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1.
Ann Surg Oncol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926210

RESUMO

BACKGROUND: Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy. PATIENTS AND METHODS: A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated. RESULTS: The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery. CONCLUSIONS: We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.

2.
J Obstet Gynaecol Res ; 50(3): 351-357, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38072834

RESUMO

AIM: We aimed to investigate the associations of endometriosis and adenomyosis with pregnancy complications by using a large-scale Japanese database. METHODS: We retrospectively analyzed 145 590 singleton pregnancies from the Japan Perinatal Registry Network Database. Pregnant women registered as having endometriosis or adenomyosis were designated as the case group (EA), whereas the control group (non-EA) was selected using propensity-score matching adjusted for variables such as age, parity, BMI, smoking history, and the use of assisted reproductive technology. The main outcomes included placental malposition, preterm birth, and hypertensive disorders of pregnancy (HDP). RESULTS: In total, 1203 patients from both the EA and non-EA groups were matched and evaluated. The EA group showed significantly higher rates of placenta previa (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.84-4.92), low-lying placenta (OR, 2.02; 95% CI, 1.06-3.86), and preterm birth (OR, 1.44; 95% CI, 1.13-1.84) than the non-EA group. However, no significant difference was observed in the incidence of HDP (OR, 1.22; 95% CI, 0.90-1.66). CONCLUSION: The use of propensity-score matching to analyze a nationwide perinatal database in Japan clarified that EA was associated with increased pregnancy complications, specifically placental malposition, including placenta previa and low-lying placenta, and preterm birth, but not with HDP.


Assuntos
Adenomiose , Endometriose , Placenta Prévia , Pré-Eclâmpsia , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Endometriose/complicações , Endometriose/epidemiologia , Placenta Prévia/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Adenomiose/complicações , Gestantes , Japão/epidemiologia , Estudos Retrospectivos , Placenta , Complicações na Gravidez/epidemiologia , Pré-Eclâmpsia/etiologia
3.
Opt Express ; 31(18): 29954-29967, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710784

RESUMO

Polarized optical microscopy (POM) images of polymer network liquid crystals (PNLCs) were first analyzed using a pretrained machine learning model for feature extraction and hierarchical clustering. The analyses worked well in predicting and improving the thermoresponsive changes individually in direct luminous and hemispheric solar transmittance, both of which are crucial properties of energy-saving smart windows. The features of a 1280 × 1920-pixel color POM image were extracted by the latest pretrained algorithm, EfficientNet-B7, as a 2560-dimensional vector and then reduced into a two-dimensional space for clustering and visualization using the uniform manifold approximation and projection (UMAP) algorithm while efficiently preserving the global structures of the distance relationship in a high-dimensional space. The feature vectors in the UMAP space were correlated with the thermoresponsive transmittance and classified using hierarchical clustering analysis. The extracted features belonging to some clusters were also correlated with the fabrication parameters. The PNLCs here were produced from various raw materials under different fabrication conditions. These analyses and predictability are extensively applied to different PNLCs for stimuli-responsive optical devices, such as solar- and privacy-control windows.

4.
EMBO Rep ; 22(2): e48351, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33403789

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer worldwide. The most commonly mutated gene in ESCC is TP53. Using a combinatorial genetic and carcinogenic approach, we generate a novel mouse model of ESCC expressing either mutant or null p53 and show that mutant p53 exhibits enhanced tumorigenic properties and displays a distinct genomic profile. Through RNA-seq analysis, we identify several endocytic recycling genes, including Rab Coupling Protein (Rab11-FIP1), which are significantly downregulated in mutant p53 tumor cells. In 3-dimensional (3D) organoid models, genetic knockdown of Rab11-FIP1 results in increased organoid size. Loss of Rab11-FIP1 increases tumor cell invasion in part through mutant p53 but also in an independent manner. Furthermore, loss of Rab11-FIP1 in human ESCC cell lines decreases E-cadherin expression and increases mesenchymal lineage-specific markers, suggesting induction of epithelial-mesenchymal transition (EMT). Rab11-FIP1 regulates EMT through direct inhibition of Zeb1, a key EMT transcriptional factor. Our novel findings reveal that Rab11-FIP1 regulates organoid formation, tumor cell invasion, and EMT.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica
5.
Acta Neurochir (Wien) ; 165(6): 1575-1584, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37119319

