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1.
BJU Int ; 131(2): 253-261, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35974700

RESUMO

OBJECTIVES: To assess the cost-effectiveness, resource use implications, quality-adjusted life-years (QALYs) and cost per QALY of care pathways starting with either extracorporeal shockwave lithotripsy (SWL) or with ureteroscopic retrieval (ureteroscopy [URS]) for the management of ureteric stones. PATIENTS AND METHODS: Data on quality of life and resource use for 613 patients, collected prospectively in the Therapeutic Interventions for Stones of the Ureter (TISU) randomized controlled trial (ISRCTN 92289221), were used to assess the cost-effectiveness of two care pathways, SWL and URS. A health provider (UK National Health Service) perspective was adopted to estimate the costs of the interventions and subsequent resource use. Quality-of-life data were calculated using a generic instrument, the EuroQol EQ-5D-3L. Results are expressed as incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: The mean QALY difference (SWL vs URS) was -0.021 (95% confidence interval [CI] -0.033 to -0.010) and the mean cost difference was -£809 (95% CI -£1061 to -£551). The QALY difference translated into approximately 10 more healthy days over the 6-month period for the patients on the URS care pathway. The probabaility that SWL is cost-effective is 79% at a society's willingness to pay (WTP) threshold for 1 QALY of £30,000 and 98% at a WTP threshold of £20,000. CONCLUSION: The SWL pathway results in lower QALYs than URS but costs less. The incremental cost per QALY is £39 118 cost saving per QALY lost, with a 79% probability that SWL would be considered cost-effective at a WTP threshold for 1 QALY of £30 000 and 98% at a WTP threshold of £20 000. Decision-makers need to determine if costs saved justify the loss in QALYs.


Assuntos
Litotripsia , Ureteroscopia , Adulto , Humanos , Análise Custo-Benefício , Qualidade de Vida , Medicina Estatal , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Acta Neurochir (Wien) ; 164(4): 1115-1123, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35039959

RESUMO

INTRODUCTION: Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively. METHODS: Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up. RESULTS: One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups. CONCLUSION: Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.


Assuntos
Apoplexia Hipofisária , Neoplasias Hipofisárias , Acidente Vascular Cerebral , Humanos , Apoplexia Hipofisária/diagnóstico por imagem , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
3.
J Frailty Sarcopenia Falls ; 6(4): 209-217, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34950811

RESUMO

OBJECTIVES: The health and well-being of older women may be influenced by frailty and low socioeconomic status (SES). This study examined the association between frailty and SES, healthcare utilisation and quality of life (QOL) among older women in regional Australia. METHODS: Cross-sectional analysis of the Geelong Osteoporosis Study was conducted on 360 women (ages ≥60yr) in the 15-year follow up. Frailty was identified using modified Fried's phenotype. Individual SES measures and healthcare utilisation were documented by questionnaire. Area-based SES was determined by cross-referencing residential addresses with the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). QOL was measured using the Australian World Health Organisation Quality of Life Instrument (WHOQoL-Bref). Multinomial logistic regression was conducted with frailty groupings as outcome. RESULTS: Sixty-two (17.2%) participants were frail, 199 (55.3%) pre-frail and 99 (27.5%) robust. Frail participants were older with higher body mass index. Frailty was associated with lower education but not marital status, occupation or IRSAD. Strong associations with frailty were demonstrated for all WHOQoL-Bref domains. Frailty was associated with more primary care doctor visits (p<0.001). CONCLUSIONS: This population-based study highlights the significant impact of frailty on older women, indicating reduced QOL and increased primary care doctor visits.

4.
J Control Release ; 332: 148-159, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33609622

RESUMO

CpG oligonucleotides are short single-stranded synthetic DNA molecules. Upon binding to Toll-like receptor 9 (TLR9), CpG activates immune cells in humans and mice. This results in robust Th1 type immunity potentially resulting in clearance of pathogens, reduction of allergy and anti-tumor immunity. However, the effectiveness of CpG as an adjuvant depends on its administration route, with only strong effects seen when CpG is administered locally. As local administration is not always feasible, we generated conjugates to specifically deliver CpG to myeloid cells often abundantly present in tumors. For this we coupled CpG (3'-Thiol-modified phosphorothioate (PTO) CpG-ODN1826 type B (5'-tccatgacgttcctgacgtt-3')) to monoclonal antibodies (mAbs) directed against the myeloid cell marker CD11b using maleimide-thiol coupling. The CD11b-CpG mAb (αCD11b-CpG) conjugates contained about four CpG molecules/conjugate and displayed binding and internalization characteristics similar to unconjugated CD11b mAbs (αCD11b). The αCD11b-CpG conjugates readily induced maturation of murine dendritic cells (DCs) in a TLR9-dependent manner in vitro. Following intravenous injection, αCD11b-CpG conjugates efficiently targeted CD11b+ immune cells in the blood, lymph nodes and spleen. Finally, injection of αCD11b-CpG conjugates, but not untargeted conjugates, induced maturation of CD11b+ cell subsets in vivo. In conclusion, conjugating CpG to αCD11b enabled specific targeting and activation of myeloid cells in vivo.


