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1.
Chembiochem ; : e202400468, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075031

RESUMO

DNA condensates, formed by liquid-liquid phase separation (LLPS), emerge as promising soft matter assemblies for creating artificial cells. The advantages of DNA condensates are their molecular permeability through the surface due to their membrane-less structure and their fluidic property. However, they face challenges in the design of their surface, e.g., unintended fusion and less regulation of permeable molecules. Addressing them, we report surface modification of DNA condensates with DNA origami nanoparticles, employing a Pickering-emulsion strategy. We successfully constructed core-shell structures with DNA origami coatings on DNA condensates and further enhanced the condensate stability toward fusion via connecting DNA origamis by responding to DNA input strands. The 'armoring' prevented the fusion of DNA condensates, enabling the formation of multicellular-like structures of DNA condensates. Moreover, the permeability was altered through the state change from coating to armoring the DNA condensates. The armored DNA condensates have significant potential for constructing artificial cells, offering increased surface stability and selective permeability for small molecules while maintaining compartmentalized space and multicellular organization.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39002122

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and efficacy (as an exploratory endpoint) of TCK-276, a novel CDK4/6 inhibitor, after multiple oral doses for 7 days in patients with active RA. METHODS: This multicentre, randomized, placebo-controlled, dose-ascending, double-blind, phase 1b, multiple-dose study included 32 patients with active RA in 4 cohorts of 8 patients (6 active and 2 matching placebo), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily). The doses of TCK-276 were 10, 25, 75, and 175 mg/day. Safety and pharmacokinetic endpoints, and exploratory disease activity parameters for RA were assessed. RESULTS: There were no deaths, serious adverse events, notable clinically meaningful laboratory findings (including hematological changes), clinically meaningful vital sign changes, or clinically meaningful electrocardiogram or cardiac telemetry changes. TCK-276 was rapidly absorbed and the half-life time ranged approximately from 6 to 12 hours. No obvious accumulation was observed, and the increase in TCK-276 exposure was dose proportional. At day 7, DAS28-CRP responses (EULAR good or moderate responses) were observed in 40%, 80%, and 66.7% at 25, 75, and 175 mg/day TCK-276, respectively, versus 12.5% in placebo; ACR20 responses were 33.3%, 60%, and 50% respectively, versus none in placebo. CONCLUSION: TCK-276 (≤175 mg) was well tolerated with no clinically meaningful safety signals in patients with active RA. Together with the preliminary efficacy (≥25 mg/day), these data warrant further study of TCK-276 for the treatment of active RA. TRIAL REGISTRATION: ClinicalTrails.gov, NCT05437419.

3.
PLoS Biol ; 19(12): e3001459, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860826

RESUMO

Memory is initially labile but can be consolidated into stable long-term memory (LTM) that is stored in the brain for extended periods. Despite recent progress, the molecular and cellular mechanisms underlying the intriguing neurobiological processes of LTM remain incompletely understood. Using the Drosophila courtship conditioning assay as a memory paradigm, here, we show that the LIM homeodomain (LIM-HD) transcription factor Apterous (Ap), which is known to regulate various developmental events, is required for both the consolidation and maintenance of LTM. Interestingly, Ap is involved in these 2 memory processes through distinct mechanisms in different neuronal subsets in the adult brain. Ap and its cofactor Chip (Chi) are indispensable for LTM maintenance in the Drosophila memory center, the mushroom bodies (MBs). On the other hand, Ap plays a crucial role in memory consolidation in a Chi-independent manner in pigment dispersing factor (Pdf)-containing large ventral-lateral clock neurons (l-LNvs) that modulate behavioral arousal and sleep. Since disrupted neurotransmission and electrical silencing in clock neurons impair memory consolidation, Ap is suggested to contribute to the stabilization of memory by ensuring the excitability of l-LNvs. Indeed, ex vivo imaging revealed that a reduced function of Ap, but not Chi, results in exaggerated Cl- responses to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in l-LNvs, indicating that wild-type (WT) Ap maintains high l-LNv excitability by suppressing the GABA response. Consistently, enhancing the excitability of l-LNvs by knocking down GABAA receptors compensates for the impaired memory consolidation in ap null mutants. Overall, our results revealed unique dual functions of the developmental regulator Ap for LTM consolidation in clock neurons and LTM maintenance in MBs.


