The effect of “Approach for Encouraging Patients' Initiative" for patients with unilateral spatial neglect

半側空間無視は右半球脳損傷による後遺症として比較的頻繁に現れ,患者の日常生活への復帰を困難にする因子として知られる.本研究はこれに対するアプローチにおいて患者の自発性という問題に焦点をあて,これを促すことが半側空間無視の改善を生むかどうかを検証することをめざしたものである.なお,本研究において“自発的解決を促す介入"とは患者が興味のある課題を行う中で,無視症状の正しい認識と代償戦略の立案・獲得を促すことを目的にデザインされたものである.2症例を対象にそれぞれA-B-A'型のシングルケースデザインを用いて実験を行った.独立変数を“自発的解決を促す介入"の有無,従属変数を半側空間無視による見落とし数を標的とした半側空間無視量とし,A,B,A'各期それぞれ10回のセッションを週3～4回の頻度で実施した.さらに汎化の程度を調べる目的で,行動性無視検査を実験開始時と各期の終了時に計4回実施した.その結果,半側空間無視量は2症例ともB期において改善を示し,行動性無視検査の成績も1症例においてB期終了後に改善を示した.また,B期で得られた代償法のA'期における使用や自発的な無視に関するコメントの出現が認められた.すなわち,“自発的解決を促す介入"は半側空間無視に対する病識の芽生えと代償法の獲得ならびに拡張的使用を促すものと判断された.Unilateral Spatial Neglect (USN) is common after right hemisphere brain damage and has beenfound to be an important predictor of functional ability after injury. In this study, the focus was on patients'own initiative to see if this initiative helps improve their USN. In this study, “Approach for EncouragingPatients'Initiative"is designed to encourage patients to acknowledge their neglect symptoms, and to planand acquire some compensations while doing their favorite tasks. The experiment was carried out on 2 cases using a single case design (A-B-A'). The independentvariable is considered to be “Approach for Encouraging Patients'Initiative", and the dependent variable tobe USN quantity. A series of 10 sessions for each of the A-B-A'stages were held at the frequency of 3-4times a week. The Behavioral Inattention Test (BIT) was administered at the beginning and at the end ofthe experiment, 4 times in total, in order to examine the degree of the generalization. As a result, both ofthe 2 cases on USN quantity showed an improvement at the B stage, and the BIT experiment alsoindicated an improvement at the end of the B stage. It allowed the compensatory methods acquired at theB stage to be used in the following A'stage. Voluntary comments about USN were also noted. It issuggested that “Approach for Encouraging Patients'Initiative"can prompt the patients'awareness ofUSN, plus the acquisition and expansion of its compensation methods

A Unique Gene-Silencing Approach, Using an Intelligent RNA Expression Device (iRed), Results in Minimal Immune Stimulation When Given by Local Intrapleural Injection in Malignant Pleural Mesothelioma

Background: We have recently introduced an intelligent RNA expression device (iRed), comprising the minimum essential components needed to transcribe short hairpin RNA (shRNA) in cells. Use of iRed efficiently produced shRNA molecules after transfection into cells and alleviated the innate immune stimulation following intravenous injection. Methods: To study the usefulness of iRed for local injection, the engineered iRed encoding luciferase shRNA (Luc iRed), complexed with cationic liposomes (Luc iRed/liposome-complexes), was intrapleurally injected into an orthotopic mesothelioma mouse model. Results: Luc iRed/liposome-complexes markedly suppressed the expression of a luciferase marker gene in pleurally disseminated mesothelioma cells. The suppressive efficiency was correlated with the expression level of shRNA within the mesothelioma cells. In addition, intrapleural injection of iRed/liposome-complexes did not induce IL-6 production in the pleural space and consequently in the blood compartment, although plasmid DNA (pDNA) or dsDNA (the natural construct for iRed) in the formulation did. Conclusion: Local delivery of iRed could augment the in vivo gene silencing effect without eliciting pronounced innate immune stimulation. Our results might hold promise for widespread utilization of iRed as an RNAi-based therapeutic for intracelial malignant cancers

JASTRO IC/IS Guideline for Gynecologic Cancers

It has been postulated that the combination of intracavitary and interstitial brachytherapy (IC/IS) is effective and safe for large and irregularly shaped uterine cervical cancer patients. However, due to its invasiveness compared to conventional intracavitary brachytherapy (ICBT), it has to be said that the implementation speed of IC/IS is slow. Until now, there have been no guidelines for required equipment, human resources, and procedural guide focusing solely on IC/IS. The purpose of this guideline is to provide radiation oncologists and medical physicists who wish to start IC/IS with practical and comprehensive guidance for a safe IC/IS introduction and to help accelerate the spread of the utilization of IC/IS nationwide. This is the English translation of the Japanese IC/IS Guidelines, and it was created in an effort to share the Japanese approach to the management of locally advanced uterine cervical cancer worldwide