RESUMO

BACKGROUND: The effect of posterior cranial fossa stroke on changes in cerebral volume is not known. We assessed cerebral volume changes in patients with acute posterior fossa stroke using CT scans, and looked for risk factors for cerebral atrophy. METHODS: Patients with cerebellar or brainstem hemorrhage/infarction admitted to the ICU, and who underwent at least two subsequent inpatient head CT scans during hospitalization were included (n = 60). The cerebral volume was estimated using an automatic segmentation method. Patients with cerebral volume reduction > 0% from the first to the last scan were defined as the "cerebral atrophy group (n = 47)," and those with ≤ 0% were defined as the "no cerebral atrophy group (n = 13)." RESULTS: The cerebral atrophy group showed a significant decrease in cerebral volume (first CT scan: 0.974 ± 0.109 L vs. last CT scan: 0.927 ± 0.104 L, P < 0.001). The mean percentage change in cerebral volume between CT scans in the cerebral atrophy group was -4.7%, equivalent to a cerebral volume of 46.8 cm3, over a median of 17 days. The proportions of cases with a history of hypertension, diabetes mellitus, and median time on mechanical ventilation were significantly higher in the cerebral atrophy group than in the no cerebral atrophy group. CONCLUSIONS: Many ICU patients with posterior cranial fossa stroke showed signs of cerebral atrophy. Those with rapidly progressive cerebral atrophy were more likely to have a history of hypertension or diabetes mellitus and required prolonged ventilation.


Assuntos
Infartos do Tronco Encefálico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Cerebelo/patologia , Tomografia Computadorizada por Raios X , Infartos do Tronco Encefálico/patologia , Fossa Craniana Posterior/diagnóstico por imagem , Fossa Craniana Posterior/patologia , Atrofia
6.
J Obstet Gynaecol Res ; 49(2): 487-492, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36418215

RESUMO

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.


Assuntos
COVID-19 , Ginecologia , Obstetrícia , Estudantes de Medicina , Feminino , Gravidez , Humanos , Ginecologia/educação , Obstetrícia/educação , Japão
7.
J Stroke Cerebrovasc Dis ; 32(3): 106948, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36634398

RESUMO

OBJECTIVES: Post-thrombectomy subarachnoid hemorrhage, which is caused by vessel stretching when retrieving a stent retriever (SR), is a complication of endovascular mechanical thrombectomy (EVT) using an SR. This in vitro study examined the association between EVT for middle cerebral artery (MCA) occlusion and M2 vessel stretching depending on the positioning of the SR or combined use of SR and aspiration catheter (AC) technique (CBT). MATERIALS AND METHODS: A silicone vascular model was used. The maximum migration distance (MMD) in the anteroposterior view of an X-ray impermeable metal marker located at an M2 trunk 20 mm distal to the M1-2 bifurcation in angiographic images during an SR retrieval was calculated. According to the positioning of SR deployment (distal or proximal) and use of an AC [SR alone without an AC (SR alone) group, stent retrieval into an AC (SA) group, and stent-AC retrieval as a unit into a guiding catheter (SA unit) group], 60 attempts were conducted with each group of 10 attempts. RESULTS: In distal SR deployment, the MMD in the CBT group, consisting of SA and SA unit groups, was significantly smaller than the SR alone group (1.36 ± 0.32 mm VS 2.39 ± 1.10 mm; p = 0.001). In proximal SR deployment, the CBT group showed a tendency to decrease MMD (1.38 ± 0.33 mm VS 1.63 ± 0.28 mm; p = 0.077). CONCLUSIONS: This in vitro study showed that CBT might help modify the stretching of M2 when an SR is distally deployed in MCA occlusion.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Resultado do Tratamento , Trombectomia/efeitos adversos , Trombectomia/métodos , Stents , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/terapia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Catéteres , Estudos Retrospectivos
8.
Gan To Kagaku Ryoho ; 50(13): 1384-1386, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303282

