IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease.

Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient (Ido1-/-) BMT to understand why myeloid IDO limits the severity of GVHD. Hosts with Ido1-/- BM exhibited increased lethality, with enhanced proinflammatory and reduced regulatory T cell responses compared with wild type (WT) allo-BMT controls. Despite the comparable expression of the myeloid-derived suppressor cell (MDSC) mediators, arginase-1, inducible nitric oxide synthase, and interleukin 10, Ido1-/- Gr-1+CD11b+ cells from allo-BMT or in vitro BM culture showed compromised immune-suppressive functions and were skewed toward the Ly6ClowLy6Ghi subset, compared with the WT counterparts. Importantly, Ido1-/-Gr-1+CD11b+ cells exhibited elevated levels of reactive oxygen species (ROS) and neutrophil numbers. These characteristics were rescued by human IDO1 with intact heme-binding and catalytic activities and were recapitulated by the treatment of WT cells with the IDO1 inhibitor L1-methyl tryptophan. ROS scavenging by N-acetylcysteine reverted the Ido1-/-Gr-1+CD11b+ composition and function to an MDSC state, as well as improved the survival of GVHD hosts with Ido1-/- BM. In summary, myeloid-derived IDO1 enhances GVHD survival by regulating ROS levels and limiting the ability of Gr-1+CD11b+ MDSCs to differentiate into proinflammatory neutrophils. Our findings provide a mechanistic insight into the immune-regulatory roles of the metabolic enzyme IDO1.

Improvement in nurse staffing ratios according to policy changes: a prospective cohort study.

BACKGROUND: Since 1999, reimbursements for nursing services for inpatients have been paid differentially according to the nurse staffing ratios in Korea. However, differentiated nursing fees are insufficient for nurse staffing; thus, steps have been taken to improve the policy. This study aimed to identify the impact of a policy that changed the method of calculating nurse staffing ratios from the nurse-to-bed ratio to the nurse-to-patient ratio on improving the nurse staffing ratio in medical institutions. METHODS: Data were collected from 1,339 medical institutions that continuously provided medical services from 2017 to of 2021, and a prospective cohort was used for analysis. A generalized estimating equation for longitudinal ordered logistic regression was used to identify the impact of this policy change on the nurse staffing ratios in medical institutions. RESULTS: During the cohort study, 59.8% of the first-applied group of medical institutions and 65.6% of the second-applied group of medical institutions improved their nurse staffing ratios. However, only 22.6% of the medical institutions to which the revised calculation method was not applied improved their nurse staffing ratios. A statistically significant difference was found in the improved nurse staffing ratio depending on whether and when the revised calculation method was applied (χ2 = 89.830, p < .001). The analysis of nurse staffing ratios of medical institutions from 2017 to 2021 showed that the likelihood of improving the nurse staffing ratio increased gradually after the revised calculation method was adopted. Also,the likelihood of the nurse staffing ratio improving in the first-applied group was 1.41 times higher (odds ratio = 1.41, 95% confidence interval = 1.04-1.92) than in the non-applied group. The odds ratio for the improvement of nurse staffing ratio in the second-applied group was 2.35 (95% confidence interval = 1.76-3.14). CONCLUSIONS: Financial incentives inherent in the new policy can be regarded as the driving force behind improvements in nurse staffing ratios. The revised calculation method should be extended to all medical institutions nationwide, and the law should be revised to secure the minimum number of nurses.

Effects of a disincentive policy on behavioral changes by South Korean medical institutions that do not submit official nursing grade data.

AIM: This study aimed to determine whether the policy of imposing deductions on medical institutions in South Korea led to increased submission of nursing grade data. BACKGROUND: In Korea, medical institutions are required to report data on their nursing workforce; however, many institutions did not comply with this regulation, making it difficult to gauge their level of nurse staffing. Therefore, in 2020, a nursing fee deduction policy was introduced that penalizes medical institutions financially for failing to submit nursing workforce data. METHODS: We prospectively collected data on the characteristics, nursing grade, and data submission status of 1,200 hospitals in South Korea from 2015 to 2021. We analyzed the submission rate of data related to nursing grades according to the characteristics of the medical institutions and evaluated the effect of policy change on data submission status using multiple logistic regression. FINDINGS: The submission rate of data increased from 50.2% in 2015 to 93.3% in 2021, and 39.3% of medical institutions that had not previously submitted data did so after the policy was introduced. The submission rate of medical institutions unaffected by the policy also increased after its introduction. Compared with 2015, the likelihood of medical institutions submitting data increased by 23.69 times in 2020 and 20.47 times in 2021. CONCLUSION: The appropriate use of disincentive policies, such as financial deductions for medical institutions showing inappropriate behavior, was found to be effective in inducing desirable changes in the behavior of medical institutions. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Properly planned and implemented policies can contribute to improved quality of medical services and patient safety through effective administrative control.

