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Background Intrahepatic cholestasis of pregnancy (ICP) is a complex liver disease with varying incidence worldwide. We compared ICP incidence and pregnancy outcomes with outcomes for normal pregnant controls. Methods We conducted a retrospective data analysis of perinatal registry data for the years 2011 and 2017 to compare the following outcome measures: stillbirths, labour induction, gestational diabetes, pre-eclampsia, antepartum haemorrhage, postpartum haemorrhage, preterm births, low Apgar score, acute neonatal respiratory morbidity, meconium aspiration and in-hospital neonatal death. Results The incidence of ICP was 8 per 1000 births from a total 31,493 singleton births with more cases in 2017 than in 2011. Women with ICP were almost six times more likely to have labour induced including significantly more moderate preterm births (defined as between 32 weeks and 36 weeks and 6 days of gestation)) seen more in 2011 than in 2017. Conclusion Women with ICP showed higher incidence of moderate preterm birth and induced labour but favourable maternal and neonatal outcomes.

This study aimed to clarify the effects of gardening on hemodynamic response, rating of perceived exertion (RPE) during exercise, and body weight in patients in whom phase 2 cardiac rehabilitation (CR) was interrupted due to the Coronavirus disease 2019 (COVID-19) pandemic. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. Patients under the age of 65 were excluded. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the gardener group and the non-gardener group. Forty-one patients were enrolled in the final analysis. After CR interruption, the gardener group did not show any significant difference in all items, whereas the non-gardener group experienced significant increase in HR (Peak) (p = 0.004) and worsening of the Borg scale scores for both dyspnea and lower extremity fatigue (p = 0.039 and p = 0.009, respectively). Older phase 2 CR patients engaged in gardening did not show any deterioration in hemodynamic response or RPE during exercise, despite CR interruption and refraining from going outside. Gardening may be recommended as one of the activities that can maintain or improve physical function in older phase 2 CR patients during the COVID-19 pandemic.

Objective Although colorectal polyps (CPs) can be observed with colon capsule endoscopy (CCE), it is difficult to determine the type of polyp using CCE. The objective of this study was to differentiate adenomatous polyps (APs) from hyperplastic polyps (HPs) with CCE. Methods In this single-center retrospective study, an analysis was conducted on the same CPs with both CCE and colonoscopy (CS) and histopathologically diagnosed as AP or HP. The color difference (ΔE) between the polyp surface and the surrounding mucosa was calculated using the CIE1976 L*a*b* color space method on white light (WL), flexible spectral imaging color enhancement (FICE), and blue mode (BM) CP images. We investigated the ability of the ratio of the color differences (ΔE') to differentiate between APs and HPs. Results The size of all 51 polyps (34 APs, 17 HPs) was 7.5±4.6 mm with CCE and 7.3±4.2 mm with CS, and this difference was not significant (p=0.28). The FICEΔE' of APs was 3.3±1.8, which was significantly higher than the FICEΔE' of HPs (1.3±0.6; p

KIT D816V mutation within exon 17 has been particularly reported as one of the poor prognostic factors in pediatric acute myeloid leukemia (AML) with RUNX1-RUNX1T1. The exact frequency and the prognostic impact of KIT D816V minor clones at diagnosis were not examined. In this study, the minor clones were examined and the prognostic significance of KIT D816V mutation in pediatric patients was investigated. Consequently, 24 KIT D816V mutations (7.2%) in 335 pediatric patients were identified, and 12 of 24 were only detected via the digital droplet polymerase chain reaction method. All 12 patients were confined in core binding factor (CBF)-AML patients. The 5 year event-free survival of the patients with KIT D816V mutation was significantly inferior to those without KIT D816V mutation (44.1% [95% confidence interval (CI), 16.0%-69.4%] vs. 74.7% [95% CI, 63.0%-83.2%] P-value = 0.02, respectively). The 5 year overall survival was not different between the two groups (92.9% [95% CI, 59.0%-NA vs. 89.7% [95% CI, 69.6%-96.8%] P-value = 0.607, respectively). In this study, KIT D816V minor clones in patients with CBF-AML were confirmed and KIT D816V was considered as a risk factor for relapse in patients with RUNX1-RUNX1T1-positive AML.

We aimed to study the maternal characteristics and obstetric and neonatal outcomes in pregnant mothers with pre-eclampsia (PE) compared to normotensive.This was a population-based retrospective data analysis. Data were obtained from the PEARL-Peristat Study perinatal registry (Perinatal Neonatal Outcomes Research Study in the Arabian Gulf) Qatar. The birth periods ranged from January to December 2017 in the main Women's Hospital (now named Women's Wellness Research Center) and March to December 2017 in other hospitals. This study examined 19762 singleton births at 24 weeks of gestation and above. This analysis included only 19,194 births with complete data in the registry database at the time of this analysis, divided into normotensive women (The prevalence of hypertensive disorders among the 19,762 singleton pregnancies was 1027/19,762 (5.1%). The incidence of pre-eclampsia was 459/19,762 (2.3%) while gestational (341/19,762 (1.7%) and chronic hypertension 219/19,762 (1.1%)). A history of PE or eclampsia in past pregnancies was reported in 12.9% vs 0.9%Women with pre-eclampsia when compared to the normotensive women, they are older, nulliparous, diabetic and obese with an increased risk of preterm birth and cesarean deliveries. It was noted that PE was significantly associated with acute maternal morbidity, still births, cesarean section and preterm births. By taking preventive measures, prompt delivery and appropriate care we can reduce the risks associated with it or prolong the pregnancy to a gestational period which is considered safe for the neonatal survival. Therefore it's imperative to be aware of the population-based risk factors and its mode of presentation in order to give a timely appropriate care and to prevent severe maternal and fetal morbidities and mortalities.

Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p

Background Malignant cutaneous adnexal tumors (MCATs) are rare and their natural history is poorly understood. Available literature indicates aggressive behavior with a significant risk of metastasis. Study Design Retrospective review of our institutional surgical oncology databases was performed for patients diagnosed with MCATs (2001-2020). We hypothesized that most patients have a low risk of lymph node involvement, recurrence, and death. Kaplan-Meier statistical analysis was used to assess risk of recurrence and 5-year survival. Results We identified 41 patients diagnosed with MCATs (median age 59 years, 68% were men). Most patients had long-standing cutaneous lesions (median 24 months) and no palpable adenopathy. Most patients had stage I or II disease (98%). Primary tumors were treated with wide local excision (n = 28 [68%]), Mohs surgery (n = 5 [12%]), or amputation (n = 8 [19%]). Of 25 patients who underwent SLNB (61%), 1 had lymphatic metastasis. These include apocrine carcinoma (1 of 3), digital papillary adenocarcinoma (0 of 8), porocarcinoma (0 of 4), and additional MCAT sub-types (0 of 10). Three patients (7%) had disease recurrence at a median interval of 3.6 years (interquartile range 1.5 to 4.4 years). Five patients (12%) died at a median interval of 7 years (interquartile range 6.7 to 9.2 years), but only 1 patient was known to have succumbed to MCAT. Overall 5-year survival rate was 96% (95% CI, 75% to 99%). Conclusions Despite the historical impression that MCATs have a high metastatic potential, most patients have low recurrence rates and excellent 5-year survival rates. Lymphatic disease identified after SLNB in early-stage tumors is rare and the value of this staging procedure in MCAT remains unclear.

Background Within every neonatal clinical setting, vascular access devices are considered essential for administration of fluids, nutrition, and medications. However, use of vascular access devices is not without danger of failure. Catheter securement adhesives are being evaluated among adult populations, but to date, studies in neonatal settings are scant. Purpose This research describes the prevalence of peripherally inserted central catheter failure related to catheter securement before and after the introduction of tissue adhesive for catheter securement. The identified modifiable risks might be used to evaluate efficacy, to innovate neonatal practice and support future policy developments. Method and setting This was a retrospective observational analysis of routinely collected anonymized intravenous therapy-related data. The study was carried out at the tertiary neonatal intensive care unit (112 beds) of the Women's Wellness and Research Center of Hamad Medical Corporation, Doha, Qatar. Results The results showed that the use of an approved medical grade adhesive for catheter securement resulted in significantly less therapy failures, compared with the control group. This remains significant after adjusting for day of insertion, gestational age, birth weight, and catheter type. Implications for practice and research In parallel with currently published international literature, this study's findings support catheter securement with an octyl-based tissue adhesive in use with central venous catheters. When device stabilization is most pertinent, securement with tissue adhesive is a safe and effective method for long-term vascular access among the neonatal population.

Objectives To examine the impact of early term caesarean section (CS) on respiratory morbidity and early neonatal outcomes when elective caesarean section was carried out before 39 completed weeks gestation in our population. Methods A one-year population-based retrospective cohort analysis using routinely collected hospital data. Livebirths from women who had elective lower segment cesarean section (ELSCS) for uncomplicated singleton pregnancies at early term (ET) 37+0 to 38+6 weeks were compared to full term (FT)≥39+0 weeks gestation. Exclusion criteria included diabetes, antenatal corticosteroid use, stillbirths, immediate neonatal deaths, normal vaginal deliveries and emergency caesareans sections. The outcomes were combined respiratory morbidity (tachypnea [TTN] and respiratory distress syndrome [RDS]), Apgar Results Out of a total of 1,466 elective CS with term livebirths, the timing of CS was early term (ET) n=758 (52%) and full term (FT) n=708 (48%). There was a higher incidence of respiratory morbidities and neonatal outcomes in the ET in comparison to FT newborns. In the univariable analysis, significant risks for outcomes were: the need for oxygen support OR 2.42 (95% C.I. 1.38–4.22), respiratory distress syndrome and/or transient tachypnea of newborn (RDSF/TTN) OR 2.44 (95% C.I. 1.33–4.47) and neonatal intensive care unit (NICU) admission OR 1.91 (95% C.I. 1.22–2.98). Only the need for oxygen support remained (OR 1.81, 95% C.I. 1.0–3.26) in the multivariable analysis. These results were observed within the context of a significantly higher proportion of older, multiparous, and higher number of previous caesarean sections in the early term CS group. Conclusions There is a significant risk of respiratory morbidities in infants born by elective cesarean section prior to full term gestation. Obstetricians should aim towards reducing the high rate of women with previous multiple cesarean sections including balancing the obstetric indication of early delivery among such women with the evident risk of neonatal respiratory morbidity.

Vibrotactile phantom sensation is an intuitive methodology for perceiving the localization of a moving object. However, the presentation area is limited to the inter-stimulus. To extend the range of presentation beyond the inter-stimulus region, we attempted to establish a novel mathematical model for representing a wider range of phantom sensation than conventional models. The experiments 1-1 and 1-2 compared three methods (linear, exponential-like, and conventional inter-stimulus models). The results indicated that the proposed linear and exponential-like models effectively generated both the sense of outer and inner movement with and without training, and that the exponential-like model is best suited to represent accurate phantom sensations that cover the extended outer region. In experiment 2, we examined the effect of γ, a parameter related to the magnitude of exponential-like model damping, on presentation accuracy. The results showed that the high-dumping model (γ=2) showed high accuracy and suggested a trade-off between presentation accuracy and range. The findings of this study are expected to provide guidelines for the effective presentation of a wide range of phantom sensations occurring outside the inter-stimulus.

