Search

Abstract Nasal respiratory disorders are linked to craniofacial anomalies and systemic dysfunctions. However, the implications of nasal respiratory disorders on brain development and their subsequent impact on brain functionalization remain largely unknown. Here, we describe that nasal obstruction from postnatal developmental stages in mice precipitates deficits in cerebellum-associated behaviors and compromised refinement and maturation of neural circuits in the cerebellum. We show that mice with nasal obstruction during developmental phases exhibit marked impairments in motor function and exhibit increased immobility time in forced swimming test. Additionally, we identified critical periods during which nasal respiration is essential for optimizing motor function and preserving mental health. Our study also reveals that nasal obstruction in mice disrupts the typical developmental process of synapse elimination in the cerebellum and hinders the normal transition of activity patterns in cerebellar Purkinje cell populations during development. Through comparing activity patterns in mouse models subjected to nasal obstruction at various stages, we suggest that the maturation of specific activity pattern among Purkinje cell populations is fundamental to the functional integrity of the cerebellum. Our findings highlight the indispensable role of adequate nasal respiration during development for the establishment and functional integrity of neural circuits, thereby significantly affecting brain function.

Abstract Masticatory muscle forces influence craniofacial morphology development. The antegonial notch (Notch) is a bony concavity on the inferior border of the mandible. Considering the Notch is located anteriorly to the insertion of the masseter muscle and varies among individuals, we hypothesised that these muscles influence the formation of the Notch. Therefore, this study aimed to investigate the correlation between mandible morphology and Notch formation. Sixty Japanese patients who visited the Department of Orthodontics at our university hospital were retrospectively evaluated. Morphological and morphometric analyses of the Notch and related craniofacial parameters were conducted using lateral cephalograms taken at the patients’ initial visits. Standard values for the Notch area and depth were determined, and the morphology of the Notch and mandible was analysed using Spearman’s rank correlation coefficient (p

Abstract Cervical radiculopathy might affect finger movement and dexterity. Postoperative features and clinical outcomes comparing C8 radiculopathies with other radiculopathies are unknown. This prospective multicenter study analyzed 359 patients undergoing single-level surgery for pure cervical radiculopathy (C5, 48; C6, 132; C7, 149; C8, 30). Background data and pre- and 1-year postoperative neck disability index (NDI) and numerical rating scale (NRS) scores were collected. The C5–7 and C8 radiculopathy groups were compared after propensity score matching, with clinical significance determined by minimal clinically important differences (MCID). Postoperative arm numbness was significantly higher than upper back or neck numbness, and arm pain was reduced the most (3.4 points) after surgery among the C5–8 radiculopathy groups. The C8 radiculopathy group had worse postoperative NDI scores (p = 0.026), upper back pain (p = 0.042), change in arm pain NRS scores (p = 0.021), and upper back numbness (p = 0.028) than the C5–7 group. NDI achieved MCID in both groups, but neck and arm pain NRS did not achieve MCID in the C8 group. In conclusion, although arm numbness persisted, arm pain was relieved after surgery for cervical radiculopathy. Patients with C8 radiculopathy exhibited worse NDI and change in NRS arm pain score than those with C5–7 radiculopathy.

Introduction: Complex corneal conditions present surgical challenges and necessitate innovation. Here, we present two cases where we performed intraocular lens trans-scleral fixation using the double-needle Yamane technique, followed by penetrating keratoplasty and vitrectomy using a temporary Landers wide-field keratoprosthesis. Case Presentation: Case 1 involved a 70-year-old man with an aphakic eye of bullous keratopathy and corneal opacity owing to multiple penetrating and endothelial keratoplasty, endophthalmitis, and herpetic keratitis. His visual acuity was counting fingers at 20 cm before surgery. Penetrating keratoplasty with vitrectomy and intraocular lens scleral fixation was performed using the double-needle Yamane technique, and 10 months postoperatively, his best-corrected visual acuity improved to 0.6, presenting a clear cornea. Case 2 involved a 62-year-old man who underwent penetrating keratoplasty twice for corneal perforation and therapeutic penetrating keratoplasty with vitrectomy for traumatic globe rupture, resulting in the loss of the intraocular lens. The patient exhibited graft failure, and his best-corrected visual acuity was 0.03. Utilizing a temporary Landers wide-field keratoprosthesis, we performed penetrating keratoplasty and intraocular lens trans-scleral fixation without complications. His final best-corrected visual acuity improved to 0.15 with a clear cornea. Conclusions: Trans-scleral fixation of intraocular lens with penetrating keratoplasty, using temporary Landers wide-field keratoprosthesis, yielded positive clinical outcomes without serious complications.

Introduction: The association between postoperative patient-reported outcomes (PROs) and patient satisfaction remains poorly defined in patients undergoing surgery for thoracic myelopathy. This study aimed to investigate PROs and patient satisfaction following surgical intervention for thoracic myelopathy. Methods: A prospective cohort of 133 patients who underwent surgery for thoracic myelopathy at 13 hospitals between April 2017 and August 2021 was enrolled. Patient demographics and perioperative complications were recorded. PROs were assessed using questionnaires administered preoperatively and 1 year postoperatively, including the EuroQol-5 dimension, physical and mental component summaries of the 12-item Short-Form Health Survey, Oswestry Disability Index, and numerical rating scales for low back, lower extremity, and plantar pain. Patients were categorized into two groups: satisfied (very satisfied, satisfied, and slightly satisfied) and dissatisfied (neither satisfied nor dissatisfied, slightly dissatisfied, dissatisfied, and very dissatisfied). Results: The mean age of the patients was 66.5 years, comprising 87 men and 46 women. The most common diagnoses were ossification of the ligamentum flavum (48.8%) and thoracic spondylotic myelopathy (26.3%). Seventy-four (55.6%) and 59 (44.3%) patients underwent decompression surgery and underwent decompression with fusion, respectively. Eight patients required reoperation due to postoperative surgical site infection, hematoma, and insufficient decompression in four, three, and one patient. Ninety (67.7%) patients completed both the preoperative and postoperative PRO questionnaires, all of which demonstrated significant improvement. Among them, 58 (64.4%) and 32 (35.6%) reported satisfaction and dissatisfaction with their treatment, respectively. The satisfied group showed superior improvement in PROs than the dissatisfied group, although there were no significant differences in complication rates between the two groups. Conclusions: The 64.4% satisfaction rate observed in patients undergoing surgery for thoracic myelopathy was lower than that reported in previous studies on cervical or lumbar spine surgery. The dissatisfied group exhibited significantly poorer quality of life (QOL) and higher pain scores than the satisfied group.

Abstract Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.

Introduction: Corneal graft detachment is a major postoperative complication of Descemet’s stripping automated endothelial keratoplasty (DSAEK). When a corneal graft becomes detached, corneal endothelial function generally fails, and repeat corneal transplantation is required. Herein, we report a rare case in which a transparent cornea was maintained after the removal of a dislocated DSAEK graft. Case Presentation: A 79-year-old woman with a residual lens cortex who had undergone cataract surgery was referred to our hospital. The cortex was removed, and bullous keratopathy progressed. Six months after the initial surgery, DSAEK was performed under topical anesthesia without any complications. Although the corneal graft had attached fairly well, it detached from the host cornea 3 weeks later. Two months after DSAEK, an air tamponade was used to treat the anterior chamber with single interrupted suturing; however, the graft detached again, except for the suture site. Because the detached cornea became cloudy in the anterior chamber, it was surgically removed 8 months after DSAEK. Accordingly, the host cornea transparency improved to a best-corrected visual acuity of 0.8 with a rigid gas permeable lens and a central corneal thickness of 580 μm. The corneal endothelial cell density was 995 cells/mm2. Conclusion: Removal of the corneal graft from the dislocated cloudy graft improved the visual acuity of this patient after DSAEK. The condition of the cornea should be carefully monitored after corneal endothelial transplantation, even after the graft has been dislocated.