RESUMO

Serial pancreatic juice aspiration cytological examination(SPACE)has been reported as a reliable preoperative diagnostic method for early pancreatic cancer, when combined with imaging findings suspecting early pancreatic cancer. Among 259 patients with suspected pancreatic cancer who underwent pancreatic resection at our hospital, SPACE was preoperatively performed in 14 cases(5.4%). Of these 14 cases, final pathological diagnosis was pancreatic cancer in 12 patients (86%), including 5 patients with Stage ⅠA pancreatic cancer(35.7%), all of whom had a mass on preoperative CT or EUS. On the other hand, in the other 2 cases(14.3%), CT/EUS detected no mass but focal pancreatic parenchymal atrophy and main pancreatic duct stenosis which were the imaging findings suspecting very early pancreatic cancer such as cancer in situ. Although preoperative SPACE results of these 2 cases were class Ⅳ, final pathological results of resected specimen were low-grade PanIN in both cases. SPACE was considered useful for preoperative diagnosis of pancreatic cancer in our study, however further study is needed to examine its diagnostic accuracy for early pancreatic cancer which does not appear as a mass in any imaging modality.


Assuntos
Suco Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Pâncreas/patologia , Pancreatectomia
9.
Exp Cell Res ; 398(1): 112390, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33227314

RESUMO

Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5-15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.


Assuntos
Antineoplásicos/farmacologia , Raios gama , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Neoplasias da Glândula Tireoide/terapia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Feminino , Humanos , Camundongos , Camundongos Congênicos , Camundongos Nus , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Neoplasias da Glândula Tireoide/patologia , Células Tumorais Cultivadas
10.
Acta Neurochir (Wien) ; 164(3): 795-803, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35138489

RESUMO

BACKGROUND: Thromboembolic complications are a relevant risk in coil embolisation of cerebral aneurysms. This retrospective study aimed to assess the treatment outcomes of unruptured middle cerebral artery (MCA) bifurcation aneurysms and the predictors for thromboembolic complications based on the aneurysm morphological characteristics. We examined the following three features: inflow angle, outflow angle (OA), and bifurcation angle, formed by the aneurysm and neighbouring blood vessels. METHODS: A total of 32 MCA bifurcation aneurysms were retrospectively investigated in 32 patients treated consecutively at our institute between April 2008 and March 2019. The predictors for thromboembolic complications were analysed in two groups: patients with and without thromboembolic complications. RESULTS: Perioperative thromboembolic complications were detected in six patients (18.8%), including two and six intra- and post-procedural thromboembolic complications, respectively; all cases were resolved. Regarding the aneurysms' morphological characteristics, the group with thromboembolic complications showed a significantly smaller OA (55.58° ± 14.05° vs. 86.04° ± 28.58°, P = 0.01) than the group without complications. Multivariate analysis revealed that smoking habits and OA < 70° were significant predictors of thromboembolic complications (smoking habits: P = 0.01, odds ratio [OR]: 6.89, 95% confidence interval [CI]: 3.78-12.62; OA < 70°: P = 0.04, OR: 3.19, 95% CI: 1.52-6.56). CONCLUSIONS: Our findings indicate significant pre-procedural predictors of thromboembolic complications to consider for safe treatment; clipping should be preferred to coil embolisation in high-risk patients. The method of choice should be considered in each case to allow the safe treatment of unruptured MCA aneurysms.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Tromboembolia , Angiografia Cerebral/métodos , Embolização Terapêutica/efeitos adversos , Humanos , Aneurisma Intracraniano/cirurgia , Artéria Cerebral Média/cirurgia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/etiologia , Resultado do Tratamento
11.
Int J Mol Sci ; 23(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36555793

