Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice.

OBJECTIVE: Food processing greatly contributed to increased food safety, diversity, and accessibility. However, the prevalence of highly palatable and highly processed food in our modern diet has exacerbated obesity rates and contributed to a global health crisis. While accumulating evidence suggests that chronic consumption of such foods is detrimental to sensory and neural physiology, it is unclear whether its short-term intake has adverse effects. Here, we assessed how short-term consumption (<2 months) of three diets varying in composition and macronutrient content influence olfaction and brain metabolism in mice. METHODS: The diets tested included a grain-based standard chow diet (CHOW; 54% carbohydrate, 32% protein, 14% fat; #8604 Teklad Rodent diet , Envigo Inc.), a highly processed control diet (hpCTR; 70% carbohydrate, 20% protein, 10% fat; #D12450B, Research Diets Inc.), and a highly processed high-fat diet (hpHFD; 20% carbohydrate, 20% protein, 60% fat; #D12492, Research Diets Inc.). We performed behavioral and metabolic phenotyping, electro-olfactogram (EOG) recordings, brain glucose metabolism imaging, and mitochondrial respirometry in different brain regions. We also performed RNA-sequencing (RNA-seq) in the nose and across several brain regions, and conducted differential expression analysis, gene ontology, and network analysis. RESULTS: We show that short-term consumption of the two highly processed diets, but not the grain-based diet, regardless of macronutrient content, adversely affects odor-guided behaviors, physiological responses to odorants, transcriptional profiles in the olfactory mucosa and brain regions, and brain glucose metabolism and mitochondrial respiration. CONCLUSIONS: Even short periods of highly processed food consumption are sufficient to cause early olfactory and brain abnormalities, which has the potential to alter food choices and influence the risk of developing metabolic disease.

Clinical study of skill assessment based on time sequential measurement changes.

Endoscopic sinus surgery is a common procedure for chronic sinusitis; however, complications have been reported in some cases. Improving surgical outcomes requires an improvement in a surgeon's skills. In this study, we used surgical workflow analysis to automatically extract "errors," indicating whether there was a large difference in the comparative evaluation of procedures performed by experts and residents. First, we quantified surgical features using surgical log data, which contained surgical instrument information (e.g., tip position) and time stamp. Second, we created a surgical process model (SPM), which represents the temporal transition of the surgical features. Finally, we identified technical issues by creating an expert standard SPM and comparing it to the novice SPM. We verified the performance of our methods by using the clinical data of 39 patients. In total, 303 portions were detected as an error, and they were classified into six categories. Three risky operations were overlooked, and there were 11 overdetected errors. We noted that most errors detected by our method involved dangers. The implementation of our methods of automatic improvement points detection may be advantageous. Our methods may help reduce the time for reviewing and improving the surgical technique efficiently.

Insulin-Dependent Maturation of Newly Generated Olfactory Sensory Neurons after Injury.

Loss of olfactory sensory neurons (OSNs) after injury to the olfactory epithelium (OE) triggers the generation of OSNs that are incorporated into olfactory circuits to restore olfactory sensory perception. This study addresses how insulin receptor-mediated signaling affects the functional recovery of OSNs after OE injury. Insulin levels were reduced in mice by ablating the pancreatic ß cells via streptozotocin (STZ) injections. These STZ-induced diabetic and control mice were then intraperitoneally injected with the olfactotoxic drug methimazole to selectively ablate OSNs. The OE of diabetic and control mice regenerated similarly until day 14 after injury. Thereafter, the OE of diabetic mice contained fewer mature and more apoptotic OSNs than control mice. Functionally, diabetic mice showed reduced electro-olfactogram (EOG) responses and their olfactory bulbs (OBs) had fewer c-Fos-active cells following odor stimulation, as well as performed worse in an odor-guided task compared with control mice. Insulin administered intranasally during days 8-13 after injury was sufficient to rescue recovery of OSNs in diabetic mice compared with control levels, while insulin administration between days 1 and 6 did not. During this critical time window on days 8-13 after injury, insulin receptors are highly expressed and intranasal application of an insulin receptor antagonist inhibits regeneration. Furthermore, an insulin-enriched environment could facilitate regeneration even in non-diabetic mice. These results indicate that insulin facilitates the regeneration of OSNs after injury and suggest a critical stage during recovery (8-13 d after injury) during which the maturation of newly generated OSNs is highly dependent on and promoted by insulin.

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury.

Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

Comparison of Current Staging Systems for Sinonasal Inverted Papilloma.