Assuntos
Relógios Biológicos/fisiologia , Encéfalo/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Proteínas com Homeodomínio LIM/metabolismo , Consolidação da Memória/fisiologia , Memória de Longo Prazo/fisiologia , Corpos Pedunculados/fisiologia , Neurônios/fisiologia , Fatores de Transcrição/metabolismo , Animais , Proteínas de Drosophila/genética , Heterozigoto , Proteínas com Homeodomínio LIM/genética , Modelos Biológicos , Mutação/genética , Fenótipo , Transmissão Sináptica/fisiologia , Fatores de Transcrição/genética , Ácido gama-Aminobutírico/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-39190721

RESUMO

OBJECTIVE: This study aimed to evaluate the feasibility of the recently commercialized reverse encoding distortion correction (RDC) method for echo-planar imaging (EPI) diffusion-weighted imaging (DWI) by applying clinical head MRI. METHODS: This study included 50 consecutive patients who underwent head MRI, including single-shot (SS) EPI DWI and RDC-EPI DWI. For evaluation of normal structures, qualitative scores for image distortion, Dice similarity coefficient (DSC) values, distortion ratios, and mean apparent diffusion coefficient (ADC) values were assessed in the pons, temporal lobe at the skull base, and frontal lobe at the level of the lateral ventricles in 30 patients. To evaluate pathologies, qualitative scores for image distortion were assessed for 25 intracranial and 21 extracranial pathologies identified in 32 patients. RESULTS: Qualitative scores for image distortion, DSC values, distortion ratios, and mean ADC values of the pons and temporal lobe were significantly different between SS-EPI DWI and RDC-EPI DWI, whereas those of the frontal lobe at the level of the lateral ventricles were not significantly different between the 2 DWIs. The qualitative scores for image distortion and mean ADC values of extracranial pathologies were significantly different between the DWIs, whereas those of intracranial pathologies were not significantly different. CONCLUSIONS: RDC-EPI DWI significantly reduced image distortion and showed higher mean ADC values of the brain parenchyma in the skull base and extracranial pathologies.

5.
Neuropathology ; 44(2): 154-160, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37717977

RESUMO

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.


Assuntos
Demência Frontotemporal , Degeneração Lobar Frontotemporal , Afasia Primária Progressiva não Fluente , Proteinopatias TDP-43 , Masculino , Humanos , Pessoa de Meia-Idade , Afasia Primária Progressiva não Fluente/patologia , Degeneração Lobar Frontotemporal/patologia , Proteinopatias TDP-43/patologia , Proteínas de Ligação a DNA/metabolismo
6.
Neuropathology ; 44(4): 298-303, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38291581

RESUMO

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.


Assuntos
Degeneração Corticobasal , Alucinações , Humanos , Masculino , Alucinações/patologia , Alucinações/etiologia , Idoso , Degeneração Corticobasal/patologia , Degeneração Corticobasal/complicações
7.
BMC Pediatr ; 24(1): 551, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192238

RESUMO

BACKGROUND: Pediatric patients with eating disorders in a multicenter joint study on 11 facilities were enrolled and prospectively investigated to determine whether improvement in body weight, eating attitudes, and psychosocial factors in children with eating disorders would also improve depressive symptoms. METHODS: In this study, 91 patients were enrolled between April 2014 and March 2016. The severity of underweight was assessed using the body mass index-standard deviation score (BMI-SDS), eating behavior was assessed using the children's eating attitude test (ChEAT26), the outcome of childhood eating disorders was assessed using the childhood eating disorder outcome scale, and depressive symptoms were assessed using the Children's Depression Inventory (CDI) score. RESULTS: After 12 months of treatment, depressive symptoms were evaluated in 62 of the 91 cases where it was evaluated at the initial phase. There was no difference in background characteristics between the included patients and the 29 patients who dropped out. A paired-sample t-test revealed a significant decrease in CDI scores after 12 months of treatment (p < 0.001, 95% CI: 2.401-7.373) and a significant increase in the BMI-SDS (p < 0.001, 95% CI: - 2.41973-1.45321). Multiple regression analysis revealed that BMI-SDS and ChEAT26 scores at the initial phase were beneficial in CDI recovery. In addition, BMI-SDS at the initial phase was useful for predicting BMI-SDS recovery after 12 months of treatment. CONCLUSIONS: Depressive symptoms in children with eating disorders improved with therapeutic intervention on body weight and eating attitudes. TRIAL REGISTRATION: The Clinical Trial Number for this study is UMIN000055004.


