Predicting the reversion from mild cognitive impairment to normal cognition based on magnetic resonance imaging, clinical, and neuropsychological examinations.

BACKGROUND: Reversion from mild cognitive impairment (MCI) to normal cognition (NC) is not uncommon and indicates a better cognitive trajectory. This study aims to identify predictors of MCI reversion and develop a predicting model. METHOD: A total of 391 MCI subjects (mean age = 74.3 years, female = 61 %) who had baseline data of magnetic resonance imaging, clinical, and neuropsychological measurements were followed for two years. Multivariate logistic analyses were used to identify the predictors of MCI reversion after adjusting for age and sex. A stepwise backward logistic regression model was used to construct a predictive nomogram for MCI reversion. The nomogram was validated by internal bootstrapping and in an independent cohort. RESULT: In the training cohort, the 2-year reversion rate was 19.95 %. Predictors associated with reversion to NC were higher education level (p = 0.004), absence of APOE4 allele (p = 0.001), larger brain volume (p < 0.005), better neuropsychological measurements performance (p < 0.001), higher glomerular filtration rate (p = 0.035), and lower mean arterial pressure (p = 0.060). The nomogram incorporating five predictors (education, hippocampus volume, the Alzheimer's Disease Assessment Scale-Cognitive score, the Rey Auditory Verbal Learning Test-immediate score, and mean arterial pressure) achieved good C-indexes of 0.892 (95 % confidence interval [CI], 0.859-0.926) and 0.806 (95 % CI, 0.709-0.902) for the training and validation cohort. LIMITATION: Observational duration is relatively short; The predicting model warrant further validation in larger samples. CONCLUSION: This prediction model could facilitate risk stratification and early management for the MCI population.

Nine-month outcomes of tracheostomy in patients with COVID-19: A retrospective study.

PURPOSE: The outcome of performing a tracheostomy in patients with coronavirus disease (COVID-19) seems promising based on the reported 30-day survival rate. However, long-term outcomes are still lacking. Therefore, our aim in this study was to evaluate the long-term outcomes of tracheostomy performed in critically ill COVID-19 patients. METHODS: This was a retrospective analysis of 27 COVID-19 patients on whom tracheostomy was performed between February 28, 2020, and April 7, 2020, at Tongji Hospital (Wuhan, China). Patients' clinical characteristics, complications, and outcomes were analyzed. RESULTS: All patients underwent successful bedside tracheostomy. Thirteen patients (48.1%) were successfully weaned off ventilation within 1 month. The survival rate at one, three, and nine months after tracheostomy were 63.0%, 37.0%, and 29.6%, respectively. At nine months after tracheostomy, 8/27 patients had survived, with five (62.5%) being discharged home while the remaining were dependent on nursing care. CONCLUSION: The survival rate of COVID-19 patients who underwent tracheotomy decreased markedly from 1 to 3 months after tracheotomy, remaining stable between 3 and 9 months. Medical support is much needed for COVID-19 patients over the first 90 days after tracheotomy.

Combination of Dexmedetomidine and Butorphanol Optimized Sedation in Drug-Induced Sleep Endoscopy: A Randomized, Double-Blind Trial.

OBJECTIVE: Drug-induced sleep endoscopy (DISE) allows for the evaluation of dynamic airway collapse in patients with obstructive sleep apnea. However, a standardized sedation regimen for DISE is not yet available. This study aimed to investigate the safety profiles and efficacies of dexmedetomidine combined with butorphanol for DISE. METHODS: Sixty patients with obstructive sleep apnea scheduled to undergo DISE were randomly divided into Group D and Group DB. All recipients were initially given intravenous butorphanol (1 mg) (Group DB) or saline (Group D). Subsequently, both groups were sedated using a loading dose of 1.0 µg/kg/h of dexmedetomidine. Hemodynamic and respiratory parameters, the time to attain sufficient sedation, wakeup time, and adverse events during DISE were recorded. RESULTS: Compared with Group D, the time until sufficient sedation and wakeup time in Group DB were significantly reduced. A higher performer satisfaction level was achieved in Group DB. Patients in Group DB showed a higher incidence of bradycardia compared with Group D. However, the bradycardia resolved spontaneously in both groups without any treatment. There was no instance of cough, hypotension, arrhythmia, nausea or vomiting in either group. CONCLUSION: Compared to dexmedetomidine alone, a small dose of butorphanol infusion (1 mg) as an adjunct treatment to dexmedetomidine during DISE can reduce the dosage of dexmedetomidine, shorten the time until sufficient sedation and enhance the performer satisfaction level. This synergistic combination could be a promising sedation regimen for DISE in terms of procedural convenience and patient safety.