Background Facial feminization surgery (FFS) includes several osseous modifications of the forehead, mandible, and chin, procedures that require precision to provide the patient with a satisfactory result. Mispositioned osteotomies can lead to serious complications and poor aesthetic outcomes. Surgical cutting guides are commonly employed in plastic and maxillofacial surgery to improve safety and accuracy. Yet, to our knowledge, there is no report in the literature on the clinical application of cutting guides in FFS. Objectives The authors sought to assess the safety and accuracy of custom surgical cutting guides in FFS procedures. Methods A prospective follow-up of 45 patients regarding FFS with preoperative virtual planning and 3-dimensional custom-made surgical guides for anterior frontal sinus wall setback, mandibular angle reduction, and/or osseous genioplasty was conducted. Accuracy (superimposing preoperative data on postoperative data by global registration with a 1-mm margin of error), safety (intradural intrusion for the forehead procedures and injury of the infra alveolar nerve for chin and mandibular angles), and patient satisfaction were assessed. Results A total 133 procedures were documented. There was no cerebrospinal fluid leak on the forehead procedures or any infra alveolar nerve or tooth root injury on both chin and mandibular angle operations (safety, 100%). Accuracy was 90.80% on the forehead (n = 25), 85.72% on the mandibular angles (n = 44), and 96.20% on the chin (n = 26). Overall satisfaction was 94.40%. Conclusions Custom-made surgical cutting guides could be a safe and accurate tool for forehead, mandibular angles, and chin procedures for FFS. Level of Evidence: 4

Plasmonic chips have wavelength-size periodic structures coated with thin metal films and can provide enhanced electric fields near the chip surfaces. Herein, a plasmonic chip was developed to carr...

Reversible post-translational modification of serine and threonine residues by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation has been indicated to regulate the activities of a number of different proteins. Augmented O-GlcNAcylation contributes to the etiologies of type 2 diabetes mellitus (T2DM) and cancer. Moreover, diabetic conditions increase the risk of colorectal cancer. However, the effect of O-GlcNAcylation in patients with colorectal cancer and concurrent T2DM has not been elucidated. The current study evaluated the level of O-GlcNAcylation in patients with colorectal cancer with or without T2DM. Notably, O-GlcNAcylation levels were significantly higher in tissues from patients with T2DM compared with those in patients without T2DM, and higher in cancer tissues compared with corresponding adjacent tissues. O-GlcNAcylation and cancer stage were more strongly correlated in cancer tissues from patients with T2DM compared with those from patients without T2DM. Additionally, distant metastasis was significantly correlated with O-GlcNAcylation in cancer tissues from patients with T2DM. β-catenin levels in colorectal cancer tissues were the highest in patients with advanced-stage cancer and concurrent T2DM. In SW480 human colon cancer cells, thiamet G (TMG) treatment and OGA silencing, which increased O-GlcNAcylation, significantly increased β-catenin and SNAIL in high-glucose, but not during normal-glucose conditions. These data suggest that O-GlcNAcylation is closely associated with distant metastasis, most likely through upregulation of the β-catenin/SNAIL signaling pathway in colorectal cancer patients with T2DM.

For anyone struck by the cinema of Armenian filmmaker Sergei Paradjanov, Gilles Deleuze’s contention that his Sayat Nova (1969) represents “ponderous matter roused by the spirit”1 is an instructive...

BACKGROUND Beetroot has attracted much attention because of its blood pressure-lowering properties. Although beetroot contains various nutritional compounds, including inorganic nitrate, some of their physiological properties are not fully understood. In this study, we examined whether betanin, a beetroot component, has a regulatory effect on vascular tone. METHODS Mechanical responses of isolated porcine coronary, mesenteric, and pulmonary arteries were assessed by organ chamber technique. In some cases, the vascular reactivity was observed in the presence of a physiological concentration of betanin (10 µM). RESULTS Betanin did not induce vasorelaxation at physiological concentrations both in endothelium-intact and -denuded coronary, mesenteric, and pulmonary arteries. The endothelium-dependent agonists, bradykinin and A23187 induced vasorelaxation of endothelium-intact coronary arteries, both of which were not affected by exposure to betanin. Likewise, endothelium-independent vasorelaxation induced by sodium nitrite and sodium nitroprusside was also not affected by the presence of betanin. In addition, exposure of endothelium-intact coronary arteries to betanin did not attenuate prostaglandin F2α- and endothelin-1-induced vasocontraction. CONCLUSIONS These findings suggest that betanin does not have a vasorelaxant activity. It is unlikely that betanin is a component directly responsible for the beetroot-induced acute blood pressure-lowering effect in a nitrate-independent manner.

Rationale, aims, and objectives Despite research being done on spinal tuberculosis, diagnosing this condition at an early stage remains problematic due to its insidious onset and the varying symptoms being associated. Most individuals present to the health care facility with either simple back pain at an early stage or neurological complications at a later stage, when spinal compression and vertebral collapse have occurred as a result of delayed diagnosis. The prevention of secondary complications is therefore dependent on early recognition and diagnosis. The objective of this review was to identify common clinical patterns in case presentations and develop an evidence-based clinical guidance tool to assist clinicians in the early identification of spinal tuberculosis. Method A comprehensive literature search was conducted for published spinal tuberculosis case studies, which yielded 28 cases after critical appraisal. Data from the studies were categorized in order to assist with a factor analysis and the development of an evidence framework for screening and diagnosing spinal tuberculosis. An evidence-based clinical guidance tool was then designed from the data obtained. Results Factors associated with spinal tuberculosis and frequently reported symptoms and physical signs with which the patient could present upon assessment were identified. Options for investigations at primary, secondary, and tertiary levels were also identified. Conclusion Through the use of an evidence-based clinical guidance tool, the clinician could be guided in the early suspicion and management of individuals with spinal tuberculosis and prevention of secondary complications.

