关键词： glucocorticoids   intra-articular injection   low disease activity   remission   rheumatoid arthritis  

摘要： Background/Objective This study aimed at investigating whether a single intra-articular (IA) injection of triamcinolone acetonide (TA) could facilitate to achieve clinical remission in patients with rheumatoid arthritis (RA) exhibiting low disease activity (LDA). Methods This longitudinal study included 22 patients with RA exhibiting LDA involving wrist arthritis at our institution between April 2016 and March 2019. A single IA injection of 20 mg TA was administered into the symptomatic wrist joint. Efficacy was assessed by the primary end point of proportion of patients reaching clinical remission. Secondary end points included Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index, adverse events, and ultrasonographic assessment of the injected wrist joints. Results Remission rates were 40% and 50% at weeks 4 and 12, respectively, and were maintained at approximately 50% until week 24. The secondary outcomes of CDAI, SDAI, and Health Assessment Questionnaire Disability Index were improved significantly at week 4, and the improvements in CDAI and SDAI continued up to week 24. Ultrasonography showed that synovial hypertrophy, power Doppler signals, and the combined score were significantly reduced at weeks 4, 12, and 24 compared with the baseline. No patient developed severe, irreversible adverse events. Conclusions Approximately half of the patients with RA exhibiting LDA who received a single IA injection of TA into the wrist joints achieved clinical remission without serious adverse events in the midterm period, suggesting that IA injection of TA might be considered as an alternative intervention to achieve remission in patients with RA exhibiting LDA.

关键词： COVID-19   Myocarditis   Vaccination  

摘要： The COVID-19 vaccine is now approved for individuals greater than 5 years of age, but vaccination rates remain lower than expected in the pediatric age group. Misinformation and widespread reporting of vaccine-related myocarditis are contributing to vaccine hesitancy. When compared to severe cardiac complications that are associated with COVID-19, vaccine-related myocarditis has a milder presentation, is easily treated, and has a good prognosis. Acute COVID-19 has been associated with higher rates of myocarditis and myocardial injury. Multisystem inflammatory syndrome in children occurs weeks after initial infection with SARS-CoV-2 and can be associated with severe cardiovascular complications and death. Cardiac complications associated with acute COVID-19 and MIS-C are more severe and occur more frequently than myocarditis after mRNA COVID-19 vaccination. Furthermore, some of the academic and social disruptions caused by the pandemic expect to be eased by widespread vaccination. For all these reasons, COVID-19 vaccination is strongly recommended for all eligible age groups.

关键词： delta PKC   Drp1   fission   inflammation   macrophage   mitochondria  

摘要： Background: Recent studies have demonstrated that alterations in mitochondrial dynamics can impact innate immune function. However, the upstream mechanisms that link mitochondrial dynamics to innate immune phenotypes have not been completely elucidated. This study asks if Protein Kinase C, subunit delta (delta PKC)-mediated phosphorylation of dynamin-related protein 1 (Drp1), a key driver of mitochondrial fission, impacts macrophage pro-inflammatory response following bacterial-derived lipopolysaccharide (LPS) stimulation. Methods: Using RAW 264.7 cells, bone marrow-derived macrophages from C57BL/6J mice, as well as human monocyte-derived macrophages, we first characterized changes in delta PKC-mediated phosphorylation of Drp1 following LPS stimulation. Next, using rationally designed peptides that inhibit delta PKC activation (delta V1-1) and delta PKC-Drp1 interaction (psi Drp1), we determined whether delta PKC-mediated phosphorylation of Drp1 impacts LPS-induced changes in mitochondrial morphology, mitochondrial function, and inflammatory response. Results: Our results demonstrated that delta PKC-dependent Drp1 activation is associated with increased mitochondrial fission, impaired cellular respiration, and increased mitochondrial reactive oxygen species in LPS-treated macrophages. This is reversed using a rationally designed peptide that selectively inhibits delta PKC phosphorylation of Drp1 (psi Drp1). Interestingly, limiting excessive mitochondrial fission using psi Drp1 reduced LPS-triggered pro-inflammatory response, including a decrease in NF-kappa B nuclear localization, decreased iNOS induction, and a reduction in pro-inflammatory cytokines (IL-1 beta, TNF alpha, IL-6). Conclusion: These data suggest that inhibiting Drp1 phosphorylation by delta PKC abates the excessive mitochondrial fragmentation and mitochondrial dysfunction that is seen following LPS treatment. Furthermore, these data suggest that limiting delta PKC-dependent Drp1 activation decreases