Assuntos
Peso Corporal , Depressão , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Masculino , Estudos Prospectivos , Criança , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Comportamento Alimentar/psicologia , Índice de Massa Corporal , Adolescente
8.
J Orthop Sci ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39147648

RESUMO

BACKGROUND: To evaluate the relationship between the pattern and severity of metatarsophalangeal (MTP) joint dislocation in the lesser toes and severity of joint destruction in rheumatoid forefoot deformities. METHODS: Participants comprised of 13 patients (16 feet) who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the MTP joints. Correlations between preoperative radiographic findings and histological grades second to fifth metatarsal heads taken intraoperatively were analyzed. RESULTS: In 62 metatarsal heads, complete dislocation of the MTP joint in the lesser toes significantly resulted in severe joint destruction compared to mild or moderate dislocation (P < 0.05). The proportion of severe cartilage damage in MTP joints with complete dislocation was 100 % in the 5th MTP joint, 83.3 % in the 4th MTP joint, and 58.3 % in the 2nd and 3rd MTP joints. Moreover, complete dislocation of the MTP joints in the lateral column showed the most severe joint destruction compared to that in the medial column (P = 0.03). CONCLUSION: Complete dislocation of the MTP joint in the lateral column is related to joint destruction in rheumatoid forefoot deformities.

9.
J Orthop Sci ; 29(2): 637-645, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36931976

RESUMO

BACKGROUND: The objectives of this study were to clarify whether localized extremity soft tissue sarcoma (STS) patients who underwent amputation surgery experienced worsened survival and to identify those patients for whom amputation surgery worsened survival. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified 8897 patients with localized extremity STS between 1983 and 2016. Of these 6431 patients, 733 patients underwent amputation surgery (Amputation group), and 5698 underwent limb-sparing surgery (Limb-sparing group). RESULTS: After adjusting for patient background by propensity score matching, a total of 1346 patients were included. Patients in the Amputation group showed worsened survival (cancer-specific survival (CSS): hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.15-1.75, overall survival (OS): HR = 1.41, 95%CI 1.20-1.65). In subclass analysis, patients with high-grade STS, spindle cell sarcoma and liposarcoma in the Amputation group showed shortened survival (high-grade-CSS: HR = 1.44, 95%CI 1.16-1.77, OS: HR = 1.38, 95%CI 1.18-1.62; spindle cell sarcoma-CSS: HR = 4.75, 95%CI 1.56-14.4, OS: HR = 2.32, 95%CI 1.45-3.70; liposarcoma-CSS: HR = 2.91, 95%CI 1.54-5.50, OS: HR = 2.32, 95%CI 1.45-3.70). CONCLUSIONS: Survival was shortened in localized extremity STS patients who received amputation surgery.


Assuntos
Lipossarcoma , Sarcoma , Humanos , Resultado do Tratamento , Extremidades/cirurgia , Sarcoma/cirurgia , Amputação Cirúrgica , Estudos Retrospectivos , Prognóstico
10.
Genes Cells ; 27(4): 266-279, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35094465