Gene Silencing Using 4′-thioDNA as an Artificial Template to Synthesize Short Hairpin RNA Without Inducing a Detectable Innate Immune Response

The development of a versatile technique to induce RNA interference (RNAi) without immune stimulation in vivo is of interest as existing approaches to trigger RNAi, such as small interfering RNA (siRNA) and plasmid DNA (pDNA) expressing short hairpin RNA (shRNA), present drawbacks arising from innate immune stimulation. To overcome them, an intelligent shRNA expression device (iRed) designed to induce RNAi was developed. The minimum sequence of iRed encodes only the U6 promoter and shRNA. A series of iRed comprises a polymerase chain reaction (PCR)-amplified 4′-thioDNA in which any one type of adenine (A), guanine (G), cytosine (C), or thymine (T) nucleotide unit was substituted by each cognate 4′-thio derivatives, i.e., dSA iRed, dSG iRed, dSC iRed, and ST iRed respectively. Each modified iRed acted as a template to transcribe shRNA with RNAi activity. The highest shRNA yield was generated using dSC iRed that exerted gene silencing activity in an orthotopic mouse model of mesothelioma. Reducing the minimal structure required to transcribe shRNA and the presence of the 4′-thiomodification synergistically function to abrogate innate immune response induced by dsDNA. The iRed will introduce a new approach to induce RNAi without inducing a detectable innate immune response

Prediction of recurrence after chemoradiotherapy

We retrospectively assessed whether magnetic resonance imaging (MRI) radiomics combined with clinical parameters can improve the predictability of out-of-field recurrence (OFR) of cervical cancer after chemoradiotherapy. The data set was collected from 204 patients with stage IIB (FIGO: International Federation of Gynecology and Obstetrics 2008) cervical cancer who underwent chemoradiotherapy at 14 Japanese institutes. Of these, 180 patients were finally included for analysis. OFR-free survival was calculated using the Kaplan–Meier method, and the statistical significance of clinicopathological parameters for the OFR-free survival was evaluated using the log-rank test and Cox proportional-hazards model. Prediction of OFR from the analysis of diffusion-weighted images (DWI) and T2-weighted images of pretreatment MRI was done using the least absolute shrinkage and selection operator (LASSO) model for engineering image feature extraction. The accuracy of prediction was evaluated by 5-fold cross-validation of the receiver operating characteristic (ROC) analysis. Para-aortic lymph node metastasis (p = 0.003) was a significant prognostic factor in univariate and multivariate analyses. ROC analysis showed an area under the curve (AUC) of 0.709 in predicting OFR using the pretreatment status of para-aortic lymph node metastasis, 0.667 using the LASSO model for DWIs and 0.602 using T2 weighted images. The AUC improved to 0.734 upon combining the pretreatment status of para-aortic lymph node metastasis with that from the LASSO model for DWIs. Combining MRI radiomics with clinical parameters improved the accuracy of predicting OFR after chemoradiotherapy for locally advanced cervical cancer

Decadal–centennial-scale solar-linked climate variations and millennial-scale internal oscillations during the Early Cretaceous

Understanding climate variability and stability under extremely warm ‘greenhouse’ conditions in the past is essential for future climate predictions. However, information on millennial-scale (and shorter) climate variability during such periods is scarce, owing to a lack of suitable high-resolution, deep-time archives. Here we present a continuous record of decadal- to orbital-scale continental climate variability from annually laminated lacustrine deposits formed during the late Early Cretaceous (123–120 Ma: late Barremian–early Aptian) in southeastern Mongolia. Inter-annual changes in lake algal productivity for a 1091-year interval reveal a pronounced solar influence on decadal- to centennial-scale climatic variations (including the ~ 11-year Schwabe cycle). Decadally-resolved Ca/Ti ratios (proxy for evaporation/precipitation changes) for a ~ 355-kyr long interval further indicate millennial-scale (~ 1000–2000-yr) extreme drought events in inner-continental areas of mid-latitude palaeo-Asia during the Cretaceous. Millennial-scale oscillations in Ca/Ti ratio show distinct amplitude modulation (AM) induced by the precession, obliquity and short eccentricity cycles. Similar millennial-scale AM by Milankovitch cycle band was also previously observed in the abrupt climatic oscillations (known as Dansgaard–Oeschger events) in the ‘intermediate glacial’ state of the late Pleistocene, and in their potential analogues in the Jurassic ‘greenhouse’. Our findings indicate that external solar activity forcing was effective on decadal–centennial timescales, whilst the millennial-scale variations were likely amplified by internal process such as changes in deep-water formation strength, even during the Cretaceous ‘greenhouse’ period

Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: Possible association with malignancy

Objectives: Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Methods: Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Results: Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb-IV). Conclusions: While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy