Postoperative Late Hearing Deterioration in Cholesteatoma with Labyrinthine Fistulas.

A labyrinthine fistula is a severe complication of middle ear cholesteatoma that can cause profound sensorineural hearing loss and vertigo. However, there is no consensus regarding the transition to postoperative hearing. Although hearing deteriorates gradually with a delay in some cases of labyrinthine fistula, insufficient consideration has been given to this point. We examined perioperative changes in cases of middle ear cholesteatoma with labyrinthine fistulas. We retrospectively reviewed the medical records of 578 patients with middle ear cholesteatoma who underwent tympanoplasty at our hospital between 2016 and 2021. Patients with labyrinthine fistulas were selected; their perioperative bone-conduction hearing was assessed. Fistula depth was determined following the classification reported by Dornhoffer et al. The hearing was compared preoperatively, early postoperatively (3-6 months), and 1 year postoperatively. Forty-eight patients (8.3%) had labyrinthine fistulas. Regarding depth, 21 cases were type I, 14 were type IIa, 3 were type IIb, and 10 were type III. Preoperative bone-conduction hearing was significantly poor in invasion type IIb or deeper cases. Cases with type IIb or deeper fistulas, multiple fistulas, or vertigo deteriorated postoperatively. Type III cases or those with multiple fistulas deteriorated further from the early postoperative period to 1 year postoperatively. Concerning frequency, 500 and 2000 Hz showed a delayed deterioration. This is a valuable report of delayed hearing loss after surgery in patients with a labyrinthine fistula. This change is associated with the labyrinthine fistula's depth and multiple fistulas-this is important during preoperative counseling of patients undergoing surgery.

Successful treatment of intestinal malakoplakia in a French Bulldog.

Malakoplakia is a rare granulomatous inflammation mainly been reported in the urinary bladder of dogs. Only one case of canine colonic malakoplakia has been reported to date; however, successful treatment of this disease has not been reported. Here, we report a case of colonic malakoplakia in a 5-month-old spayed female French Bulldog. The dog was referred to a veterinarian because of chronic diarrhea and mucinous blood feces; empirical treatment did not improve its condition. Histologically, numerous macrophages containing periodic acid-Schiff-positive granules infiltrated the lamina propria of the large intestine. Furthermore, targetoid basophilic inclusion bodies (Michaelis-Gutmann bodies) were observed. Complete clinical remission was achieved after 8 months of enrofloxacin treatment and favorable progress after 2 months of medication.

Visualization of intracellular ATP dynamics in different nephron segments under pathophysiological conditions using the kidney slice culture system.

ATP depletion plays a central role in the pathogenesis of kidney diseases. Recently, we reported spatiotemporal intracellular ATP dynamics during ischemia reperfusion (IR) using GO-ATeam2 mice systemically expressing an ATP biosensor. However, observation from the kidney surface did not allow visualization of deeper nephrons or accurate evaluation of ATP synthesis pathways. Here, we established a novel ATP imaging system using slice culture of GO-ATeam2 mouse kidneys, evaluated the ATP synthesis pathway, and analyzed intracellular ATP dynamics using an ex vivo IR-mimicking model and a cisplatin nephropathy model. Proximal tubules (PTs) were found to be strongly dependent on oxidative phosphorylation (OXPHOS) using the inhibitor oligomycin A, whereas podocytes relied on both OXPHOS and glycolysis using phloretin an active transport inhibitor of glucose. We also confirmed that an ex vivo IR-mimicking model could recapitulate ATP dynamics in vivo; ATP recovery in PTs after reoxygenation varied depending on anoxic time length, whereas ATP in distal tubules (DTs) recovered well even after long-term anoxia. After cisplatin administration, ATP levels in PTs decreased first, followed by a decrease in DTs. An organic cation transporter 2 inhibitor, cimetidine, suppressed cisplatin uptake in kidney slices, leading to better ATP recovery in PTs, but not in DTs. Finally, we confirmed that a mitochondria protection reagent (Mitochonic Acid 5) delayed the cisplatin-induced ATP decrease in PTs. Thus, our novel system may provide new insights into the energy dynamics and pathogenesis of kidney disease.

Efficient pathway-driven scyllo-inositol production from myo-inositol using thermophilic cells and mesophilic inositol dehydrogenases: a novel strategy for pathway control.

