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This corrects the article DOI: 10.1103/PhysRevLett.130.211001.
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Detailed measurements of the spectral structure of cosmic-ray electrons and positrons from 10.6 GeV to 7.5 TeV are presented from over 7 years of observations with the CALorimetric Electron Telescope (CALET) on the International Space Station. The instrument, consisting of a charge detector, an imaging calorimeter, and a total absorption calorimeter with a total depth of 30 radiation lengths at normal incidence and a fine shower imaging capability, is optimized to measure the all-electron spectrum well into the TeV region. Because of the excellent energy resolution (a few percent above 10 GeV) and the outstanding e/p separation (10^{5}), CALET provides optimal performance for a detailed search of structures in the energy spectrum. The analysis uses data up to the end of 2022, and the statistics of observed electron candidates has increased more than 3 times since the last publication in 2018. By adopting an updated boosted decision tree analysis, a sufficient proton rejection power up to 7.5 TeV is achieved, with a residual proton contamination less than 10%. The observed energy spectrum becomes gradually harder in the lower energy region from around 30 GeV, consistently with AMS-02, but from 300 to 600 GeV it is considerably softer than the spectra measured by DAMPE and Fermi-LAT. At high energies, the spectrum presents a sharp break around 1 TeV, with a spectral index change from -3.15 to -3.91, and a broken power law fitting the data in the energy range from 30 GeV to 4.8 TeV better than a single power law with 6.9 sigma significance, which is compatible with the DAMPE results. The break is consistent with the expected effects of radiation loss during the propagation from distant sources (except the highest energy bin). We have fitted the spectrum with a model consistent with the positron flux measured by AMS-02 below 1 TeV and interpreted the electron+positron spectrum with possible contributions from pulsars and nearby sources. Above 4.8 TeV, a possible contribution from known nearby supernova remnants, including Vela, is addressed by an event-by-event analysis providing a higher proton-rejection power than a purely statistical analysis.
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We present the observation of a charge-sign dependent solar modulation of galactic cosmic rays (GCRs) with the Calorimetric Electron Telescope onboard the International Space Station over 6 yr, corresponding to the positive polarity of the solar magnetic field. The observed variation of proton count rate is consistent with the neutron monitor count rate, validating our methods for determining the proton count rate. It is observed by the Calorimetric Electron Telescope that both GCR electron and proton count rates at the same average rigidity vary in anticorrelation with the tilt angle of the heliospheric current sheet, while the amplitude of the variation is significantly larger in the electron count rate than in the proton count rate. We show that this observed charge-sign dependence is reproduced by a numerical "drift model" of the GCR transport in the heliosphere. This is a clear signature of the drift effect on the long-term solar modulation observed with a single detector.
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Radiação Cósmica , Voo Espacial , Telescópios , Prótons , ElétronsRESUMO
We present the results of a direct measurement of the cosmic-ray helium spectrum with the CALET instrument in operation on the International Space Station since 2015. The observation period covered by this analysis spans from October 13, 2015, to April 30, 2022 (2392 days). The very wide dynamic range of CALET allowed for the collection of helium data over a large energy interval, from â¼40 GeV to â¼250 TeV, for the first time with a single instrument in low Earth orbit. The measured spectrum shows evidence of a deviation of the flux from a single power law by more than 8σ with a progressive spectral hardening from a few hundred GeV to a few tens of TeV. This result is consistent with the data reported by space instruments including PAMELA, AMS-02, and DAMPE and balloon instruments including CREAM. At higher energy we report the onset of a softening of the helium spectrum around 30 TeV (total kinetic energy). Though affected by large uncertainties in the highest energy bins, the observation of a flux reduction turns out to be consistent with the most recent results of DAMPE. A double broken power law is found to fit simultaneously both spectral features: the hardening (at lower energy) and the softening (at higher energy). A measurement of the proton to helium flux ratio in the energy range from 60 GeV/n to about 60 TeV/n is also presented, using the CALET proton flux recently updated with higher statistics.
