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1.
J Exp Bot ; 75(8): 2435-2450, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38243353

RESUMO

WRKY transcription factors play a central role in controlling plant organ senescence; however, it is unclear whether and how they regulate petal senescence in the widely grown ornamental plant tulip (Tulipa gesneriana). In this study, we report that TgWRKY75 promotes petal senescence by enhancing the synthesis of both abscisic acid (ABA) and salicylic acid (SA) in tulip and in transgenic Arabidopsis. The expression level of TgWRKY75 was up-regulated in senescent petals, and exogenous ABA or SA treatment induced its expression. The endogenous contents of ABA and SA significantly increased during petal senescence and in response to TgWRKY75 overexpression. Two SA synthesis-related genes, TgICS1 and TgPAL1, were identified as direct targets of TgWRKY75, which binds to their promoters. In parallel, TgWRKY75 activated the expression of the ABA biosynthesis-related gene TgNCED3 via directly binding to its promoter region. Site mutation of the W-box core motif located in the promoters of TgICS1, TgPAL1, and TgNCED3 eliminated their interactions with TgWRKY75. In summary, our study demonstrates a dual regulation of ABA and SA biosynthesis by TgWRKY75, revealing a synergistic process of tulip petal senescence through feedback regulation between TgWRKY75 and the accumulation of ABA and SA.


Assuntos
Arabidopsis , Tulipa , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ácido Abscísico/metabolismo , Tulipa/metabolismo , Ácido Salicílico/metabolismo , Regulação da Expressão Gênica de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo
2.
Int J Mol Sci ; 25(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38203734

RESUMO

Anthocyanins play a paramount role in color variation and significantly contribute to the economic value of ornamental plants. The conserved activation complex MYB-bHLH-WD40 (MBW; MYB: v-myb avian myeloblastosis viral oncogene homolog; bHLH: basic helix-loop-helix protein; WD40:WD-repeat protein) involved in anthocyanin biosynthesis has been thoroughly researched, but there have been limited investigations into the function of repressor factors. In this study, we characterized TgMYB4, an R2R3-MYB transcriptional repressor which is highly expressed during petal coloration in red petal cultivars. TgMYB4-overexpressing tobaccos exhibited white or light pink petals with less anthocyanin accumulation compared to control plants. TgMYB4 was found to inhibit the transcription of ANTHOCYANIDIN SYNTHASE (TfANS1) and DIHYDRO-FLAVONOL-4-REDUCTASE (AtDFR), although it did not bind to their promoters. Moreover, the TgMYB4 protein was able to compete with the MYB activator to bind to the :bHLHprotein, thereby suppressing the function of the activator MBW complex. These findings demonstrate that TgMYB4 plays a suppressive role in the regulation of anthocyanin synthesis during flower pigmentation.


Assuntos
Tulipa , Antocianinas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Flavonóis , Flores/genética
3.
Genes (Basel) ; 14(10)2023 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-37895323

RESUMO

To investigate the cold response mechanism and low temperature regulation of flowering in tulips, this study identified 32 MADS-box transcription factor family members in tulips based on full-length transcriptome sequencing, named TgMADS1-TgMADS32. Phylogenetic analysis revealed that these genes can be divided into two classes: type I and type II. Structural analysis showed that TgMADS genes from different subfamilies have a similar distribution of conserved motifs. Quantitative real-time PCR results demonstrated that some TgMADS genes (e.g., TgMADS3, TgMADS15, TgMADS16, and TgMADS19) were significantly upregulated in buds and stems under cold conditions, implying their potential involvement in the cold response of tulips. In summary, this study systematically identified MADS family members in tulips and elucidated their evolutionary relationships, gene structures, and cold-responsive expression patterns, laying the foundation for further elucidating the roles of these transcription factors in flowering and the cold adaptability of tulips.