RESUMO

A newly formed memory is initially unstable. However, if it is consolidated into the brain, the consolidated memory is stored as stable long-term memory (LTM). Despite the recent progress, the molecular and cellular mechanisms of LTM have not yet been fully elucidated. The fruitfly Drosophila melanogaster, for which various genetic tools are available, has been used to clarify the molecular mechanisms of LTM. Using the Drosophila courtship-conditioning assay as a memory paradigm, we previously identified that the circadian clock gene period (per) plays a vital role in consolidating LTM, suggesting that per-expressing clock neurons are critically involved in LTM. However, it is still incompletely understood which clock neurons are essential for LTM. Here, we show that dorsal-lateral clock neurons (LNds) play a crucial role in LTM. Using an LNd-specific split-GAL4 line, we confirmed that disruption of synaptic transmission in LNds impaired LTM maintenance. On the other hand, induction of per RNAi or the dominant-negative transgene of Per in LNds impaired LTM consolidation. Our results reveal that transmitter release and Per function in LNds are involved in courtship memory processing.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Memória de Longo Prazo/fisiologia , Corpos Pedunculados/fisiologia , Neurônios/fisiologia
11.
Eur Radiol ; 33(1): 348-359, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35751697

RESUMO

OBJECTIVES: To compare the performance of radiologists in characterizing and diagnosing pulmonary nodules/masses with and without deep learning (DL)-based computer-aided diagnosis (CAD). METHODS: We studied a total of 101 nodules/masses detected on CT performed between January and March 2018 at Osaka University Hospital (malignancy: 55 cases). SYNAPSE SAI Viewer V1.4 was used to analyze the nodules/masses. In total, 15 independent radiologists were grouped (n = 5 each) according to their experience: L (< 3 years), M (3-5 years), and H (> 5 years). The likelihoods of 15 characteristics, such as cavitation and calcification, and the diagnosis (malignancy) were evaluated by each radiologist with and without CAD, and the assessment time was recorded. The AUCs compared with the reference standard set by two board-certified chest radiologists were analyzed following the multi-reader multi-case method. Furthermore, interobserver agreement was compared using intraclass correlation coefficients (ICCs). RESULTS: The AUCs for ill-defined boundary, irregular margin, irregular shape, calcification, pleural contact, and malignancy in all 15 radiologists, irregular margin and irregular shape in L and ill-defined boundary and irregular margin in M improved significantly (p < 0.05); no significant improvements were found in H. L showed the greatest increase in the AUC for malignancy (not significant). The ICCs improved in all groups and for nearly all items. The median assessment time was not prolonged by CAD. CONCLUSIONS: DL-based CAD helps radiologists, particularly those with < 5 years of experience, to accurately characterize and diagnose pulmonary nodules/masses, and improves the reproducibility of findings among radiologists. KEY POINTS: • Deep learning-based computer-aided diagnosis improves the accuracy of characterizing nodules/masses and diagnosing malignancy, particularly by radiologists with < 5 years of experience. • Computer-aided diagnosis increases not only the accuracy but also the reproducibility of the findings across radiologists.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Radiologistas , Diagnóstico por Computador/métodos , Computadores , Neoplasias Pulmonares/diagnóstico por imagem , Sensibilidade e Especificidade , Nódulo Pulmonar Solitário/diagnóstico por imagem
12.
J Clin Periodontol ; 50(10): 1406-1418, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37534736

RESUMO

AIM: To investigate the role of Ebi3-related cytokines (i.e., interleukin [IL]-35 and/or IL-27) in experimental periodontitis using Ebi3 knockout (KO) mice. MATERIALS AND METHODS: The maxillary right second molar teeth of Ebi3 KO mice and C57BL/6 mice were tied with a silk ligature to induce periodontitis. Three days after ligation, gingival tissues were collected for gene expression analyses. Five days after ligation, the maxillae were removed for haematoxylin and eosin staining and immunohistochemistry. Seven days after ligation, the maxillae were removed for micro-computed tomography. RESULTS: The ligated side of Ebi3 KO mice showed intense alveolar bone resorption, which was substantially more pronounced than in wild-type (WT) mice. IL-17A expression was significantly higher in the gingiva of the ligated side of Ebi3 KO mice compared with WT mice. IL-10 expression was significantly lower in Ebi3 KO mice than in WT mice. The ligature-induced alveolar bone resorption in Ebi3 KO mice that received recombinant IL-35 injection was significantly less compared with that in Ebi3 KO mice that received control injection. CONCLUSIONS: Together, these findings suggest that Th17 cells exacerbate experimental periodontitis in mice lacking Ebi3 and that IL-35 may play a critical role in inhibiting periodontal tissue destruction.