关键词： Neurological manifestations   Pediatrics   SARS-CoV-2   Child development  

摘要： Background: Our objective was to characterize the frequency, early impact, and risk factors for neuro-logical manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). Methods: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition be-tween January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neuro-logical manifestations was performed. Results: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological mani-festation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diag-nosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15;and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00);all P < 0.05. Conclusions: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuro-protective strategies are vitally needed. (c) 2021 Elsevier Inc

ISBN: (纸本)9787559841681

关键词： Natural sausage casing   Waste-gastro-intestinal wall   Alkaline hydrolysis   Dunaliella salina  

摘要： In the production of natural sausage casings, three layers of serosa, muscular, and mucosa are removed from gastro-intestinal wall of sheep as waste materials. The submocusa layer is taken for further processing. There is no report about generating added value out of these wastes. In this study, a novel approach was introduced for bioconversion of waste gastro-intestinal wall (WGW) to a value-added product. Alkaline hydrolysis of WGW was investigated and the hydrolysate was utilized for cultivation of Dunaliella salina, a value-added biomass. The hydrolysate that contained the highest total soluble protein was used for three sets of cultivations on different medium compositions, i.e., (1) cultivations on the modified Johnson's medium enriched with different percentage of hydrolysate (0.5, 1, 2.5, 5, and 10 (%v/v)), (2) cultivations on modified Johnson's medium which was free of nitrogen and carbon sources and enriched with different percentage of hydrolysate (0.5, 1, 2.5, 5, and 10 (%v/v), and (3) cultivation on modified Johnson's medium which was free of nitrogen source and enriched with 2.5% hydrolysate. The results showed that WGW contained 60.7, 8.4, 15.8, and 15.2% protein, lipid, moisture, and ash, respectively and the enrichment of the medium with the hydrolysate (2.5%) increased biomass productivity by 20%. Additionally, substitution of 2.5% hydrolysate for nitrogen source (KNO3) resulted in the same biomass productivity. The results of this study revealed the potential of the hydrolysate as an alternative for KNO3 in cultivation of D. salina. Overall, this work proposed a novel approach for converting waste gastro-intestinal wall to value.

关键词： breast cancer   neoadjuvant chemotherapy   oncoplastic surgery   mastectomy   immediate breast reconstruction   aesthetic and oncological outcomes   quality of life  

摘要： Simple Summary In patients with breast cancers larger than 2 cm undergoing neoadjuvant chemotherapy, there is a poor evaluation regarding the equivalence between oncoplastic surgery level II (OPSII) and mastectomy with immediate breast reconstruction (MIBR) regarding the aesthetic and oncological outcomes. The aim of our retrospective study was to assess whether OPSII is a safe alternative to MIBR. We confirmed the uniformity of the two techniques after neoadjuvant chemotherapy concerning loco-regional and systemic disease-free survival and overall survival in a population of 297 patients (87 undergoing OPSII, and 210 MIBR). In addition, we have highlighted how OPSII results in a lower loss of breast sensitivity after surgery and a better physical well-being of the chest. Therefore, in selected cases, OPSII should be preferred over MIBR, as it does not affect the oncological outcome, but improves physical well-being and allows the preservation of breast sensitivity in patients undergoing surgical treatment. Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared;the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS ra

关键词： C-H functionalization   C-X functionalization   Green chemistry   Mechanochemistry   Medicinal chemistry  

