Loss of pex5 sensitizes zebrafish to fasting due to deregulated mitochondria, mTOR, and autophagy.

Animal models have been utilized to understand the pathogenesis of Zellweger spectrum disorders (ZSDs); however, the link between clinical manifestations and molecular pathways has not yet been clearly established. We generated peroxin 5 homozygous mutant zebrafish (pex5-/-) to gain insight into the molecular pathogenesis of peroxisome dysfunction. pex5-/- display hallmarks of ZSD in humans and die within one month after birth. Fasting rapidly depletes lipids and glycogen in pex5-/- livers and expedites their mortality. Mechanistically, deregulated mitochondria and mechanistic target of rapamycin (mTOR) signaling act together to induce metabolic alterations that deplete hepatic nutrients and accumulate damaged mitochondria. Accordingly, chemical interventions blocking either the mitochondrial function or mTOR complex 1 (mTORC1) or a combination of both improve the metabolic imbalance shown in the fasted pex5-/- livers and extend the survival of animals. In addition, the suppression of oxidative stress by N-acetyl L-cysteine (NAC) treatment rescued the apoptotic cell death and early mortality observed in pex5-/-. Furthermore, an autophagy activator effectively ameliorated the early mortality of fasted pex5-/-. These results suggest that fasting may be detrimental to patients with peroxisome dysfunction, and that modulating the mitochondria, mTORC1, autophagy activities, or oxidative stress may provide a therapeutic option to alleviate the symptoms of peroxisomal diseases associated with metabolic dysfunction.

2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Comparison of the skeletodental effects of miniscrew-anchored and tooth-anchored facemask treatment in growing patients with skeletal class III malocclusions.

INTRODUCTION: This retrospective study aimed to evaluate the skeletal and dental effects of the miniscrew-anchored facemask in skeletal Class III growing patients and compare them with those of conventional tooth-anchored facemasks. METHODS: Retrospectively a total of 50 patients with skeletal Class III (mean ANB: -1.12°) were investigated and divided into two groups according to the treatment modality. Twenty-five patients were treated using the conventional tooth-anchored facemask (T group: mean age 9.3 ± 1.1 years, mean ANB: -0.93°) whereas the other 25 were treated using a miniscrew-anchored facemask (M group: mean age 9.7 ± 1.3 years. mean ANB: -1.61°). Two miniscrews were placed on the palate for bone anchorage. In both T and M groups, facemasks applied a force of 20-30° down on the occlusal plane, and the force increased from 200 g to 300-350 g per side throughout the treatments. The patients were instructed to wear facemasks for at least 14 h per day. A total of 16 angular and 11 linear cephalometric measurements were analysed to determine the skeletal and dental changes before and after facemask treatment. A paired t-test was used to verify the effects before and after treatment in each group. RESULTS: All miniscrews were well maintained during treatment. The values of SNA, SN-ANS, ANB and A to N-Perp, which indicate anterior protraction of the maxilla, were significantly higher in the M group compared with the T group (P < .05). Proclination of the maxillary incisors, extrusion and mesialization of the maxillary molars were significantly greater in the T group (P < .05). CONCLUSIONS: Miniscrew-anchored facemask treatment increased the amount of maxillary protraction and reduced the dental side effects compared with conventional tooth-anchored facemask treatment in growing patients with skeletal Class III malocclusion.

Maxillary basal arch forms in operated adult patients with cleft lip and palate using root apices: A pilot study.

