Randomized Trial to Test a Chemo-Mechanical Antiplaque Regimen as Adjunct to Periodontal Therapy.

BACKGROUND: The control of dental biofilm regrowth after nonsurgical periodontal therapy is associated with better clinical outcomes. However, many patients have difficulty achieving optimal plaque control. Subjects with diabetes, in which immune and wound-healing responses are typically impaired, may benefit from intensive antiplaque control regimens after scaling and root planing (SRP). OBJECTIVES: This study aimed to evaluate the effects of an intensive, at-home, chemical, and mechanical antiplaque regimen as an adjunct to SRP for the treatment of moderate to severe periodontitis. A secondary objective was to compare responses in subjects with type 2 diabetes and nondiabetics. METHODS: This was a 6-mo, single-center, parallel-group, randomized trial. The test group received SRP and oral hygiene instructions, and subjects were instructed to use a 0.12% chlorhexidine gluconate mouthrinse twice a day for 3 mo and utilize rubber interproximal bristle cleaners twice a day for 6 mo. The control group received SRP and oral hygiene instructions. The main outcome was change in mean probing depth (PD) from baseline to 6 mo. Secondary outcomes included change in sites with deep PDs, mean clinical attachment level, bleeding on probing, plaque index, hemoglobin A1C, fasting blood glucose, C-reactive protein, and taste assessment. This study was registered at ClinicalTrials.gov as NCT04830969. RESULTS: In total, 114 subjects were randomized to either treatment. Eighty-six subjects completed the trial with no missing visits. Neither an intention-to-treat nor a per-protocol analysis showed statistically significant differences between treatment groups in mean PD at 6 mo. In a subgroup analysis, subjects with diabetes in the test group showed a statistically significant greater reduction in mean PD at 6 mo when compared to subjects with diabetes receiving the control treatment (Δ = 0.15, P = 0.04), while there were no differences within nondiabetics (Δ = 0.02, P = 0.75). CONCLUSION: Outcomes in subjects with diabetes may be improved by chemo-mechanical antiplaque measures after nonsurgical periodontal therapy. KNOWLEDGE TRANSFER STATEMENT: This study suggests diabetic subjects may benefit from an intensive, at-home, chemical, and mechanical antiplaque regimen to improve nonsurgical periodontal therapy outcomes.

Interobserver Reliability on Intravoxel Incoherent Motion Imaging in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Noninvasive perfusion-weighted imaging with short scanning time could be advantageous in order to determine presumed penumbral regions and subsequent treatment strategy for acute ischemic stroke (AIS). Our aim was to evaluate interobserver agreement and the clinical utility of intravoxel incoherent motion MR imaging in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively studied 29 patients with AIS (17 men, 12 women; mean age, 75.2 [SD, 12.0 ] years; median, 77 years). Each patient underwent intravoxel incoherent motion MR imaging using a 1.5T MR imaging scanner. Diffusion-sensitizing gradients were applied sequentially in the x, y, and z directions with 6 different b-values (0, 50, 100, 150, 200, and 1000 seconds/mm2). From the intravoxel incoherent motion MR imaging data, diffusion coefficient, perfusion fraction, and pseudodiffusion coefficient maps were obtained using a 2-step fitting algorithm based on the Levenberg-Marquardt method. The presence of decreases in the intravoxel incoherent motion perfusion fraction and pseudodiffusion coefficient values compared with the contralateral normal-appearing brain was graded on a 2-point scale by 2 independent neuroradiologists. Interobserver agreement on the rating scale was evaluated using the κ statistic. Clinical characteristics of patients with a nondecreased intravoxel incoherent motion perfusion fraction and/or pseudodiffusion coefficient rated by the 2 observers were also assessed. RESULTS: Interobserver agreement was shown for the intravoxel incoherent motion perfusion fraction (κ = 0.854) and pseudodiffusion coefficient (κ = 0.789) maps, which indicated almost perfect and substantial agreement, respectively. Patients with a nondecreased intravoxel incoherent motion perfusion fraction tended to show recanalization of the occluded intracranial arteries more frequently than patients with a decreased intravoxel incoherent motion perfusion fraction. CONCLUSIONS: Intravoxel incoherent motion MR imaging could be performed in < 1 minute in addition to routine DWI. Intravoxel incoherent motion parameters noninvasively provide feasible, qualitative perfusion-related information for assessing patients with acute ischemic stroke.