RESUMO

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1ß-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in vivo model. Furthermore, the role of CCL4 in CD69 expression-a marker of activated eosinophils-as well as the signaling pathways involved in CCL4-mediated eosinophil activation were investigated. Notably, CCL4 expression, but not CCL5, CCL11, or CCL26, was found to be significantly increased in nasal polyps from patients with ECRS associated with eosinophil infiltration as well as in BEAS-2B cells co-incubated with eosinophils. In an OVA-induced allergic mouse model, CCL4 increased eosinophil accumulation in the nasal mucosa and the bronchoalveolar lavage (BALF). Moreover, we found that CD69 expression was upregulated in CCL4-stimulated eosinophils; similarly, phosphorylation of several kinases, including platelet-derived growth factor receptor (PDGFR)ß, SRC kinase family (Lck, Src, and Yes), and extracellular signal-regulated kinase (ERK), was upregulated. Further, CCR5, PDGFRß, and/or Src kinase inhibition partially restored CCL4-induced CD69 upregulation. Thus, CCL4, which is derived from airway epithelial cells, plays a role in the accumulation and activation of eosinophils at inflammatory sites. These findings may provide a novel therapeutic target for eosinophilic airway inflammation, such as ECRS.


Assuntos
Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Animais , Camundongos , Eosinófilos/metabolismo , Rinite/patologia , Pólipos Nasais/patologia , Eosinofilia/complicações , Sinusite/metabolismo , Inflamação/metabolismo , Doença Crônica
12.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077268

RESUMO

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.


Assuntos
Quinolinas , Simportadores , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/metabolismo , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Simportadores/genética , Simportadores/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/radioterapia
13.
Gan To Kagaku Ryoho ; 49(12): 1369-1371, 2022 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-36539252

RESUMO

A 70-year-old woman underwent conservative treatment for abscess-forming appendicitis. A contrast-enhanced abdominal computed tomography(CT)revealed a cystic lesion at the appendiceal base while the abscess had disappeared posttreatment. With the diagnosis of a low-grade appendiceal mucinous neoplasm(LAMN), a laparoscopic-assisted ileocolic resection was performed. The appendix was distended with mucus in the lumen. Histopathological examination showed that the tumor cells were more atypical than that of low-grade appendiceal mucinous neoplasm. There were no findings of adenocarcinoma, such as invasive growth. Therefore, high-grade appendiceal mucinous neoplasm(HAMN)was diagnosed. HAMN is a term advocated by Carr et al in 2016 to classify appendiceal mucinous neoplasm and was noted as a new category of mucinous tumors among appendiceal epithelial tumors in the fifth edition of the 2019 revised WHO classification. HAMN is a rare disease and only one case has been reported in Japan. It has not yet been noted in the Japanese Colorectal Cancer Treatment Manual. Here, we report this rare case with a review of the study.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Apêndice , Neoplasias Císticas, Mucinosas e Serosas , Feminino , Humanos , Idoso , Abscesso , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Neoplasias do Apêndice/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia
14.
Angew Chem Int Ed Engl ; 61(27): e202201883, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35485137

RESUMO

We have achieved the first anti-borylstannylation of alkynes by using (o-phenylenediaminato)borylstannanes. This reaction afforded 1-boryl-2-stannylalkenes with excellent regio- and stereoselectivity by a radical mechanism. This anti-addition manner is in sharp contrast to the syn-selectivity obtained during transition metal-catalyzed borylstannylation. The mild radical conditions enabled a broad substrate scope, and various types of aromatic and aliphatic alkynes were applicable. The origin of regio- and stereoselectivity was elucidated by DFT calculation of the reaction mechanism. The application of the borylstannylation products to cross- or homocoupling reactions provided ready access to either triarylethenes or bisborylbutadienes.


Assuntos
Alcinos , Elementos de Transição , Catálise
15.
J Am Chem Soc ; 143(25): 9308-9313, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34075740

RESUMO

Site-selective and direct C-F bond transformation of perfluoroalkylarenes was achieved with allylic stannanes via an iridium photoredox catalyst system. The present defluoroallylation proceeds exclusively at the benzylic position through perfluoroalkyl radicals generated by a single-electron transfer from an excited photoredox catalyst to perfluoroalkylarenes. A variety of perfluoroalkyl groups are applicable: linear perfluoroalkyl-substituted arenes such as Ar-nC4F9 and Ar-nC6F13 and heptafluoroisopropylarenes (Ar-CF(CF3)2) underwent site-selective defluoroallylation. DFT calculation studies revealed that the in situ generated Bu3SnF traps F- to prevent a retroreaction from the unstable perfluoroalkyl radical intermediate, and the radical intermediate favorably reacts with allylic stannanes. The synthesis of a bis(trifluoromethyl)methylene unit containing compound, which is an analog that is useful as a pharmaceutical agent for the prophylaxis or treatment of diabetes and inflammatory diseases, demonstrated the utility of this reaction.