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BACKGROUND: Limited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology. PATIENTS AND METHODS: The study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index. RESULTS: The distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model. CONCLUSIONS: The pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
The relative abundance of cosmic ray nickel nuclei with respect to iron is by far larger than for all other transiron elements; therefore it provides a favorable opportunity for a low background measurement of its spectrum. Since nickel, as well as iron, is one of the most stable nuclei, the nickel energy spectrum and its relative abundance with respect to iron provide important information to estimate the abundances at the cosmic ray source and to model the Galactic propagation of heavy nuclei. However, only a few direct measurements of cosmic-ray nickel at energy larger than â¼3 GeV/n are available at present in the literature, and they are affected by strong limitations in both energy reach and statistics. In this Letter, we present a measurement of the differential energy spectrum of nickel in the energy range from 8.8 to 240 GeV/n, carried out with unprecedented precision by the Calorimetric Electron Telescope (CALET) in operation on the International Space Station since 2015. The CALET instrument can identify individual nuclear species via a measurement of their electric charge with a dynamic range extending far beyond iron (up to atomic number Z=40). The particle's energy is measured by a homogeneous calorimeter (1.2 proton interaction lengths, 27 radiation lengths) preceded by a thin imaging section (3 radiation lengths) providing tracking and energy sampling. This Letter follows our previous measurement of the iron spectrum [1O. Adriani et al. (CALET Collaboration), Phys. Rev. Lett. 126, 241101 (2021).PRLTAO0031-900710.1103/PhysRevLett.126.241101], and it extends our investigation on the energy dependence of the spectral index of heavy elements. It reports the analysis of nickel data collected from November 2015 to May 2021 and a detailed assessment of the systematic uncertainties. In the region from 20 to 240 GeV/n our present data are compatible within the errors with a single power law with spectral index -2.51±0.07.
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We present the measurement of the energy dependence of the boron flux in cosmic rays and its ratio to the carbon flux in an energy interval from 8.4 GeV/n to 3.8 TeV/n based on the data collected by the Calorimetric Electron Telescope (CALET) during â¼6.4 yr of operation on the International Space Station. An update of the energy spectrum of carbon is also presented with an increase in statistics over our previous measurement. The observed boron flux shows a spectral hardening at the same transition energy E_{0}â¼200 GeV/n of the C spectrum, though B and C fluxes have different energy dependences. The spectral index of the B spectrum is found to be γ=-3.047±0.024 in the interval 25
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A precise measurement of the cosmic-ray proton spectrum with the Calorimetric Electron Telescope (CALET) is presented in the energy interval from 50 GeV to 60 TeV, and the observation of a softening of the spectrum above 10 TeV is reported. The analysis is based on the data collected during â¼6.2 years of smooth operations aboard the International Space Station and covers a broader energy range with respect to the previous proton flux measurement by CALET, with an increase of the available statistics by a factor of â¼2.2. Above a few hundred GeV we confirm our previous observation of a progressive spectral hardening with a higher significance (more than 20 sigma). In the multi-TeV region we observe a second spectral feature with a softening around 10 TeV and a spectral index change from -2.6 to -2.9 consistently, within the errors, with the shape of the spectrum reported by DAMPE. We apply a simultaneous fit of the proton differential spectrum which well reproduces the gradual change of the spectral index encompassing the lower energy power-law regime and the two spectral features observed at higher energies.
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XPC deficiency is associated with mitochondrial dysfunction, increased mitochondrial H2O2 production and sensitivity to the Complex III inhibitor antimycin A (AA), through a yet unclear mechanism. We found an imbalanced expression of several proteins that participate in important mitochondrial function and increased expression and phosphorylation of the tumor suppressor p53 in Xeroderma pigmentosum complementation group C (XP-C) (XPC-null) cells compared with an isogenic line corrected in locus with wild-type XPC (XPC-wt). Interestingly, inhibition of p53 nuclear import reversed the overexpression of mitochondrial proteins, whereas AA treatment increased p53 expression more strongly in the XP-C cells. However, inhibition of p53 substantially increased XP-C cellular sensitivity to AA treatment, suggesting that p53 is a critical factor mediating the cellular response to mitochondrial stress. On the other hand, treatment with the antioxidant N-acetylcysteine increased glutathione concentration and decreased basal H2O2 production, p53 levels and sensitivity to AA treatment in the XPC-null back to the levels found in XPC-wt cells. Thus, the results suggest a critical role for mitochondrially generated H2O2 in the regulation of p53 expression, which in turn modulates XP-C sensitivity to agents that cause mitochondrial stress.