An environmental study of tracheostomy on eight COVID-19 patients.

BACKGROUND: Tracheostomy, as an aerosol-generating procedure, is considered as a high-risk surgery for health care workers (HCWs) during the coronavirus disease (COVID-19) pandemic. Current recommendations are to perform tracheostomy after a period of intubation of > 14 days, with two consecutive negative throat swab tests, to lower the risk of contamination to HCWs. However, specific data for this recommendation are lacking. Therefore, this study aimed to evaluate viral shedding into the environment, including HCWs, associated with bedside tracheostomy in the intensive care unit. METHODS: Samples obtained from the medical environment immediately after tracheostomy, including those from 19 surfaces, two air samples at 10 and 50 cm from the surgical site, and from the personal protective equipment (PPE) of the surgeon and assistant, were tested for the presence of severe acute respiratory syndrome coronavirus 2 in eight cases of bedside tracheostomy. We evaluated the rate of positive tests from the different samples obtained. RESULTS: Positive samples were identified in only one of the eight cases. These were obtained for the air sample at 10 cm and from the bed handrail and urine bag. There were no positive test results from the PPE samples. The patient with positive samples had undergone early tracheostomy, at 9 days after intubation, due to a comorbidity. CONCLUSIONS: Our preliminary results indicate that delayed tracheostomy, after an extended period of endotracheal intubation, might be a considerably less contagious procedure than early tracheostomy (defined as < 14 days after intubation).

Hemokinin-1 stimulates C-C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps.

BACKGROUND: The mechanisms underlying mucosal eosinophilia in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly clarified. The nervous system and neuropeptides play an important role in the regulation of immune response. Herein we explore the expression and function of hemokinin-1 (HK-1), a newly identified tachykinin, along with its receptor neurokinin 1 receptor (NK1R) in CRSwNP. METHODS: HK-1, NK1R, and C-C motif chemokine ligand 24 (CCL24) expression in nasal tissues (53 eosinophilic CRSwNP, 32 non-eosinophilic CRSwNP, and 33 controls) was investigated by quantitative reverse transcript polymerase chain reaction (RT-PCR) and immunofluorescence staining. THP-1, a human monocytic leukemia cell line, and eosinophilic polyp tissues were stimulated with HK-1. Cells, tissues, and culture supernatants were subsequently collected for detection of the production of various inflammatory cytokines and chemokines by quantitative RT-PCR and enzyme-linked immunoassay. RESULTS: HK-1 and NK1R mRNA and protein expression were upregulated in eosinophilic and non-eosinophilic nasal polyps compared with control tissues, with eosinophilic polyps demonstrating a higher upregulation compared with that of non-eosinophilic polyps. Eosinophils constituted the major source of HK-1, whereas macrophages were the predominant cell type exhibiting NK1R in eosinophilic polyps. HK-1 induced CCL24 production from macrophages differentiated from THP-1 cells; this was abolished by an NK1R antagonist. HK-1 also induced CCL24 production from ex vivo-cultured eosinophilic nasal polyps. CCL24 was expressed by macrophages in eosinophilic but not non-eosinophilic polyps. The expression level of HK-1 correlated with CCL24 expression and tissue eosinophilia in eosinophilic nasal polyps. CONCLUSION: Eosinophil-derived HK-1 induces CCL24 production from macrophages and therefore exaggerates eosinophilic inflammation in CRSwNP.

Allergen immunotherapy improves defective follicular regulatory T cells in patients with allergic rhinitis.