BACKGROUND: A staging system is essential for determining the optimal surgical approach and predicting postoperative outcomes for inverted papilloma (IP). Although staging systems based on the extent to which the location is occupied by an IP have been widely used, an origin site-based classification of IP using unsupervised machine learning algorithms has recently been reported. OBJECTIVE: To determine the most appropriate of five staging systems for sinonasal IP by comparing recurrence rates for each stage according to each of those systems. METHODS: Eighty-seven patients with sinonasal IP were enrolled in the study. Their tumors were retrospectively categorized according to the Krouse, Oikawa, Cannady, and Han staging systems, which are based on the extent of IP, and the Meng system, which is based on the site of origin. The rates of recurrence for each stage of the five systems were compared. RESULTS: Seven of the 87 patients (8.0%) had recurrences during an average 45.5 months (12-138 months) of follow-up. There were significant differences in disease-free survival between the stages specified by Han and Meng (p = 0.027 and p < 0.001, respectively), but not between the stages specified by Krouse, Oikawa, and Cannady (p = 0.236, 0.062, and 0.130, respectively). Cox proportional hazard models revealed that Meng system (adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.10-17.04) and presence of dysplasia (aHR 7.42, 95% CI 1.15-47.85) were significantly associated with recurrence. CONCLUSION: The staging systems proposed by Han and Meng were found to be accurate in terms of tumor recurrence. We recommend use of the Han staging system before surgery and the Meng system after intraoperative identification of the origin of the tumor.

Prelacrimal approach vs conventional surgery for inverted papilloma in the maxillary sinus.

BACKGROUND: The prelacrimal approach, termed endoscopic modified medial maxillectomy (EMMM), has recently been applied for treatment of inverted papilloma (IP) in the maxillary sinus. EMMM provides wider access to the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct. METHODS: We reviewed patients with IP in the maxillary sinus to compare the surgical results obtained by conventional surgery (ie, endoscopic maxillary sinus antrostomy or in combination with the Caldwell-Luc approach) with those obtained by EMMM. RESULTS: All patients had a T3 on the Krouse staging system, and the average follow-up time was 46.0 months. Of the 18 patients in the conventional group, recurrence was seen in 3 patients (16.6%). No recurrence was seen in the 27 patients who showed preservation of the inferior turbinate and nasolacrimal duct, and no complications occurred in the EMMM group. CONCLUSIONS: EMMM is an effective surgical approach that reduces recurrence with fewer complications.

Comparative analysis of surgical processes for image-guided endoscopic sinus surgery.

PURPOSE: This study proposes a method to analyze surgical performance by modeling, aligning, and comparing surgical processes. This method is intended to serve as a means to support the enhancement of surgical skills for endoscopic sinus surgeries (ESSs). We focus on surgical navigation systems used in image-guided ESSs and aim to construct a comparative analysis method for surgical processes based on the information about the surgical instruments motion obtained from the navigation system. METHODS: The proposed method consists of the following three parts: quantification of surgical features, modeling of surgical processes, and alignment and comparison of surgical process models (SPMs). First, we defined time-series parameters using the navigation-based surgical data. Second, we created SPMs by applying the defined parameters and the relative positional information of the instruments to the patient's anatomy. Third, we constructed a method to align and compare SPMs based on dynamic time warping with barycenter averaging. RESULTS: The proposed method was validated on a dataset containing surgical data obtained by an optical tracking system from 14 clinical ESS cases. We evaluated the validity of the comparative analysis by aligning and comparing SPMs between experts and residents. The validation results suggested that the proposed method could achieve proper alignment of the SPMs and clarify the differences in surgical processes between experts and residents. CONCLUSION: We developed a method to enable a time-series comparative analysis of surgical processes based on the surgical data from the navigation system. This method can allow surgeons to identify differences between their procedures and reference procedures such as experts' procedures.

Prognostic value of C-reactive protein/albumin ratio for patients with hypopharyngeal and laryngeal cancer undergoing invasive surgery involving laryngectomy.

BACKGROUND: The C-reactive protein/albumin (CRP/Alb) ratio has been recently established as a prognostic indicator in various cancer types. However, few reports regarding the prognostic value of the CRP/Alb ratio in head and neck cancer exist. This study aimed to investigate the significance of the CRP/Alb ratio in clinical outcomes after invasive surgery involving laryngectomy for hypopharyngeal and laryngeal cancer. METHODS: We evaluated 56 patients who underwent total laryngectomy or total pharyngolaryngectomy between 2003 and 2012. Univariate and multivariate analyses were retrospectively performed to examine the prognostic value of the CRP/Alb ratio in these patients. RESULTS: The optimal cutoff value of the CRP/Alb ratio was 0.32. Multivariate analysis showed that the CRP/Alb ratio was a significant and independent predictor of poor overall and disease-free survival. CONCLUSION: The CRP/Alb ratio may be a novel and useful indicator for predicting postoperative outcomes in patients with hypopharyngeal and laryngeal cancer.