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Proteínas de Ligação a DNA/genética , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Transformada , HumanosRESUMO
BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
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Neoplasias do Colo , Estudo de Associação Genômica Ampla , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia , Oxaliplatina/efeitos adversos , Estudos ProspectivosRESUMO
Hybridization of Bogoliubov quasiparticles (BQPs) between the CuO_{2} layers in the triple-layer cuprate high-temperature superconductor Bi_{2}Sr_{2}Cu_{2}Cu_{3}O_{10+δ} is studied by angle-resolved photoemission spectroscopy (ARPES). In the superconducting state, an anticrossing gap opens between the outer- and inner-BQP bands, which we attribute primarily to interlayer single-particle hopping with possible contributions from interlayer Cooper pairing. We find that the d-wave superconducting gap of both BQP bands smoothly develops with momentum without an abrupt jump in contrast to a previous ARPES study. Hybridization between the BQPs also gradually increases in going from the off nodal to the antinodal region, which is explained by the momentum dependence of the interlayer single-particle hopping. As possible mechanisms for the enhancement of the superconducting transition temperature, the hybridization between the BQPs as well as the combination of phonon modes of the triple CuO_{2} layers and spin fluctuations represented by a four-well model are discussed.
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The Calorimetric Electron Telescope (CALET), in operation on the International Space Station since 2015, collected a large sample of cosmic-ray iron over a wide energy interval. In this Letter a measurement of the iron spectrum is presented in the range of kinetic energy per nucleon from 10 GeV/n to 2.0 TeV/n allowing the inclusion of iron in the list of elements studied with unprecedented precision by space-borne instruments. The measurement is based on observations carried out from January 2016 to May 2020. The CALET instrument can identify individual nuclear species via a measurement of their electric charge with a dynamic range extending far beyond iron (up to atomic number Z=40). The energy is measured by a homogeneous calorimeter with a total equivalent thickness of 1.2 proton interaction lengths preceded by a thin (3 radiation lengths) imaging section providing tracking and energy sampling. The analysis of the data and the detailed assessment of systematic uncertainties are described and results are compared with the findings of previous experiments. The observed differential spectrum is consistent within the errors with previous experiments. In the region from 50 GeV/n to 2 TeV/n our present data are compatible with a single power law with spectral index -2.60±0.03.
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Nesfatin-1, a pleotropic peptide, was recently implicated in the regulation of anxiety and depression-like behavior in rats. However, the underlying mechanisms remain unclear so far. Thus, this study aimed to investigate the role of endogenous nesfatin-1 in the mediation of anxiety and depression-like behavior induced by corticotropin-releasing factor (CRF). Therefore, normal weight male intracerebroventricularly (icv) cannulated Sprague Dawley rats received two consecutive icv injections of anti-nesfatin-1 antibody or IgG control antibody followed by CRF or saline, before being exposed to a behavioral test. In the elevated zero maze test, assessing anxiety and explorative behavior, blockade of nesfatin-1 using an anti-nesfatin-1 antibody under basal conditions increased the number of entries into the open arms compared to control antibody/vehicle (1.6-fold, p < 0.05) and the time in open arms compared to the other groups (p < 0.05). Control antibody/CRF-treated animals tended to spend less time in the open arms compared to control antibody/vehicle (0.7-fold, p = 0.17), an effect not altered by the nesfatin-1 antibody (control antibody/CRF-treated animals vs. nesfatin-1 antibody/CRF group, p = 1.00). In the novelty-induced hypophagia test, assessing anhedonia as part of depression-like behavior, no significant differences were observed between the four groups for the latency to the first bout, number of bouts and the amount of palatable snack eaten (p > 0.05). In summary, CRF tended to increase anxiety and explorative behavior an effect not altered by blockade of nesfatin-1, whereas no significant effect of CRF on anhedonia was observed. Blockade of endogenous nesfatin-1 significantly decreased anxiety-like behavior giving rise to a physiological role of brain nesfatin-1 in the mediation of anxiety.
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Ansiolíticos/uso terapêutico , Anticorpos/uso terapêutico , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Hormônio Liberador da Corticotropina , Nucleobindinas/antagonistas & inibidores , Animais , Ansiedade/prevenção & controle , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/prevenção & controle , Masculino , Ratos Sprague-DawleyRESUMO
Peroxiredoxins (PRXs) are intracellular anti-oxidative enzymes but work as inflammatory amplifiers under the extracellular condition. To date, the function of PRXs in the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is not fully understood. The aim of this study was to investigate whether PRXs play a role in the pathogenesis of MS and NMOSD. We analyzed levels of PRXs (PRX1, PRX5 and PRX6) in the cerebrospinal fluid (CSF) and serum of 16 patients with MS, 16 patients with NMOSD and 15 patients with other neurological disorders (ONDs). We identified potential correlations between significantly elevated PRXs levels and the clinical variables in patients with MS and NMOSD. Additionally, pathological analyses of PRXs (PRX1-6) in the central nervous system (CNS) were performed using the experimental autoimmune encephalomyelitis (EAE), animal model of MS. We found that serum levels of PRX5 and PRX6 in patients with MS and NMOSD were higher compared with those in patients with ONDs (P < 0·05). Furthermore, high levels of PRX5 and PRX6 were partly associated with blood-brain barrier dysfunction and disease duration in NMOSD patients. No significant elevation was found in CSF PRXs levels of MS and NMOSD. Spinal cords from EAE mice showed remarkable PRX5 staining, especially in CD45+ infiltrating cells. In conclusion, PRX5 and PRX6 may play a role in the pathogeneses of MS and NMOSD.
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Encefalomielite Autoimune Experimental/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Peroxirredoxinas/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Barreira Hematoencefálica/enzimologia , Barreira Hematoencefálica/patologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Neuromielite Óptica/patologia , Medula Espinal/enzimologia , Medula Espinal/patologiaRESUMO
AIMS: Nakajo-Nishimura syndrome (NNS) is an autosomal recessive disease caused by biallelic mutations in the PSMB8 gene that encodes the immunoproteasome subunit ß5i. There have been only a limited number of reports on the clinicopathological features of the disease in genetically confirmed cases. METHODS: We studied clinical and pathological features of three NNS patients who all carry the homozygous p.G201V mutations in PSMB8. Patients' muscle specimens were analysed with histology and immunohistochemistry. RESULTS: All patients had episodes of typical periodic fever and skin rash, and later developed progressive muscle weakness and atrophy, similar to previous reports. Oral corticosteroid was used for treatment but showed no obvious efficacy. On muscle pathology, lymphocytes were present in the endomysium surrounding non-necrotic fibres, as well as in the perimysium perivascular area. Nearly all fibres strongly expressed MHC-I in the sarcolemma. In the eldest patient, there were abnormal protein aggregates in the sarcoplasm, immunoreactive to p62, TDP-43 and ubiquitin antibodies. CONCLUSIONS: These results suggest that inflammation, inclusion pathology and aggregation of abnormal proteins underlie the progressive clinical course of the NNS pathomechanism.
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Eritema Nodoso/genética , Eritema Nodoso/patologia , Dedos/anormalidades , Corpos de Inclusão/genética , Corpos de Inclusão/patologia , Miosite/genética , Miosite/patologia , Retículo Sarcoplasmático/patologia , Adulto , Idade de Início , Pré-Escolar , Exantema/genética , Exantema/patologia , Feminino , Febre/genética , Febre/patologia , Dedos/patologia , Genes MHC Classe I/genética , Humanos , Lactente , Linfócitos/patologia , Masculino , Debilidade Muscular/genética , Debilidade Muscular/patologia , Mutação/genética , Fibras Nervosas/patologia , Complexo de Endopeptidases do Proteassoma/genética , Sarcolema/patologia , Adulto JovemRESUMO
BACKGROUND: The right hepatic venous system consists of the right hepatic vein (RHV) and inferior RHVs (IRHVs). When the right posterior section is used as a graft for liver transplantation, understanding variations and relationships between the RHV and IRHVs is critical for graft venous return and hepatic vein reconstruction. This study aimed to evaluate variations in the hepatic veins and the relationships between them. METHODS: The medical records and CT images of patients who underwent hepatectomy as liver donors were assessed retrospectively. The relationship between the veins was evaluated by three-dimensional CT. RESULTS: The configuration of the posterior section was classified into one of eight types based on the RHV and IRHVs in 307 patients. Type 1a (103 of 307), type 1b (139 of 307) and type 2a (40 of 307) accounted for 91·9 per cent of the total. The diameter of the RHV extending towards the inferior vena cava had a significant inverse correlation with that of the IRHV (r2 = -0·615, P < 0·001). Type 1a, which had no IRHVs, had the RHV with the largest diameter; conversely, type 2a, which had a large IRHV, had the RHV with the smallest diameter. CONCLUSION: The hepatic venous system of the right posterior section was classified into eight types, with an inverse relationship between RHV and IRHV sizes. This information is useful for segment VII resection or when the right liver is used as a transplant graft.