16.
Chemistry ; 27(12): 3891, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33475218

RESUMO

Invited for the cover of this issue are Kensuke Suzuki, Yoshihiro Nishimoto and Makoto Yasuda from Osaka University. The image depicts a circus trapeze act, with different elements of the picture representing components of the borylation reaction reported in this work. Read the full text of the article at 10.1002/chem.202004692.

17.
Chemistry ; 27(12): 3968-3973, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33205553

RESUMO

(o-Phenylenediamino)borylstannanes were newly synthesized to achieve radical boryl substitutions of a variety of alkyl radical precursors. Dehalogenative, deaminative, decharcogenative, and decarboxylative borylations proceeded in the presence of a radical initiator to give the corresponding organic boron compounds. Radical clock experiments and computational studies have provided insights into the mechanism of the homolytic substitution (SH 2) of the borylstannanes with alkyl radical intermediates. DFT calculation disclosed that the phenylenediamino structure lowered the LUMO level including the vacant p-orbital on the boron atom to enhance the reactivity to alkyl radicals in SH 2. Moreover, C(sp3 )-H borylation of THF was accomplished using the triplet state of xanthone.

18.
J Stroke Cerebrovasc Dis ; 30(1): 105420, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33161351

RESUMO

BACKGROUND: Hyper-responsiveness to clopidogrel abnormally inhibits platelet aggregation and increases hemorrhagic complications. The present study investigated clinical factors related to clopidogrel hyper-responsiveness in neuro-interventional procedures. METHODS: Two hundred twenty-four patients receiving clopidogrel for coil embolization to treat unruptured cerebral aneurysm or carotid artery stenting to treat carotid artery stenosis at the internal carotid artery origin were retrospectively reviewed for their P2Y12 reactivity unit (PRU) values and clinical characteristics. Hyper-responsiveness to clopidogrel was defined as a PRU of <95. RESULTS: The mean PRU was 218.2 ± 77.8. Hyper-responsiveness to clopidogrel was observed in 12 patients (5.4%). Hyper-responsiveness was observed in younger patients, patients with a lower concentration of hemoglobin A1c, and patients with a higher low-density lipoprotein cholesterol (LDL-C) concentration compared with non-hyper-responsive patients (P = 0.01, P < 0.01, P < 0.01, respectively). On analysis of concomitant drugs, the patients in the hyper-responsive group were less frequently administered calcium channel blockers (CCBs) compared with the non-hyper-responsive group (P = 0.01). No significant differences in the usage of proton pump inhibitors or statins were observed. A LDL-C concentration of >120 mg/dL and no usage of CCBs were significant independent predictors of hyper-responsiveness to clopidogrel with a multivariate analysis (OR; 6.16, 95% CI, 1.57-26.64, P = 0.01, OR; 0.09, 95% CI, 0.01-0.82, P = 0.03, respectively). CONCLUSION: The present study shows that a higher LDL-C concentration and no usage of CCBs are independent predictors of clopidogrel hyper-responsiveness. These results are useful to predict perioperative hemorrhagic complications. Considering dose reduction of clopidogrel or alternative drugs in high risk cases is necessary to prevent perioperative hemorrhagic complications.


Assuntos
Estenose das Carótidas/terapia , Clopidogrel/efeitos adversos , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Hemorragia/induzido quimicamente , Aneurisma Intracraniano/terapia , Inibidores da Agregação Plaquetária/efeitos adversos , Idoso , Estenose das Carótidas/diagnóstico por imagem , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Resultado do Tratamento
19.
Allergol Int ; 70(1): 9-18, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33243693