ABSTRACT Human parainfluenza virus (HPIV) causes respiratory infections, which are exacerbated in children and older people. Correct evaluation of viral characteristics is essential for the study of countermeasures. However, adaptation of viruses to cultured cells during isolation or propagation might select laboratory passage-associated mutations that modify the characteristics of the virus. It was previously reported that adaptation of HPIV3, but not other HPIVs, was avoided in human airway epithelia. To examine the influence of laboratory passage on the genomes of HPIV1–HPIV4, we evaluated the occurrence of mutations after passage in primary human bronchial/tracheal epithelial cell air-liquid interface (HBTEC-ALI) culture and conventional cultured cells (Vero cells expressing the transmembrane protease, serine 2, and normal Vero cells). The occurrence of mutations was significantly lower in HBTEC-ALI than in conventional culture. In HBTEC-ALI culture, most of the mutations were silent or remained at low variant frequency, resulting in less impact on the viral consensus sequence. In contrast, passage in conventional culture induced or selected genetic mutations at high frequency with passage-associated unique substitutions. High mutagenesis of hemagglutinin-neuraminidase was commonly observed in all four HPIVs, and mutations even occurred in a single passage. In addition, in HPIV1 and HPIV2, mutations in the large protein were more frequent. These results indicate that passage in HBTEC-ALI culture is more suitable than conventional culture for maintaining the original characteristics of clinical isolates in all four HPIVs, which can help with the understanding of viral pathogenesis.IMPORTANCEAdaptation of viruses to cultured cells can increase the risk of misinterpretation in virological characterization of clinical isolates. In human parainfluenza virus (HPIV) 3, it has been reported that the human airway epithelial and lung organoid models are preferable for the study of viral characteristics of clinical strains without mutations. Therefore, we analyzed clinical isolates of all four HPIVs for the occurrence of mutations after five laboratory passages in human bronchial/tracheal epithelial cell air-liquid interface (HBTEC-ALI) or conventional culture. We found a high risk of hemagglutinin-neuraminidase mutagenesis in all four HPIVs in conventional cultured cells. In addition, in HPIV1 and HPIV2, mutations of the large protein were also more frequent in conventional cultured cells than in HBTEC-ALI culture. HBTEC-ALI culture was useful for maintaining the original sequence and characteristics of clinical isolates in all four HPIVs. The present study contributes to the understanding of HPIV pathogenesis and antiviral strategies.

Introduction: Inflammatory juvenile conjunctival nevus (IJCN) is a rare condition affecting both children and adolescents. It has misleading clinical and histopathological features; therefore, careful assessment is necessary. We present a case of IJCN with a rare pathological type and misleading histopathological features. Case Presentation: A 13-year-old girl with IJCN in the right eye was treated with antiallergic and steroid eye drops but showed no response and was referred to our hospital for excisional biopsy. Slit-lamp examination revealed a nonpigmented juxtalimbal tumor in the right eye. Histopathologically, nevus cells with mild nuclear atypia proliferated within the conjunctival epithelium. Confluent growth of junctional nests, conjunctival cysts, and prominent inflammatory infiltration were also observed. Considering the young age of the patient and immunohistochemical characteristics (HMB-45, SOX10, p16 and Ki-67), the patient was finally diagnosed with IJCN. IJCN has three pathological subtypes – compound, subepithelial, and junctional – depending on the location of the nevus cells. This case was diagnosed as a rare junctional type, as most of the examined sections only showed lesions within the epithelium; no lesions were clearly identified extending beneath the epithelium. Conclusion: The pathological diagnosis of IJCN is difficult because some features of IJCN suggest malignancy. Detailed microscopic examination, immunohistochemical staining, and the patient’s young age helped render a final diagnosis.

Abstract Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease that can compromise the functioning of various organs, including the salivary glands (SG). The purinergic system is one of the most important inflammatory pathways in T2DM condition, and P2X7R and P2X4R are the primary purinergic receptors in SG that regulate inflammatory homeostasis. This study aimed to evaluate P2X7R and P2X4R expression, and morphological changes in the submandibular gland (SMG) in T2DM. Twenty-four 5-week-old mice were randomly assigned to control (CON) and diabetes mellitus (DM) groups (n = 12 each). Body weight, diet, and blood glucose levels were monitored weekly. The histomorphology of the SMG and the expression of the P2X7R, and P2X7R was evaluated by immunohistochemistry (IHC) staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 11 and 13 weeks of age. Our findings indicate a significant increase in food consumption, body weight, and blood glucose levels in the DM group. Although a significant increase in P2X7R and P2X4R expression was observed in the DM groups, the receptor location remained unchanged. We also observed a significant increase in the acinar area in the DM13w group, and a significant decrease in the ductal area in the DM11w and DM13w groups. Targeting purinergic receptors may offer novel therapeutic methods for diabetic complications.

Abstract Background There are currently no studies that quantitatively compare the relationship of root resorption to the patient’s systemic history or craniofacial and intraoral morphology, especially in relation to possible host factors. Thus, this study aimed to clarify the factors associated with root resorption in retained mandibular second deciduous molars with the congenital absence of second premolars and predict the prognosis of retained mandibular second deciduous molars. Methods A cohort of 5547 patients who visited the orthodontic clinic at Tokyo Medical and Dental University Dental Hospital between 2013 and 2022 was screened. Lateral cephalometric radiographs, panoramic radiographs, upper and lower dental models, and orthodontic treatment questionnaires were used as reference materials to apply the inclusion and exclusion criteria. Ultimately, 111 patients were included in the analyses. The patients were divided into two groups based on the root resorption levels of the retained mandibular second deciduous molars. Those with less root resorption were classified under the good condition (GC) group, whereas those with more root resorption were classified under the poor condition (PC) group. Demographic, clinical, and cephalometric parameters were compared between the groups. A multivariate logistic regression model was used to predict the probability of root resorption. Results The prevalence of congenitally missing mandibular second premolars with persistent mandibular second deciduous molars was 2.0%. In a total of 111 patients, eighty-three teeth (53.2%) were classified into the GC group, whereas 73 teeth (46.8%) were classified into the PC group. The Frankfort-mandibular plane angle (FMA) [odds ratio (OR): 0.87], Frankfort-mandibular incisor angle (FMIA) (OR: 0.93), overbite (OR: 1.38), adjacent interdental space (OR: 1.46), distance from occlusal plane (OR: 0.80), and caries treatment (OR: 7.05) were significantly associated with the root resorption of the retained mandibular second deciduous molars. Conclusions Our findings suggest that skeletal morphology, oral morphological patterns, and history contribute to root resorption in retained mandibular second deciduous teeth with congenital absence of subsequent permanent teeth.

Purpose: This report presents a case of fungal keratitis treated with penetrating keratoplasty using a cryopreserved cornea, highlighting the successful maintenance of corneal transparency post infection resolution. Observations: A 57-year-old man complaining of pain in the right eye was referred to our hospital. Although diagnosed with fungal keratitis, his corneal scraping indicated the presence of Fusarium sp, and he was unresponsive to voriconazole, micafungin, and pimaricin treatments. His right visual acuity was hand motion. Therefore, we performed penetrating keratoplasty using a cryopreserved cornea. A cornea frozen and stored at −80 °C was used, with an 8.5-mm-diameter graft covering the infected area. Fungal keratitis subsided after corneal transplantation, and approximately 2 months later, corneal thickness gradually decreased, leading to improved corneal transparency. Therefore, a secondary optical corneal transplantation was deemed unnecessary. The final best-corrected visual acuity after additional cataract surgery was 20/40. Transparency was subsequently maintained for over a year. Conclusions and importance: Cryopreserved corneas in penetrating keratoplasty may be viable for maintaining corneal transparency. Additionally, waiting several months for secondary optical corneal transplantation after therapeutic keratoplasty may be a good approach.