Assuntos
Oligodesoxirribonucleotídeos , Receptor Toll-Like 9 , Animais , Células Dendríticas , Camundongos , Células Mieloides , Baço
5.
Quant Plant Biol ; 2: e7, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37077204

RESUMO

Efficient photosynthesis requires a balance of ATP and NADPH production/consumption in chloroplasts, and the exportation of reducing equivalents from chloroplasts is important for balancing stromal ATP/NADPH ratio. Here, we showed that the overexpression of purple acid phosphatase 2 on the outer membranes of chloroplasts and mitochondria can streamline the production and consumption of reducing equivalents in these two organelles, respectively. A higher capacity of consumption of reducing equivalents in mitochondria can indirectly help chloroplasts to balance the ATP/NADPH ratio in stroma and recycle NADP+, the electron acceptors of the linear electron flow (LEF). A higher rate of ATP and NADPH production from the LEF, a higher capacity of carbon fixation by the Calvin-Benson-Bassham (CBB) cycle and a greater consumption of NADH in mitochondria enhance photosynthesis in the chloroplasts, ATP production in the mitochondria and sucrose synthesis in the cytosol and eventually boost plant growth and seed yields in the overexpression lines.

6.
Quant Plant Biol ; 2: e10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37077212

RESUMO

Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.

7.
Calcif Tissue Int ; 107(3): 220-229, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32617612

RESUMO

Few studies have investigated the prevalence of frailty in the Australian general population. This study determined the prevalence of frailty in a population-based sample of older adults and examined the relationship between frailty and comorbid conditions. Men (n = 347) and women (n = 360) aged ≥ 60 year from the Geelong Osteoporosis Study (GOS) were assessed between 2016-2019 and 2011-2014, respectively. Frailty was identified using a modified Fried frailty phenotype. Prevalence estimates were standardised to the 2011 Australian population. Kruskal-Wallis test and χ2 test were used to analyse data. For women, mean standardised prevalence estimates were 18.3% (14.1-22.5) for frail, 54.1% (47.3-60.8) pre-frail and 22.9% (18.9-26.8) robust. Corresponding estimates for men were 13.1% (9.8-16.3) frail, 47.8% (42.0-53.6) pre-frail and 27.3% (22.7-31.8) robust. Women who were frail were older, shorter, tended to have a higher body mass index (BMI) and used more medications compared to other groups. Compared to robust women, those who were frail were more likely to have cardio-metabolic (OR 3.5 (0.7-20.0)), pulmonary (OR 3.5 (1.5-8.4)) and musculoskeletal (OR 10.1 (2.1-48.0)) conditions. Frail men were older, had a higher BMI and were more likely to have musculoskeletal conditions (OR 5.8 (2.8-12.3)) and tended to be from a lower SES. No further associations were observed. This study reported the prevalence of frail and pre-frail individuals in a population-based sample of Australian men and women. Frailty was associated with musculoskeletal conditions for both men and women; however, associations with cardio-metabolic and pulmonary comorbidities were evident in women only.


Assuntos
Idoso Fragilizado , Fragilidade , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Fragilidade/epidemiologia , Humanos , Masculino , Prevalência
8.
Clin Implant Dent Relat Res ; 22(1): 128-137, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31912661