Assuntos
Tulipa , Tulipa/genética , Tulipa/metabolismo , Filogenia , Proteínas de Domínio MADS/metabolismo , Genoma de Planta , Fatores de Transcrição/genética
4.
J Environ Sci Health B ; 58(12): 718-725, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37897250

RESUMO

The aim of this study was to gain a better understanding of how Tulipa luanica adapts to growth in soil with higher concentrations of heavy metals and to assess potential toxic effects using various biomarkers, in comparison to Tulipa kosovarica, a typical serpentine species. For this purpose, we analyzed the concentrations of Al, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, and Zn in the soil, as well as their accumulation in plants and their associated stress effects. The results indicate that, despite the presence of some metals in very high concentrations in the soil (Al, Fe, Mn, and Ni), they are translocated in minimal amounts within plant organs, particularly in T. luanica. Nearly all metals exhibited significantly higher concentrations in T. kosovarica when compared to T. luanica. Based on the analysis of biomarkers, it is apparent that T. luanica shows greater sensitivity to these conditions. This is evident through the decreased activity of δ-aminolevulinic acid dehydratase and levels of δ-aminolevulinic acid, malondialdehyde, and glutathione observed in T. luanica. It appears that T. luanica effectively restricts the absorption of metals in serpentine soils; however, it experiences oxidative stress induced by these metals, setting it apart from the more resilient T. kosovarica.


Assuntos
Metais Pesados , Poluentes do Solo , Tulipa , Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Monitoramento Ambiental/métodos
5.
Neurosurg Focus ; 55(1): E5, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37392770

RESUMO

OBJECTIVE: The incidence of sacroiliac joint (SIJ) dysfunction after lumbosacral fusion is high. Upfront bilateral SIJ fusion using novel fenestrated self-harvesting porous S2-alar iliac (S2AI) screws could reduce the incidence of SIJ dysfunction and need for subsequent SIJ fusion. In this study, the authors report their early clinical and radiographic results of SIJ fusion using this novel screw. METHODS: The authors began using self-harvesting porous screws in July 2022. This is a retrospective review of consecutive patients at a single institution who underwent long thoracolumbar surgery with extension to the pelvis using this porous screw. Radiographic parameters of regional and global alignment were collected preoperatively and at the time of last follow-up. The incidence of intraoperative complications and need for revision were collected. The incidences of mechanical complications, including screw breakage, implant loosening/pullout, and screw cap dislocation at the time of last follow-up were also collected. RESULTS: Ten patients with a mean age of 67 years were included, 6 of whom were male. Seven patients had a thoracolumbar construct with extension to the pelvis. Three patients had upper instrumented vertebrae at the proximal lumbar spine. Intraoperative breach was not encountered in any of the patients (0%). Postoperatively, 1 patient (10%) had screw breakage at the neck of the tulip of the modified iliac screw discovered at routine follow-up without clinical sequalae. CONCLUSIONS: Use of self-harvesting porous S2AI screws incorporated into long thoracolumbar constructs was safe and feasible, demanding unique technical considerations. Long-term clinical and radiographic follow-up with a large patient cohort is necessary to determine their durability and efficacy to achieve SIJ arthrodesis and prevent SIJ dysfunction.


Assuntos
Doenças da Coluna Vertebral , Fusão Vertebral , Tulipa , Humanos , Masculino , Idoso , Feminino , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/cirurgia , Porosidade , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Parafusos Ósseos
6.
Z Naturforsch C J Biosci ; 78(9-10): 353-363, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37402691

RESUMO

Tuliposides (Pos) are major defense-related secondary metabolites in tulip, having 4-hydroxy-2-methylenebutanoyl and/or (3S)-3,4-dihydroxy-2-methylenebutanoyl groups at the C-1 and/or C-6 positions of d-glucose. The acyl group at the C-6 position is converted to antimicrobial lactones (tulipalins) by an endogenous Pos-converting enzyme. Based on this enzyme activity, we examined tulip bulb extracts and detected HPLC peaks that disappeared following the reaction by the Pos-converting enzyme. Spectroscopic analyses of the three purified compounds revealed that one of them was a glucose ester-type Pos, while the other two were identified as a glucoside ester-type Pos. These compounds were designated as PosK, L, and M. They were specific to bulbs, with the highest content in the outermost layer, but they were markedly less abundant than PosG, the minor bulb Pos we identified earlier. The study results suggest that tulip bulbs contain at least four minor Pos in addition to the major 6-PosA. Although PosK-M were present in almost all of the tested tulip cultivars, they were detected in only a few wild species, indicative of their potential utility as chemotaxonomic markers in tulip. Identification of PosK-M as 6-PosA derivatives unveils the biosynthetic diversity of Pos, the well-known group of secondary metabolites in tulip.