Effects of antipsychotics on intravenous sedation with midazolam and propofol during dental treatment for patients with intellectual disabilities.

BACKGROUND: Some patients with intellectual disabilities (ID) are prescribed antipsychotic drugs for symptomatic treatment of behavioural disorders. Nevertheless, it can still prove difficult to perform dental treatments safely for some patients with ID. In such cases, treatment under intravenous sedation (IVS) is one option. Sedative, hypnotic and α-blocking effects of antipsychotic drugs may cause adverse events, such as severe hypotension, among patients who take antipsychotic drugs regularly. This study aimed to investigate the effects of oral antipsychotic medication on cardiovascular function during IVS. Accordingly, we compared mean blood pressure (MBP) and heart rate (HR) between patients who regularly take antipsychotic drugs and patients who do not. METHODS: Thirty-seven patients with ID were enrolled in this study. All participants were outpatients of Special Care Dentistry of general hospital and received dental treatment under IVS performed with a combination of midazolam and propofol. Eighteen patients regularly took antipsychotics (medication group), and 19 patients were not currently taking antipsychotics (non-medication group). MBP, HR, dose, and effect-site concentration of intravenous sedative medications were measured at three points: 'before IVS', 'at optimal sedation', and 'during dental treatment'. RESULTS: The magnitude of reduction of MBP was significantly smaller in the medication group than in the non-medication group (P < 0.023). However, there were no differences in MBP, HR, dose, and effect-site concentration of midazolam and propofol between groups at any point. CONCLUSION: These results suggest that antipsychotic medication may not have clinically significant adverse effects on cardiovascular fluctuations during dental treatment under IVS for persons with ID.

Bicarbonate in Arteries Measured Preoperatively for Cadaveric Single-lung Transplantation is Related to Intraoperative Extra-Corporeal Membrane Oxygenation Use: A Retrospective Preliminary Study.

Background: There are no known predictors of extracorporeal membrane oxygenation (ECMO) induction for single lung transplantation. Objective: The purpose of the present study was to clarify the relationship between variables and ECMO requirements in single lung transplantation. Methods: This study included adult patients who underwent cadaveric single lung transplantation between 2010 and 2019. After general anesthesia, the transplanted lungs were ventilated in all cases. The analysis included 38 patients in the ECMO required (RQ) group and 12 patients in the ECMO non-required (FR) group. Comparisons were made between the two groups for data affecting ECMO implementation, and data that were significantly different were subjected to multivariate analysis. Results: Prior to anesthesia, the bicarbonate (HCO3-) value of the FR group was lower than that of the RQ group (24.6±2.7 vs. 29.7±5.3 mmol/L, p=0.005). Multivariate analysis showed that the cut-off bicarbonate value was 29.6. The area under the receiver operating characteristic curve (AUROC) of the model was 0.869 (R2: 0.331), with a sensitivity of 79% and a specificity of 88%. The odds ratio was 1.63 for every unit increase in the bicarbonate value (95%CI: 1.11-2.39, p<0.001). Further, the FR group had higher arterial blood pressure (mean: 79.0±11.5 vs. 68.9±8.3 mmHg, p=0.030), less blood loss (432±385 vs. 1,623±1,997 g, p<0.001), shorter operation time (417±44 vs. 543±111 min, p<0.001), and shorter ICU stay (11±9 vs. 25±38 days, p=0.039). Conclusion: Preoperative evaluation of bicarbonate could predict the need for ECMO for single lung transplantation.

Effects of age at estrogen replacement therapy initiation on trabecular bone score in Japanese adults with Turner syndrome.