Recent advances in the genetic understanding of acute myeloid leukemia (AML) have improved clinical outcomes in pediatric patients. However, ∼40% of patients with pediatric AML relapse, resulting in a relatively low overall survival rate of ∼70%. The objective of this study was to reveal the comprehensive genetic background of pediatric AML. We performed transcriptome analysis (RNA sequencing [RNA-seq]) in 139 of the 369 patients with de novo pediatric AML who were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial and investigated correlations between genetic aberrations and clinical information. Using RNA-seq, we identified 54 in-frame gene fusions and 1 RUNX1 out-of-frame fusion in 53 of 139 patients. Moreover, we found at least 258 gene fusions in 369 patients (70%) through reverse transcription polymerase chain reaction and RNA-seq. Five gene rearrangements were newly identified, namely, NPM1-CCDC28A, TRIP12-NPM1, MLLT10-DNAJC1, TBL1XR1-RARB, and RUNX1-FNBP1. In addition, we found rare gene rearrangements, namely, MYB-GATA1, NPM1-MLF1, ETV6-NCOA2, ETV6-MECOM, ETV6-CTNNB1, RUNX1-PRDM16, RUNX1-CBFA2T2, and RUNX1-CBFA2T3. Among the remaining 111 patients, KMT2A-PTD, biallelic CEBPA, and NPM1 gene mutations were found in 11, 23, and 17 patients, respectively. These mutations were completely mutually exclusive with any gene fusions. RNA-seq unmasked the complexity of gene rearrangements and mutations in pediatric AML. We identified potentially disease-causing alterations in nearly all patients with AML, including novel gene fusions. Our results indicated that a subset of patients with pediatric AML represent a distinct entity that may be discriminated from their adult counterparts. Based on these results, risk stratification should be reconsidered.

Although infants (age

Introduction Diroximel fumarate (DRF) is a novel oral fumarate in development for patients with relapsing forms of multiple sclerosis (MS). Clinical findings from the DRF development program suggest that rates of gastrointestinal (GI) treatment-emergent adverse events (TEAEs) and discontinuation due to GI TEAEs are low, based on clinical and real-world observations of other fumaric acid esters, including dimethyl fumarate (DMF). The incidence of GI TEAEs varies from 40 to 88% in clinical and real-world studies of DMF. The objective of this study is to present GI tolerability findings from the EVOLVE-MS-1 study and present biologic hypotheses for the improved GI properties of DRF. Methods GI TEAEs and treatment discontinuation because of GI TEAEs were assessed in DRF-treated patients with relapsing-remitting MS who were participating in the ongoing, 96-week, open-label, phase 3 EVOLVE-MS-1 study. Results As of March 30, 2018, a total of 696 patients were enrolled in EVOLVE-MS-1. GI TEAEs were reported in 30.9% (215/696) of patients; the vast majority (96%; 207/215) experienced events that were mild or moderate in severity. When GI AEs did occur, they occurred early in treatment, resolved (88.8%; 191/215), and were of short duration [median 7.5 (range 1–87) days] in most patients. GI TEAEs led to < 1% of patients discontinuing treatment. Conclusions We suggest that the distinct chemical structure of DRF contributes to the observed low rates of GI TEAEs and GI-associated treatment discontinuations, possibly due to a combination of several factors. We hypothesize that these factors may include less reactivity with off-target proteins and/or lower production of a methanol leaving group that may contribute to GI irritation. A direct comparison of GI tolerability with DRF versus DMF is being evaluated in the EVOLVE-MS-2 study. Trial Registration ClinicalTrials.gov number NCT02634307. Funding Alkermes Inc. (Waltham, MA, USA) and Biogen (Cambridge, MA, USA). Electronic supplementary material The online version of this article (10.1007/s12325-019-01085-3) contains supplementary material, which is available to authorized users.

Background Cutaneous T-cell lymphoma (CTCL), including subtypes mycosis fungoides (MF) and Sezary syndrome (SS), represents a rare group of non-Hodgkin lymphomas. Mogamulizumab is a first-in-class monoclonal antibody that selectively binds to C-C chemokine receptor 4, which is overexpressed on the surface of tumor cells in T-cell malignancies, including MF/SS-type CTCL. Objectives This review identifies common diagnostic features of MF/SS, the efficacy and side effect profile of mogamulizumab, and practical management strategies for optimizing the nursing care of patients with MF/SS-type CTCL. Methods Case studies are used to describe the role of mogamulizumab in CTCL and to review practical considerations when administering mogamulizumab to patients. Findings Mogamulizumab is an effective treatment for adult patients with relapsed or refractory MF/SS-type CTCL who have received at least one prior systemic therapy. Infusion reactions and drug eruptions require prompt diagnosis and treatment.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

OBJECTIVETo examine the association between cesarean section and neonatal mortality Nigeria.METHODA retrospective analysis using Nigeria Demographic Health Survey 2013 national population-based cross-sectional survey. The national prevalence of cesarean section was calculated, and logistic regression was used to estimate the odds of neonatal mortality outcome following cesarean delivery.RESULTSThe national cesarean section rate for the 2009–2013 period was 2.1% among 31,495 deliveries. The odds of having a neonatal death was twice as high in cesarean deliveries in comparison to noncesarean deliveries (aOR = 2.56, 95% CI 1.75 to 3.74).CONCLUSIONCesarean section increases the odds of neonatal mortality in Nigeria. There is a need to scale up the quality and timeliness of emergency obstetric services offered to pregnant women.

A precise understanding of the near-field distributions of plasmonic nanostructures is indispensable for their practical applications. In this study, we directly visualized near-field distributions on two-dimensional nanohole arrays covered with a gold film (plasmonic chip) by scanning near-field optical microscopy. In the near-field images, strong extinction spots were observed not only inside the nanoholes but also on the outside. We also found that the spatial characteristics outside the nanoholes are strongly dependent on the excitation wavelength. From the electromagnetic simulations, we revealed that the positions of the extinction spots in the near-field images are well correlated with the locations for the enhanced electric fields. We also found that the excitation wavelength dependency on the near-field distributions are rationalized with the classical grating coupling conditions for the plasmonic chip. These findings provide new physical insights into the near-field characteristics of the metall...

