used for the detection of cells that experienced a cisplatin-induced electrophilic stress response.
Display omitted
•Stabilization of Neh2-Cre fusion protein is regulated by KEAP1.•Transgenic mice expressing Neh2-Cre were generated.•Neh2-Cre:tdTomato mouse was used to monitor the exposure history to electrophiles.•Repetitive CDDO-Im treatment induces tdTomato expression in various tissues.•Repetitive cisplatin treatment induces tdTomato expression in inner ear and kidney.
Abstract
Background
The outcome of head and neck cancer has improved in recent years but survival is not yet satisfactory. Interleukin (IL)-6 is a representative inflammatory cytokine and inducer of ...systemic inflammatory response. It is not known whether preoperative serum level of IL-6 is a prognostic factor in head and neck cancer surgery.
Methods
We studied 181 consecutive patients who underwent head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) between September 2016 and December 2020. Whether preoperative serum IL-6 level was a prognostic risk factor was retrospectively investigated by univariate and multivariate analyses. We also investigated the association between preoperative IL-6 level and representative systemic inflammatory response markers.
Results
The preoperative IL-6 ≥ 8 pg/mL group had a significantly worse prognosis than the preoperative IL-6 < 8 pg/mL group (overall survival OS: hazard ratio HR 3.098, P = 0.0006; disease-specific survival DSS: HR 3.335, P = 0.0008). In multivariate analysis, IL-6 ≥ 8 pg/mL and age ≥ 70 years were independent poor prognostic factors for OS (HR 1.860, P = 0.0435 and HR 1.883, P = 0.0233, respectively). The only independent poor prognostic factor for DSS was IL-6 ≥ 8 pg/mL (HR 2.052, P = 0.0329). Serum albumin was significantly lower and serum C-reactive protein and neutrophil-to-lymphocyte ratio were significantly higher in the IL-6 ≥ 8 pg/mL group than in the IL-6 < 8 pg/mL group (all P < 0.0001).
Conclusions
Preoperative serum IL-6 level is an independent poor prognostic factor for both OS and DSS after HNS-FTTR, reflecting the degree of preoperative systemic inflammatory response.
Preoperative serum IL-6 level was an independent poor prognostic factor for both OS and DSS after head and neck surgery with free tissue transfer reconstruction.
PDF