The effects of the age at estrogen replacement therapy (ERT) initiation on bone quality in Turner syndrome were evaluated using trabecular bone score. Early puberty ERT positively correlated with increase in bone quality. Early initiation of ERT is necessary for the acquisition of bone quality as well as bone density. INTRODUCTION: Studies have reported associations between bone mineral density and estrogen replacement therapy (ERT) in Turner syndrome (TS) patients; however, few studies exist on the effect on bone quality. The aim of this study was to evaluate the effects of the age at ERT initiation on bone quality of Japanese TS patients, cross-sectionally and longitudinally. METHODS: Cross-sectionally, 95 TS patients were divided into three groups based on their age at initiation of ERT: A (12-14 years, 11 patients), B (15-17 years, 47 patients), and C (over 18 years, 37 patients). To assess bone quality, trabecular bone score (TBS) was used. The effects of age at initiation and duration of ERT on TBS were examined using multiple regression analysis. In the longitudinal study, 48 patients who underwent dual-energy X-ray absorptiometry multiple times were divided into three groups: D (12-14 years, 8 patients), E (15-17 years, 18 patients), and F (over 18 years, 22 patients). Each group was analyzed for the rate of change in TBS per year. RESULTS: Cross-sectionally, the TBS showed significant differences among the three groups (TBS A, 1.302; B, 1.299; C, 1.245) (p = 0.013); group C was significantly lower than B (p = 0.014); bone quality was degraded. Multiple regression analysis revealed that age at ERT initiation significantly affected the increase in TBS (p = 0.002). Longitudinally, the rate of change of TBS was not significantly different in the three groups (p = 0.73). CONCLUSION: Early initiation of ERT may have positive effects on bone quality in TS. Large prospective studies will be needed.

Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Fermionic order by disorder in a van der Waals antiferromagnet.

CeTe3 is a unique platform to investigate the itinerant magnetism in a van der Waals (vdW) coupled metal. Despite chemical pressure being a promising route to boost quantum fluctuation in this system, a systematic study on the chemical pressure effect on Ce3+(4f1) states is absent. Here, we report on the successful growth of a series of Se doped single crystals of CeTe3. We found a fluctuation driven exotic magnetic rotation from the usual easy-axis ordering to an unusual hard-axis ordering. Unlike in localized magnetic systems, near-critical magnetism can increase itinerancy hand-in-hand with enhancing fluctuation of magnetism. Thus, seemingly unstable hard-axis ordering emerges through kinetic energy gain, with the self-consistent observation of enhanced magnetic fluctuation (disorder). As far as we recognize, this order-by-disorder process in fermionic system is observed for the first time within vdW materials. Our finding opens a unique experimental platform for direct visualization of the rich quasiparticle Fermi surface deformation associated with the Fermionic order-by-disorder process. Also, the search for emergent exotic phases by further tuning of quantum fluctuation is suggested as a promising future challenge.

Creatinine to Cystatin C Ratio as a Marker of Bone Property in Older Adults: The J-SHIPP Study.

OBJECTIVES: To clarify whether serum creatinine to cystatin C ratio (CCR), a marker of muscle mass and muscle function may be used as a simple marker of bone property. DESIGN: A cross-sectional analysis. SETTING: A general population-based observation study. PARTICIPANTS: 1,606 middle-aged to elderly (≥50 years, mean age: 66.9 ± 7.5 years old) men (n = 642) and post-menopausal women (n = 964). MEASUREMENT: Speed of sound (SOS) at the calcaneal bone was used as a surrogate marker of bone mineral density. The cross-sectional area of the muscle at the mid-thigh was measured using computed tomography. RESULTS: There was significant linear correlation between the quartiles of CCR and SOS (Q1: 1,495 ± 25, Q2: 1,499 ± 24, Q3: 1,507 ± 26, Q4: 1,511 ± 25 m/sec; P < 0.001) even in a sex-separated analysis. This association was independent of major covariates (Q1: ß = -0.126, P < 0.001; Q2: ß = -0.096, P = 0.001; Q3: ß = -0.022; P = 0.412, Q4: reference) and the mid-thigh muscle mass, while creatinine alone or eGFR did not show clear association with SOS. CONCLUSION: The CCR may be used as a simple marker of bone property independently of muscle mass in a general population with preserved renal function.

Development and validation of a model to predict the need for emergency front-of-neck airway procedures in trauma patients.