IntroductionMaternal obstructive sleep apnea (OSA) during pregnancy is the risk factor for impaired fetal growth with low birth weight in the offspring. However, it is unclear whether gestational intermittent hypoxia (IH, a hallmark of maternal OSA) has long-term detrimental consequences on the skeletal development of offspring. This study aimed to investigate postnatal maxillofacial bone growth and cartilage metabolism in male and female offspring that were exposed to gestational IH.MethodsMother rats underwent IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) for 8 h per day during gestational days (GD) 7–20, and their male and female offspring were analyzed postnatally at 5 and 10 weeks of age. All male and female offspring were born and raised under normoxic conditions.ResultsThere was no significant difference in whole-body weight and tibial length between the IH male/female offspring and their control counterparts. In contrast, the mandibular condylar length was significantly shorter in the IH male offspring than in the control male offspring at 5 and 10 weeks of age, while there was no significant difference in the female offspring. Real-time polymerase chain reaction (PCR) showed that gestational IH significantly downregulated the mRNA level of SOX9 (a chondrogenesis marker) and upregulated the mRNA level of HIF-1α (a hypoxia-inducible factor marker) in the mandibular condylar cartilage of male offspring, but not in female offspring.ConclusionGestational IH induced underdeveloped mandibular ramus/condyles and reduced mRNA expression of SOX9, while enhancing mRNA expression of HIF-1α in a sex-dependent manner.

Abstract The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring. Phosphate-buffered saline, immunoglobulin G (IgG) isotype control antibody, or anti-SDF-1 neutralizing monoclonal antibody were injected at the M1 and M2 interproximal areas (10 μg/0.1 mL) for the first three days. Analyses were performed after 1, 3, and 7 days (n = 7). The results demonstrated a significant increase in SDF-1 expression from day 1, which was effectively blocked via anti-SDF-1 neutralizing monoclonal antibody injection. On day 3, the M2 OTM distance and the number of positively stained osteoclasts significantly reduced alongside a reduction in inflammatory markers in the experimental group. Our results demonstrated that serial local injection of the anti-SDF-1 neutralizing monoclonal antibody reduces M2 OTM, osteoclast accumulation, and localized inflammatory responses in an OTM model with tooth extraction-induced RAP.

Abstract Optogenetics enables precise regulation of intracellular signaling in target cells. However, the application of optogenetics to induce the differentiation of precursor cells and generate mature cells with specific functions has not yet been fully explored. Here, we focused on osteoclasts, which play an important role in bone remodeling, to develop a novel optogenetics tool, Opto-RANK, which can manipulate intracellular signals involved in osteoclast differentiation and maturation using blue light. We engineered Opto-RANK variants, Opto-RANKc and Opto-RANKm, and generated stable cell lines through retroviral transduction. Differentiation was induced by blue light, and various assays were conducted for functional analysis. Osteoclast precursor cells expressing Opto-RANK differentiated into multinucleated giant cells on light exposure and displayed upregulation of genes normally induced in differentiated osteoclasts. Furthermore, the differentiated cells exhibited bone-resorbing activities, with the possibility of spatial control of the resorption by targeted light illumination. These results suggested that Opto-RANK cells differentiated by light possess the features of osteoclasts, both morphological and functional. Thus, Opto-RANK should be useful for detailed spatiotemporal analysis of intracellular signaling during osteoclast differentiation and the development of new therapies for various bone diseases.

Background: Incretins, i.e., glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) promote insulin secretion to reduce postprandial blood sugar. Previous studies found incretins in the salivary glands. However, the role of GLP-1 and GIP in the submandibular gland (SMG) is unclear. This study investigates the effects of a high-fat diet (HFD) on the expression of GLP-1 and GIP throughout the development of rat SMG.Methods: Pregnant 11-week-old Wistar rats were divided into two groups: those fed on a standard diet (n = 5) and those fed on a HFD (n = 5). From day 7 of pregnancy and throughout the lactation period, all the rats were fed on either a chow diet or HFD. The newborns were divided into four subgroups (n = 6): standard diet males (SM), HFD males (HM), standard diet females (SF), and HFD females (HF). The SMGs of 3- and 10-week-old rats from each subgroup were collected under general anesthesia. Moreover, body weight, food intake, and fasting blood sugar were measured. The mRNA expression of GLP-1 and GIP was quantified, and the localization was observed using immunohistochemistry (p < 0.05).Results: GLP-1 mRNA expression was statistically significantly more upregulated in HM than in HF at 3 weeks. Moreover, GLP-1 mRNA expression was significantly higher in HM than in both SM and HF at 10 weeks. Although a decreasing trend was observed in GIP mRNA expression in both 3- and 10-week-old rats fed on a HFD, a significant difference between HM and SM only occurred at 3 weeks. Furthermore, the GIP mRNA expression of HM was lower than that of HF at 10 weeks. Immunohistochemical staining revealed GLP-1 and GIP expression mainly in the SMG duct system. Moreover, vacuolated cytoplasm in the duct was observed in rats fed on a HFD.Conclusion: Exposure to HFD during pre- and post-natal periods increased GLP-1 mRNA expression in the SMGs of male rats. However, GIP expression decreased following the HFD in male newborns. Furthermore, a decreasing trend of GIP mRNA expression was observed in male newborns after HFD feeding. Sex influenced incretin hormones secretion and obesity-related conditions. HFD during pre- and post-natal periods reprograms the epigenome, contributing to subsequent disease development.

Toxicity of Paederus species to eyes has scarcely been reported. This report presents a case of chemical blepharokeratoconjunctivitis with delayed re-epithelialization caused by Paederus fuscipes in a patient with dry eye after laser-assisted in situ keratomileusis (LASIK). A 47-year-old woman who had undergone LASIK for myopia 10 years prior experienced visual disturbance and pain in her left eye after being hit by a P. fuscipes insect in her eye 1 day prior to evaluation. At the initial presentation, dermatitis around the patient’s left eye, eyelid oedema, conjunctival chemosis, corneal epithelial defects, and a best corrected visual acuity (BCVA) of 20/200 were noted. No gram-positive/negative bacteria or indication of cellulitis/elevated inflammation was detected. Administration of topical steroids (betamethasone) and antibiotics (topical: cefmenoxime and levofloxacin; intravenous: ceftriaxone) improved the non-infectious chemical blepharokeratoconjunctivitis; however, the large corneal epithelial defect remained for 10 days. Switching from betamethasone to a preservative-free form facilitated re-epithelialization, and the patient’s BCVA improved to 20/16 after 2 months. Ophthalmologists should consider the toxicity of the Paederus species on the ocular surface and eyelid.

Background: Tobacco exposure during pregnancy is associated with several adverse outcomes in infants. We investigated the association between tobacco exposure during pregnancy (both active and second-hand) and various infections in infants up to 1 year. Methods: This prospective cohort study used a fixed dataset (jecs-an-20180131) from the Japan Environment and Children’s Study of registered births in Japan during 2011–2014 that included 104,065 fetal records from enrolled pregnant women. Based on the participants’ responses to the questionnaire on smoking status, mothers were first divided into “never smoked,” “quit smoking,” and “current smoker” groups and then into “no second-hand smoking (SHS)” and “SHS” groups. Infectious diseases included central nervous system infection, otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastroenteritis (GI), and urinary tract infection. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis and adjusted for maternal, socioeconomic, and postnatal confounding factors. Results: Among the 73,205 newborns enrolled, multivariable analysis revealed that the aOR of LRTI and GI was 1.20 (95% CI, 1.07–1.33) and 1.18 (95% CI, 1.04–1.35), respectively, for the “current smoker with/without SHS” group compared with the “never smoked without SHS” group. “Quit smoking without SHS” was not associated with the risk of LRTI. SHS was associated with an increased risk of OM, URTI, LRTI, and GI, especially with LRTI and GI. Conclusion: Exposure to tobacco smoke during pregnancy was associated with an increased risk of OM, URTI, LRTI, and GI in infants during their first year of life.