OBJECTIVES: The purpose was to identify the maxillary basal arch forms utilizing the root apices and compare the maxillary basal arch form of groups with cleft lip and palate (CLP) and normal group. MATERIALS AND METHODS: This study included 30 patients (21.8 ± 3.5 years old) with unilateral CLP (ULCP group) and 30 patients (20.9 ± 2.2 years old) with bilateral CLP (BCLP group). The normal group consisted of 30 non-cleft patients (21.2 ± 2.3 years old) with normal occlusion. Three-dimensional (3D) Cartesian coordinates of the root apices of each tooth were determined using cone-beam computed tomography. The 3D coordinates were projected onto the palatal plane to create the 2D coordinates. Thereafter, the basal arch forms were constructed by the Procrustes superimposition. Finally, For the basal arch form comparisons among groups, the inter-root widths were measured. RESULTS: Both CLP groups had a narrower inter-root width than the normal group. The BCLP group had significantly narrower premolar and molar widths than the UCLP group (P < .05). Especially, the inter-first molar width of the UCLP and BCLP groups was 3.7 ± 0.7 (P < .001) and 6.6 ± 0.8 (P < .001) mm smaller than that of the normal group, respectively. CONCLUSIONS: We used the root apices to identify the basal arch forms. The basal arch form of patients with CLP was narrower than that of the normal group. The basal arch form of patients with BCLP was narrower than that of patients with UCLP. Our findings may help clinicians better comprehend basal arch forms in patients with CLP and transverse discrepancies.

Inhibition of Soluble Epoxide Hydrolase Activity by Components of Glycyrrhiza uralensis.

Soluble epoxide hydrolase (sEH) is a target enzyme for the treatment of inflammation and cardiovascular disease. A Glycyrrhiza uralensis extract exhibited ~50% inhibition of sEH at 100 µg/mL, and column chromatography yielded compounds 1-11. Inhibitors 1, 4-6, 9, and 11 were non-competitive; inhibitors 3, 7, 8, and 10 were competitive. The IC50 value of inhibitor 10 was below 2 µM. Molecular simulation was used to identify the sEH binding site. Glycycoumarin (10) requires further evaluation in cells and animals.

Hispidulin Inhibits the Vascular Inflammation Triggered by Porphyromonas gingivalis Lipopolysaccharide.

Hispidulin is a natural bioactive flavonoid that has been studied for its potential therapeutic properties, including its anti-inflammatory, antioxidant, and neuroprotective effects. The aim of this study was to explore whether hispidulin could inhibit the endothelial inflammation triggered by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The adhesion of monocytes to the vascular endothelium was evaluated through in vitro and ex vivo monocyte adhesion assays. We analyzed the migration of monocytes across the endothelial layer using a transmigration assay. The results showed that treatment with hispidulin decreased the P. gingivalis LPS-induced adhesion of monocytes to endothelial cells and their migration by suppressing the P. gingivalis LPS-triggered expression of intercellular adhesion molecule-1 (ICAM-1) through downregulating nuclear factor-қB (NF-қB). In addition, hispidulin inhibited P. gingivalis LPS-induced mitogen-activated protein kinases (MAPKs) and AKT in endothelial cells. Altogether, the results indicate that hispidulin suppresses the vascular inflammation induced by P. gingivalis LPS. Mechanistically, it prevents the adhesion of monocytes to the vascular endothelium and migration and inhibits NF-қB, MAPKs, and AKT signaling in endothelial cells.

Comparison of root apex's position between unilateral and bilateral palatally impacted canines: A pilot study.

INTRODUCTION: The purpose was to determine whether the location of the root apices of unilateral palatally impacted canines differs from that of bilateral palatally impacted canines using cone-beam computed tomography. METHODS: The subjects were divided into 3 groups: a bilateral palatally impacted canine group (BPG; n = 28), a unilateral palatally impacted canine group (UPG; n = 28), and a control group (CG; n = 28) that included contralateral normally erupted canines in the UPG. After selecting the root apex in the onDemand3D program, 3-dimensional coordinates were extracted. These 3-dimensional coordinates were converted using the MATLAB program to 2-dimensional coordinates via projection on the palatal plane. Procrustes analysis was used to superimpose these 2-dimensional coordinates. The x- and y-coordinates of the root apices were used to measure the distance between the origin and root apex. RESULTS: The distance between the root apex of the canine and the origin was 17.43 ± 1.78 mm in BPG, 17.96 ± 1.87 mm in UPG, and 13.96 ± 0.95 mm in CG. There was no statistically significant difference between UPG and BPG. However, there was a statistically significant difference between the CG and impacted groups (UPG and BPG). The same results were found for the x- and y-coordinates. CONCLUSIONS: The location of the root apices of unilateral palatally impacted canines is similar to that of bilateral palatally impacted. The location of root apices of palatally impacted canines differs from that of normally erupted canines.