BACKGROUND: The function of follicular regulatory T (TFR) cells, especially in regulating IgE production in patients with allergic diseases, is poorly understood. OBJECTIVE: We sought to investigate the phenotype, function, and clinical relevance of TFR cells in patients with allergic rhinitis (AR). METHODS: The phenotype and frequency of tonsillar and circulating TFR cells were characterized by using flow cytometry. TFR cell function was examined in an assay by coculturing with follicular helper T cells and B cells. The associations between TFR cells and the clinical features in patients with AR before and after allergen immunotherapy (AIT) were analyzed. RESULTS: TFR cells were detected in germinal centers of tonsils, but compared with subjects without AR, the frequencies decreased in patients with AR who were allergic to house dust mites. Circulating TFR cells in blood were phenotypically and numerically correlated with tonsillar TFR cells, and a reduction of circulating TFR cells but not total or CXCR5- regulatory T cells was noted in patients with AR compared with healthy control subjects. Moreover, circulating TFR cells in patients with AR showed a specific defect in suppressing IgE production but were capable of suppressing production of other immunoglobulin types. We identified negative associations of circulating TFR cell frequencies and function with antigen-specific IgE levels or disease severity in patients with AR. After AIT, the frequencies and function of circulating TFR cells were improved, which positively associated with disease remission. CONCLUSION: Impairment in TFR cells might contribute to aberrant IgE production in patients with AR, and AIT improves defective TFR cell function. TFR cells might serve as a potential biomarker to monitor clinical response to AIT.

Increased accumulation of CD30 ligand-positive mast cells associates with eosinophilic inflammation in nasal polyps.

OBJECTIVE: Activation of mast cells associates with eosinophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). The disease-specific mast cell-triggering mechanisms apart from immunoglobulin E are poorly understood in CRSwNP. CD30L/CD30 are members of the tumor necrosis factor/receptor superfamily and display immune modulatory function on mast cells. The aim of this study was to explore the expression and function of CD30 and CD30L in CRSwNP. METHODS: The mRNA expression of CD30 and CD30L was analyzed by real-time polymerase chain reaction. The cellular expression of CD30L was determined by immunofluorescence staining. The soluble CD30 levels in nasal tissues were detected by enzyme-linked immunosorbent assay. HMC-1 cells, a human mast cell line, were cultured and stimulated with CD30. RESULTS: Compared with control tissues, CD30 mRNA expression levels were increased in eosinophilic polyps, and soluble CD30 protein levels were upregulated in both eosinophilic and noneosinophilic polyps with a greater increase in eosinophilic type. CD30 was expressed by T cells and B cells in nasal polyps. The CD30L mRNA expression levels and the number of CD30L+ cells and CD30L+ tryptase+ mast cells were increased in eosinophilic polyps but not in noneosinophilic polyps as compared with control tissues. Mast cells accounted for 60% of CD30L+ cells in eosinophilic polyps. CD30 induced HMC-1 cells to produce interleukin (IL)-4 and IL-13 without degranulation. Mast cells expressed IL-4 and IL-13 in eosinophilic polyps. The number of CD30L+ tryptase+ mast cells was positively correlated with the number of eosinophils and total inflammatory cells in eosinophilic polyps. CONCLUSION: CD30/CD30L-mediated mast cell activation may promote the eosinophilic inflammation in CRSwNP. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E110-E117, 2019.

Deficiency in interleukin-10 production by M2 macrophages in eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: M2 macrophages are characterized by high interleukin-10 (IL-10) expression and are critical for resolving inflammation. Although increased accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly the eosinophilic type, their functional relevance in CRSwNP remains poorly understood. METHODS: M1 and M2 macrophages and IL-10 expression in sinonasal tissues were detected by double-immunofluorescence staining. THP-1 cells, a human monocytic leukemia cell line, were stimulated with various cytokines to study macrophage polarization and IL-10 expression. Polyp size, computed tomography (CT) scans, and symptom severity were scored. RESULTS: Compared with numbers in control tissues, the numbers of total CD68+ macrophages, interferon regulatory factor 5-positive and CD68+ M1 macrophages, and CD163+ CD68+ and CD206+ CD68+ M2 macrophages were increased in both eosinophilic and non-eosinophilic polyps. However, compared with non-eosinophilic polyps, eosinophilic polyps contained fewer M1 macrophages and more M2 macrophages. Consistent with this, the M1/M2 macrophage ratio was increased in non-eosinophilic polyps, whereas it decreased in eosinophilic polyps. Strikingly, the numbers of IL-10+ CD68+ macrophages and the percentage of IL-10+ CD68+ macrophages relative to the total number of macrophages were decreased in eosinophilic polyps, despite the upregulation of M2 macrophages in this type of polyp. The number of IL-10+ CD68+ M2 macrophages correlated negatively with total symptoms scores, polyp sizes, total CT scores, and the total number of inflammatory cells in patients with eosinophilic CRSwNP. Poly I:C downregulated IL-10 expression in M2 macrophages differentiated from THP-1 cells in vitro. CONCLUSION: Impaired IL-10 production by M2 macrophages may contribute to sustained inflammation in eosinophilic CRSwNP.vv.