ABSTRACT Genetic diagnostic assays for the detection of respiratory viruses sometimes show simultaneous multiple infections with low copy numbers. In such cases, the disease is considered caused by a single etiologic agent and others are nonspecific reactions and/or contaminations. Interferon-dependent interference is seen in dual infections of influenza and respiratory syncytial virus, which are the main causes of respiratory infections. Virus isolation is one of the answers in detecting other active viruses present in specimens, and the air–liquid interface culture of human bronchial/tracheal epithelial cells (HBTEC-ALI) is optimal for the isolation of respiratory viruses owing to its wide range of susceptibility. In this study, we successfully confirmed the replications of various viruses from specimens with low copy numbers and simultaneous passage of two to three viruses using HBTEC-ALI cultures, mainly including human bocavirus 1 and/or human rhinovirus. IMPORTANCE Since the pandemic of coronavirus diseases 2019, the use of real-time PCR assay has become widespread among people who were not familiar with it in virus detection. As a result, whether a high real-time PCR value in one time test indicates virus transmissibly became a complicated social problem, regardless of the difference in assays and/or amplification conditions, the time and number of diagnostic test during the time course of infection. In addition, the multiple positives in the test of respiratory viruses further add to the confusion in the interpretation of the infection. To address this issue, we performed virus isolation using pediatric SARI (severe acute respiratory infections) specimens on air–liquid interface culture of human bronchial/tracheal epithelial cell culture. The result of this study can be a strong evidence that the specimens showing positivity for multiple agents in real-time PCR tests possibly contain infectious viruses.

Abstract The impact of body mass index (BMI) on outcomes after lumbar spine surgery is currently unknown. Previous studies have reported conflicting evidence for patients with high BMI, while little research has been conducted on outcomes for underweight patients. This study aims to examine the impact of BMI on outcomes after lumbar spine surgery. This prospective cohort study enrolled 5622 patients; of which, 194, 5027, and 401 were in the low (

Abstract The adverse effects of hard contact lenses (HCL) on the corneal endothelium have been studied in the short term; however, long-term effects remain still unclear. In this study, we analyzed the effect of long-term HCL use on corneal endothelial cell density (ECD) and morphology in healthy Japanese individuals. This cross-sectional observational study included individuals using HCL for refractive errors examined at a single specialty eye hospital. Patient age, duration of HCL usage, ECD, coefficient of variation of the cell area (CV), and rate of appearance of hexagonal cells (6A) obtained via non-contact specular microscopy were assessed. We analyzed 8604 eyes (mean age: 35.6 ± 10.0 years, 837 males, 3465 females). The mean duration of HCL usage was 14.7 ± 9.1 (range, 1–50) years. Multivariate analysis revealed that ECD significantly correlated with age (P

Abstract The aim of the study was to address the genioglossus muscle physiological and histological changes after unilateral nasal obstruction in growing rats. Fifty-four 6-day-old male Wistar albino rats were randomly divided into control (n = 27) and experimental (n = 27) groups. Unilateral nasal obstruction was performed at 8 days old. Contractile properties of the genioglossus whole muscle were measured at 5-, 7- and 9-week-old, including the twitch and tetanic forces, contraction time, half-decay time, and fatigue index. The histological characteristics of the genioglossus were also evaluated at 5-, 7- and 9-week-old, analyzing the myosin heavy chain composition of the slow, fast, IIa and IIb muscle fiber type, by measuring the number, rate, diameter and cross-sectional area. The maximal twitch force, and tetanic force at 60 Hz and 80 Hz force was significantly increased at all ages after nasal obstruction. The fatigue index was decreased at 5 weeks-old after nasal obstruction. The diameter and cross-sectional area of the fast, IIa and IIb muscle fiber types were increased at 7 and 9 weeks after nasal obstruction, while only the diameter of IIa type and cross-sectional area of IIb type were increased at 5 weeks-old after nasal obstruction. Nasal obstruction during growth affects the whole genioglossus muscle contractile properties and histological characteristics, increasing its force, the diameter and area of its muscle fibers. These changes in the genioglossus muscle may affect the normal growth, development and function of the craniofacial complex.

Abstract Study design A prospective cohort study. Objectives Thrombin-gelatin matrix (TGM) is a rapid and potent hemostatic agent, but it has some limitations, including the cost and its preparation time. The purpose of this study was to investigate the current trend in the use of TGM and to identify the predictors for TGM usage in order to ensure its proper use and optimized resource allocation. Methods A total of 5520 patients who underwent spine surgery in a multicenter study group within a year were included in the study. The demographic factors and the surgical factors including spinal levels operated, emergency surgery, reoperation, approach, durotomy, instrumented fixation, interbody fusion, osteotomy, and microendoscopy-assistance were investigated. TGM usage and whether it was routine or unplanned use for uncontrolled bleeding were also checked. A multivariate logistic regression analysis was used to identify predictors for unplanned use of TGM. Results Intraoperative TGM was used in 1934 cases (35.0%), among which 714 were unplanned (12.9%). Predictors of unplanned TGM use were female gender (adjusted odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.02–1.43, p = 0.03), ASA grade ≥ 2 (OR: 1.34, 95% CI: 1.04–1.72, p = 0.02), cervical spine (OR: 1.55, 95% CI: 1.24–1.94, p

Abstract High-fat diet (HFD) leads to multiple complications, including taste alteration. This study observed the effect of a two-generation exposure to an HFD on the peripheral taste system in offspring. Ten pregnant Wistar rats were assigned a standard diet (SD) (n = 5) or HFD (n = 5) from day 7 of pregnancy through the lactation. Thirty-six male and female 3-week-old offspring were measured for body weight and blood glucose level, and the circumvallate papillae were collected. The other twenty-four 3-week-old offspring were weaned on the same diet as their mothers and raised individually. The taste preference behaviors were studied using the two-bottle taste preference test and analyzed five basic tastes (sweet, bitter, umami, sour, and salty). The expressions of epithelial sodium channel alpha subunit (ENaCα) and angiotensin II receptor type 1 (AT1) in the circumvallate papilla were analyzed by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We found increased body weight and salty taste preference of offspring from the HFD group in both sexes. Correspondingly, the AT1 level of the taste bud cells significantly increased in 3-week-old female offspring from the HFD group. An increase in AT1 levels may be a risk factor for changes in salty taste preference.

This study aimed to analyze the relationship between bone density, habitual chewing side (HCS), and mini-screw stability to investigate the intra-individual factors contributing to mini-screw failure. This retrospective study included 86 sides in 43 adults, who underwent bilateral maxillary mini-screw placement with subsequent unilateral failure of the mini-screw. Pre-treatment cone-beam computed tomography was used to measure the buccal cortical bone thickness and bone density on the failed and successful sides. Pre-treatment mandibular kinesiographic records were used to determine the HCS. Paired t-tests, one-proportion z-tests, and multivariable multilevel Poisson regression were used to examine the statistical significance. The buccal cortical bone thicknesses were 0.93 ± 0.27 mm (unsuccessful side) and 1.01 ± 0.27 mm (successful side), with no significant difference. The bone density on the unsuccessful side (1059.64 ± 202.64 mg/cm3) was significantly lower than the success side (1317.89 ± 332.23 mg/cm3). Regarding HCS, 27.9% of failures occurred on the preferred side, and 62.8% occurred on the non-preferred side. After adjusting for all factors, the non-preferred side showed a 2.22 times higher prevalence ratio for mini-screw failure than the preferred side. HCS is significantly related to mini-screw stability, while the cortical bone thickness, bone density, and site of mini-screw implantation were not correlated.