Treatment of facial asymmetry and severe midline deviation with orthodontic mini-implants.

This case report describes the treatment of a 29-year-old woman with facial asymmetry and 2 hopeless teeth. Her lower dental midline was shifted to the left side, and the mandibular left second molar would need to be extracted because of severe caries. The maxillary right second premolar was root rest, and the upper dental midline was shifted to the right side. Because of the patient's asymmetry and Class III skeletal pattern, a severe Class III relationship in the right canine region and lingual crossbite in the left side was observed. She did not want jaw surgery. The mandibular right first premolar, 2 hopeless teeth, and maxillary left second premolar were extracted, and orthodontic mini-implants were used to correct the dental midline, crossbite, and crowding. The mandibular left third molar was moved to the second molar extraction space by using orthodontic mini-implant anchorage. Adequate functional and esthetic results were obtained. Correction of the crossbite on the left side could improve facial asymmetry by changing the drape of the overlying lips.

Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation.

Prolonged hyperinsulinemic hypoglycemia in infancy can result in developmental sequelae. A mutation in the paired box-6 gene (PAX6) has been reported to cause disorders in oculogenesis and neurogenesis. A limited number of cases of diabetes mellitus in adults with a PAX6 mutation suggest that the gene also plays a role in glucose homeostasis. The present case report describes a boy with a PAX6 mutation, born with anophthalmia, who underwent hypoglycemic seizures starting at 5 months old, and showed a prediabetic condition at 60 months. This patient provides novel evidence that connects PAX6 to glucose homeostasis and highlights that life-threatening hypoglycemia or early onset glucose intolerance may be encountered. The role of PAX6 in glucose metabolism and insulin regulation should be further investigated.

Buckled carbon nanotube network thin-film fabricated using chemically swelled elastomer substrates.

We report on the fabrication of buckled carbon nanotube thin-film networks (CNTN) that increases in conductivity with applied tactile pressure. When tactile pressure was applied, the buckled nanotubes collapsed and increased in interconnected density and as a result increased the thin-film conductivity. Unlike conventional methods using mechanically expanded elastomers, we utilize chemically swollen elastomers as the expanded substrate to transfer the CNTN. As the chemical evaporates, it compresses the CNTN causing the thin-film to buckle. The CNTN compression can be controlled by using organic solvents with differing elastomer absorption rates. Our method requires no mechanical instruments and shows in-plane multi-axial uniform strain for the entire substrate surface. Since the buckling was controlled chemically, the buckled CNTN can be produced reliably, furthering the possibility of its application as the active sensing material for highly sensitive tactile pressure sensors.

Vertical control of a Class II deep bite malocclusion with the use of orthodontic mini-implants.

To improve the facial profile of a Class II patient with chin deficiency, orthodontists have traditionally used incisor retraction or jaw surgery. Recently, a new technique was introduced that uses orthodontic mini-implants to intrude the incisors and rotate the mandibular plane counterclockwise. In patients with deep bite, heavy anterior occlusal contact can make it difficult to use intrusion for profile improvement. This case report shows the successful treatment of a patient with Class II deep bite and chin deficiency by means of intrusion of the maxillary and mandibular dentition with multiple orthodontic mini-implants.

Asymmetric extractions in a patient with a hopeless maxillary central incisor, followed by treatment with mini-implant anchorage.

Premolar extraction is 1 option for treatment of patients with malocclusion and severe crowding or protrusion. When the patient has missing or hopeless teeth other than premolars, it is possible to consider removal of those teeth to use the space to decrease crowding. A 15-year-old girl sought treatment for severe crowding. She had already lost her maxillary right first premolar as a result of caries 1 year previously and had a hopeless maxillary right central incisor. Her mandibular left first molar still caused discomfort even after endodontic treatment. Extractions of the maxillary right central incisor and mandibular right first premolar and left first molar were chosen to resolve the occlusion problems. Orthodontic mini-implants were placed to translocate the maxillary left central incisor across the midpalatal suture to use the space in the maxillary right quadrant to relieve the crowding. Although a different extraction option was used in each quadrant, the final occlusion was acceptable. After debonding, porcelain crowns were placed on the anterior teeth to improve esthetics. The treatment result remained stable after 2 years of retention.