摘要： In the pursuit of clean pharmaceutical production, chemists in medicinal industry require access to new sustainable methodologies to reduce and even eliminate pollution, which is mainly produced by the overuse of organic solvents during chemical synthesis of active pharmaceutical ingredients (APIs). In this context, the solvent-free/less mechanochemical functionalization of small molecules has gradually emerged as a powerful strategy for the green synthesis and modification of APIs, bioactive compounds, and functional materials. In this review, we present an overview of mechanochemical C-X/C-H functionalization applications to medicinal chemistry, involving cross-coupling, cross-dehydrogenative coupling, oxidative coupling (via C-H activation pathway), and direct coupling (via radical pathway) as key steps for the preparation of APIs and bioactive compounds.

关键词： 高中生物   继发性前概念   概念转变   教学策略  

摘要： 生物学概念是生物学知识的基本组成单位，生物学教学必须关注学生对概念的理解与掌握。生物学概念教学中，教师不仅要明确学生在概念学习前知道什么，也要关注概念教学后学生形成了什么。学生在接受课堂教学后对新知识经过原有认知加工所产生的与科学概念不一致的观点，称为继发性前概念。学生存在的继发性前概念不及时纠正会进一步干扰学生对于其它知识的学习，以至产生更多的继发性前概念。因此，教学中如何调查学生存在的继发性前概念？学生为什么存在这些继发性前概念？采用何种教学策略能够帮助学生转变这些继发性前概念？应该是教师进行生物学概念教学时需要关注的问题。　　首先在查阅国内外相关文献的基础上，确定了研究思路与方法。其次，通过访谈调查一线教师对于继发性前概念的了解，以及学生在“基因突变及其他变异”这一章节存在的继发性前概念。在此基础上编制了三阶层测试卷，以研究校高三年级两个班级为对象，调查了学生存在的继发性前概念，分析发现学生产生继发性前概念的原因主要包括：受原有认知的影响；相似概念的干扰；概念理解不深入；科学概念容易被遗忘；教师不重视概念教学等。并将这些继发性前概念划分为：空壳概念、不完整概念、异质性概念、条件缺失概念及绝对化概念五种类型。研究针对五种继发性前概念分别提出概念转变教学策略，并进行概念转变教学实践。　　教学实践后，通过纸笔测试、学生访谈以及课堂观察等方法检测学生概念转变效果，发现：研究所提的概念转变教学策略能够明显转变学生存在的继发性前概念。最后，提出生物学概念教学中减少学生产生继发性前概念的几点建议：教师应重视概念教学；鼓励学生表达不同观点；及时复习强化科学概念。

关键词： Ammonia  

摘要： The anaerobic digestion (AD) of N-enriched waste streams combined with nutrient recovery from AD effluents represents a cost-effective waste treatment technology for simultaneous production of biogas and recycled fertilizers. Herein, we demonstrate an efficient route towards S- or P-containing NH4NO3-based fertilizers via Ni(OH)(2)-catalyzed electrochemical oxidation of ammonia (AOR) to NH4NO3 in 0.1 M K2SO4 and 0.1 M K2HPO4 electrolytes. In this study, we examine how operating parameters, including the electrolyte, pH, applied potential, ammonia concentration, and temperature affect the AOR product distribution at Ni(OH)(2) anodes. We show that under optimized conditions concentrated ammonia solutions can be efficiently converted into NH4NO3 with up to 72% faradaic efficiencies and up to 98% ammonia removal. Based on our extensive experimental data, we propose detailed mechanisms for the formation of major products (dinitrogen, nitrite, and nitrate) and for the first time experimentally demonstrate that ammonia-to-nitrite oxidation proceeds spontaneously on NiOOH, while the nitrite-to-nitrate step is purely electrochemical. The results of this work are expected to enable integration of AOR into AD of N-containing waste, thereby enabling a promising nutrient recovery strategy for building a circular economy.