The present study aimed to develop and validate a model for predicting the need for emergency front-of neck airway (eFONA) procedures among trauma patients. This was a multicentre retrospective cohort study using data from the Japan Trauma Data Bank between January 2004 and December 2017. Only adult trauma patients were included. The cohort was divided into development and validation cohorts. A simple scoring system was developed to predict the necessity for emergency front-of neck airway procedures in the development cohort using a logistic regression model. The external validity and diagnostic ability of the scoring system was assessed in the validation cohort. In total, 198,182 out of 294,274 patients were included; emergency front-of-neck airway occurred in 467 patients (0.24%) they were divided into development (n = 100,120 with 0.22% undergoing emergency front-of neck airway) and validation (n = 98,062 with 0.25% undergoing emergency front-of neck airway) cohorts. The 'eFONA' prediction scoring system was developed in the development cohort, with a score of +1 for each of the following: Eye opening (no eye opening in response to any stimuli); Fall from height or motor bike; Oral-maxillofacial injury; Neck tracheal injury; and Airway management by paramedics. In the validation cohort, the C-statistic of the scoring system was 0.820. Setting the cut-off value at one for rule-out, the sensitivity and negative likelihood ratios were 0.86 and 0.22, respectively. Setting the cut-off value at two for rule-in, the specificity and positive likelihood ratios were 0.91 and 6.6, respectively. The present scoring system may assist in predicting the need for emergency front-of neck airway procedures among the general trauma population.

Safety of tooth extraction in patients receiving direct oral anticoagulant treatment versus warfarin: a prospective observation study.

The aim of this study was to compare the safety of tooth extraction in patients receiving direct oral anticoagulants (DOACs) or warfarin without cessation of their antithrombotic treatment. This prospective observational study included 367 patients undergoing tooth extraction (119 receiving DOACs and 248 receiving warfarin). All extractions in DOAC patients were performed 6-7h after taking DOACs in consideration of the half-life in blood under continued antithrombotic treatment. To examine the potential postoperative bleeding risk related to the time of extraction and the drug concentration of blood, activated partial thromboplastin time (APTT) in dabigatran and prothrombin time (PT) in rivaroxaban were measured three times after administration. A total of 390 tooth extractions were performed: 128 in the DOAC patients and 262 in warfarin patients. Postoperative bleeding occurred in four extractions (3.1%) in the DOAC group and in 23 (8.8%) in the warfarin group. There was no statistically significant difference between the two groups (odds ratio: 2.362, 95% confidence interval (CI) 0.819-6.815, p=0.112). APTT and PT prolongation in almost all cases decreased with time after taking the medicine. Our findings suggest that interruption of DOAC therapy is not necessary for tooth extraction if the procedure is performed at least 6h after the last dose.

Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)-mediated hyaluronan degradation and skin wrinkling.

OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBID-mediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecular-weight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. CONCLUSION: Sanguisorba officinalis root extract showed an anti-HYBID-mediated HA degradation activity and anti-wrinkle activity on human facial skin, which is accompanied by the improvement in elasticity. Our study provides the possibility of a new strategy to inhibit HYBID-mediated HA degradation for anti-wrinkle care.