Impact of residual frontal recess cells on frontal sinusitis after endoscopic sinus surgery.

PURPOSE: Endoscopic sinus surgery (ESS) is a well-established treatment for chronic rhinosinusitis (CRS). However, ESS for frontal sinusitis remains complicated and challenging. The aim of this study was to identify the relationship between residual frontal recess cells and primary ESS failure in the frontal sinus. METHODS: We prospectively collected information on 214 sides of 129 patients with CRS who underwent standard ESS from June 2010 to May 2011. To identify risk factors, we retrospectively analyzed clinical data and computed tomography (CT) images before and 3 months after surgery. RESULTS: The posterior side of the frontal recess cells remained relatively common: suprabullar cells (SBCs) were found in 12.2% (16 sides), suprabullar frontal cells (SBFCs) in 20.3% (12 sides), and supraorbital ethmoid cells in 23.7% (14 sides). In contrast, the anterior side of the frontal recess cells, agger nasi cells, supra agger cells, and supra agger frontal cells remained at < 10.0%. Frontal septal cells persisted in 25.0% (5 sides). The presence of residual frontal recess cells was an independent risk factor for postoperative frontal sinus opacification as were well-recognized risk factors such as nasal polyps, the peripheral eosinophil count, and the CT score. Among residual frontal recess cells, SBCs and SBFCs were independent risk factors for opacification. CONCLUSIONS: Residual frontal recess cells, especially SBCs and SBFCs, were independent risk factors for postoperative opacification of the frontal sinus. Complete surgical excision of frontal recess cells may improve surgical outcomes.

Nasal silicone splints and quilting sutures using a septum stitch device following septoplasty: a prospective comparative study.

PURPOSE: Although nasal splints and trans-septal sutures are preferred for septal closure following septoplasty, quilting sutures, also known as continuous mattress sutures, are technically challenging and thus time consuming. Recently, the utility of a novel stitch device was demonstrated for quilting sutures; however, whether it contributes to the technical solution and time management of septal sutures remains unclear. This study aims to quantify the time and cost of septal closure following septoplasty by comparing nasal splints with quilting sutures using the septum stitch device. METHODS: We prospectively examined 23 patients who underwent septoplasty and assigned them to the following two groups: group 1, underwent the quilting suture for septal closure following septoplasty; group 2 underwent the nasal silicone splint method. We recorded the total operation time and surgical time for septal closure. Furthermore, we evaluated postoperative symptoms with Visual Analogue Scale (VAS) scores and compared the complication rate. RESULTS: We observed no significant difference in the average of total operating time (P = 0.641) and the surgical time for septal closure (P = 0.886). Among postoperative symptoms, only nasal bleeding was significantly worse in group 1 on postoperative day 1 (P = 0.023). In addition, the occurrence of postoperative complications was insignificant between both groups. CONCLUSIONS: The septum stitch facilitated safe and easy quilting suturing without significant increase of operation time.

Assessment of suitable reference genes for RT-qPCR studies in chronic rhinosinusitis.

Reverse transcription-quantitative polymerase chain reaction is a valuable and reliable method for gene quantification. Target gene expression is usually quantified by normalization using reference genes (RGs), and accurate normalization is critical for producing reliable data. However, stable RGs in nasal polyps and sinonasal tissues from patients with chronic rhinosinusitis (CRS) have not been well investigated. Here, we used a two-stage study design to identify stable RGs. We assessed the stability of 15 commonly used candidate RGs using five programs-geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. Ribosomal protein lateral stalk subunit P1 (RPLP1) and ribosomal protein lateral stalk subunit P0 (RPLP0) were the two most stable RGs in the first stage of the study, and these results were validated in the second stage. The commonly used RGs ß-actin (ACTB) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were unstable according to all of the algorithms used. The findings were further validated via relative quantification of IL-5, CCL11, IFN-γ, and IL-17A using the stable and unstable RGs. The relative expression levels varied greatly according to normalization with the selected RGs. Appropriate selection of stable RGs will allow more accurate determination of target gene expression levels in patients with CRS.

Yellow Nail Syndrome With Dramatic Improvement of Nail Manifestations After Endoscopic Sinus Surgery.