ANTECEDENTES: El sistema venoso hepático derecho consiste en la vena hepática derecha (right hepatic vein, RHV) y las RHVs inferiores (IRHVs). Cuando se utiliza la sección posterior derecha hepática como injerto para el trasplante hepático, es fundamental conocer las variaciones e interrelaciones entre la RHV y las IRHVs para el retorno venoso del injerto y la reconstrucción de la vena hepática. El objetivo de este estudio fue determinar las variaciones en las venas hepáticas y sus interrelaciones. MÉTODOS: Se evaluaron retrospectivamente las historias clínicas y las imágenes de la tomografía computarizada de los pacientes que se sometieron a una hepatectomía como donantes vivos para trasplante hepático. La interrelación entre las venas se evaluó mediante imágenes de CT tridimensional. RESULTADOS: La configuración de la sección posterior clasificó a 307 pacientes en base a la RHV y a las IRHVs. Se clasificaron en 8 tipos, de los cuales el Tipo 1a (103/307), el Tipo 1b (139/307) y el Tipo 2a (40/307) representaron el 92% del total. El diámetro de la RHV que se extiende hacia la vena cava inferior presentó una correlación inversa significativa con la de las IRHV (r2: −0,632, P < 0,0001). El diámetro mayor de la RHV se observó en el Tipo 1a, que no presentaba IRHVs; por el contrario, el diámetro más pequeño se observó en el Tipo 2a que presentaba una IRHV grande. CONCLUSIÓN: El sistema venoso hepático de la sección posterior derecha se clasificó en 8 subtipos con una relación inversa entre los tamaños de la RHV y las IRHV. Esta información es útil cuando se practica una resección del segmento 7 o cuando se utiliza el hígado derecho como injerto para el trasplante.
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Veias Hepáticas/diagnóstico por imagem , Doadores de Tecidos , Veias Hepáticas/anatomia & histologia , Veias Hepáticas/cirurgia , Humanos , Imageamento Tridimensional , Fígado/irrigação sanguínea , Transplante de Fígado/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
In this paper, we present the measurement of the energy spectra of carbon and oxygen in cosmic rays based on observations with the Calorimetric Electron Telescope on the International Space Station from October 2015 to October 2019. Analysis, including the detailed assessment of systematic uncertainties, and results are reported. The energy spectra are measured in kinetic energy per nucleon from 10 GeV/n to 2.2 TeV/n with an all-calorimetric instrument with a total thickness corresponding to 1.3 nuclear interaction length. The observed carbon and oxygen fluxes show a spectral index change of â¼0.15 around 200 GeV/n established with a significance >3σ. They have the same energy dependence with a constant C/O flux ratio 0.911±0.006 above 25 GeV/n. The spectral hardening is consistent with that measured by AMS-02, but the absolute normalization of the flux is about 27% lower, though in agreement with observations from previous experiments including the PAMELA spectrometer and the calorimetric balloon-borne experiment CREAM.