Ambient Humidity-Induced Phase Separation for Fiber Morphology Engineering toward Piezoelectric Self-Powered Sensing.

Electrospun polymeric piezoelectric fibers have a considerable potential for shape-adaptive mechanical energy harvesting and self-powered sensing in biomedical, wearable, and industrial applications. However, their unsatisfactory piezoelectric performance remains an issue to be overcome. While strategies for increasing the crystallinity of electroactive ß phases have thus far been the major focus in realizing enhanced piezoelectric performance, tailoring the fiber morphology can also be a promising alternative. Herein, a design strategy that combines the nonsolvent-induced phase separation of a polymer/solvent/water ternary system and electrospinning for fabricating piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE) fibers with surface porosity under ambient humidity is presented. Notably, electrospun P(VDF-TrFE) fibers with higher surface porosity outperform their smooth-surfaced counterparts with a higher ß phase content in terms of output voltage and power generation. Theoretical and numerical studies also underpin the contribution of the structural porosity to the harvesting performance, which is attributable to local stress concentration and reduced dielectric constant due to the air in the pores. This porous fiber design can broaden the application prospects of shape-adaptive energy harvesting and self-powered sensing based on piezoelectric polymer fibers with enhanced voltage and power performance, as successfully demonstrated in this work by developing a communication system based on self-powered motion sensing.

Diagnostic and prognostic values of 2-[18F]FDG PET/CT in resectable thymic epithelial tumour.

OBJECTIVES: We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). METHODS: One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. RESULTS: The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. CONCLUSION: SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. KEY POINTS: • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.

Surgical Outcomes of Non-Small Cell Lung Cancer in Single-Zone N2 in the Aortopulmonary Zone.

OBJECTIVES: We evaluate the surgical outcome of clinically single-zone N2 lung cancer limited to aortopulmonary zone (AP zone; lymph node #5 or #6). PATIENTS AND METHODS: We performed a retrospective analysis of patients with non-small cell lung cancer, in whom mediastinal lymph node metastasis was confined to AP zone. RESULTS: A total of 84 patients who underwent upfront surgery were included in final analysis. Among these patients, pathological nodal outcomes were pN0-1 in 27 patients (32.1%), pN2a in 31 (36.9%), and pN2b in 26 (31.0%). In multivariate analysis, adenocarcinoma (p = 0.005) and staging workup without endobronchial ultrasound-transbronchial needle aspiration (p = 0.002) were independent risk factors for unexpected pN2b. The 5-year overall survival (OS) and disease-free survival (DFS) were 55.9 and 54.4%, respectively. There was no survival difference among patients with pN0-1, pN2a, and pN2b (p = 0.717). In survival analysis, there were no significant risk factors for OS. However, female sex and the ratio of positive lymph nodes to removed lymph nodes were significant risk factors for DFS in multivariate analysis (p = 0.032 and p = 0.009). CONCLUSION: In this study, cN2a in the AP zone with current diagnostic tool exhibited a relatively high false-positive rate (cN2/pN0-1; 32.1%). However, despite the possibility of pN2b, there were no significant differences in survival outcome according to the pathologic nodal stage.

Effect of Observer's Sex and Chin Prominences on the Perception of the Lower Lip-Chin Prominence Angle.