AIM To examine the factors associated with the risk of neonatal mortality following caesarean births at country-level in sub-Saharan Africa. METHODS We used meta-analytic procedure to synthesize the results of most recent nationally representative cross-sectional Demographic and Health Survey (DHS) datasets for 33 sub-Saharan Africa countries conducted between 2010 and 2018. Pooled odds ratio (OR) and 95% confidence intervals (CI) were computed for all countries. RESULTS The overall caesarean section (CS) rate was 4.9%, neonatal mortality was 2.8% and Post-CS neonatal mortality was 4.3%. The rates of CS were generally low and only five countries had CS rates at or above 10%. The overall pooled result showed a statistically significant increase in the odds of neonatal mortality after a caesarean section (CS) OR 1.7 (95% CI 1.53 -1.89; I2 = 39.3%, p

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar &lt, 7 at 1 and 5 minutes and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.

Handheld dynamometry (HHD) using external fixation has demonstrated high inter- and intra-rater reliability. Handheld dynamometry offers an objective way to quantify strength; however, setting up external stabilization devices for HHD can be time consuming. This study examined the reliability of HHD for lower extremity strength in dancers using body weight stabilization. Twenty-six pre-professional dancers (age: 20.64 ± 2.21 years) were recruited and assessed by three testers: an experienced physical therapist (ePT), a novice physical therapist (nPT), and a student physical therapist (SPT). To avoid testing fatigue, dancers were divided into two testing groups and were evaluated on separate weekends. Testers used HHD to test isometric force production of six muscle groups in the first cohort and seven dif- ferent muscle groups in the second cohort. Testing positions were standardized and utilized a "make" test protocol. Intra- class correlation coefficients (ICC), 95% confidence interval, and standard error of measurement were calculated for each position. Inter-rater reliability was > 0.75 for all ICC measures except knee extension and ankle eversion. Intra-rater reliability was > 0.75 for all ICC measures except the ePT (tester A) day 2 for hip extension, internal rotation seated, knee extension, and ankle dorsiflexion; nPT (tester B) day 1 knee flexion; and SPT (tester C) for day 1 knee extension and ankle eversion and days 1 and 2 for ankle dorsiflexion and inversion. It is concluded that HHD can reliably measure force production of hip, knee, and ankle muscle groups without use of external fixation devices.

There is no established view of how gastric acid suppression affects the time for gastric emptying. Vonoprazan fumarate shows potent and durable gastric acid inhibitory effects, but its effects on gastric emptying have not been studied widely. We investigated the effects of vonoprazan fumarate on gastric emptying and measured serum gastrin and plasma ghrelin levels in healthy adults. Ten participants were administered 10 mg vonoprazan fumarate daily for 14 days, then 20 mg vonoprazan fumarate daily for 14 days. The gastric emptying breath test was performed and serum gastrin levels were measured at baseline and after each medication administration period. The protocol was then repeated, with the gastric emptying breath test and serum gastrin and plasma desacyl-ghrelin levels measured at baseline and the end of the medication trial. Mean serum gastrin levels increased in a dose-dependent manner [baseline: 104.7 ± 50.4, after 10 mg protocol: 328 ± 123.8, after 20 mg protocol: 555 ± 378.8 (pg/mL, mean ± standard deviation), p = 0.0008]. There was a significant difference between the gastric emptying breath test Tmax at baseline and just after the 20 mg protocol (baseline: 45.5 ± 15.3, after 20 mg protocol: 60.5 ± 19.6 min, p = 0.0418). Plasma desacyl-ghrelin levels increased significantly just after the 20 mg protocol compared to those at baseline [baseline: 222.3 ± 106.4, after 20 mg protocol: 366.2 ± 178.6 (fmol/mL), p = 0.0008]. In healthy adults, 14 days of vonoprazan fumarate administration at 20 mg/day delayed gastric emptying. This clinical trial was registered in the University hospital Medical Information Network Clinical Trial Registry (Trial No. UMIN000039199 and UMIN000042969).

The anaerobic threshold (AT), obtained during cardiopulmonary exercise testing (CPET), is an important prognostic measure and can be used to develop an exercise prescription in patients after a myocardial infarction (post-MI). The purpose of this study was to examine the central and peripheral determinants of AT in post-MI patients end-tidal oxygen partial pressure (PETO2) measures. We performed cardiopulmonary exercise testing (CPET) on 148 consecutively enrolled post-MI patients to determine PETO2 measured at the AT (AT PETO2) and ΔPETO2 (difference between resting PETO2 and AT PETO2). We subsequently investigated the relationship between these measures of PETO2 and the individual AT for each patient. Multivariate linear regression analysis indicated that AT PETO2 and ΔPETO2 were independently and significantly associated with the AT (β = −0.344, p