Fixed-functional appliance treatment combined with growth hormone therapy.

The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant. This case report demonstrates that the mandible grew significantly during fixed functional appliance treatment combined with GH therapy, with stable results during 2 years 11 months of retention. More studies are needed to evaluate GH therapy as a supplement in Class II treatment.

Quality of Life and Self-Esteem of Female Orthognathic Surgery Patients.

PURPOSE: To evaluate the effect of severe malocclusion requiring orthognathic surgery on the self-esteem (SE) and quality of life (QOL) of female adult patients undergoing orthognathic surgery compared with a group with minor malocclusions seeking only orthodontic treatment. MATERIALS AND METHODS: Female patients, aged 18 to 30 years, who had presented for an orthodontic consultation for correction of a malocclusion were enrolled during an 18-month period. In group 1, all the patients required 2-jaw surgery, and they were subdivided into those with a Class II or Class III malocclusion. This group was further subdivided into those with and without clinically significant asymmetry. A second comparison group was selected. These patients had minor malocclusion. Group 2 (the minor malocclusion group; MMG) included patients with a Class I molar relationship with less than 5 mm on the irregularity index in the upper anterior teeth. Each participant completed the Rosenberg's self-esteem scale (RSE) and the Orthognathic Quality of Life Questionnaire (OQLQ) before starting treatment. The RSE and OQLQ measurements were compared using 1-way analysis of variance and Scheffe's multiple comparison. The level of statistical significance was set at P < .05. RESULTS: The MMG group (n = 52) showed significantly better RSE and OQOL values compared with those with Class II (n = 37) and Class III (n = 47) malocclusion (P < .01). In the OQLQ measurements, the social aspects, aesthetics, and oral function scores were also better in the MMG group (P < .01). Only the awareness component did not reveal a significant difference. No significant differences were found in QOL or SE between those with Class II and Class III malocclusion. The influence of asymmetry on the RSE and OQLQ results was not significant in the Class II and III patients. CONCLUSIONS: Female adult orthognathic patients showed significant impairments in QOL and SE compared with those with mild malocclusion.

An analysis of the activity and muscle fatigue of the muscles around the neck under the three most frequent postures while using a smartphone.

[Purpose] The purpose of this study was to identify changes in the activity and fatigue of the splenius capitis and upper trapezius muscles, which are agonists to the muscles supporting the head, under the three postures most frequently adopted while using a smartphone. [Subjects and Methods] The subjects were 15 college students in their 20s. They formed a single group and had to adopt three different postures (maximum bending, middle bending, and neutral). While the 15 subjects maintained the postures, muscle activity and fatigue were measured using surface electromyography. [Results] Comparison of the muscle fatigue caused by each posture showed statistically significant differences for the right splenius capitis, left splenius capitis, and left upper trapezius muscles. In addition, maintaining the maximum bending posture while using a smartphone resulted in higher levels of fatigue in the right splenius capitis, left splenius capitis, and left upper trapezius muscles compared with those for the middle bending posture. [Conclusion] Therefore, this study suggests that individuals should bend their neck slightly when using a smartphone, rather than bending it too much, or keep their neck straight to reduce fatigue of the cervical erector muscles.

Types of subtalar joint facets.

Articular facets of the clinical subtalar joint (CSTJ) were analyzed using a total of 118 (right 57, left 61) dry, paired calcanei and tali from 68 Korean adult cadavers. The CSTJ facets were classified into the following three types depending on their continuity: type A, all three facets are separated; type B, the anterior and middle facets are partially connected; and type C, the anterior and middle facets are fused to form a single facet. The continuity between the anterior and middle facets was represented by the degree of separation (DS), which ranged between 2.00 (type A) and 1.00 (type C). Type A was most common (39.0 %) in calcanei and rarest (11.0 %) in tali. Matching of calcaneus-talus pairs yielded five combined types: A-A (11.0 %), A-B (28.0 %), B-B (18.6 %), B-C (13.6 %), and C-C (28.8 %). The mean DS was slightly greater in calcanei (1.53) than in tali (1.32), and decreased in the order of types A-A, A-B, B-B, B-C, and C-C. The intersecting angles between the anterior and middle facets, which are related to the mobility of the CSTJ, were inversely related to the DS. These findings indicate that the anterior and middle facets are fused more frequently in tali than in calcanei, and combinations of different CSTJ facet types (A-B, B-C) exist over 40 % of feet. Our results indicate that types with a smaller DS (such as B-C and C-C) are relatively mobile but less stable compared to those with a greater DS (such as A-A and A-B).