MicroRNA in United Airway Diseases.

The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD.

Distinct mucosal immunopathologic profiles in atopic and nonatopic chronic rhinosinusitis without nasal polyps in Central China.

BACKGROUND: The role of atopy to aeroallergens in chronic rhinosinusitis without nasal polyps (CRSsNP) remains unclear. This study aimed to investigate the mucosal immunopathologic characteristics of CRSsNP with and without atopy to inhalant allergens. METHODS: Thirteen nonatopic CRSsNP patients, 9 atopic CRSsNP patients, and 11 nonatopic control subjects were enrolled in this study. The expression of type 1, 2, and 17 cytokines, growth factors, and chemokines for T cell subsets and granulocytes in sinonasal mucosa was detected using Bio-Plex suspension chip technology or enzyme-linked immunosorbent assay (ELISA). Subjective symptoms were scored on a visual analogue scale (VAS), while disease severity on computed tomography (CT) was graded by the Lund-Mackay CT scoring system. RESULTS: There was no significant difference in VAS and CT scores between atopic and nonatopic CRSsNP. Compared with control, both atopic and nonatopic CRSsNP demonstrated increased interferon γ (IFN-γ) levels in sinonasal mucosa. In contrast, although no difference in interleukin 5 (IL-5), IL-13 and eotaxin-1 expression, or mucosal eosinophil infiltration, was found between the control and whole CRSsNP group, atopic CRSsNP manifested an increased expression of IL-5, IL-13 and eotaxin-1, as well as an enhanced infiltration of mucosal eosinophils in comparison with control and nonatopic CRSsNP. Mucosal eosinophil infiltration correlated with IL-5 and eotaxin-1 expression. No difference in IL-12, IL-4, IL-6, IL-17A, IL-8, myeloperoxidase, "regulated upon activation normal T cell expressed and presumably secreted" (RANTES), or chemokine (C-X-C motif) ligand 10 (CXCL10) protein expression was found among control, atopic CRSsNP, and nonatopic CRSsNP. CONCLUSION: Atopic and nonatopic CRSsNP have distinct mucosal immunopathologic profiles. CRSsNP is a heterogeneous disorder consisting of multiple groups of biological subtypes, or "endotypes," which may argue for different therapeutic strategies.

MicroRNA in chronic rhinosinusitis and allergic rhinitis.

Inflammatory upper airway diseases, particularly chronic rhinosinusitis (CRS) and allergic rhinitis (AR), have a high worldwide prevalence. CRS and AR involve sustained and exaggerated inflammation that is associated with marked changes in gene and protein expression under tight regulation. A novel group of gene expression regulators is a class of short single-stranded RNA molecules termed microRNAs (miRNAs). miRNAs can cause gene silencing through degradation of target mRNAs or inhibition of translation. Dysregulated expression of miRNAs has been shown in various human diseases, such as cancer, inflammatory skin and bowel diseases, rheumatoid arthritis, and asthma. Although studies of miRNAs in inflammatory upper airway diseases are relatively new and few, emerging evidence implicates an involvement of miRNAs in shaping the inflammation pattern in upper airways. The purpose of this review is to provide an overview on our current understanding of miRNA expression and function in CRS and AR, and to underscore the potential for clinical usage of miRNAs in CRS and AR.