OBJECTIFS: l'acide hyaluronique (AH), un composant important de la matrice extracellulaire de la peau, assure de nombreuses activités biologiques, telles que l'hydratation qui contribue à la fermeté et l'élasticité de la peau. Nous avons rapporté que la réduction d'AH dans le derme papillaire et une surexpression de la protéine de liaison de l'AH impliquée dans la dépolymérisation de l'AH (HYBID, alias KIAA1199 ou CEMIP), une molécule clé de la dégradation de l'AH des fibroblastes cutanés, sont impliquées dans la formation des rides au niveau de la peau du visage chez les femmes d'origine japonaise et caucasienne. Cependant, peu ou aucune information n'est disponible concernant les substances qui inhibent la dégradation de l'AH provoquée par la protéine HYBID. MÉTHODES: l'inhibition de l'extrait de racine de la pimprenelle (Sanguisorba officinalis) et du ziyuglycoside I, l'un des composants de l'extrait de racine de Sanguisorba officinalis, sur la dégradation de l'AH provoquée par la protéine HYBID a été évaluée à l'aide d'une chromatographie par exclusion stérique de l'AH dépolymérisé par des transfectants stables de la protéine HYBID dans les cellules HEK293 (cellules HYBID/HEK293) ou les fibroblastes cutanés humains normaux (lignée cellulaire Detroit 551 et cellules des fibroblastes du derme humain chez l'adulte). L'expression de l'ARNm et de la protéine HYBID a été examinée par PCR quantitative en temps réel et par immuno-empreinte des fibroblastes cutanés traités avec de l'extrait de racine de Sanguisorba officinalis, et l'attribution des tailles des nouveaux échantillons produits de l'AH a été évaluée par préparation d'AH radiomarqué métaboliquement. Une étude en double aveugle, randomisée et contrôlée par placebo a été menée auprès des 21 femmes japonaises en bonne santé, qui ont été traitées localement avec la formulation élaborée à partir d'extraits de racine de Sanguisorba officinalis ou un placebo, sur chaque côté du visage, notamment sur la zone à pattes d'oie. RÉSULTATS: l'extrait de racine de Sanguisorba officinalis a permis d'arrêter la dégradation de l'AH provoquée par la protéine HYBID par les cellules HYBID/HEK293, mais ce n'était pas le cas du ziyuglycoside I. L'extrait de racine de Sanguisorba officinalis a également inhibé la dégradation de l'AH provoquée par la protéine HYBID des fibroblastes cutanés en diminuant l'expression de l'ARNm et des protéines HYBID. Bien que les fibroblastes cutanés témoins non traités aient produit de l'AH polydispersé, les cellules traitées aux extraits de racine de Sanguisorba officinalis ont produit uniquement de l'AH de haut poids moléculaire. Le traitement par lotion formulée à partir d'extraits de racine de Sanguisorba officinalis a amélioré de manière significative l'élasticité de la peau et réduit les scores de vieillissement du coin extérieur de la peau autour des yeux, par rapport à la formulation placebo. CONCLUSION: l'extrait de racine de Sanguisorba officinalis a démontré une action anti-dégradation de l'AH provoquée par la protéine HYBID et une activité antirides au niveau de la peau du visage humain, s'accompagnant d'une amélioration de l'élasticité. Notre étude fournit la possibilité d'une nouvelle stratégie pour inhiber la dégradation de l'AH provoquée par la protéine HYBID dans le cadre des soins antirides.

Management of De Novo Mycobacterial Infection After Lung Transplantation Without Rifampicin: Case Series of a Single Institution.

BACKGROUND AND OBJECTIVES: To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. METHODS: To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. RESULTS: Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. CONCLUSIONS: We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

Sustained-Release Tacrolimus Stabilizes Decline of Forced Expiratory Volume in 1 Second Through Decreasing Fluctuation of Its Trough Blood Level.

BACKGROUND: Calcineurin inhibitors are a commonly used immunosuppressive drug and over 80% of lung transplant (LTx) recipients use tacrolimus. Sustained-release tacrolimus (SRT) was developed as a once-daily formulation, resulting in slower release and reduction in peak concentration compared with twice-daily immediate-release tacrolimus (IRT). Previous reports indicate that SRT may carry fewer side effects than IRT; however, the impact of SRT in bronchiolitis obliterans syndrome (BOS) after LTx is unclear. OBJECTIVE: Our study objective was to evaluate the effect of SRT in BOS after LTx. MATERIALS AND METHODS: We investigated the effect of SRT for BOS among 75 LTx recipients who were alive in 2017 in our LTx program. All analyses were carried out using student t test or F test. RESULTS: Thirty-five recipients took IRT, 32 recipients used SRT, 7 recipients used cyclosporine, and 1 patient who received bone marrow and a lung graft from the same donor did not use a calcineurin inhibitor. The most frequent reason for conversion of IRT to SRT was kidney dysfunction, followed by other IRT complications. Five recipients underwent conversion of IRT to SRT because of decline of forced expiratory volume in 1 second (FEV1) with fluctuation of the tacrolimus trough level. After induction of SRT, the fluctuation of the tacrolimus trough level was significantly reduced in 4 of 5 patients (P < .05). Before drug form conversion, the FEV1 in these 5 patients was significantly decreased; however, this exacerbation of FEV1 was attenuated after SRT induction (P < .05). CONCLUSION: SRT appeared to stabilize decline of FEV1 in patients with BOS possibly due to reducing the fluctuation of tacrolimus trough blood concentration.