Mesophilic enzymes, which are active at moderate temperatures, may dominate enzymatic reactions even in the presence of thermophilic crude enzymes. This study was conducted to investigate this hypothesis with mesophilic inositol dehydrogenases (IolG and IolX) produced in Geobacillus kaustophilus HTA426. To ensure the efficient production of mesophilic enzymes, we first screened for promoters induced at moderate temperatures using transcriptome analysis and identified four genes highly expressed at 30°C in the thermophile. We further characterized these promoters using fluorescent reporter assays to determine that the mti3 promoter could direct efficient gene expression at 40°C. We cloned the promoter into an Escherichia coli-Geobacillus shuttle plasmid and confirmed that the resulting vector functioned in G. kaustophilus and other thermophiles. We then used this vector for the cooperative expression of the iolG and iolX genes from Bacillus subtilis 168. G. kaustophilus cells carrying the expression vector were incubated at 60°C for cellular propagation and then at 40°C for the production of IolG and IolX. When the cells were permeabilized, IolG and IolX acted as catalysts to convert exogenous myo-inositol into scyllo-inositol at 30°C. In a scaled-up reaction, 10 g of myo-inositol was converted to 1.8 g of scyllo-inositol, which was further purified to yield 970 mg of pure powder. Notably, myo-inositol was degraded by intrinsic enzymes of G. kaustophilus at 60°C but not at 30°C, supporting our initial hypothesis. We indicate that this approach is useful for preparing enzyme cocktails without the need for purification. IMPORTANCE: Enzyme cocktails are commonly employed for cell-free chemical synthesis; however, their preparation involves cumbersome processes. This study affirms that mesophilic enzymes in thermophilic crude extracts can function as specific catalysts at moderate temperatures, akin to enzyme cocktails. The catalyst was prepared by permeabilizing cells without the need for concentration, extraction, or purification processes; hence, its preparation was considerably simpler compared with conventional methods for enzyme cocktails. This approach was employed to produce pure scyllo-inositol from an economical substrate. Notably, this marks the first large-scale preparation of pure scyllo-inositol, holding potential pharmaceutical significance as scyllo-inositol serves as a promising agent for certain diseases but is currently expensive. Moreover, this approach holds promise for application in pathway engineering within living cells. The envisioned pathway is designed without chromosomal modification and is simply regulated by switching culture temperatures. Consequently, this study introduces a novel platform for both whole-cell and cell-free synthetic systems.

Factors related to the surgical outcomes of type I tympanoplasty for tympanic membrane perforation in children.

BACKGROUND: Factors related to surgical outcomes of type I tympanoplasty for tympanic membrane (TM) perforation in children are controversial. OBJECTIVES: To investigate factors related to anatomical results of type I tympanoplasty for TM perforation 1 year after surgery. MATERIAL AND METHODS: We examined 68 ears. Anatomical results were determined based on the presence or absence of re-perforation, atelectasis, and otitis media with effusion. We retrospectively analyzed factors based on age (≤8 and >8 years), cause and size of TM perforation (<50% and ≥50%), history of asthma and cleft palate, and size of mastoid air cell system in bilateral ears before tympanoplasty. Audiological prognosis was evaluated in ears with anatomical success 1 year after surgery. RESULTS: Anatomical success was achieved in 80.9% (55/68) of the ears. No significant differences were observed between these factors and anatomical results. All children with cleft palate had anatomical success. Mean pure-tone average (0.5-4 kHz) was 16.25 dB HL for ears with both TM perforations <50% and ≥50%. CONCLUSION AND SIGNIFICANCE: We observed no significant relationship between factors considered and surgical outcomes. However, audiological prognosis was favorable for anatomical success regardless of TM perforation size. Accordingly, type I tympanoplasty is considered useful for TM perforation in children.

Vortioxetine Exposure During Pregnancy and Lactation: A Japanese Case Study of Neonatal Implications and Quantitative Milk and Plasma Analyses.