Expression of microRNA machinery proteins in different types of chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: Dysregulation of microRNAs (miRNAs) has recently been shown in chronic rhinosinusitis (CRS), the biogenesis and function of which are modulated by miRNA machinery proteins. The expression of these proteins in inflammatory airway diseases is unclear. The aim of this study was to investigate the expression of miRNA machinery components in CRS. STUDY DESIGN: Case-control experimental study. METHODS: The mRNA expression levels of miRNA machinery components including Drosha, Dicer, protein activator of the interferon-induced protein kinase (PACT), human immunodeficiency virus transactivating response RNA-binding protein, fragile X mental retardation protein, and argonaute 2/eukaryotic translation initiation factor 2C, 2 in nasal biopsies from control, CRS without nasal polyps (CRSsNP), eosinophilic, and noneosinophilic CRS with nasal polyps (CRSwNP) subjects were determined by quantitative reverse transcription polymerase chain reaction. Immunohistochemical staining was employed to examine the protein expression of PACT and the cellular source of PACT. RESULTS: Among the tested components, only PACT mRNA expression was found to be altered in CRS, the levels of which were upregulated in CRSwNP as compared with control. In comparison with control and CRSsNP, PACT protein expression was also significantly upregulated in CRSwNP, with a further increase in eosinophilic CRSwNP. PACT was mainly expressed in CD138(+) plasma cells. A higher percentage of PACT-positive plasma cells in total plasma cells was detected in eosinophilic CRSwNP than in noneosinophilic CRSwNP. PACT protein expression correlated with disease severity and eosinophil infiltration. CONCLUSIONS: PACT may be associated with the plasma cell function and eosinophilic inflammation in CRSwNP. However, further experimentation is needed to clarify the functions of PACT.

Overexpression of miR-125b, a novel regulator of innate immunity, in eosinophilic chronic rhinosinusitis with nasal polyps.

RATIONALE: Eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) represents a hard-to-treat subtype of CRS. OBJECTIVES: To determine the pattern of expression and biologic role of microRNAs (miRNAs) in CRS, particularly in eosinophilic CRSwNP. METHODS: Global miRNA expression in sinonasal mucosa from controls, CRS without nasal polyps (CRSsNP), and patients with eosinophilic CRSwNP was compared using miRNA microarrays. MiR-125b expression was detected by means of quantitative reverse-transcriptase polymerase chain reaction. The cellular localization of miR-125b was determined by in situ hybridization. MiR-125b functional assays were performed on airway epithelial cells and mice. MiR-125b expression regulation was studied by tissue and cell culture. MEASUREMENTS AND MAIN RESULTS: CRSsNP and eosinophilic CRSwNP exhibited distinct miRNA expression profiles. MiR-125b was specifically up-regulated in eosinophilic CRSwNP. MiR-125b was mainly expressed by sinonasal and bronchial epithelial cells. EIF4E-binding protein 1 (4E-BP1) was identified as a direct target of miR-125b. MiR-125b mimic or inhibitor enhanced or decreased IFN-α/ß production elicited by dsRNA in vitro or in vivo, respectively. 4E-BP1 expression was decreased, whereas IFN regulatory factor-7 and IFN-ß expression was increased, in eosinophilic CRSwNP. IFN-ß mRNA levels positively correlated with IL-5 mRNA levels and eosinophil infiltration in sinonasal mucosa. IFN-ß stimulated B cell-activating factor of the tumor necrosis factor family production in airway epithelial cells. miR-125b could be induced by lipopolysaccharide, dsRNA, and IL-10. CONCLUSIONS: The up-regulated expression of miR-125b may enhance type I IFN expression through suppressing 4E-BP1 protein expression in airway epithelial cells, which potentially contributes to mucosal eosinophilia in eosinophilic CRSwNP.

Theoretical studies on the mechanism and stereoselectivity of Rh(Phebox)-catalyzed asymmetric reductive aldol reaction.

Density functional theory calculations (B3LYP) have been carried out to understand the mechanism and stereochemistry of an asymmetric reductive aldol reaction of benzaldehyde and tert-butyl acrylate with hydrosilanes catalyzed by Rh(Phebox-ip)(OAc)(2)(OH(2)). According to the calculations, the reaction proceeds via five steps: (1) oxidative addition of hydrosilane, (2) hydride migration to carbon-carbon double bond of tert-butyl acrylate, which determines the chirality at C2, (3) tautomerization from rhodium bound C-enolate to rhodium bound O-enolate, (4) intramolecular aldol reaction, which determines the chirality at C3 and consequently the anti/syn-selectivity, and (5) reductive elimination to release aldol product. The hydride migration is the rate-determining step with a calculated activation energy of 23.3 kcal mol(-1). In good agreement with experimental results, the formation of anti-aldolates is found to be the most favorable pathway. The observed Si-facial selectivity in both hydride migration and aldol reaction are well-rationalized by analyzing crucial transition structures. The Re-facial attack transition state is disfavored because of steric hindrance between the isopropyl group of the catalyst and the tert-butyl acrylate.

Let-7a microRNA functions as a potential tumor suppressor in human laryngeal cancer.