This study aimed to clarify the effects of the interruption of cardiac rehabilitation (CR) and refraining from going outside due to the COVID-19 pandemic on hemodynamic response and rating of perceived exertion (RPE) during exercise including differences by age in phase 2 CR outpatients. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Chronic tear deficiency enhances the excitability of corneal cold-sensitive nerves that detect ocular dryness, which can lead to discomfort in patients with dry eye disease (DED). However, changes in corneal nerve excitations through the polymodal nociceptor “transient receptor potential vanilloid 1” (TRPV1) and the potential link between this receptor and symptoms of DED remain unclear. In this study, we examined the firing properties of corneal cold-sensitive nerves expressing TRPV1 and possible contributions of chronic tear deficiency to corneal nerve excitability by TRPV1 activation. The bilateral excision of lacrimal glands in guinea pigs decreased the tear volume and increased the frequency of spontaneous eyeblinks 1–4 weeks after surgery. An analysis of the firing properties of the cold-sensitive nerves was performed by single-unit recordings of corneal preparations 4 weeks after surgery in both the sham-operated and gland-excised groups. Perfusion of the TRPV1 agonist, capsaicin (1 μM), transiently increased the firing frequency in approximately 46–48% of the cold-sensitive nerves characterized by low-background activity and high threshold (LB-HT) cold thermoreceptors in both groups. Gland excision significantly decreased the latency of capsaicin-induced firing in cold-sensitive nerves; however, its magnitude was unchanged. Calcium imaging of cultured trigeminal ganglion neurons from both groups showed that intracellular calcium elevation of corneal neurons induced by a low concentration of capsaicin (0.03 μM) was significantly larger in the gland excision group, regardless of responsiveness to cold. An immunohistochemical study of the trigeminal ganglion revealed that gland excision significantly increased the proportion of corneal neurons enclosed by glial fibrillary acidic protein (GFAP)-immunopositive satellite glial cells. Topical application of the TRPV1 antagonist, A784168 (30 μM), on the ocular surface attenuated eye-blink frequency after gland excision. Furthermore, gland excision enhanced blink behavior induced by a low concentration of capsaicin (0.1 μM). These results suggest that chronic tear deficiency sensitizes the TRPV1-mediated response in the corneal LB-HT cold thermoreceptors and cold-insensitive polymodal nociceptors, which may be linked to dry eye discomfort and hyperalgesia resulting from nociceptive stimuli in aqueous-deficient dry eyes.

Increased expression of developmentally silenced fetal globin (HBG) reduces the clinical severity of β-hemoglobinopathies. Benserazide has a relatively benign safety profile having been approved for 50 years in Europe and Canada for Parkinson's disease treatment. Benserazide was shown to activate HBG gene transcription in a high throughput screen, and subsequent studies confirmed fetal hemoglobin (HbF) induction in erythroid progenitors from hemoglobinopathy patients, transgenic mice containing the entire human β-globin gene (β-YAC) and anemic baboons. The goal of this study is to evaluate efficacies and plasma exposure profiles of benserazide racemate and its enantiomers to select the chemical form for clinical development. Intermittent treatment with all forms of benserazide in β-YAC mice significantly increased proportions of red blood cells expressing HbF and HbF protein per cell with similar pharmacokinetic profiles and with no cytopenia. These data contribute to the regulatory justification for development of the benserazide racemate. Additionally, dose ranges and frequencies required for HbF induction using racemic benserazide were explored. Orally administered escalating doses of benserazide in an anemic baboon induced γ-globin mRNA up to 13-fold and establish an intermittent dose regimen for clinical studies as a therapeutic candidate for potential treatment of β-hemoglobinopathies.

Background: Idiopathic scoliosis (IS) is a common musculoskeletal condition with a multi-factorial aetiology characterised by a three-dimensional torsional deformity of the spine. Objectives: To ascertain the current level of knowledge on IS among registered practising physiotherapists who expressed an interest in orthopaedic, muscular, manual and manipulative therapy in South Africa (SA). Method: An online survey was used to collect the data. The questions were based on an existing questionnaire, validated by a South African panel of experts in the field of musculoskeletal physiotherapy and updated based on the 2016 Society of Scoliosis Orthopaedic Rehabilitation Treatment (SOSORT) guidelines for the assessment and management of IS. Results: Two hundred and twenty-three physiotherapists spread across the nine provinces of SA met the inclusion criteria and were included in our study. Our findings showed that about one-third (33.6%) of the physiotherapists could answer more than 50% of these questions correctly, and 16.5% could answer 70% of the questions correctly in relation to the widely accepted guidelines on IS management. Conclusion: The participants had a poor understanding of the diagnosis and treatment involved in managing patients with IS and a lack of knowledge regarding the methods of conservative treatment for scoliosis. Future studies should be aimed at assessing intervention strategies to improve the knowledge of IS in physiotherapists in SA, especially regarding diagnosis and identifying appropriate management strategies. Clinical implications: Physiotherapists are often the first contact practitioners for patients presenting with scoliosis and therefore need to have the necessary clinical knowledge on the assessment and management of IS. Our study can improve the awareness among the South African physiotherapists regarding IS and its complex presentation and management.

Background: Despite improved immunological and viral load control, the prevalence of HIV/AIDS-related peripheral neuropathy among survivors on highly active antiretroviral therapy (HAART) is rising globally raising public health concerns. Objectives: To determine the prevalence and clinical characteristics of peripheral neuropathy amongst persons on HAART attending Comprehensive Care Clinics in Busia County, Kenya. Method: This cross-sectional descriptive quantitative study utilised purposive sampling and included 289 adults living with HIV/AIDS. Data collection was undertaken using the Clinical HIV Associated Neuropathy Tool (CHANT) and analysed using the Statistical Package for the Social Sciences version 25.0. Results: Of people on HAART, 68.17% (197 amongst 289) had peripheral neuropathy. The majority were female 76.8% ( n = 222), 38.1% ( n = 110) were between 41 and 50, and 35% ( n = 101) were widowed. The most common primary symptom was reduced right foot big toe vibration (76.8%, n = 222). There was a strong positive relationship ( r = 0.621, P = 0.000) between foot vibration and illness. There was a statistically significant influence of demographic characteristics of persons on HAART on PN as they accounted for 98.5% of the variance ( R 2 = 0.985). Conclusion: Peripheral neuropathy is prevalent and is significantly influenced by socio-demographic characteristics of persons on HAART-PN. Early diagnosis and exercise guidance by physiotherapists is key in forestalling severe symptoms, disability and poor quality of life. Clinical implications: There is need to screen persons living with HIV on HAART for PN to establish their medical, physiotherapy and rehabilitation needs. Early diagnosis will encourage healthcare workers to start interventions to prevent progression of impairment, onset of disability and decrease in quality of life. Therefore, adaptation of PN screening tools and physiotherapeutic interventions should be considered.