Assuntos
Tulipa , Tulipa/química , Glucosídeos/química , Glucose , Lactonas , Ésteres
7.
BMC Surg ; 23(1): 152, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280570

RESUMO

BACKGROUND: The removal of spinal implants is needed in revision surgery or in some cases whose fracture had healed or fusion had occurred. The slip of polyaxial screw or mismatch of instruments would make this simple procedure intractable. Here we introduce a simple and practical method to address this clinical dilemma. METHODS: This is a retrospective study. The patients underwent new technique for retrieving the implants from July 2019 to July 2022 were labeled as group A, while the patients underwent traditional implants retrieval technique from January 2017 to January 2020 were labeled as group B. Patients in each group were subdivided into revision surgery group (r group) and simple implants removal group (s group) according to the surgery fashion. For the new technique, the retrieved rod was cut off to a proper length which was matched with the size of tulip head, and was replaced into the tulip head. After tightened with nut, a monoaxial screw-rod "construct" was formed. Then the "construct" can be retrieved by a counter torque. The operation duration, intraoperative blood loss, post-operative bacteria culture, hospital stay and costs were analyzed. RESULTS: A total of 116 polyaxial screws with difficult retrieval (43 screws in group A, 73 screws in group B) in 78 patients were recorded, in which 115 screws were successfully retrieved. Significant differences were found in the mean operation duration, intraoperative blood loss when comparing the r group in group A and B, as well as the s group in group A and B (P < 0.05). There were no significant differences in hospital stay and costs between group A and B. Three patients were found positive bacteria culture of drainage tube/tape in group A (3/30), while 7 patients in group B (7/48). The most prevalent bacteria was Propionibacterium acnes. CONCLUSION: This technique is practical and safe in retrieving tulip head poly-axial screw. Reduced operation duration and intraoperative bloods loss may potentially alleviate the hospitalization burden of patients. Positive bacterial cultivation results are common after implants removal surgery, but they rarely represent an organized infection. A positive culture with P. acnes or S. epidermidis should be interpreted with caution.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Tulipa , Humanos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia
8.
J Vasc Interv Radiol ; 34(2): 261-267.e2, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-37190972

RESUMO

PURPOSE: To describe the natural history of Gunther Tulip filter (GTF) strut penetration based on the computed tomography (CT)-documented distance penetrated over time and any clinical manifestations. MATERIALS AND METHODS: The records of 203 patients (mean age, 59.1 years; 59.4% men) who had had an infrarenal GTF placed for venous thromboembolism (84.2%) with contraindications to anticoagulation (95.1%) and had CT follow-up were reviewed retrospectively for clinical or imaging evidence of complications. Filter strut penetration was measured on axial images from the outer caval wall to the inner edge of the distal end of each strut. Filter strut behavior over time was modeled using a linear mixed model. RESULTS: The extent of penetration correlated positively with filter dwell time (P < .001) but plateaued at 3.3 mm at 10-year follow-up. At median 4.7-year follow-up 79.3% of patients had at least 1 strut that was >0.2 mm and 31% had a strut >3 mm from the inferior vena caval wall. The extent of strut penetration was greater at all time points for women (P = .002). Abutment or entry into an adjacent structure was identified in 183 struts of 105 (52.7%) filters; of the 80 filters with CT follow-up, 47% showed progression and 19% regressed. There were no symptoms referable to filter strut penetration. CONCLUSIONS: GTF struts often penetrate the inferior vena cava progressively; however, this tends to plateau by 10 years. The limited long-term progression and a very low incidence of symptomatic complications together support a noninterventional approach to the finding of an asymptomatic GTF strut penetration.