Assuntos
Perda do Osso Alveolar , Periodontite , Animais , Camundongos , Microtomografia por Raio-X , Células Th17 , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Periodontite/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Receptores de Citocinas
13.
J Assist Reprod Genet ; 40(12): 2787-2797, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37779181

RESUMO

PURPOSE: Although recent in vitro maturation (IVM) studies in pediatric patients have demonstrated successful retrieval and maturation of oocytes, the studies included only a small number of premenarchal patients. In the present study, we examined the potential use of oocyte retrieval and maturation for pediatric patients who undergo ovarian tissue cryopreservation (OTC). METHODS: We retrospectively examined the clinical records of pediatric patients who underwent OTC at our institution between October 2015 and December 2022. Data on the age, primary disease, menstrual history, pre-procedure chemotherapy, anti-Müllerian hormone (AMH) level, number of oocytes collected ex vivo from ovarian tissue, and number of mature oocytes from IVM were examined. RESULTS: Data of 60 pediatric patients (aged 1 to 17 years) were included for analysis. Oocytes were retrieved from 36 patients; the oocytes of 18 of these patients could be cryopreserved. The IVM rate was significantly lower in the premenarchal patients than in the postmenarchal patients. The number of mature oocytes retrieved from IVM was higher in the no-chemotherapy group than in the chemotherapy group. A significant positive correlation was observed between the AMH level and the IVM outcomes. CONCLUSION: Oocyte retrieval and maturation in pediatric patients undergoing OTC is particularly useful in those not receiving chemotherapy. In patients receiving chemotherapy, the AMH level may be useful for predicting the IVM outcome. Activation of the oocyte maturation process in vivo in pediatric patients and better understanding of the major regulators of oocyte maturation are necessary to improve the utility of the IVM procedure.


Assuntos
Preservação da Fertilidade , Humanos , Criança , Preservação da Fertilidade/métodos , Técnicas de Maturação in Vitro de Oócitos/métodos , Estudos Retrospectivos , Oócitos/fisiologia , Criopreservação/métodos , Hormônio Antimülleriano
14.
J Orthop Sci ; 28(6): 1392-1399, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36163118

RESUMO

BACKGROUND: The Japanese Orthopaedic Association National Registry (JOANR) was recently launched in Japan and is expected to improve the quality of medical care. However, surgeons must register ten detailed features for total hip arthroplasty, which is labor intensive. One possible solution is to use a system that automatically extracts information about the surgeries. Although it is not easy to extract features from an operative record consisting of free-text data, natural language processing has been used to extract features from operative records. This study aimed to evaluate the best natural language processing method for building a system that automatically detects some elements in the JOANR from the operative records of total hip arthroplasty. METHODS: We obtained operative records of total hip arthroplasty (n = 2574) in three hospitals and targeted two items: surgical approach and fixation technique. We compared the accuracy of three natural language processing methods: rule-based algorithms, machine learning, and bidirectional encoder representations from transformers (BERT). RESULTS: In the surgical approach task, the accuracy of BERT was superior to that of the rule-based algorithm (99.6% vs. 93.6%, p < 0.001), comparable to machine learning. In the fixation technique task, the accuracy of BERT was superior to the rule-based algorithm and machine learning (96% vs. 74%, p < 0.0001 and 94%, p = 0.0004). CONCLUSIONS: BERT is the most appropriate method for building a system that automatically detects the surgical approach and fixation technique.


Assuntos
Inteligência Artificial , Ortopedia , Humanos , Algoritmos , Sistema de Registros , Japão , Procedimentos Cirúrgicos Operatórios , Prontuários Médicos , Aprendizado de Máquina
15.
Allergol Int ; 72(3): 394-401, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36868950