RESUMO

Eosinophils not only play a critical role in the pathogenesis of eosinophil-associated diseases, but they also have multiple important biological functions, including the maintenance of homeostasis, host defense against infections, immune regulation through canonical Th1/Th2 balance modulation, and anti-inflammatory and anti-tumorigenic activities. Recent studies have elucidated some emerging roles of eosinophils in steady-state conditions; for example, eosinophils contribute to adipose tissue metabolism and metabolic health through alternatively activated macrophages and the maintenance of plasma cells in intestinal tissue and bone marrow. Moreover, eosinophils exert tissue damage through eosinophil-derived cytotoxic mediators that are involved in eosinophilic airway inflammation, leading to diseases including asthma and chronic rhinosinusitis with nasal polyps characterized by fibrin deposition through excessive response by eosinophils-induced. Thus, eosinophils possessing these various effects reflect the heterogenous features of these cells, which suggests the existence of distinct different subpopulations of eosinophils between steady-state and pathological conditions. Indeed, a recent study demonstrated that instead of dividing eosinophils by classical morphological changes into normodense and hypodense eosinophils, murine eosinophils from lung tissue can be phenotypically divided into two distinct subtypes: resident eosinophils and inducible eosinophils gated by Siglec-Fint CD62L+ CD101low and Siglec-Fhigh CD62L- CD101high, respectively. However, it is difficult to explain every function of eosinophils by rEos and iEos, and the relationship between the functions and subpopulations of eosinophils remains controversial. Here, we overview the multiple roles of eosinophils in the tissue and their biological behavior in steady-state and pathological conditions. We also discuss eosinophil subpopulations.


Assuntos
Plasticidade Celular , Suscetibilidade a Doenças , Eosinófilos/fisiologia , Homeostase , Animais , Biomarcadores , Comunicação Celular/imunologia , Plasticidade Celular/imunologia , Humanos , Imunofenotipagem , Especificidade de Órgãos/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
20.
Environ Health Prev Med ; 26(1): 29, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657995

RESUMO

BACKGROUND: Public perceptions and personal characteristics are heterogeneous between countries and subgroups, which may have different impacts on health-protective behaviors during the coronavirus disease 2019 (COVID-19) pandemic. To assess whether self-reported perceptions of COVID-19 and personal characteristics are associated with protective behaviors among general adults and to compare patterns in six different countries. METHODS: This cross-sectional study uses the secondary data collected through an online survey between 15 and 23 April 2020 across six countries (China, Italy, Japan, Korea, the UK, and the USA). A total of 5945 adults aged 18 years or older were eligible for our analysis. A logistic regression model was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) of three recommended behaviors (wearing a mask, handwashing, and avoiding social gatherings). RESULTS: In most countries except for China, the participants who perceived wearing a mask as being extremely effective to curtail the pandemic were more likely to wear a mask (OR, 95%CI: Italy: 4.14, 2.08-8.02; Japan: 3.59, 1.75-7.30; Korea: 7.89, 1.91-31.63: UK: 9.23, 5.14-17.31; USA: 4.81, 2.61-8.92). Those who perceived that handwashing was extremely effective had higher ORs of this preventive behavior (OR, 95%CI: Italy: 16.39, 3.56-70.18; Japan: 12.24, 4.03-37.35; Korea: 12.41, 2.02-76.39; UK: 18.04, 2.60-152.78; USA: 10.56, 2.21-44.32). The participants who perceived avoiding social gathering as being extremely effective to curtail the pandemic were more likely to take this type of preventive behavior (OR, 95%CI: China: 3.79, 1.28-10.23; Korea: 6.18, 1.77-20.60; UK: 4.45, 1.63-11.63; USA: 4.34, 1.84-9.95). The associations between personal characteristics, living environment, psychological status, and preventive behaviors varied across different countries. Individuals who changed their behavior because of recommendations from doctors/public health officials were more likely to take preventive behaviors in many countries. CONCLUSIONS: These findings suggest that higher perceived effectiveness may be a common factor to encourage preventive behaviors in response to the COVID-19 pandemic. These results may provide a better understanding of the homogeneity and heterogeneity of factors related to preventive behaviors and improve public health policies in various countries and groups.


Assuntos
Atitude Frente a Saúde , COVID-19/prevenção & controle , COVID-19/psicologia , Comportamentos Relacionados com a Saúde , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , Estudos Transversais , Feminino , Desinfecção das Mãos , Humanos , Masculino , Máscaras , Pessoa de Meia-Idade , Distanciamento Físico , SARS-CoV-2 , Autorrelato , Conformidade Social , Adulto Jovem
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