The dorsalis pedis reconstruction requires to bring a thin tissue to recover every noble structure of the foot including tendons, nerves and vessels while resisting the stress induced on these structures when walking or wearing shoes. We report the case of a thirteen year-old child who presented a third-degree burn sequelae on the dorsalis pedis with scar retraction and chronic ulceration on the fifth metatarsal despite multiple skin grafts. He couldn't put on his shoes because of the pain and walking was difficult. We performed a SCIP flap (Superficial Circumflex Iliac Artery Perforator) to reconstruct this defect. The flap measuring 12×7cm has been harvested on the right groin and anastomosed with the pedicle of the first intermetatarsal space. At 3 months postoperatively, the child can put on his shoes again and walk without pain. The donor site is discrete in the inguinal crease, hidden in the underwear. The SCIP flap is a thin and pliable flap with a discrete donor site. It is suitable for reconstructions of distal extremities of limbs, both in adults and children.

Objectives A recent discussion surrounding the extension of antenatal corticosteroid (ACS) use beyond 34 weeks of gestation did not include the subgroup of infants of diabetic mothers (IDM). We aimed to examine the association between ACS exposure and outcomes in neonates born at term and at near-term gestation in a large cohort of IDMs. Methods We selected 13976 eligible near-term and term infants who were included in the PEARL-Peristat Perinatal Registry Study (PPS). We assessed the association of ACS exposure with neonatal outcomes in a multivariate regression model that controlled for diabetes mellitus (DM) and other perinatal variables. Results The incidence of DM was 28% (3,895 of 13,976) in the cohort. Caesarean section was performed in one-third of the study population. The incidence of ACS exposure was low (1.8%) and typically occurred>2 weeks before delivery. The incidence rates of respiratory distress syndrome (RDS)/ transient tachypnoea of newborns (TTN), all-cause neonatal intensive care unit (NICU) admissions, NICU admissions for hypoglycaemia, and low 5-min Apgar scores were 3.5, 8.8, 1.3, and 0.1%, respectively. In a multivariate regression model, ACS was associated with a slight increase in NICU admissions (OR: 1.44; 95% CI: 1.04–2.03; p=0.028), but not with RDS/TTN. Conclusions Although the low exposure rate was a limitation, ACS administration did not reduce respiratory morbidity in near-term or term IDMs. It was independently associated with an increase in NICU admissions. Randomized controlled trials are required to assess the efficacy and safety of ACS administration in diabetic mothers at late gestation.

Under current AJCC staging criteria, stage IIC patients paradoxically have worse outcomes than IIIA patients despite the lack of nodal metastatic disease. This study sought to identify additional clinicopathologic characteristics correlated with worse patient outcomes. Retrospective chart review of stage IIC and IIIA melanoma patients were evaluated between 1995 and 2011 with clinical follow-up through 2015. Records were reviewed for demographics, clinical characteristics, and tumor pathology. Fisher's exact test and Wilcoxon's rank-sum test were used to assess group differences. Clinicopathologic features were evaluated relative to overall survival (OS), time to distant metastases, and local/regional recurrence. Overall, 128 patients were included (45 stage IIC and 83 stage IIIA) with a median follow-up time of 5.7 years. Compared with stage IIIA patients, stage IIC patients were older, and their melanomas were more likely to be nodular, amelanotic, thicker, have higher mitotic rate, tumor lymphocytic infiltrate, no radial growth phase, and less likely to have associated precursor lesions. Stage IIC patients had shorter OS and time to distant metastases; multivariate regression revealed that older age (>55 years) and mitotic rate (>5 mitoses/mm) were independent predictors of OS. Melanomas in stage IIC disease may be biologically distinct from those that are seen in stage IIIA. While sentinel node biopsies remain the standard-of-care, these results suggest that clinicians may want to assess the clinicopathologic characteristics described above to aggressively counsel, screen for distant disease, and consider adjuvant therapy, in particular for older patients and higher mitotic rates in thicker primary tumors, regardless of nodal status.

Mixed-lineage leukemia (MLL) gene rearrangements are among the most frequent chromosomal abnormalities in acute myeloid leukemia (AML). MLL fusion patterns are associated with the patient’s prognosis; however, their relationship with driver mutations is unclear. We conducted sequence analyses of 338 genes in pediatric patients with MLL-rearranged (MLL-r) AML (n = 56; JPLSG AML-05 study) alongside data from the TARGET study’s pediatric cohorts with MLL-r AML (n = 104), non–MLL-r AML (n = 581), and adult MLL-r AML (n = 81). KRAS mutations were most frequent in pediatric patients with high-risk MLL fusions (MLL-MLLLT10, MLL-MLLT4, and MLL-MLLT1). Pediatric patients with MLL-r AML (n = 160) and a KRAS mutation (KRAS-MT) had a significantly worse prognosis than those without a KRAS mutation (KRAS-WT) (5-year event-free survival [EFS]: 51.8% vs 18.3%, P < .0001; 5-year overall survival [OS]: 67.3% vs 44.3%, P = .003). The adverse prognostic impact of KRAS mutations was confirmed in adult MLL-r AML. KRAS mutations were associated with adverse prognoses in pediatric patients with both high-risk (MLLT10+MLLT4+MLLT1; n = 60) and intermediate-to-low–risk (MLLT3+ELL+others; n = 100) MLL fusions. The prognosis did not differ significantly between patients with non–MLL-r AML with KRAS-WT or KRAS-MT. Multivariate analysis showed the presence of a KRAS mutation to be an independent prognostic factor for EFS (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.35-3.59; P = .002) and OS (HR, 1.85; 95% CI, 1.01-3.31; P = .045) in MLL-r AML. The mutation is a distinct adverse prognostic factor in MLL-r AML, regardless of risk subgroup, and is potentially useful for accurate treatment stratification. This trial was registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry (UMIN-CTR; http://www.umin.ac.jp/ctr/index.htm) as #UMIN000000511., 急性骨髄性白血病の予後を予測する新規マーカーを発見 --リスクに応じた適切な治療につながる可能性--. 京都大学プレスリリース. 2020-10-02.