RESUMO

BACKGROUND: Peri-implant soft tissues esthetics varies and depends on the restoration type such as implant-supported single crowns, adjacent multiple single crowns, and fixed partial dentures (FPD). PURPOSE: The aim of this prospective study was to assess the esthetic outcome of the peri-implant soft tissues of (NobelBiocare™) implant-supported single crowns, adjacent multiple single crowns, and FPD. A potential association between the esthetic risk profile and the esthetic outcome was assessed. MATERIALS AND METHODS: Between 03/11 and 03/17, 300 NobelActive implants were installed in 153 partially edentulous patients. Prior to the fabrication of the final restoration, the esthetic risk profile (ERP) of the patient was determined. The pink esthetic score (PES) and white esthetic score (WES) were assessed by three investigators at 6 and 12 months post-insertion of the final restoration. Patients' appreciation was assessed on a visual analogue scale (VAS) at the 1-year follow-up. RESULTS: The clinical acceptable limit for PES (≥6) was achieved in 56% to 68% of the single crowns at 6 and 12 months, respectively. Clinically unacceptable PES scores were recorded for 48% of the adjacent multiple single crowns and 63% of the FPDs at both time points. The association of a high ERP with WES and PESWES was noticed for single implant-supported crowns. For the latter restoration type, a ≤5 mm distance between the crestal bone level and the proximal contact positively influenced the PES and combined PESWES scores. No correlation was found between PES or WES and patient satisfaction. Mesial papilla formation was more pronounced compared to the distal one for the single implant crowns and for implant-supported FPD. CONCLUSION: When high esthetic demands are expected, assessment of ERP prior to implant treatment is advised in order to estimate a realistic outcome.


Assuntos
Implantes Dentários para Um Único Dente , Implantes Dentários , Coroas , Prótese Dentária Fixada por Implante , Prótese Parcial Fixa , Estética Dentária , Humanos , Estudos Prospectivos , Resultado do Tratamento
9.
Arch Pediatr ; 26(6): 365-369, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31353149

RESUMO

A vascular mass localized in the face and the neck was displayed by ultrasonography in a 38-week-old male fetus. At birth, the mass was bulky and purplish. The newborn breathed spontaneously but with severe desaturation. During laryngoscopy, we observed an obstruction of the larynx with a left-shift caused by the hemorrhagic mass. Blood analysis revealed anemia, severe thrombocytopenia, and coagulation disorders. The diagnosis of kaposiform hemangioendothelioma (KHE) complicated by a Kasabach-Merritt phenomenon (KMP) was put forward and treatment with propranolol, corticoids, and vincristine was initiated. Platelets were transfused daily for 8 days but did not resolve the thrombocytopenia. At day 8, we added sirolimus to the treatment and noted a rapid response with the normalization of the platelet count within 1 week and a significant regression of the mass. In this paper, we review the clinical and biological features of hemangioendothelioma associated with KMP and discuss its current and future treatment. Sirolimus seems to be very promising.


Assuntos
Hemangioendotelioma/diagnóstico , Síndrome de Kasabach-Merritt/diagnóstico , Sarcoma de Kaposi/diagnóstico , Terapia Combinada , Hemangioendotelioma/terapia , Humanos , Recém-Nascido , Síndrome de Kasabach-Merritt/terapia , Masculino , Sarcoma de Kaposi/terapia
10.
Eur J Cancer ; 113: 41-44, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30965214

RESUMO

Because of the failure of immunotherapy as single agent in a number of cancers, current clinical trials are focusing on combining immunotherapy with other therapies. The most frequently chosen combination for immunotherapy is chemotherapy. However, almost no preclinical data on this combination is available. Some studies even showed a dismal effect of combining chemotherapy with immunotherapy. Taken into account that each of the therapies chosen in a combination will influence the cancer cells but also immune effector cells as well as immunosuppressive cells, and that these three partners will also interact with each other, launching a combination to the patient without proper immune monitoring and preclinical evidence might be devastating.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Humanos , Neoplasias/imunologia , Microambiente Tumoral
11.
Natl Sci Rev ; 6(6): 1073-1076, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34691977
12.
Front Plant Sci ; 9: 982, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30042778