Objectives To investigate the effect of the COVID-19 pandemic on surgical volume and outcomes in spine surgery.Design A retrospective cohort study using prospectively collected data.Setting and participants A total of 9935 patients who underwent spine surgery between January 2019 and December 2021 at eight high-volume spine centres in the Greater Tokyo metropolitan area were included.Outcome measures The primary outcome measures were the number of surgical cases, perioperative complications and patient-reported outcomes, including numerical rating scales for each body part, Euro quality of life 5-dimension (EQ5D), Neck Disability Index and Oswestry Disability Index (ODI).Results The total number of surgeries in 2020 and 2021 remained lower than that of 2019, with respective percentages of 93.1% and 95.7% compared with the prepandemic period, with a marked reduction observed in May 2020 compared with the same period in 2019 (56.1% decrease). There were no significant differences between the prepandemic and postpandemic groups in the incidence of perioperative complications, although the frequency of reoperation tended to be higher in the postpandemic group (3.04% vs 3.76%, p=0.05). Subgroup analysis focusing on cervical spine surgery revealed significantly worse preoperative EQ5D scores in the postpandemic group (0.57 vs 0.54, p=0.004). Similarly, in lumbar spine surgery, the postpandemic group showed higher levels of leg pain (5.7 vs 6.1 to 0.002) and worse ODI scores (46.2 vs 47.7 to 0.02). However, postoperative outcomes were not different between pre and post-pandemic groups.Conclusions The COVID-19 pandemic has significantly impacted spinal surgeries in Japan, leading to a decrease in surgical volumes and changes in patient characteristics and surgical procedures. However, surgical outcomes remained comparable between the pre and postpandemic periods, indicating the resilience and adaptability of healthcare systems.

Abstract Background Whether lumbar decompression with fusion surgery is effective against Meyerding grade 2 degenerative spondylolisthesis (DS) is unknown. Therefore, the current study aimed to compare the surgical outcomes between posterior decompression alone and posterior decompression with fusion surgery among patients with grade 2 DS with central canal stenosis. Methods This retrospective cohort study included prospectively registered patients (n = 3863) who underwent surgery for degenerative lumbar spinal canal stenosis at nine high-volume spine centers from April 2017 to July 2019. Patients with grade 2 DS and central canal stenosis were included in the analysis. Patients with radiculopathy, including foraminal stenosis, degenerative scoliosis, and concomitant anterior spinal fusion, and those with a previous history of lumbar surgery were excluded. The participants were divided into the decompression alone group (group D) and decompression with fusion surgery group (group F). Data about patient-reported outcomes, including Numeric Rating Scale (low back pain, leg pain, leg numbness, and foot numbness), Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 2 years postoperatively. Results In total, 2354 (61%) patients, including 42 (1.8%) with grade 2 DS (n = 18 in group D and n = 24 in group F), completed the 2-year follow-up. Group D had a higher proportion of female patients than group F. However, the two groups did not significantly differ in terms of other baseline demographic characteristics. Group D had a significantly shorter surgical time and lower volume of intraoperative blood loss than group F. Postoperative patient-reported outcomes did not significantly differ between the two groups, although the preoperative degree of low back pain was higher in group F than in group D. The slip degree of group D did not worsen during the follow-up period. Conclusion The surgical outcomes were similar regardless of the addition of fusion surgery among patients with grade 2 DS. Decompression alone was superior to decompression with fusion surgery as it was associated with a lower volume of intraoperative blood loss and shorter surgical time.

Abstract Bullous keratopathy (BK) is known to present with corneal edema and Descemet's folds, which can cause corneal astigmatism. However, no report quantitatively evaluated BK astigmatism by separating it into regular and irregular astigmatism. This study investigated the regular and irregular astigmatism of the anterior and posterior corneal surface with Fourier harmonic analysis and anterior segment optical coherence tomography. Preoperative data from 43 eyes of 41 BK patients who received corneal endothelial transplantation were compared with the data from 43 eyes of 43 subjects without corneal disease. Anterior and posterior cylinder power, central corneal thickness (CCT) and thinnest corneal thickness were significantly greater in BK. With Fourier harmonic analysis, BK eyes were found to have significantly larger anterior and posterior regular astigmatism, asymmetry component and higher-order irregularity. Asymmetry component and higher-order irregularity that accounted for the posterior irregular astigmatism increased as CCT increased in BK. Higher-order irregularity in the posterior cornea also positively correlated with worsening best corrected visual acuity. Subgroup analysis found significant correlations between CCT and posterior higher-order irregularity for intraocular surgery and laser iridotomy, but not Fuchs endothelial corneal dystrophy. This study has significance in that it revealed the characteristics of the corneal posterior irregular astigmatism of BK.

ABSTRACT Human respiratory syncytial viruses (HRSVs) are divided into subgroups A and B, which are further divided based on the nucleotide sequence of the second hypervariable region (HVR) of the attachment glycoprotein (G) gene. Understanding the molecular diversity of HRSV before and during the coronavirus disease 2019 (COVID-19) pandemic can provide insights into the effects of the pandemic on HRSV dissemination and guide vaccine development. Here, we analyzed HRSVs isolated in Fukushima Prefecture from September 2017 to December 2021. Specimens from pediatric patients were collected at two medical institutions in neighboring cities. A phylogenetic tree based on the second HVR nucleotide sequences was constructed using the Bayesian Markov chain Monte Carlo method. HRSV-A (ON1 genotype) and HRSV-B (BA9 genotype) were detected in 183 and 108 specimens, respectively. There were differences in the number of HRSV strains within clusters prevalent at the same time between the two hospitals. The genetic characteristics of HRSVs in 2021 after the COVID-19 outbreak were similar to those in 2019. HRSVs within a cluster may circulate within a region for several years, causing an epidemic cycle. Our findings add to the existing knowledge of the molecular epidemiology of HRSV in Japan. IMPORTANCE Understanding the molecular diversity of human respiratory syncytial viruses during pandemics caused by different viruses can provide insights that can guide public health decisions and vaccine development.

IntroductionPolydipsia, prevalent in 6%–20% of patients with schizophrenia, results in seclusion and prolonged hospitalization. It is also observed in autistic individuals, with previous studies reporting that autism accounted for 20% of all hospitalized patients with polydipsia. The current study investigated the association between polydipsia and autistic traits in patients with schizophrenia spectrum disorders (SSDs) based on the hypothesis that higher autistic traits would be observed in schizophrenic patients with polydipsia.MethodsIn the first study (study A), the autism-spectrum quotient [(AQ); Japanese version] scores of long-stay inpatients with and without polydipsia were compared. Furthermore, the association between polydipsia and autistic traits was also examined in short-stay inpatients and outpatients with SSDs (study B).ResultsStudy A showed that patients with polydipsia scored significantly higher on the three AQ subscales (attention switching; communication; and imagination) compared to those without. Study B also showed that patients with polydipsia had significantly higher AQ scores overall and for several subscales compared to those without polydipsia. Binary logistic regression analysis of the combined sample showed that male gender and higher autistic traits were significant predictors of polydipsia.DiscussionThe study highlights the importance of focusing on such traits to understand the pathogenesis of polydipsia in SSD patients.

Abstract Although patients with diabetes reportedly have more peripheral neuropathy, the impacts of diabetes on postoperative recovery in pain and patient-reported outcome measures (PROMs) after laminoplasty for cervical spondylotic myelopathy (CSM) is not well characterized. The authors aimed to elucidate the effects of diabetes on neck/arm/hand/leg/foot pain and PROMs after laminoplasty CSM. The authors retrospectively reviewed 339 patients (82 with diabetes and 257 without) who underwent laminoplasty between C3 and C7 in 11 hospitals during April 2017 –October 2019. Preoperative Numerical Rating Scale (NRS) scores in all five areas, the Short Form-12 Mental Component Summary, Euro quality of life 5-dimension, Neck Disability Index, and the Core Outcome Measures Index-Neck) were comparable between the groups. The between-group differences were also not significant in NRS scores and PROMs one year after surgery. The change score of NRS hand pain was larger in the diabetic group than the nondiabetic group. The diabetic group showed worse preoperative score but greater improvement in the Short Form-12 Physical Component Summary than the nondiabetic group, following comparable score one year after surgery. These data indicated that the preoperative presence of diabetes, at least, did not adversely affect pain or PROMs one year after laminoplasty for CSM.