ABSTRACT: This study aimed to identify the preferred range of lower lip-chin prominence angles in the Korean population and evaluate the effect of the individual lower lip-chin prominence angle on perceptions of esthetic chin profile.Chin prominence silhouettes were used to assess the lower lip-chin prominence preference. The observers randomly categorized each image as (1) normal, (2) slightly abnormal but not requiring surgical correction, and (3) abnormal and requiring surgery. Individual lower-chin prominence angles of all observers were analyzed using standardized clinical photographs.The normal range of lower lip-chin prominence angle is 0° to 25°; socially acceptable range is 0° to -10°, 25° to 40°; range needing surgery is -10° to -30° and 40° to 45°. Women are more tolerant to chin protrusion. A protrusive chin is more acceptable in observers with retrusive chin profile.Skeletal Class II profile is more acceptable than skeletal Class III in the Korean population. The individual lower-chin prominence angle could affect perception of desired surgery. These findings indicate that patient-specific treatment planning is important in achieving satisfaction in chin surgery.

Methods in Genetic Analysis for Evaluation Mandibular Shape and Size Variations in Human Mandible.

ABSTRACT: The human mandible has been investigated from both clinical and evolutionary perspectives. Recent advances in genome science have identified the genetic regulation of human mandibular shape and size. Identification of genes that regulate mandibular shape and size would not only enhance our understanding of the mechanisms of mandibular growth and development but also help define a strategy to prevent mandibular dysplasia. This review provides a comprehensive summary of why and how the mandible was evaluated in the human mandible genome study. The variation in human mandibular shape and size has been progressively clarified, not only by focusing on the mandible alone but also by using extremely diverse approaches. The methods of data acquisition for evaluating human mandibular shape and size variation are well established. Furthermore, this review explains how to proceed with future research.

Morphologic changes of the incisive canal and its proximity to maxillary incisor roots after anterior tooth movement.

INTRODUCTION: The objectives were to evaluate the morphologic changes of the incisive canal (IC) and the influence of IC proximity to apical root resorption of maxillary central incisors after anterior tooth movement. METHODS: Pretreatment and posttreatment cone-beam computed tomography images of adults (aged 18-47 years) were retrospectively evaluated. Subjects were divided into control group with minimal incisor movement (n = 32; maxillary incisor tip movement <2 mm) and maximum retraction group (n = 35; maxillary incisor tip movement >4 mm). The shape, direction, morphologic changes of the IC, the proximity of the central incisor root to IC, and the amount of apical root resorption associated with the proximity after orthodontic treatment were compared. RESULTS: Changes in the shape of the IC were not observed in both control and retraction groups. However, 11.4% (4 of 35 subjects) in the retraction group indicated changes in the direction of the IC from slanted-straight to slanted-curved type after the direction of anterior retraction. The thickness of the cortical bone surrounding the IC and the distance between the incisor root and IC significantly decreased after orthodontic treatment in both groups (P <0.05). However, these changes were significantly greater in the retraction group than in control (P <0.0001). Contact or invasion of the incisor root to the IC was more prominent in the retraction group (42.8%-54.3%) than the control (10.9%-12.5%) (P <0.0001). The amount of root resorption indicated a tendency to increase in the order of separation, approximation, contact, and invasion in relation to IC. CONCLUSIONS: Although remodeling of IC was evident in some patients, contact or invasion of the maxillary central incisor roots to IC was fairly high after maximum anterior retraction.

Methodology for Mapping the Residual Stress Field in Serviced Rails Using LCR Waves.

Non-destructive stress measurement by ultrasonic testing is based on calculating the acoustoelastic modulus obtained from the relationship between material stress and sound wave velocity. A critically refracted longitudinal (LCR) wave, which is a bulk longitudinal wave penetrating below and parallel to the surface below an effective depth, is most suitable for ultrasonic stress measurement tests because it exhibits a relatively large change in travel time in response to a change in stress. In particular, the residual stress distribution through the thickness of the subject can be calculated if transducers of different frequencies are applied because of the characteristic of propagation to different depths of penetration depending on the frequency. The main purpose of this study was to visualize the internal or residual stress distribution through the thickness of rails using LCR waves. To this end, LCR probes with different center frequencies were designed and manufactured, and the residual stress values ​​of an unused railroad rail and two used railroad rails operated under different conditions were calculated. This was done using the ultrasonic signals received from each probe, of which the distributions were mapped. Through these mapping results, different residual stress values could be calculated according to the depth. The differences in residual stress generation and distribution according to the conditions surrounding the contact between train wheels and rails, and their characteristics, were visualized and analyzed. As a result, it could be concluded that the non-destructive evaluation technique using LCR waves could detect differences in the residual stress of a rail, and thus can be used to measure the residual stress of the rail accurately.