Background: Information about influences of vortioxetine on pregnant women and neonates during perinatal period is almost unknown. Case Presentation: The case was a 28-year-old Japanese woman in her first pregnancy, treated for depression with vortioxetine (20 mg daily) among other medications. At 36 weeks of gestation, she was admitted for premature rupture of the membranes and delivered a girl with no apparent congenital anomalies. Immediately after birth, the neonate required brief respiratory support due to her dyspnea and poor muscle tone. Her respiratory condition improved in 6 days after delivery, and she demonstrated normal developmental progress afterward. Maternal plasma and breast milk samples, collected 4 days postpartum, revealed vortioxetine concentrations of 11.4 ng/mL and 9.3 ng/mL, respectively. The calculated relative infant dose (RID) was estimated at 0.32%. After discharge from hospital, the infant presented no detectable drug-related adverse effects, with over 50% of nutrition derived from breastfeeding. Conclusion: This case showed minimal transfer of vortioxetine into breast milk, reflected in a low RID. The findings suggest limited neonatal exposure to the drug, with no adverse developmental effects observed in the infant. However, the case also indicated the potential for vortioxetine use during pregnancy to contribute to the onset of severe neonatal asphyxia. Further research is needed for a comprehensive understanding of its impact on neonatal health.

3D Printer-Assisted Layered Fabrication of a Novel Appliance for Oral Myofunctional Therapy and Functional Evaluation of Its Effects on Orofacial Muscles During Wear.

Aim Balanced function of the orofacial muscles is important for normal occlusion and dentition; however, patients with malocclusion often present with myofunctional disorder (MFD). Myofunctional therapy (MFT) has received much attention as a method for reducing MFD. Moreover, prefabricated functional appliances (PFAs) have been developed as a method to eliminate abnormal muscle pressure and guide the tongue into the correct position. However, PFAs have disadvantages, such as poor intraoral retention, limited usage time due to discomfort and poor patient compliance, and changes in the axis of the mandibular anterior teeth. Therefore, this study aimed to develop a new custom-made splint-type orthodontic appliance with CAD/CAM technology. Moreover, we evaluated the characteristics of the appliance and conducted functional tests to determine the effects of the appliance on the orofacial muscles and the discomfort associated with its use. Materials and methods Twenty-five volunteers (nine females and 16 males; mean age 28.4 ± 3.4 years) with normal swallowing function were included in the study. Lip-closing strength (LCS), electromyogram during swallowing, oxygen saturation, and pulse rate were measured and compared when the appliance was not worn and when it was worn. In addition, tongue habits were evaluated, and the maximum tongue pressure was measured when the appliance was not worn. The subjects were asked to answer a questionnaire using a numerical rating scale (NRS) regarding discomfort when wearing the appliance. The evaluation items were swallowing difficulty, speaking difficulty, and breathlessness, which were rated on an 11-point scale ranging from 0 to 10. Statistical tests were conducted using IBM SPSS version 28.0.1 (IBM, Armonk, NY, USA) with the Shapiro-Wilk and Levene's test, followed by the Wilcoxon signed rank sum test. The significance level was set at α = 0.05. The measurement error for each measurement item was evaluated using an intraclass correlation coefficient. Results A new custom-made splint-type orthodontic appliance was fabricated for each subject. The fit and retention of the appliance in the mouth were good when fitted, and a comparison of the functional test measurements of 25 subjects with and without the appliance showed that the LCS decreased significantly (p<0.05) before and after wearing the appliance. However, no statistically significant differences were found for the other items. The Mann-Whitney U test regarding the effects of sex, previous orthodontic treatment, or MFT, and oral habits did not statistically significantly influence the effects of wearing the device. In the NRS results, "difficulty swallowing" was observed in half of the subjects, "difficulty breathing" was rarely observed, and "difficulty speaking" was observed in all subjects. Conclusions A novel custom-made splint-type orthodontic appliance was designed and fabricated using digital workflow and 3D printing technology. This appliance was designed to correct oral habits and was made from a new material classified as a class II medical appliance according to the international harmonized classification.

Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.

Characteristics of Craniofacial Morphology and Occlusion in Shwachman-Diamond Syndrome: A Case Report of a Japanese Sibling Pair.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome gene on chromosome 7q11. Although skeletal abnormalities are a feature of SDS, no reports have focused on the craniofacial morphology of patients with SDS. Moreover, the detailed dental characteristics of SDS remain unknown. In the present case report, we evaluated the craniofacial morphology and dental findings of two patients with SDS. A Japanese adolescent sibling pair with SDS had the chief complaint of excessive overjet. Cephalometric analysis revealed similar craniofacial morphology in both patients: skeletal class I malocclusion with a hypodivergent pattern and labial inclination of the maxillary and mandibular incisors. A panoramic photograph showed the tendency of delayed permanent tooth eruption and replacement in both patients. These cases suggest that malocclusion requiring orthodontic treatment might be a feature of patients with SDS.