Plants of the Araceae family exude a sap containing calcium oxalate, a toxic substance that causes dermatitis. However, ocular injury due to exposure to Araceae sap has rarely been reported. Herein, we present a case of severe pseudomembranous conjunctivitis following exposure to Arisaema ringens, an Araceae species and popular houseplant in Japan. A 67-year-old man presented with pain in his right eye after exposure to the sap of A. ringens. At presentation, the best corrected visual acuity and intraocular pressure in the right eye were 20/800 and 15 mm Hg. Slit-lamp examination showed strong hyperemia, conjunctival chemosis, and corneal edema with many pseudomembranes, and fluorescein staining revealed corneal epithelial defects in the central area of the cornea. We washed the ocular surface with saline and initiated treatment with topical instillations of 1.5% levofloxacin and 0.1% betamethasone, combined with ofloxacin eye ointment. After repeatedly removing the pseudomembranes and increasing the frequency of the topical instillations, pseudomembranous conjunctivitis and corneal erosion gradually improved. One week following the injury, the corneal epithelial defects were no longer detectable, and the patient’s best corrected visual acuity recovered to 20/25. It is important for ophthalmologists and primary care physicians to be aware of the ocular toxicity of A. ringens and should counsel their patients accordingly. Moreover, preventative measures, such as the use of protective eyewear, should be taken when cutting this houseplant.

Abstract Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear. We generated NNMT-deficient mice and a unilateral ureter obstruction (UUO) model and conducted two clinical studies on human CKD to investigate the role of NNMT in CKD and fibrosis. In UUO, renal NNMT expression and the degraded metabolites of NAM increased, while NAD + and NAD + precursors decreased. NNMT deficiency ameliorated renal fibrosis; mechanistically, it (1) increased the DNA methylation of connective tissue growth factor (CTGF), and (2) improved renal inflammation by increasing renal NAD + and Sirt1 and decreasing NF-κB acetylation. In humans, along with CKD progression, a trend toward a decrease in serum NAD + precursors was observed, while the final NAD + metabolites were accumulated, and the level of eGFR was an independent variable for serum NAM. In addition, NNMT was highly expressed in fibrotic areas of human kidney tissues. In conclusion, increased renal NNMT expression induces NAD + and methionine metabolism perturbation and contributes to renal fibrosis.

Abstract Background Although treatment options for rheumatoid arthritis (RA) have evolved significantly since the introduction of biologic agents, degenerative lumbar disease in RA patients remains a major challenge. Well-controlled comparisons between RA patients and their non-RA counterparts have not yet been reported. The objective of the present study was to compare postoperative outcomes of lumbar spine surgery between RA and non-RA patients by a retrospective propensity score-matched analysis. Methods Patients who underwent primary posterior spine surgery for degenerative lumbar disease in our prospective multicenter study group between 2017 and 2020 were enrolled. Demographic data including age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, diabetes mellitus, smoking, steroid usage, number of spinal levels involved, and preoperative patient-reported outcome (PRO) scores (numerical rating scale [NRS] for back pain and leg pain, Short Form-12 physical component summary [PCS], EuroQOL 5-dimension [EQ-5D], and Oswestry Disability Index [ODI]) were used to calculate a propensity score for RA diagnosis. One-to-one matching was performed and 1-year postoperative outcomes were compared between groups. Results Among the 4567 patients included, 90 had RA (2.0%). RA patients in our cohort were more likely to be female, with lower BMI, higher ASA grade and lower current smoking rate than non-RA patients. Preoperative NRS scores for leg pain, PCS, EQ-5D, and ODI were worse in RA patients. Propensity score matching generated 61 pairs of RA and non-RA patients who underwent posterior lumbar surgery. After background adjustment, RA patients reported worse postoperative PCS (28.4 vs. 37.2, p = 0.008) and EQ-5D (0.640 vs. 0.738, p = 0.03), although these differences were not significant between RA and non-RA patients not on steroids. Conclusions RA patients showed worse postoperative quality of life outcomes after posterior surgery for degenerative lumbar disease, while steroid-independent RA cases showed equivalent outcomes to non-RA patients.

Abstract Background Cancer treatment requires a multidisciplinary approach. Therefore, multidisciplinary team meetings (MDTMs) have been widely used to determine the direction of treatment. However, no standard provisions exist for conducting MDTMs, and recommendations discussed in MDTMs are sometimes not implemented. ​This study analyzed the indications for radiotherapy discussed and recommended at MDTMs, identified the rate of radiotherapy recommendations for patients that were not implemented, and clarified the reasons at a single academic center in Japan. Methods This was a cross-sectional study that analyzed the minutes and electronic medical records of cases discussed at MDTMs held between April 2012-March 2017 at Yamagata University Hospital. We categorized how radiotherapy was initially presented at MDTMs, determined the rate of radiotherapy recommendations made through MDTMs, analyzed whether treatment recommendations were subsequently implemented, and examined the causes of non-implementation. We performed a statistical analysis to assess some clinical factors (sex, age, number of multidisciplinary team meetings, and classification of planned treatment) associated with the non-implementation of radiotherapy recommendations from MDTMs. Results A total of 1813 cases were discussed at MDTMs, of which 71% (1293 cases) were presented with treatment plans, including radiotherapy. Further, 66% (1205 cases) were recommended for radiotherapy through the MDTMs. Recommendations from MDTMs were not implemented in 7% (142 cases). The most typical reason for non-implementation was the clinician’s opinion (30%), followed by patient preferences (27%) and disease progression (20%). Change in cancer stage and improvement in symptoms were 12% and 4%, respectively. These ratios were similar each year. We could not find the factors associated with the non-implementation of radiotherapy recommendations from MDTMs. Conclusions MDTMs had a significant effect on the recommendation of radiotherapy for each patient with a tumor. The primary reason for the non-implementation of decisions made at MDTMs was the opinion of clinicians and the patient’s preference. These results were similar to previous studies. We need to establish a monitoring system where patients themselves can decide the treatments based on their choices while using the recommendations from MDTMs.

Abstract Background Clostridium perfringens sepsis associated with massive intravascular hemolysis has an extremely poor prognosis. We here report a case of C. perfringens sepsis associated with massive intravascular hemolysis that developed secondary to a post-pancreaticoduodenectomy (PD) hepatic abscess. Case presentation A 70-year-old man with Type 2 diabetes underwent PD for an ampulla of Vater carcinoma. His postoperative course was uneventful. He was discharged on the 16th post-operative day (POD 16) after confirming no major abnormalities on abdominal contrast computed tomography (CT) on POD 14 or laboratory results on POD 16. Two days after discharge, he was readmitted because of fever and chills. Laboratory tests showed only a mild inflammatory reaction (white blood cell count, 11,980/mm3; C-reactive protein, 2.07 mg/dL). Abdominal CT showed an irregular, approximately 20-mm diameter, low-density area in the liver S6 region that had not been seen on a recent previous scan. We initially suspected postoperative cholangitis associated with biliary reconstruction and started empirical treatment with sulbactam/ampicillin after drawing blood for culture. Eight hours after admission, he developed septic shock with body temperature 40.0 ℃ and blood pressure 70/40 mm Hg. Laboratory findings showed a severe inflammatory reaction, severe anemia, and massive hemolysis (white blood cell count, 37,400/mm3; hemoglobin, 7.7 g/dL; total bilirubin, 8.05 mg/dL; direct bilirubin, 2.66 mg/dL; and lactate dehydrogenase, 1686 U/L). Hemoglobinuria was noted in the urinary catheter output. Repeat CT 9 h after admission showed the low-density area in S6 had become a gas-forming abscess. C. perfringens sepsis was strongly suspected on the basis of these findings and the abscess was drained percutaneously immediately after its diagnosis. His vital signs improved dramatically and he recovered within 24 h. Blood and abscess cultures grew C. perfringens 4 days after admission, leading to a definitive diagnosis of C. perfringens sepsis associated with massive intravascular hemolysis. He was discharged 18 days after admission. His sepsis has not recurred. Conclusions Clostridium perfringens infection should be considered in patients who have undergone PD and present with gas-forming hepatic abscesses and/or sepsis associated with intravascular hemolysis. Prompt aggressive treatment is crucial, because C. perfringens infections can cause death within hours.