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in newly diagnosed multiple myeloma: a systematic review and meta-analysis.

OBJECTIVES: We performed a systematic review and meta-analysis on the prognostic values of 18F-FDG PET/CT in patients with newly diagnosed multiple myeloma (MM). METHODS: PubMed and Embase were searched until July 10, 2019, for studies that reported the prognostic significance of 18F-FDG PET in patients with newly diagnosed MM, with overall (OS) and progression-free survival (PFS) included as outcomes. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. RESULTS: Fifteen studies (1670 patients) were included for qualitative synthesis. Among multiple PET parameters, the presence of extramedullary disease (EMD), more than three focal lesions (FLs), and high FDG uptake were widely evaluated and significantly associated with shorter OS and PFS in most of the included studies. Among 11 studies included in quantitative synthesis, the overall HRs of EMD, more than three FLs, and high FDG uptake on PFS were 2.12 (95% CI, 1.52-2.96), 2.38 (95% CI, 1.84-3.07), and 2.02 (95% CI, 1.51-2.68), respectively. The pooled HRs of those three parameters on OS were 2.37 (95% CI, 1.77-3.16), 3.29 (95% CI, 2.38-4.56), and 2.28 (95% CI, 1.67-3.13). No statistical differences were found across parameters for either PFS (p = 0.6822) or OS (p = 0.2147). CONCLUSIONS: Pretreatment 18F-FDG PET/CT is a significant predictor for disease progression and survival in patients with MM. It may be a useful prognostic biomarker capable of accurate risk stratification and application in clinical decision-making for newly diagnosed MM. KEY POINTS: • There remain unmet clinical needs for reliable prognostic biomarkers in patients with newly diagnosed multiple myeloma. • This meta-analysis shows that the presence of extramedullary disease, more than three focal lesions, and high FDG uptake from baseline 18F-FDG PET are significant prognostic factors. • These imaging biomarkers might help the accurate stratification of patient prognosis which is required for choosing an appropriate therapeutic strategy in clinical practice.

Optimizing antiemetic treatment for chemotherapy-induced nausea and vomiting in Japan: Update summary of the 2015 Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis.

Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0).

Assessment of Inflammation in Pulmonary Artery Hypertension by 68Ga-Mannosylated Human Serum Albumin.

Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.

Roles of autophagy in orthodontic tooth movement.

INTRODUCTION: Orthodontic tooth movement (OTM) relies on efficient remodeling of alveolar bone. While a well-controlled inflammatory response is essential during OTM, the mechanism regulating inflammation is unknown. Autophagy, a conserved catabolic pathway, has been shown to protect cells from excess inflammation in disease states. We hypothesize that autophagy plays a role in regulating inflammation during OTM. METHODS: A split-mouth design was used to force load molars in adult male mice, carrying a GFP-LC3 transgene for in vivo detection of autophagy. Confocal microscopy, Western blot, and quantitative polymerase chain reaction analyses were used to evaluate autophagy activation in tissues of loaded and control molars at time points after force application. Rapamycin, a Food and Drug Administration-approved immunosuppressant, was injected to evaluate induction of autophagy. RESULTS: Autophagy activity increases shortly after loading, primarily on the compression side of the tooth, and is closely associated with inflammatory cytokine expression and osteoclast recruitment. Daily administration of rapamycin, an autophagy activator, led to reduced tooth movement and osteoclast recruitment, suggesting that autophagy downregulates the inflammatory response and bone turnover during OTM. CONCLUSIONS: This is the first demonstration that shows that autophagy is induced by orthodontic loading and plays a role during OTM, likely via negative regulation of inflammatory response and bone turnover. Exploring roles of autophagy in OTM holds great promise, as aberrant autophagy is associated with periodontal disease and its related systemic inflammatory disorders.