Assuntos
Tulipa , Filtros de Veia Cava , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Seguimentos , Desenho de Prótese , Estudos Retrospectivos , Remoção de Dispositivo/métodos , Fatores de Tempo , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia
9.
Physiol Plant ; 175(3): e13939, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37243848

RESUMO

The floral coloration of tulip flowers is one of the most prominent traits contributing to its high ornamental value. The molecular mechanisms of petal coloration remain elusive in tulip species. In this study, we performed comparative metabolome and transcriptome analyses using four tulip cultivars with distinguished petal colors. Four types of anthocyanins were identified, including cyanidin derivatives and pelargonidin derivatives. Comparative transcriptome analysis identified 22,303 differential expressed genes (DEGs) from the four cultivars, and 2589 DEGs were commonly regulated in three comparison groups (colored vs. white cultivar), including anthocyanins biosynthesis-related genes and regulatory transcription factors. Two basic helix-loop-helix (bHLH) transcription factors, TgbHLH42-1 and TgbHLH42-2, with differential expression levels among cultivars and petal developmental stages, have high homology to TRANSPARENT TESTA 8 (AtTT8) of Arabidopsis. The anthocyanins accumulation in TgbHLH42-1 overexpressing (OE) seedlings was markedly greater than that in wild-type seedlings in the presence of methyl jasmonate (MeJA), but not for TgbHLH42-2 OE seedlings. Both TgbHLH42-1 and TgbHLH42-2 restored pigmentation defects in tt8 mutant seeds after complementation assay. TgbHLH42-1 could interact with MYB protein AtPAP1 to synergistically activate the transcription of AtDFR, whereas TgbHLH42-2 failed to. Silencing TgbHLH42-1 or TgbHLH42-2 individually could not, but simultaneously silencing both TgbHLH42 could reduce the anthocyanin in tulip petals. These results indicate that TgbHLH42-1 and TgbHLH42-2 function partially redundantly to positively regulate anthocyanin biosynthesis during tulip petal coloration.


Assuntos
Antocianinas , Tulipa , Antocianinas/metabolismo , Tulipa/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Pigmentação , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
10.
Ann Rheum Dis ; 82(5): 639-645, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36690388

RESUMO

OBJECTIVES: In patients with systemic lupus erythematosus (SLE), lupus low disease activity state (LLDAS) attainment is associated with improved outcomes. We investigated LLDAS attainment in anifrolumab-treated patients. METHODS: We performed post hoc analysis of pooled Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP-1) (NCT02446912) and TULIP-2 (NCT02446899) anifrolumab phase 3 trial data in patients with moderate to severe SLE receiving standard therapy. LLDAS was defined as: SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician's Global Assessment ≤1, prednisone ≤7.5 mg/day and no non-standard immunosuppressant dosing. Time to first LLDAS attainment was compared between groups using Cox regression modelling; responses were compared using logistic regression. RESULTS: Agnostic to treatment, 205/819 (25.0%) patients attained LLDAS at week 52; 186/205 (90.7%) were also British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA)-responders. Among BICLA-responders at week 52, 186/318 (58.5%) attained LLDAS; 203/380 (53.4%) SLE Responder Index-4 (SRI(4)) responders attained LLDAS. Improvements from baseline in patient global assessment scores at week 52 were threefold greater in LLDAS-attainers. At week 52, 30.0% of anifrolumab-treated patients and 19.6% of placebo were in LLDAS (OR 1.8, 95% CI 1.3 to 2.5, p=0.0011). Compared with placebo, anifrolumab treatment was associated with earlier LLDAS attainment (time to first LLDAS, HR 1.76, 95% CI 1.35 to 2.30, p<0.0001), increased cumulative time in LLDAS (p<0.0001) and higher likelihood of sustained LLDAS (p<0.001). Anifrolumab treatment was also associated with higher rates of Definition of Remission in SLE remission at week 52 (15.3% vs 7.6%; OR 2.2, 95% CI 1.4 to 3.6, p=0.0013). CONCLUSIONS: LLDAS attainment was highly associated with, but more stringent than, BICLA and SRI(4) responses. Compared with placebo, anifrolumab treatment was associated with earlier, more frequent, and more prolonged and sustained LLDAS. TRIAL REGISTRATION NUMBERS: NCT02446912 and NCT02446899.