Abstract Background Human herpesvirus 6B (HHV-6B) is known to cause exanthema subitem and has been detected in various ocular diseases, including keratitis, uveitis, optic neuritis, and endophthalmitis; however, the long-term outcome after the reactivation of HHV-6B has not been well-addressed. Sugita et al. previously reported the concomitant presence of HHV-6B with herpes simplex virus-1 (HSV-1) in the aqueous fluid at the onset of corneal endotheliitis. We focused on the same patient with corneal endotheliitis, in whom both HSV-1 and HHV-6B sequences were observed, and reported the clinical course and long-term outcomes. Case presentation A 64-year-old woman was referred to our center for visual disturbances in the left eye. Her best-corrected visual acuity in the left eye was 0.5 and the left intraocular pressure was elevated to 33 mmHg. Mid-sized keratic precipitates and 2+ cells were observed in the anterior chamber with corneal endothelial edema and reduction of the corneal endothelial cell density to 1828 cells/mm2. The patient was diagnosed with corneal endotheliitis with increased intraocular pressure. Polymerase chain reaction analysis revealed the concomitant presence of both HSV-1 and HHV-6B sequences in the left aqueous fluid. After treatment with oral valacyclovir and topical betamethasone, her intraocular inflammation gradually improved and has not recurred at 12 years after corneal endotheliitis onset although corneal opacity remained. Conclusions Reactivation of HHV-6B infection might be associated with HSV-1 corneal endotheliitis; however, no serious late sequelae occurred after appropriate treatment for HSV-1 infection in this immunocompetent host.

Descemet’s membrane endothelial keratoplasty (DMEK) for patients with corneal endothelial loss rarely results in graft rejection. Herein, we report a rare case of graft rejection following DMEK, in which peripheral anterior synechiae were observed postoperatively. A 66-year-old woman was referred to our hospital after complaints of decreased visual acuity of her right eye after laser iridotomy for primary angle closure 3 years earlier. Her right cornea had bullous keratopathy with mild cataract, and her best-corrected visual acuity (BCVA) was 20/40. After cataract surgery, DMEK was successfully performed, except for development of peripheral anterior synechiae at the temporal cornea. Her BCVA recovered to 20/20. However, when topical instillation was changed to 0.1% fluorometholone from 0.1% betamethasone once a day, corneal edema reappeared with hyperemia, mutton fat keratic precipitates (KPs), and cells in the anterior chamber. The BCVA worsened to 20/32. Graft rejection was diagnosed, and subconjunctival injection of dexamethasone was performed 3 times, once every few days, with 0.1% topical betamethasone instillation. Subsequently, the hyperemia, mutton fat KPs, and cells in the anterior chamber disappeared with a recovered BCVA of 20/20 after 2 weeks. Ten months after graft rejection, there was no recurrence of intraocular inflammation, and only topical betamethasone was administered twice daily. It is important to exercise caution in cases with peripheral anterior synechiae after DMEK. Long-term steroid administration is necessary to prevent graft rejection.

Background. Epikeratophakia is a refractive surgical procedure used to correct aphakic eyes, hyperopia, and keratoconus and is often performed in children. In this report, we present the long-term effects of epikeratophakia on the progression of keratoconus in a patient who underwent surgery. Case Presentation. The patient was a 17-year-old boy with keratoconus who had difficulty wearing hard contact lenses. As a solution, he underwent right eye epikeratophakia with a plano-powered lenticule. We followed up the patient for 30 years. Although the progression of keratoconus ceased in the operated eye, it continued in the nonoperated left eye and resulted in acute hydrops 9 years and 10 months after surgery. Subsequently, 20 years after the operation, anterior-segment optical coherence tomography was performed, which revealed that the progression of keratoconus had been interrupted in the right eye but had continued in the left eye, as evidenced by the parameters of the average and maximum keratometry and thinnest corneal thickness. Conclusions. Herein, we reported the longest follow-up to date of a case of keratoconus, in which one eye was treated with epikeratophakia. The progression of keratoconus was halted in the treated eye but continued in the nonoperated contralateral eye.

The hygiene hypothesis suggests that pet exposure is effective in preventing allergic disease, and some studies have reported the beneficial effects of dog exposure during fetal development or early infancy on food allergy. However, the effects of exposure to pets other than dogs on the kinds of food allergies remains unaddressed. This study aimed to explore the effect of exposure to various species of pets on the risk of food allergies. We obtained information on pet exposure and food allergy from the Japan Environment and Children's Study, a nationwide, prospective birth cohort study that included 97,413 mothers and their children. We examined the associations between exposure to various species of pets during fetal development or early infancy and the incidence risk of food allergies. We conducted logistic regression analysis for each pet species, causative food, and timing of exposure. Exposure to dogs or cats during fetal development or early infancy was estimated to reduce the incidence risk of food allergies until the age of 3 years. Dog exposure was estimated to reduce the incidence risk of egg, milk, and nut allergies, and cat exposure was estimated to reduce the incidence risk of egg, wheat, and soybean allergies. However, hamster exposure was estimated to increase the incidence risk of nut allergy. In conclusion, the association between pet exposure and food allergies might differ depending on the pet species and causative food. Continued dog and cat exposure from fetal development to infancy was estimated to reduce the incidence risk of food allergies. The findings of this study shall aid in the design of future studies.

Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.

Abstract Background Several studies have indicated that self-stigma is associated with depressive symptoms and could be a barrier to recovery in patients with schizophrenia-spectrum disorders. More recently, an association between autistic symptoms and self-stigma was found in schizophrenia-spectrum patients. This study aimed to investigate the association between self-stigma, autistic and depressive symptoms, and recovery in patients with schizophrenia. Methods In total, 105 participants were evaluated using the Autism Spectrum Quotient, the Internalized Stigma of Mental Illness Scale, the Quick Inventory of Depressive Symptomatology, and the Recovery Assessment Scale to investigate autistic symptoms, self-stigma, depressive symptoms, and recovery, respectively. The relationship between self-stigma, autistic symptoms, depressive symptoms, and recovery was assessed using structural equation modeling analysis. Results Impaired attention switching, one symptom of autism, was found to positively affect stereotype endorsement, which negatively influenced recovery through depressive symptoms. Moreover, problems with communication skills negatively affected recovery through depressive symptoms. Concerning self-stigma, stereotype endorsement and perceived discrimination had a negative effect on recovery through depressive symptoms, whereas stigma resistance had a direct negative effect on recovery. Conclusions This study may provide meaningful insight into the psychological structure of recovery and could inform effective interventions for patients with schizophrenia-spectrum disorders. This was a cross-sectionally designed study; therefore, further longitudinal studies are needed to identify the causal relationships between self-stigma, autistic and depressive symptoms, and recovery.