RESUMO

BACKGROUND: The considerable prevalence and worse outcomes of asthma-COPD overlap (ACO) in COPD have been reported, and optimal introduction of ICS is essential for ACO. However, diagnostic criteria for ACO consist of multiple laboratory tests, which is challenging during this COVID-19 era. The purpose of this study was to create a simple questionnaire to diagnose ACO in patients with COPD. METHODS: Among 100 COPD patients, 53 were diagnosed with ACO based on the Japanese Respiratory Society Guidelines for ACO. Firstly, 10 candidate questionnaire items were generated and further selected by a logistic regression model. An integer-based scoring system was generated based on the scaled estimates of items. RESULTS: Five items, namely a history of asthma, wheezing, dyspnea at rest, nocturnal awakening, and weather- or season-dependent symptoms, contributed significantly to the diagnosis of ACO in COPD. History of asthma was related to FeNO >35 ppb. Two points were assigned to history of asthma and 1 point to other items in the ACO screening questionnaire (ACO-Q), and the area under the receiver operating characteristic curve was 0.883 (95% CI: 0.806-0.933). The best cutoff point was 1 point, and the positive predictive value was 100% at a cutoff of 3 points or higher. The result was reproducible in the validation cohort of 53 patients with COPD. CONCLUSIONS: A simple questionnaire, ACO-Q, was developed. Patients with scores ≥3 could be reasonably recommended to be treated as ACO, and additional laboratory testing would be recommended for patients with 1 and 2 points.


Assuntos
Asma , COVID-19 , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Asma/diagnóstico , Asma/epidemiologia , Dispneia , Inquéritos e Questionários , Teste para COVID-19
16.
Plant Physiol ; 185(4): 1429-1442, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33793920

RESUMO

Parasitic plants infect other plants by forming haustoria, specialized multicellular organs consisting of several cell types, each of which has unique morphological features and physiological roles associated with parasitism. Understanding the spatial organization of cell types is, therefore, of great importance in elucidating the functions of haustoria. Here, we report a three-dimensional (3-D) reconstruction of haustoria from two Orobanchaceae species, the obligate parasite Striga hermonthica infecting rice (Oryza sativa) and the facultative parasite Phtheirospermum japonicum infecting Arabidopsis (Arabidopsis thaliana). In addition, field-emission scanning electron microscopy observation revealed the presence of various cell types in haustoria. Our images reveal the spatial arrangements of multiple cell types inside haustoria and their interaction with host roots. The 3-D internal structures of haustoria highlight differences between the two parasites, particularly at the xylem connection site with the host. Our study provides cellular and structural insights into haustoria of S. hermonthica and P. japonicum and lays the foundation for understanding haustorium function.


Assuntos
Arabidopsis/parasitologia , Interações Hospedeiro-Parasita/fisiologia , Orobanchaceae/parasitologia , Orobanchaceae/ultraestrutura , Oryza/parasitologia , Raízes de Plantas/ultraestrutura , Striga/parasitologia , Striga/ultraestrutura , Arabidopsis/fisiologia , Imageamento Tridimensional , Orobanchaceae/fisiologia , Oryza/fisiologia , Raízes de Plantas/parasitologia
17.
Reprod Biomed Online ; 44(4): 667-676, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35279375

RESUMO

RESEARCH QUESTION: Are the revised patient selection criteria for fertility preservation of children and adolescents appropriate? DESIGN: A retrospective and prospective observational cohort study implemented at a university hospital approved for fertility preservation by an academic society. The characteristics of children and the process of fertility preservation consultation were investigated. Mortality, the longitudinal course of the endocrine profile and the menstrual cycle were confirmed in patients who underwent ovarian tissue cryopreservation (OTC) before the age of 18 years. RESULTS: Of the 74 children and adolescents referred for a fertility preservation consultation, 40 (54.1%) had haematological disease, which included patients with rare diseases. The mean age of patients was 11.1 ± 4.3 years (median 12 years, range 1-17 years). In accordance with the revised criteria, 31 (41.9%) patients had their ovarian tissue cryopreserved. Two out of 31 had complications after surgery (infection and drug allergy) and one patient with leukaemia (3.2%) had minimum residual disease on the extracted ovarian tissue. Of the 14 patients (>12 years) who completed treatment, 12 (85.7%) had primary ovarian insufficiency (POI) more than a year after treatment. Two out of 31 (6.5%) died because of recurrence of their underlying disease (median 28 months, range 0-60 months). Oocyte cryopreservation, as an additional and salvage fertility preservation treatment, was suggested to five patients with biochemical status POI (procedures pending). CONCLUSION: The primary disease and patients' ages varied in fertility preservation for children and adolescents. Our patient selection criteria might be appropriate over a short follow-up period.