MicroRNAs (miRNAs) are endogenously expressed non-coding RNAs, which are involved in the gene expression regulation. Lethal-7a (let-7a) is a founding member of miRNA family and recently it was found to be associated with several cancers, such as lung and colon cancers. In the present study, we found that let-7a miRNA expression was significantly downregulated both in human laryngeal squamous cancer tissues and in Hep-2 cells, a laryngeal cancer cell line, as compared with adjacent normal tissues and BEAS-2B cells, respectively. Moreover, we found that let-7a expression levels were significantly further decreased in non-differentiated (G3) cancer tissues as compared with moderately and well differentiated cancer tissues (G2 and G1), although no significant difference in let-7a expression levels between the cancer specimens with different T stages or specimens from patients with different lymph node metastasis status was revealed. In Hep-2 cells, let-7a mimics transfection markedly suppressed proliferation and induced apoptosis of Hep-2 cells under the treatment of diamminedichloroplatinum or not and downregulated RAS and c-MYC protein expression without affecting the mRNA levels. In parallel, RAS and c-MYC protein levels were found significantly upregulated only in cancer tissues with downregulated let-7a expression. Thus, we propose that let-7a may be a tumor suppressor in laryngeal cancer by inhibiting cell growth, inducing cell apoptosis and downregulating the oncogenes expression.

Histological and immunological observations of bacterial and allergic chronic rhinosinusitis in the mouse.

BACKGROUND: The purpose of this study was to elucidate histological and immunologic features of mouse models of bacterial chronic rhinosinusitis (BCRS) and allergic chronic rhinosinusitis (ACRS). METHODS: A BCRS mouse model was established using Streptococcus pneumoniae inoculation plus Merocel (Medtronic, Jacksonville, FL) ostiomeatal obstruction for 12 weeks. An ACRS mouse model was developed by means of ovalbumin (OVA) i.p. injection and subsequent repeated OVA intranasal challenge for 12 weeks. Histological changes of sinonasal mucosa of both models were examined by means of hematoxylin and eosin staining for general morphology and inflammatory cell, periodic acid-Schiff staining for goblet cell, and Masson-trichrome staining for collagen. Enzyme-linked immunosorbent assay was used to detect the concentrations of various cytokines in nasal lavage fluid. RESULTS: Polymorphonuclear neutrophil infiltration in lamina propria was more obvious in the BCRS model, whereas eosinophil infiltration was more apparent in the ACRS model. Significant goblet cell and subepithelial gland hyperplasia, subepithelial fibrosis, epithelial thickening, and mononuclear cell infiltration were shown in both models with more severe extent found in the ACRS model. Interleukin (IL)-6 and tumor necrosis factor alpha levels in NLF from both models were increased and peaked at 1 week. Interferon gamma levels were also up-regulated in both models but reached maximum at 1 week in the BCRS model and 4 weeks in the ACRS model. IL-8 (CXCL8) levels were only increased in BCRS mice and peaked at 1 week, whereas IL-5, IL-13, and eotaxin (CCL11) levels were only enhanced in ACRS mice and peaked at 1 week. The Th1/Th2 ratio in BCRS mice was significantly higher than that in ACRS mice (6.68 +/- 2.33 versus 1.37 +/- 0.86; p < 0.01). CONCLUSION: Histological and immunologic features of BCRS and ACRS mouse models were similar to those of human noneosinophilic and eosinophilic CRS, respectively. BCRS and ACRS mouse models have distinct immunologic characteristics and are applicable for CRS research.

A DFT study on the mechanism of hydrosilylation of unsaturated compounds with neutral hydrido(hydrosilylene)tungsten complex.

Recently, Tobita et al. reported stoichiometric hydrosilylation reactions of acetone and acetonitrile with neutral hydrido(hydrosilylene)tungsten complexes Cp'(CO)2(H)W=Si(H)[C(SiMe(3))(3)] (Cp' = Cp*, C(5)Me(4)Et). The mechanisms of the hydrosilylation reactions of unsaturated compounds (ketone and nitrile) with the tungsten complexes have been investigated with the B(3)LYP density functional theory method. Four possible reaction mechanisms were studied. The results of the calculations indicate that the hydrosilylation of acetone proceeds via a metal hydride migration mechanism proposed by Tobita et al., while the hydrosilylation of nitrile occurs through a silyl migration mechanism, analogous to the modified Chalk-Harrod mechanism. The [2(sigma)+2(pi)] additions of various CX (CX = C=O or CN) multiple bonds with the Si-H bonds in the neutral complexes have very high barriers although similar additions were found feasible in other related cationic complexes. All the hydrosilylation reactions studied here give stable tungsten-silylene or tungsten-silyl products, which are not easily converted into the starting hydrido(hydrosilylene)tungsten complexes when reacting with a hydrosilane substrate molecule. Therefore, we predict that hydrosilylation of acetonitrile and acetone catalyzed by these tungsten complexes is difficult to achieve.