Abstract We aimed to investigate the cell density and morphology of the corneal endothelium in ophthalmologically healthy young Japanese, given the lack of normative data in literature. This observational study included eyes without ophthalmologic diseases, besides refractive errors, examined between 1996 and 2015 at Miyata Eye Hospital. Eyes with a history of ophthalmologic diseases or contact lens usage were excluded. Correlation of corneal endothelial cell density (ECD), coefficient of variation (CV), appearance rate of hexagonal cells (6A), and cell area with age were examined. Multivariate linear regression analysis was performed to determine the predictors of corneal parameters. We included 16842 eyes of 8421 individuals (19.6 ± 8.7 years). ECD was 3109.0 ± 303.7 cells/mm2 and significantly reduced with age (p

In this study, we aimed to determine the effects of functional mandibular lateral shift (FMLS) on the muscle mass, fiber size, myosin heavy chain fiber type, and related gene expression in masticatory muscles (masseter and temporalis), as well as whether the baseline levels could be recovered after FMLS correction in growing rats. The FMLS appliance was placed to shift the mandible leftward by approximately 2 mm. After FMLS placement for 2 and 4 weeks, the muscles on the left side had significantly lower wet weight, mean cross-sectional area, and proportion of type IIa fibers than those on the right side or in the control groups (p < 0.05), with downregulation and upregulation of IGF-1 and GDF-8 gene expression, respectively (p < 0.05). Following 2 weeks devoted to recovery from FMLS, the muscle parameters in the recovery group were not significantly different to those of the control group, and IGF-1 expression in the left-side muscles was enhanced and GDF-8 expression was simultaneously suppressed. These findings indicate that the masticatory muscle changes induced via FMLS tend to revert to normal conditions if the intervention is eliminated at an early stage. Therefore, appropriate orthodontic treatment for FMLS during the growth period is advisable to prevent asymmetric alterations in masticatory muscles.

This study aimed to investigate whether the morphology of the temporomandibular joint (TMJ) is associated with chewing patterns while considering skeletal morphology, sex, age, and symptoms of temporomandibular disorder (TMD). A cross-sectional observational study of 102 TMJs of 80 patients (age 16–40 years) was performed using pretreatment records of cone-beam computed tomography imaging of the TMJ, mandibular kinesiographic records of gum chewing, lateral and posteroanterior cephalometric radiographs, patient history, and pretreatment questionnaires. To select appropriate TMJ measurements, linear regression analyses were performed using TMJ measurements as dependent variables and chewing patterns as the independent variable with adjustment for other covariates, including Nasion-B plane (SNB) angle, Frankfort-mandibular plane angle (FMA), amount of lateral mandibular shift, sex, age, and symptoms of TMD. In multiple linear regression models adjusted for other covariates, the length of the horizontal short axis of the condyle and radius of the condyle at 135° from the medial pole were significantly (p < 0.05) associated with the chewing patterns in the frontal plane on the working side. “Non-bilateral grinding” displayed a more rounded shape of the mandibular condyle. Conversely, “bilateral grinding” exhibited a flatter shape in the anteroposterior aspect. These findings suggest that the mandibular condyle morphology might be related to skeletal and masticatory function, including chewing patterns.

Although a few cases of dermatitis or keratitis caused by exposure to the sap of Euphorbia trigona have been reported, we present a rare case of transient corneal endothelial dysfunction following exposure to the sap, resulting in corneal edema. A woman in her 70s complained of reduced vision, redness, and teariness in her left eye 2 days after exposure to the sap of E. trigona at home. Upon examination, hyperemia, serious corneal edema, and anterior uveitis with hypopyon were observed in her left eye, without corneal epithelial defects or keratic precipitates. The best-corrected visual acuity (BCVA) was 2.0 (logarithm of the minimum angle of resolution), and the measured central corneal thickness (CCT) was 812 µm. The patient was treated with topical instillation of 1.5% levofloxacin and 0.1% dexamethasone to reduce intraocular inflammation and corneal edema. Three weeks later, the BCVA reached 0, the CCT was 519 μm, and the corneal endothelial cell density was 3,233 cells/mm2. Six months after the injury, the patient had good visual acuity, and the cornea was completely transparent. No recurrence of corneal edema or anterior uveitis was observed. Exposure to the sap of E. trigona can lead to severe corneal edema with anterior uveitis, impairing visual acuity. Taking precautions to prevent the exposure of the eye to the sap of this plant is crucial.

Abstract Objective The lateral pterygoid is vital in coordinating multidimensional jaw movements. Since a vector in three‐dimensional (3D) space is defined by two 3D points, the role of the lateral pterygoid in 3D jaw movements is defined by its origin and insertion. Reportedly, the lateral pterygoid is inserted into not only the pterygoid fovea but also into the medial surface of the condylar process. The objective was to investigate the morphological features of the region of the lateral pterygoid that inserted into the medial surface of the condylar process. Material and Methods Ten head halves of seven cadaveric donors were analyzed. In all specimens, the insertion area on the medial surface of the condylar process was measured based on microcomputed tomography images. Muscle fibers were separated into ≥50 small bundles, and positional relationships between the origins and insertions were investigated. Results Overall, 28.8 ± 5.0% of the insertion area of the lateral pterygoid was situated on the medial surface of the condylar process. Moreover, muscle fiber arrangement revealed that origins of the muscle bundles inserting into the medial surface in seven specimens posteriorly occupied the lateral plate of the pterygoid process longitudinally, whereas those in three specimens mainly occupied the posteroinferior portion. Conclusions Muscle bundle inserting on the medial surface of the condylar process had a broad insertion area and a distinct origin on the posterior region of the lateral plate of the pterygoid process. This muscle bundle could act as one of the significant subunits within the lateral pterygoid. Therefore, anatomical coordination mechanisms underlying jaw movement cannot be elucidated without considering this subunit.

Abstract Although patients with diabetes reportedly have more back pain and worse patient-reported outcomes than those without diabetes after lumbar spine surgery, the impact of diabetes on postoperative recovery in pain or numbness in other regions is not well characterized. In this study, the authors aimed to elucidate the impact of diabetes on postoperative recovery in pain/numbness in four areas (back, buttock, leg, and sole) after lumbar spine surgery. The authors retrospectively reviewed 993 patients (152 with diabetes and 841 without) who underwent decompression and/or fixation within three levels of the lumbar spine at eight hospitals during April 2017–June 2018. Preoperative Numerical Rating Scale (NRS) scores in all four areas, Oswestry Disability Index (ODI), and Euro quality of life 5-dimension (EQ-5D) were comparable between the groups. The diabetic group showed worse ODI/EQ-5D and greater NRS scores for leg pain 1 year after surgery than the non-diabetic group. Although other postoperative NRS scores tended to be higher in the diabetic group, the between-group differences were not significant. Diabetic neuropathy caused by microvascular changes may induce irreversible nerve damage especially in leg area. Providers can use this information when counseling patients with diabetes about the expected outcomes of spine surgery.

Abstract The effect of altered occlusal force on masticatory-related neuromuscular control, which projects from the anterior part of the cortical masticatory area (A-CMA), during growth remains unclear. This study sought to evaluate the effect of occlusal hypofunction on neuromuscular development of jaw muscle activities and cortically-induced rhythmic jaw movements (RJMs) in growing rats. Sixty-four 2-week-old male albino Wistar rats were divided into the control (fed normal diet) and experimental (fed soft diet) groups soon after weaning. Electromyographic activity was recorded at 5, 7, 9, and 11 weeks from the right masseter and anterior digastric along with RJMs. We found a significantly longer onset latency and smaller peak-to-peak amplitude in the experimental group than that in the control group. The RJMs showed an increase in gape size and lateral excursion until up to 9 weeks in both groups. However, both the average gape size and lateral excursion were significantly smaller in the experimental group than that in the control group after 9 weeks. The jaw movement pattern also showed a significant decrease at the maximum opening period in the experimental group. Our findings indicate that inadequate occlusal function during growth alters neuromuscular control of masticatory behaviors and impairs the pattern of RJMs.