Augmented Reality-Assisted Transcanal Endoscopic Ear Surgery for Middle Ear Cholesteatoma.

Background: The indications for transcanal endoscopic ear surgery (TEES) for middle ear cholesteatoma have expanded for cases involving mastoid extension. However, TEES is not indicated for all cases with mastoid extension. In addition, predicting the extent of external auditory canal (EAC) removal needed for cholesteatoma resection is not always easy. The purpose of this study was to use augmented reality (AR) to project the lesion onto an intraoperative endoscopic image to predict EAC removal requirements and select an appropriate surgical approach. Methods: In this study, patients showing mastoid extension were operated on using a navigation system with an AR function (Stryker). Results: The results showed that some cases with lesions slightly extending into the antrum required extensive resection of the EAC, while cases with lesions extending throughout the antrum required smaller resection of the EAC, indicating TEES. Conclusions: By predicting the extent of the needed EAC removal, it is possible to determine whether TEES (a retrograde approach) or canal wall-up mastoidectomy, which preserves as much of the EAC as possible, should be performed. We believe that our findings will contribute to the success of middle ear surgeries and the implementation of robotic surgery in the future.

Gene expression of cytokines and prostaglandin metabolism-related proteins in eosinophilic otitis media.

The objective of this study was to investigate the levels of gene expression in the middle ear mucosa of 2 patients diagnosed with eosinophilic otitis media. One patient with severe hearing loss showed high expression levels of genes encoding IL-5 and IL-33 receptors.

Nonlocal Spin Correlation as a Signature of Ising Anyons Trapped in Vacancies of the Kitaev Spin Liquid.

In the Kitaev chiral spin liquid, Ising anyons are realized as Z_{2} fluxes binding Majorana zero modes, which, however, are thermal excitations with finite decay rates. On the other hand, a lattice vacancy traps a Z_{2} flux even in the ground state, resulting in the stable realization of a Majorana zero mode in a vacancy. We demonstrate that spin-spin correlation functions between two vacancy sites exhibit long-range correlation arising from the fractionalized character of Majorana zero modes, in spite of the strong decay of bulk spin correlations. Remarkably, this nonlocal spin correlation does not decrease as the distance between two vacancy sites increases, signaling Majorana teleportation. Furthermore, we clarify that the nonlocal correlation can be detected electrically via the measurement of nonlocal conductance between two vacancy sites, which is straightforwardly utilized for the readout of Majorana qubits. These findings pave the way to the measurement-based quantum computation with Ising anyons trapped in vacancies of the Kitaev spin liquid.

Association between Hospital-acquired Disability and Clinical Outcomes in Older Patients Who Underwent Cardiac Surgical.

OBJECTIVE: This study aimed to clarify the association between hospital-acquired disability (HAD) and prognosis in older patients who underwent cardiac surgery. METHODS: This single-center, retrospective, observational study included 141 patients aged ≥65 years who underwent cardiac surgery at our hospital from November 2016 to August 2021. The primary endpoint of this study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) within 2 years of hospital discharge. HAD was defined as a score of ≤5 on any one of the functional independence measure (FIM) subitems at discharge compared to preoperatively. RESULTS: MACCE was observed in 16.3%, and the incidence of MACCE was significantly higher in the HAD group than that in the non-HAD group (12.1 vs. 34.5%, log-rank, p = 0.003). HAD was also significantly associated with the MACCE (hazard ratio [HD]: 2.575, 95% confidence interval [CI]: 1.001-9.655, p = 0.046). The incidence rate of HAD was 20.6%, with age (odds ratio [OR]: 1.260, 95% CI: 1.080-1.470, p = 0.004), preoperative short physical performance battery (SPPB) score (OR: 0.462, 95% CI: 0.301-0.708, p <0.001), and postoperative delirium (OR: 6.660, 95% CI: 1.480-30.000, p = 0.014) identified as significant factors. CONCLUSION: HAD is an independent predictor of MACCE in older patients who underwent cardiac surgery.