Submorphotypes of the maxillary first molar and their effects on alignment and rotation.

INTRODUCTION: The aim of this study was to explore the shape differences in maxillary first molars with orthographic measurements using 3-dimensional virtual models to assess whether there is variability in morphology that could affect the alignment results when treated by straight-wire appliance systems. METHODS: A total of 175 maxillary first molars with 4 cusps were selected for classification. With 3-dimensional laser scanning and reconstruction software, virtual casts were constructed. After performing several linear and angular measurements on the virtual occlusal plane, the teeth were clustered into 2 groups by the method of partitioning around medoids. To visualize the 2 groups, occlusal polygons were constructed using the average data of these groups. RESULTS: The resultant 2 clusters showed statistically significant differences in the measurements describing the cusp locations and the buccal and lingual outlines. The rotation along the centers made the 2 cluster polygons look similar, but there was a difference in the direction of the midsagittal lines. CONCLUSIONS: There was considerable variability in morphology according to 2 clusters in the population of this study. The occlusal polygons showed that the outlines of the 2 clusters were similar, but the midsagittal line directions and inner geometries were different. The difference between the morphologies of the 2 clusters could result in occlusal contact differences, which might be considered for better alignment of the maxillary posterior segment.

Treatment outcome and long-term stability of orthognathic surgery for facial asymmetry: A systematic review and meta-analysis.

Objective: : This systematic review aimed to provide a comparative analysis of the treatment outcomes, including hard and soft tissues, postoperative stability, temporomandibular disorders (TMD), and quality of life (QoL), in patients with facial asymmetry who underwent orthognathic surgery. Methods: : The primary objective was to address the question, "How do different factors related to surgery affect the outcomes and stability of orthognathic surgery in the correction of facial asymmetry?" A meta-analysis was conducted on the outcome parameters, such as skeletal, dental, and soft tissue symmetry, TMD, QoL, and relapse, using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Subgroup analyses were conducted considering surgery-related factors such as surgical techniques (one-jaw vs. two-jaw), use of the surgery-first approach, utilization of computer simulation, and analytical methods employed to evaluate asymmetry (2D vs. 3D). Results: : Forty-nine articles met the inclusion criteria. The meta-analysis demonstrated a significant improvement in the symmetry of hard and soft tissues. The subgroup analysis indicated that the treatment outcomes showed significant improvement, regardless of the factors related to surgery. Changes in TMD signs and symptoms varied according to the surgical technique used. Quality of life improved in the facial, oral, and social domains. Skeletal relapse was observed during the follow-up. Conclusions: : Our findings support the positive outcomes of orthognathic surgery in the treatment of facial asymmetry in terms of skeletal and soft tissue improvements, stability, relief of TMD symptoms, and enhancement of QoL. However, most of the included studies showed a low certainty of evidence and high heterogeneity.

Inhibited apoptosis of C(2)C(1)2 myoblasts by a Eupatorium chinense var. simplicifolium root extract.

We investigated the effects of a Eupatorium chinense var. simplicifolium (EUC) root extract on muscle disorders and explored the underlying mechanism for oxidative stress-induced C(2)C(12) myoblast damage. An EUC pre-treatment reduced the decreased cell viability after an H2O2 treatment. The heat shock protein (HSP) 70 level increased, and the phosphorylation of Jun amino-terminal kinases (JNKs) decreased in the EUC-pre-treated C(2)C(12) myoblasts. The results of the present study demonstrate the potential benefit of a herbal medicine in treating oxidative stress-related muscle disorders.

Treatment of anterior open bite and multiple missing teeth with lingual fixed appliances, double jaw surgery, and dental implants.