Background/Aims: Soluble guanylate cyclase (sGC) exists as reduced, oxidized, and heme-free forms. Currently, it is unclear whether endovascular mechanical stenosis has an impact on vascular tone control by drugs targeting sGC, namely cGMP generators. Methods: Pharmacological responses to acidified sodium nitrite (reduced sGC stimulant) and BAY 60-2770 (oxidized/heme-free sGC stimulant) were studied in balloon-injured rat carotid arteries at several time points. In addition, sGC expression was detected by immunohistochemistry. Results: At 1 day after injury, acidified sodium nitrite-induced relaxation was attenuated in the injured artery, whereas BAY 60-2770-induced relaxation was augmented. Similar attenuation of response to acidified sodium nitrite was seen at 7 and 14 days after injury. On the other hand, the augmentation of response to BAY 60-2770 disappeared at 7 and 14 days after injury. At 1 day after injury, the immunohistochemical expression pattern of sGC in the smooth muscle layer of the injured artery was not different from that of the uninjured artery. However, in the injured artery, the intensity of sGC staining was weak at 7 and 14 days after injury. Conclusion: Balloon injury alters vascular responsiveness to cGMP generators, which seems to be associated with the form and/or expression of sGC.

The variability in myelosuppression after chemotherapy for acute myeloid leukaemia (AML) can affect its prognosis; however, the underlying mechanism remains controversial. In the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study, we showed that prolonged neutropenia was associated with high overall survival (P = 0·011) and low frequency of relapse (P = 0·042) in patients without granulocyte-colony stimulating factor (G-CSF) who completed the indicated treatment protocol. Our data indicate that predisposition to prolonged neutropenia after chemotherapy is correlated with a better outcome of AML treatment. Our results promote the usage of individualised drug dosing strategies to improve the therapeutic outcome in AML patients.

The outdoor field test of the 4-terminal III-V on Si tandem photovoltaic module (specifically, InGaP/GaAs on Si) was investigated and performance model, considering spectrum change affected by fluctuation of atmospheric parameters, was developed and validated. The 4-terminal III-V on Si tandem photovoltaic module had about 40 % advantage in seasonal performance loss compared with standard InGaP/GaAs/InGaAs 2-terminal tandem photovoltaic module. This advantage is expanded in (subarctic zone) < (temperate zone) < (subtropical zone).

Quantum dots (QDs) are semiconductor nanoparticles showing many advantages for photoluminescence (PL) applications. Since common QDs contain toxic elements such as Cd, Pb, Se, and Te, ZnS-AgInS2 (ZAIS) has been developed as a quantum nanomaterial with low cytotoxicity. In this study, ZAIS@ZnS core-shell QDs coated with carboxyl groups (ZAIS@ZnS-MPA) were prepared as water-soluble nanoparticles. The PL characteristics of ZAIS@ZnS-MPA were studied on a plasmonic chip, which is a substrate with wavelength-scale periodic structures coated with thin metal films, and the PL enhancement of ZAIS by an electromagnetic field derived from grating-coupled surface plasmon resonance (GC-SPR) was also evaluated. The PL spectroscopic characteristics obtained on the grating patterns with a 480 nm-pitch were enhanced in a wider wavelength range. Furthermore, photobleaching, which occurs in conventional fluorescence molecules, was not observed under halogen lamp illumination. The PL and spectroscopic imaging under a microscope indicated the PL characteristics of the ZAIS@ZnS-MPA nanoparticles on the plasmonic chip under appropriate conditions.

In acute myeloid leukemia (AML), MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities; however, knowledge of the genetic landscape of MLL-rearranged AML is limited. In this study, we performed whole-exome sequencing (n = 9) and targeted sequencing (n = 56) of samples from pediatric MLL-rearranged AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. Additionally, we analyzed 105 pediatric t(8;21) AML samples and 30 adult MLL-rearranged AML samples. RNA-sequencing data from 31 patients published in a previous study were also reanalyzed. As a result, we identified 115 mutations in pediatric MLL-rearranged AML patients (2.1 mutations/patient), with mutations in signaling pathway genes being the most frequently detected (60.7%). Mutations in genes associated with epigenetic regulation (21.4%), transcription factors (16.1%), and the cohesin complex (8.9%) were also commonly detected. Novel CCND3 mutations were identified in 5 pediatric MLL-rearranged AML patients (8.9%) and 2 adult MLL-rearranged AML patients (3.3%). Recurrent mutations of CCND1 (n = 3, 2.9%) and CCND2 (n = 8, 7.6%) were found in pediatric t(8;21) AML patients, whereas no CCND3 mutations were found, suggesting that D-type cyclins exhibit a subtype-specific mutation pattern in AML. Treatment of MLL-rearranged AML cell lines with CDK4/6 inhibitors (abemaciclib and palbociclib) blocked G1 to S phase cell-cycle progression and impaired proliferation. Pediatric MLL-MLLT3–rearranged AML patients with coexisting mutations (n = 16) had significantly reduced relapse-free survival and overall survival compared with those without coexisting mutations (n = 9) (P = .048 and .046, respectively). These data provide insights into the genetics of MLL-rearranged AML and suggest therapeutic strategies., 急性骨髄性白血病の新規遺伝子変異を発見 --乳がんの既存薬が治療に有効である可能性--. 京都大学プレスリリース. 2018-11-01.