Assuntos
Lúpus Eritematoso Sistêmico , Tulipa , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Lupus Sci Med ; 10(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36639192

RESUMO

OBJECTIVES: To evaluate the time course of clinical response following anifrolumab treatment in patients with SLE. METHODS: A post hoc analysis was conducted using pooled data from phase III, randomised, 52-week, placebo-controlled, Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-1 and TULIP-2 trials of intravenous anifrolumab (every 4 weeks, 48 weeks) in patients with moderate-to-severe SLE receiving standard therapy. Anifrolumab 300 mg and placebo groups were compared for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response over time, time to sustained BICLA response, SLE Responder Index ≥4 (SRI(4)) response over time, time to sustained Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) response and change in glucocorticoid dosage over time. All p values for comparisons were nominal. RESULTS: Of the 726 evaluated patients (anifrolumab 300 mg, n=360; placebo, n=366), a greater proportion attained a BICLA response in the anifrolumab versus the placebo group from Week 8 (p<0.001); treatment group differentiation was maintained at all subsequent visits to Week 52. Consistently, more patients achieved a BICLA response sustained to Week 52 in the anifrolumab versus placebo group (HR=1.73, 95% CI 1.37 to 2.20). More patients attained SRI(4) response with anifrolumab than placebo from Week 12 (p=0.005). As early as Week 8, more patients achieved CLASI-A skin response sustained to Week 52 with anifrolumab versus placebo (HR=1.72, 95% CI 1.17 to 2.55). Glucocorticoid dosage reductions from baseline were greater in anifrolumab-treated versus placebo-treated patients from Week 20 (p=0.010) through Week 52. CONCLUSIONS: Anifrolumab treatment was associated with sustained improvements in overall SLE disease activity and skin responses versus placebo from Week 8, which likely led to greater glucocorticoid reductions in the anifrolumab versus placebo groups from Week 20. These findings provide insights to physicians and patients on when to expect potential clinical responses following anifrolumab treatment.


Assuntos
Lúpus Eritematoso Sistêmico , Tulipa , Humanos , Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico
12.
Clin Neuropsychol ; 37(1): 60-80, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35225154

RESUMO

Neuropsychological assessment of culturally diverse populations is hindered by barriers in language, culture, education, and a lack of suitable tests. Furthermore, individuals from diverse backgrounds are often unfamiliar with being cognitively tested. The aim of this study was to develop a new neuropsychological test battery and study its feasibility in multicultural memory clinics.Composition of the TULIPA battery (Towards a Universal Language: Intervention and Psychodiagnostic Assessment) entailed a literature review and consultation with experts and individuals from diverse backgrounds. Feasibility was investigated by examining administration and completion rates and the frequency of factors complicating neuropsychological assessment in 345 patients from 37 countries visiting four multicultural memory clinics in the Netherlands.The test battery included existing tests such as the Cross-Cultural Dementia screening (CCD), Rowland Universal Dementia Assessment Scale (RUDAS), tests from the European Cross-Cultural Neuropsychological Test Battery, and newly developed tests. Completion rates for the test battery were generally high (82%-100%), except for CCD Dots subtest B (58%). Although tests of the "core" TULIPA battery were administered often (median: 6 of 7, IQR: 5-7), supplementary tests were administered less frequently (median: 1 of 9; IQR: 0-3). The number of administered tests correlated with disease severity (RUDAS, ρ=.33, adjusted p < .001), but not with other patient characteristics. Complicating factors were observed frequently, e.g. suboptimal effort (29%-50%), fatigue (29%), depression (37%-57%).The TULIPA test battery is a promising new battery to assess culturally diverse populations in a feasible way, provided that complicating factors are taken into account.Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2022.2043447 .