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BACKGROUND AND PURPOSE: The silent progression of patients with multiple sclerosis (MS) has been reported. The aim of this study was to investigate the association between brain atrophy rates and disease-modifying drugs (DMDs) in patients with MS during their relapse-free period. METHODS: Patients with relapsing-remitting MS were classified into two groups on the basis of clinical records, i.e. a first-generation DMD group treated with interferon-beta-1a, interferon-beta-1b or glatiramer acetate and a second-generation DMD group treated with dimethyl fumarate, fingolimod or natalizumab. Brain volume was calculated with SPM12. RESULTS: A total of 45 patients with relapsing-remitting MS were enrolled in the first-generation (n = 22) or second-generation (n = 23) DMD group. The annualized relapse rate was lower in the first-generation than in the second-generation DMD group (median 0.26 vs. 0.59; P < 0.001). The annualized atrophy rate of the normalized brain volume was not different between the first- and second-generation DMD groups after analysis of covariance (median 0.13% vs. 0.59%; P = 0.17). CONCLUSIONS: The median annualized atrophy rate of normalized brain volume in the first-generation DMD group was similar to the previously reported annual brain atrophy rate of healthy controls, which may suggest that treatment with a first-generation DMD need not be changed when patients with MS are clinically inactive.
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Esclerose Múltipla Recidivante-Remitente , Atrofia , Encéfalo/diagnóstico por imagem , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/uso terapêutico , Humanos , Imunossupressores , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , RecidivaRESUMO
BACKGROUND: Palliative care (PC) is increasingly recognized as essential for oncology care, and several academic societies strongly recommend integrating oncology and palliative care (IOP) in daily practice. Similarly, the Japanese government encouraged the implementation of IOP through the Cancer Control Act of 2007; however, its detailed progress remains unclear. Therefore, this cross-sectional nationwide survey was conducted to investigate the current status and hospital executive physicians' perception of IOP. METHODS: The questionnaire was developed based on IOP indicators with international consensus. It was distributed to executive physicians at all government-designated cancer hospitals (DCHs, n = 399) and matched non-DCHs (n = 478) in November 2017 and the results were compared. RESULTS: In total, 269 (67.4%) DCHs and 259 (54.2%) non-DCHs responded. The number of PC resources in DCHs was significantly higher than those in non-DCHs (e.g., full-time PC physicians and nurses, 52.8% vs. 14.0%, p < 0.001; availability of outpatient PC service ≥3 days per week, 47.6% vs. 20.7%, p < 0.001). Routine symptom screening was more frequently performed in DCHs than in non-DCHs (65.1% vs. 34.7%, p < 0.001). Automatic trigger for PC referral availability was limited (e.g., referral using time trigger, 14.9% vs. 15.3%, p = 0.700). Education and research opportunities were seriously limited in both types of hospitals. Most executive physicians regarded IOP as beneficial for their patients (95.9% vs. 94.7%, p = 0.163) and were willing to facilitate an early referral to PC services (54.7% vs. 60.0%, p < 0.569); however, the majority faced challenges to increase the number of full-time PC staff, and < 30% were planning to increase the staff members. CONCLUSIONS: This survey highlighted a considerable number of IOP indicators met, particularly in DCHs probably due to the government policy. Further efforts are needed to address the serious research/educational gaps.
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Prestação Integrada de Cuidados de Saúde/tendências , Serviço Hospitalar de Oncologia/tendências , Cuidados Paliativos/métodos , Estudos Transversais , Prestação Integrada de Cuidados de Saúde/métodos , Prestação Integrada de Cuidados de Saúde/normas , Humanos , Japão , Serviço Hospitalar de Oncologia/normas , Cuidados Paliativos/normas , Cuidados Paliativos/tendências , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Although potato as a crop is commercially grown from seed tubers, plants grown from tissue culture plantlets are often used in physiological studies including freezing tolerance determination. OBJECTIVE: This study aimed to examine the effects of the source of plants on freezing tolerance of potato plants at young developmental stages. MATERIALS AND METHODS: We compared freezing tolerance and contents of soluble proteins and sugars of Solanum tuberosum plants derived from tissue culture with those derived from tubers before and after cold acclimation. RESULTS: Tuber-derived plants showed significantly higher freezing tolerance than tissue-culture-derived plants after cold acclimation, although non-acclimated plants did not show any marked differences. Soluble protein contents were higher in tuber-derived plants regardless of cold acclimation. Sucrose content increased to a higher level in tuber-derived plants after cold acclimation. CONCLUSION: These results suggest that source of plant tissue can have a significant effect on the response of young potato plants to freezing stress and that the use of tissue culture plants in freezing tolerance studies may not accurately reflect the frost tolerance of commercially grown plants.