The treatment of adult patients with severe anterior open bite frequently requires orthognathic surgery, especially when the chin is retruded severely. If a patient has multiple missing posterior teeth, it is difficult to control the occlusal plane because it is challenging to obtain anchorage during orthodontic treatment. We report on a 25-year-old woman who had a skeletal Class II malocclusion, severe anterior open bite, vertical maxillary asymmetry, and severe dental caries on her molars. There was no posterior occlusal contact between the maxillary and mandibular molars since 5 of her molars had to be extracted because of severe caries. Lingual fixed appliances and double jaw surgery were performed to treat her skeletal and dental problems, and dental implants helped restore her masticatory function. Pretreatment, posttreatment, and retention photographs demonstrate effective, esthetically pleasing, and stable treatment results.

Autotransplantion of a displaced mandibular second premolar to its normal position.

The patient was a 13-year-old Korean girl who had a displaced mandibular second premolar. She was reluctant to undergo a lengthy orthodontic treatment and opted instead for transplantation of the premolar to its usual site. On the basis of computed tomography, a replica tooth model was manufactured to shorten the extraoral time, and a root canal treatment was performed because root formation was complete. No negative signs or symptoms were found during a 3-year follow up. Autotransplantation for this patient obviated the need for orthodontic traction and prosthetic therapy.

Systematic Review and Meta-analysis: Real-World Accuracy of Children's Developmental Screening Tests.

OBJECTIVE: This review presents a list of developmental screening tests used in clinical settings worldwide and provides a broad estimate of their accuracy (PROSPERO: CRD42021236474). METHOD: Following the PRISMA Diagnostic Test Accuracy (DTA) guidelines, this review involved searching PubMed, PsycINFO, Cochrane, EMBASE, CINAHL, and Google Scholar (for manual searching). Inclusion criteria included studies published in English through 2020 that compared the accuracy of developmental screening tests against developmental diagnostic tests among children under 13 years of age. Six researchers, in pairs, independently selected the studies and extracted the data. A hierarchical model was applied to meta-analyze the diagnostic accuracy of the tests, and meta-regression was used to identify the moderators using R 4.1.3 software. RESULTS: The meta-analysis included 56 studies (17 screening tests and 61 outcomes). The most frequently used screening tests were the Ages and Stages Questionnaire (ASQ), Denver Developmental Screening Test (DDST), and Parent's Evaluation of Developmental Status (PEDS). The pooled sensitivity and specificity were 0.75 (95% CI = 0.69-0.80) and 0.76 (95% CI = 0.71-0.80), and the overall diagnostic accuracy of the total outcomes (area under the curve) was 0.80. High heterogeneity was observed between the included studies with various thresholds of the tests. Participants' developmental concerns at the baseline significantly moderated the accuracy of the screening tests, resulting in double the positive predictive value and prevalence compared to those without the concerns. CONCLUSION: We recommend a standardized process of validation studies for diagnostic accuracy, to ensure the effectiveness of developmental screening tests in clinical settings. STUDY PREREGISTRATION INFORMATION: Accuracy of Developmental Screening Tools among Children in Real World: a Systematic Review and Meta Analysis; https://www.crd.york.ac.uk/; CRD42021236474.

An integrated public health response to an outbreak of Murray Valley encephalitis virus infection during the 2022-2023 mosquito season in Victoria.

Introduction: Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known to cause infrequent yet substantial human outbreaks around the Murray Valley region of south-eastern Australia, resulting in significant mortality. Methods: The public health response to MVEV in Victoria in 2022-2023 included a climate informed pre-season risk assessment, and vector surveillance with mosquito trapping and laboratory testing for MVEV. Human cases were investigated to collect enhanced surveillance data, and human clinical samples were subject to serological and molecular testing algorithms to assess for co-circulating flaviviruses. Equine surveillance was carried out via enhanced investigation of cases of encephalitic illness. Integrated mosquito management and active health promotion were implemented throughout the season and in response to surveillance signals. Findings: Mosquito surveillance included a total of 3,186 individual trapping events between 1 July 2022 and 20 June 2023. MVEV was detected in mosquitoes on 48 occasions. From 2 January 2023 to 23 April 2023, 580 samples (sera and CSF) were tested for flaviviruses. Human surveillance detected 6 confirmed cases of MVEV infection and 2 cases of "flavivirus-unspecified." From 1 September 2022 to 30 May 2023, 88 horses with clinical signs consistent with flavivirus infection were tested, finding one probable and no confirmed cases of MVE. Discussion: The expanded, climate-informed vector surveillance system in Victoria detected MVEV in mosquitoes in advance of human cases, acting as an effective early warning system. This informed a one-health oriented public health response including enhanced human, vector and animal surveillance, integrated mosquito management, and health promotion.