Assuntos
Demência , Tulipa , Humanos , Demência/diagnóstico , Testes Neuropsicológicos , Estudos de Viabilidade , Idioma
14.
Mod Rheumatol ; 33(1): 134-144, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35134970

RESUMO

OBJECTIVES: Evaluate the efficacy and safety of anifrolumab in the subpopulation of Japanese patients with systemic lupus erythematosus (SLE) in phase 3 TULIP-2 trial. METHODS: TULIP-2 was a 52-week randomized placebo-controlled trial (N = 362) that evaluated efficacy and safety of anifrolumab 300 mg IV every 4 weeks vs. placebo in patients with moderate to severe SLE who were receiving standard therapy. We performed a post hoc analysis of the primary and key secondary endpoints, and safety, of TULIP-2 in the Japanese subpopulation. RESULTS: In the Japanese subpopulation (anifrolumab, n = 24; placebo, n = 19), the proportion of patients who achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment response at Week 52 (primary endpoint) was greater in the anifrolumab group vs. placebo [50.0% (12/24) vs. 15.8% (3/19); treatment difference: 34.2%, 95% confidence interval 6.9, 61.5; nominal p = .014]. Improvement in skin activity and flare rates (key secondary endpoints) were favourable for anifrolumab vs. placebo. Consistent with the overall population, anifrolumab had an acceptable safety and tolerability profile. CONCLUSIONS: The efficacy and safety of anifrolumab 300 mg in Japanese patients with SLE was consistent with the demonstrated clinical profile of anifrolumab for the overall TULIP-2 population.


Assuntos
Lúpus Eritematoso Sistêmico , Tulipa , Humanos , População do Leste Asiático , Anticorpos Monoclonais Humanizados/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego
15.
Rheumatology (Oxford) ; 62(4): 1526-1534, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36018235

RESUMO

OBJECTIVES: Glucocorticoid sparing is a key priority for SLE management. We evaluated the effects of sustained glucocorticoid tapering in patients with SLE. MATERIAL AND METHODS: This was a post hoc analysis of the randomized, placebo-controlled, 52-week phase 3 Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-1 and TULIP-2 trials of anifrolumab (300 mg i.v. once every 4 weeks for 48 weeks) plus standard therapy in patients with moderate to severe SLE. In a cohort of patients receiving glucocorticoids (prednisone or equivalent) 10 mg or more per day at baseline, we assessed changes in glucocorticoid dosage, patient-reported outcomes (PROs) and safety. Outcome measures were compared between sustained glucocorticoid taper responders (7.5 mg or less per day by week 40 sustained through week 52) and non-responders, regardless of treatment group, and between patients receiving anifrolumab or placebo. RESULTS: Among the 726 patients in the TULIP trials, 375 patients received glucocorticoids 10 mg or more per day at baseline, and of these, 155 (41%) patients were sustained glucocorticoid taper responders. Compared with non-responders (n = 220), sustained glucocorticoid taper responders reduced their mean cumulative glucocorticoid dose by 32%, improved PRO scores, reduced blood pressure and experienced fewer serious adverse events. Sustained glucocorticoid tapering was achieved by 51% (96/190) of patients receiving anifrolumab vs 32% (59/185) receiving placebo. Compared with placebo, more anifrolumab-treated patients achieved both sustained glucocorticoid taper and reduced overall disease activity [38% (72/190) vs 23% (43/185)]. CONCLUSIONS: Sustained glucocorticoid tapering is associated with clinical benefits. Anifrolumab treatment has potential to reduce disease activity and glucocorticoid exposure, a key goal of SLE management. STUDY REGISTRATION: ClinicalTrials.gov identifier: NCT02446912 and NCT02446899.


Assuntos
Lúpus Eritematoso Sistêmico , Tulipa , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Glucocorticoides , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/induzido quimicamente , Resultado do Tratamento
16.
BJU Int ; 131(4): 494-502, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36208033

RESUMO

OBJECTIVE: To develop a standardised tool to evaluate flexible ureterorenoscopes (fURS). MATERIALS AND METHODS: A three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement. RESULTS: The panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories. CONCLUSION: This modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS - The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS.