Reaction of Ta(NMe2)5 with O2: formation of aminoxy and unusual (aminomethyl)amide oxo complexes and theoretical studies of the mechanistic pathways.

Reaction of d0 Ta(NMe2)5 (1) with O2 yields two aminoxy complexes (Me2N)(n)Ta(eta2-ONMe2)(5-n) (n = 4, 2; 3, 3) as well as (Me2N)4Ta2[eta2-N(Me)CH2NMe2]2(mu-O)2 (4) and (Me2N)6Ta3[eta2-N(Me)CH2NMe2]2(eta2-ONMe2)(mu-O)3 (5) containing novel chelating (aminomethyl)amide-N(Me)CH2NMe2 ligands. The crystal structures of 2-5 have been determined by X-ray crystallography. (Me2N)4Ta(eta2-ONMe2) (2) converts to (Me2N)3Ta(eta2-ONMe2)2 (3) in its reaction with O2. In addition, the reaction of Ta(NMe2)5 with 3 gives 2 only at elevated temperatures. Density functional theory (DFT) calculations have been used to investigate the mechanistic pathways in the reactions of Ta(NMe2)5 (1) with triplet O2. Monomeric reaction pathways in the formation of 2-5 are proposed. A key step is the oxygen insertion into a Ta-N bond in 1 through an intersystem conversion from triplet to singlet energy surface to give an active peroxide complex (Me2N)4Ta(eta2-O-O-NMe2) (A4). The DFT studies indicate that the peroxide ligand plays an important role, including oxidizing an amide to an imine ligand through the abstraction of a hydride. Insertion of Me-N=CH2 into a Ta-amide bond yields the unusual -N(Me)CH2NMe2 ligands.

Pyridyne radical cations produced by photodissociation of Mg*+ (multifluoro-pyridine) complexes: a combined experimental and theoretical study.

Gas phase complexes Mg*+ (2,6-difluoropyridine) (1) and Mg*+ (pentafluoropyridine) (2) have been subjected to photodissociation in the spectral range of approximately 230-440 nm. Except for the evaporative photofragment Mg*+ , the primary photoproduct for is C(5)H(3)N*(+), which is associated with the rupture of two C-F bonds by the photoexcited Mg*+ , forming very stable MgF(2). In contrast, the direct loss of MgF(+) is more favorable for due to fluorine substitution. Given enough energy, C(5)H(3)N*(+) can undergo decomposition to form C(4)H(2)*(+) and HCN. These results are very different from those for Mg*+ (2-fluoropyridine), highlighting the significance of the additional F at C6 of and . Density functional theory (DFT) calculations have been employed to examine the geometries and energetics of the complexes as well as relevant reaction mechanisms. All of the complexes feature the direct attachment of Mg*+ to the N atom. The key intermediate is found to be FMg(+) (C(5)H(x)F(4-x)N) (x = 3 or 0), which can lead to the formation of MgF(+) directly or MgF(2) through activation of another C-F bond adjacent to N, producing the pyridyne radical cations. However, hydrogen-transfer prior to the rupture of the second C-F bond followed by ring-opening of C(5)H(3)N*(+) may result in the formation of chain forms of C(5)H(3)N*(+). The influence of the fluorine substitution on the competition of the two routes have been demonstrated.

Synthetic study of 1,3-butadiene-based IMDA approach to construct a [5-7-6] tricyclic core and its application to the total synthesis of C8-epi-guanacastepene O.

An efficient intramolecular Diels-Alder (IMDA) strategy for the construction of the [5-7-6] tricyclic core (18) of guanacastepenes has been developed from cis- and trans-1,3-butadiene-tethered 4-oxopent-2-ynoic acid ethyl esters 10 and 11. This method facilitates the synthesis of C8-epi-guanacastepene O (36) in a very efficient manner.