OBJECTIVES: Yellow nail syndrome (YNS) is a rare disease of unknown cause characterized by the triad of yellow nails, respiratory manifestations, and lymphedema. Although several therapies for YNS have been reported, there is no common consensus in the treatment. In this case report, we present a case of 56-year-old woman with YNS, whose nail manifestation was dramatically improved after endoscopic sinus surgery for the treatment of chronic rhinosinusitis. METHODS: Endoscopic sinus surgery involving middle meatal antrostomy was performed for the case of YNS with chronic rhinosinusitis and bronchiectasis resistant to antibacterial drugs. RESULTS: A month after the surgery, the patient's nails eventually showed dramatic improvement. CONCLUSIONS: Otorhinolaryngologists should recognize that chronic rhinosinusitis can be a symptom of YNS, and that the aggressive treatment including surgical approach for chronic rhinosinusitis may be a useful in the control of nail manifestation in YNS.

Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder.

A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology.

Prognostic factors for recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps.

OBJECTIVE: In this study, we aimed to clarify the prognostic factors affecting the ethmoid condition during a long-term follow-up after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Thirty-six patients with CRSwNP underwent surgery from December 2008 to February 2012. All surgeries were performed by one surgeon, and all patients were followed up for at least 2 years postoperatively. We investigated the association of postoperative endoscopic findings with clinical parameters, mucosal eosinophil count and mRNA expression of CCL11, IL-5, and IFN-gamma in nasal polyps. RESULTS: Seventeen patients (47.2%) had severe mucosal edema, and the patency of each sinus was not confirmed during the >2-year follow-up. The mucosal eosinophil count and two eosinophil-associated factors, namely the CCL11 and IL-5 mRNA levels, were higher in the severe mucosal edema group than in the control group. The severe mucosal edema group was divided into two subgroups: the steroid-responsive and -resistant groups. Five patients (13.9%) had frank polyp formation because the oral steroids were less effective. The mucosal eosinophil count was significantly different among the four groups, including the control group (p=0.001); however, the CCL11, IL-5, and IFN-gamma mRNA levels were not significantly different. Although the IL-5 mRNA level was not significantly different among the four groups, it tended to increase when the sinus condition worsened. In the severe mucosal edema group, a higher IL-5 mRNA level was associated with earlier severe mucosal edema in the ethmoid cavity. CONCLUSION: The IL-5 mRNA level is associated with the time of severe edema formation in the ethmoid cavity. This finding permits early intervention on the postoperative course and would prevent polyp recurrence.

Endoscopic single-handed septoplasty with batten graft for caudal septum deviation.

OBJECTIVE: Septoplasty is usually performed with a Killian incision in Japan. However, the major drawback of the Killian incision is the inability to correct deviations of the caudal part of the septum. For patients with mild deviation of the caudal part of the septum but with a straight caudal end, we performed a modified Killian incision and used a batten graft to correct the deviated cartilage under endoscopy. The aim of this study was to evaluate the usefulness of our surgical technique for these cases. METHODS: We prospectively collected data of 17 patients who underwent endoscopic septoplasty with a batten graft. Objective assessment by computed tomography and subjective assessment by questionnaire were performed before and 3 months after the surgery. RESULTS: On computed tomography, the ratio of the area of the convex side to that of the concave side in the anterior portion of the nasal cavity was significantly improved after surgery (p<0.001). Subjective assessment revealed a significant improvement in nasal obstruction (p=0.002). There were no complications in this study. CONCLUSION: The herein-described septoplasty with a batten graft is technically easy and considered to be useful for deviation of the caudal part of the septum in selected cases.

New technique using an energy-based device versus conventional technique in open thyroidectomy.

OBJECTIVE: Thyroid surgery is a common basic procedure in otorhinolaryngology. The purpose of this study was to assess the efficiency of using a new LigaSure(®) vessel sealing system (LigaSure(®) Small Jaw Instrument; Covidien, Boulder, CO, USA). METHODS: We evaluated 83 patients who underwent thyroid surgery between July 2009 and June 2012. The patients were allocated to two groups, which underwent thyroid surgery using either the LigaSure(®) Small Jaw Instrument or conventional techniques. We investigated the duration of operation, estimated blood loss, pathological characteristics, postoperative complications, and length of hospital stay. As for duration of operation and estimated blood loss, we also performed analyses by subgroups according to the extent of thyroid resection, as either total thyroidectomy or hemithyroidectomy. RESULTS: The study groups showed no significant differences in age, sex, indications, extent of operation and estimated blood loss. Complication rates for recurrent laryngeal nerve palsy, hypoparathyroidism, hematoma, and wound infection did not differ between groups, except for temporary hypoparathyroidism. Operation time was significantly shorter in the LigaSure(®) Small Jaw Instrument group than in the conventional group for all extents of thyroid resection. CONCLUSION: Use of the LigaSure(®) Small Jaw Instrument seems likely to reduce the operating time for thyroid surgery without increasing estimated blood loss or the frequency of postoperative complications compared to conventional techniques.