Assuntos
Preservação da Fertilidade , Ovário , Adolescente , Criança , Criopreservação/métodos , Feminino , Preservação da Fertilidade/métodos , Humanos , Seleção de Pacientes , Estudos Prospectivos , Estudos Retrospectivos
18.
J Surg Oncol ; 126(7): 1299-1305, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35938632

RESUMO

BACKGROUND AND OBJECTIVES: Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. METHODS: We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. RESULTS: After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). CONCLUSIONS: Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.


Assuntos
Neoplasias Ósseas , Fibrossarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Neoplasias de Tecidos Moles/patologia , Fibrossarcoma/patologia , Modelos de Riscos Proporcionais , Extremidades/patologia , Programa de SEER
19.
J Surg Oncol ; 126(6): 1074-1079, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35791961

RESUMO

BACKGROUND AND OBJECTIVES: Noncontrast computed tomography of the chest is the standard imaging modality for cancer staging in patients with soft tissue sarcoma (STS), but appropriate candidates for liver screening have not been clarified. METHODS: We reviewed all patients with STS diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results database. Incidence of liver metastasis at initial presentation and high incidence of liver metastasis by histological subtype were investigated. In addition, risk factors for liver metastasis were investigated by multiple logistic regression analysis. RESULTS: After excluding patients without information about liver metastasis, cause of death or primary liver tumor, 47 260 patients were included in this study. Of those, 1471 patients (3.2%) showed liver metastasis at initial presentation. The histological subtype showing the highest incidence of liver metastasis was desmoplastic small round cell tumor (30.3%), followed by malignant hemangioendothelioma (11.5%) and angiomyoliposarcoma (10.5%). Deep-rooted tumor, location in the body wall, retroperitoneum, or thorax/peritoneum, high histological grade, and higher T stage were associated with higher incidences of liver metastasis at initial presentation. CONCLUSION: Risk factors for liver metastasis were deep location, trunk development, larger tumor size, high histological grade, and specific histological subtypes.


Assuntos
Neoplasias Hepáticas , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia
20.
Inorg Chem ; 61(19): 7537-7545, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35504293

RESUMO

Hexagonal perovskite-related oxides have garnered a great deal of research interest because of their high oxide-ion conductivity at intermediate temperatures, with Ba7Nb4MoO20 being a notable example. However, concomitant proton conduction in Ba7Nb4MoO20 may cause a decrease in power efficiency when used as the electrolyte in conventional solid oxide fuel cells. Here, through investigations of the transport and structural properties of Ba7Nb4-xWxMoO20+x/2 (x = 0-0.25), we show that the aliovalent substitution of Nb5+ by W6+ not only increases the oxide-ion conductivity but also dramatically lowers proton conductivity. The highest conductivity is achieved for x = 0.15 composition, with 2.2 × 10-2 S cm-1 at 600 °C, 2.2 times higher than that of pristine Ba7Nb4MoO20. The proton transport number of Ba7Nb3.85W0.15MoO20.075 is smaller compared with Ba7Nb4MoO20, Ba7Nb3.9Mo1.1O20.05, and Ba7Ta3.7Mo1.3O20.15. The structure analyses of neutron diffraction data of Ba7Nb3.85W0.15MoO20.075 at 25 and 800 °C reveal that the aliovalent W6+ doping introduces interstitial oxide ions in the intrinsically oxygen-deficient c' layers, thereby simultaneously increasing the carrier concentration for oxide-ion conduction and decreasing oxygen vacancies responsible for dissociative absorption of water. Neutron scattering length density distribution was examined using the maximum-entropy method and neutron diffraction data at 800 °C, which indicates the interstitialcy oxide-ion diffusion in the c' layers of Ba7Nb3.85W0.15MoO20.075. Ba7Nb3.85W0.15MoO20.075 exhibits extremely high chemical and electrical stability in the wide oxygen partial pressure P(O2) region [ex. 10-23 ≤ P(O2) ≤ 1 atm at 903 °C]. The present results offer a strategy for developing pure oxide-ion conducting hexagonal perovskite-related oxides for possible industrial applications.

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