Assuntos
Tulipa , Humanos , Consenso , Técnica Delfos , Rim , Inquéritos e Questionários
17.
Anesth Prog ; 69(3): 9-12, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36223186

RESUMO

OBJECTIVE: Mask ventilation can be difficult in elderly edentulous patients. Various solutions have been proposed to address this challenge. This study assessed the use of a new airway-securing device called the Tulip Airway and investigated its application in simulated edentulous patients. METHODS: This pilot study utilized a modified edentulous airway training mannequin and a high-performance simulator. Participants attempted to ventilate the edentulous mannequin using a Guedel oropharyngeal airway and face mask (M method) or the Tulip Airway (T method). Successful inflation of the mannequin model lung was confirmed visually. The time required for the insertion of the Tulip Airway was also assessed. A high-performance simulator was then used to compare ventilation volumes achieved using the M and T methods, and data subsequently analyzed. RESULTS: In the edentulous mannequin, lung inflation was not achieved by any participants using the M method, but all were successful using the T method. Insertion time for the Tulip Airway was ∼8 seconds. Median ventilation volumes achieved using the high-performance simulator were higher for the T method (308 mL) compared with the M method (192 mL; P < .05). CONCLUSION: The results of this pilot study indicate that the Tulip Airway is an effective airway device for use in edentulous patients with difficult mask ventilation.


Assuntos
Máscaras Laríngeas , Tulipa , Idoso , Humanos , Intubação Intratraqueal , Manequins , Projetos Piloto
18.
Plant Physiol ; 190(3): 1960-1977, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35900170

RESUMO

Petal senescence is a crucial determinant for ornamental quality and economic value of floral crops. Salicylic acid (SA) and reactive oxygen species (ROS) are two prominent factors involved in plant senescence regulation. In this study, tulip TgNAP (NAC-like, activated by APETALA3/PISTILLATA) was characterized as positively regulating tulip petal senescence through dually regulating SA biosynthesis and ROS detoxification pathways. TgNAP was upregulated in senescing petals of tulip while exogenous SA and H2O2 treatments substantially promoted petal senescence in tulip. Silencing of TgNAP by VIGS assay delayed SA and H2O2-induced petal senescence in tulip, whereas overexpression of TgNAP promoted the senescence process in Arabidopsis (Arabidopsis thaliana) plants. Additionally, inhibition of SA biosynthesis prolonged the lifespan of TgNAP-silenced petal discs. Further evidence indicated that TgNAP activates the transcriptions of two key SA biosynthetic genes ISOCHORISMATE SYNTHASE 1 (TgICS1) and PHENYLALANINE AMMONIA-LYASE 1 (TgPAL1) through directly binding to their promoter regions. Meanwhile, TgNAP repressed ROS scavenging by directly inhibiting PEROXIDASE 12 (POD12) and POD17 expression. Taken together, these results indicate that TgNAP enhances SA biosynthesis and ROS accumulation to positively regulate petal senescence in tulip.


Assuntos
Arabidopsis , Tulipa , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo
19.
Sci Rep ; 12(1): 9786, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697708

RESUMO

Tulipa sylvestris, commonly called the "wild tulip", was introduced from the Mediterranean to northern Europe in the sixteenth century and became widely naturalized. Research has focused on tulips that came from the Ottoman Empire, but the introduction path of this native European, early ornamental tulip is unclear, and so is its taxonomic status: three subspecies are provisionally accepted, sometimes treated as species. Here we elucidate the history of introduction of T. sylvestris and discuss its taxonomy based on our historical findings. The first bulbs came from Bologna (northern Italy) and Montpellier (southern France) in the 1550-1570 s. Several renowned botanists were involved in their introduction, namely Gessner, Wieland, Aldrovandi, De Lobel, Clusius, and Dodoens. There were various introduction routes, including one from Spain which was apparently unsuccessful. The strong sixteenth-century Flemish botanical network facilitated the introduction and naturalization of T. sylvestris across Europe. Based on the latest tulip taxonomy, the diploid subspecies australis is native in the Mediterranean, and the tetraploid sylvestris is naturalized over Europe, but our historical findings show that both sylvestris and australis were introduced to northern Europe. This underlines the need to reconsider the taxonomic status of T. sylvestris, highlighting the importance of botanical history in understanding the complex taxonomy of naturalized cultivated plants.


Assuntos
Tulipa , Europa (Continente) , Raízes de Plantas , Plantas , Espanha
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