Correction: Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Owing to the insufficient specificity of the anti-myeloproliferative leukemia protein (MPL) antibody in the original version of this Article, Figure 6 and parts of Figures 2a, 4e, and 5a do not represent the correct information. The corrected version of Figure 6 is in this correction and those of Figures 2a, 4e, and 5a are shown in the supplemental information.

Auraptene in the Peels of Citrus Kawachiensis (Kawachibankan) Contributes to the Preservation of Cognitive Function: A Randomized, Placebo-Controlled, Double-Blind Study in Healthy Volunteers.

OBJECTIVES: Dementia, which is characterized by a progressive decline in cognitive function, is a major concern in aging societies. Although a number of treatments have been approved, an effective therapy to prevent the disorder is lacking. A supplement that improves cognitive function would benefit patients. The aim of this study was to assess whether auraptene, a citrus coumarin, has a protective effect on cognitive decline. DESIGN: A randomized, placebo-controlled, double-blind study SETTING: Outpatient medical check-up program for cognitive disorders PARTICIPANTS: 84 adult volunteers (they are cognitively normal) met inclusion and exclusion criteria to participate. INTERVENTION: 42 participants received auraptene enriched (containing 6.0 mg/day of auraptene) test juice, and another participants received placebo juice. MEASUREMENTS: 1) Mild Cognitive Impairment (MCI) Screen using the 10-word immediate recall test. 2) The Mini-Mental State Examination (MMSE). Cognitive assessment ware carried out baseline and at 24 weeks. RESULTS: Auraptene enriched test juice did not improve cognitive function after 24 weeks compared with baseline data. However, there was a significant difference in the percentage change in cognitive function between the test and placebo orange juice groups (6.3 ± 18.9 vs. -2.4 ± 14.8, P < 0.05). Multiple regression analysis demonstrated a significant independent relationship between the percentage change in the 10-word immediate recall test score and test juice consumption including baseline 10-word immediate recall test score in all subjects. CONCLUSION: This is the first study to assess the effectiveness of auraptene in the prevention of cognitive decline. Our results suggest that auraptene is a safe supplement for the prevention of cognitive decline.

A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities.

Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules µm-2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules µm-2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1.

Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women.

BACKGROUND: Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women. METHODS: The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID. RESULTS: Among the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID-immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high-HYBID-expression group compared with the low-HYBID-expression group, respectively. CONCLUSION: Our data suggest that like Japanese women, HYBID-mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.

Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury.

BACKGROUND: Hydrogen (H2) and carbon monoxide (CO) gas are both reported to reduce reactive oxygen species and alleviate tissue ischemia-reperfusion (I-R) injury. The present study was conducted to evaluate the effects of a mixture of H2 gas and CO gas (dual gas) in comparison with hydrogen gas (H2: 2%) alone on I-R renal injury (composition of dual gas; N2: 77.8%; O2: 20.9%; H2: 1.30%; CO: 250 parts per million). METHODS: Adult male Sprague-Dawley rats (body weight 250-280 g) were divided into 5 groups: (1) sham operation control, (2) dual gas inhalation (dual treatment) without I-R treatment, (3) I-R renal injury, (4) H2 gas alone inhalation (H2 treatment) with I-R renal injury, and (5) dual treatment with I-R renal injury. I-R renal injury was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, and then contralateral nephrectomy was performed 2 weeks later. Renal function was markedly decreased at 24 hours after reperfusion, and thereafter the effects of dual gas were assessed by histologic examination and determination of the superoxide radical, together with functional and molecular analyses. RESULTS: Pathologic examination of the kidney of I-R rats revealed severe renal damage. Importantly, cytoprotective effects of the dual treatment in comparison with H2 treatment and I-R renal injury were observed in terms of superoxide radical scavenging activity and histochemical features. Rats given dual treatment and I-R renal injury showed significant decreases in blood urea nitrogen. Increased expression of several inflammatory cytokines (tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, nuclear factor-κB, hypoxia inducible factor-1α, and heme oxygenase-1) was attenuated by the dual treatment. CONCLUSIONS: Dual gas inhalation decreases oxidative stress and markedly improves I-R-induced renal injury.