RESUMO

Phosphorylation of the transit peptides of nuclear-encoded preprotein is a well-known regulatory process of protein import in plant chloroplasts. In the Arabidopsis Protein Phosphorylation Site Database, 103 out of 802 mitochondrial proteins were found to contain one or more experimentally proven phosphorylation sites in their first 60 amino acid residues. Analysis of the N-terminal sequences of selected mitochondrial preproteins and their homologs from 64 plant species showed high conservation among phosphorylation sites. The ability of kinases from various sources including leaf extract (LE), root extract (RE), wheat germ lysate (WGL), and STY kinases to phosphorylate N-terminal sequences of several respiratory chain proteins were examined by in vitro kinase assays. The three STY kinases were shown to phosphorylate the N-terminal sequences of some proteins we tested but exhibited different specificities. Interestingly, the N-terminal sequences of two mitochondrial ATP synthase beta subunit 1/3 (pF1ß-1/3) could be phosphorylated by LE and RE but not by STY kinases, suggesting that there are uncharacterized presequence-phosphorylating kinases other than STY kinases present in RE and LE. Mitochondrial import studies showed that the import of RRL-synthesized pF1ßs was impeded by the treatment of LE, and the addition of a short SSU transit peptide containing a phosphorylatable 14-3-3 binding site could enhance the import of LE-treated pF1ßs. Our results suggested that the transit peptide of pSSU can compete with the presequences of pF1ßs for an uncharacterized kinase(s) in leaf. Altogether, our data showed that phosphorylation of transit peptides/presequences are not uncommon for chloroplast-targeted and mitochondria-targeted proteins, albeit possibly differentially regulated.

13.
Front Plant Sci ; 9: 410, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670639

RESUMO

Plant-type ferredoxins in Arabidopsis transfer electrons from the photosystem I to multiple redox-driven enzymes involved in the assimilation of carbon, nitrogen, and sulfur. Leaf-type ferredoxins also modulate the switch between the linear and cyclic electron routes of the photosystems. Recently, two novel ferredoxin homologs with extra C-termini were identified in the Arabidopsis genome (AtFdC1, AT4G14890; AtFdC2, AT1G32550). FdC1 was considered as an alternative electron acceptor of PSI under extreme ferredoxin-deficient conditions. Here, we showed that FdC1 could interact with some, but not all, electron acceptors of leaf-type Fds, including the ferredoxin-thioredoxin reductase (FTR), sulfite reductase (SiR), and nitrite reductase (NiR). Photoreduction assay on cytochrome c and enzyme assays confirmed its capability to receive electrons from PSI and donate electrons to the Fd-dependent SiR and NiR but not to the ferredoxin-NADP+ oxidoreductase (FNR). Hence, FdC1 and leaf-type Fds may play differential roles by channeling electrons from photosystem I to different downstream electron acceptors in photosynthetic tissues. In addition, the median redox potential of FdC1 may allow it to receive electrons from FNR in non-photosynthetic plastids.

14.
Br J Dermatol ; 178(2): 473-481, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28986976

RESUMO

BACKGROUND: An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome. OBJECTIVES: To reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS. METHODS: Thirty-six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a three-round e-Delphi process using online surveys, participants repeatedly rated the importance of these domains on a five-point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was predefined as 80% agreement on the importance of a domain among both the physician group and the patient/parent group. Outcomes were then re-evaluated in an online consensus meeting. RESULTS: 167 physicians and 134 patients and parents of patients with LM (n = 50), VM (n = 71) and AVM (n = 29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician-reported location-specific signs, patient-reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type-specific signs and symptoms were included for LM, VM and AVM, separately. CONCLUSIONS: Our recommendation is that therapeutic-efficacy studies on peripheral vascular malformations should measure at least these core outcome domains.


Assuntos
Malformações Vasculares/terapia , Malformações Arteriovenosas/terapia , Consenso , Técnica Delphi , Humanos , Sistema Linfático/anormalidades , Resultado do Tratamento
15.
Clin Exp Immunol ; 192(1): 104-119, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29178470

RESUMO

Haemophagocytic lymphohistiocytosis (HLH) constitutes a spectrum of immunological disorders characterized by uncontrolled immune activation and key symptoms such as fever, splenomegaly, pancytopenia, haemophagocytosis, hyperferritinaemia and hepatitis. In genetic or primary HLH, hyperactivated CD8+ T cells are the main drivers of pathology. However, in acquired secondary HLH, the role of lymphocytes remains vague. In the present study the involvement of lymphocytes in the pathogenesis of a cytomegalovirus-induced model of secondary HLH was explored. We have previously reported CD8+ T cells to be redundant in this model, and therefore focused on CD4+ helper and regulatory T cells. CD4+ T cells were activated markedly and skewed towards a proinflammatory T helper type 1 transcription profile in mice displaying a severe and complete HLH phenotype. Counter to expectations, regulatory T cells were not reduced in numbers and were, in fact, more activated. Therapeutic strategies targeting CD25high hyperactivated T cells were ineffective to alleviate disease, indicating that T cell hyperactivation is not a pathogenic factor in cytomegalovirus-induced murine HLH. Moreover, even though T cells were essential in controlling viral proliferation, CD4+ T cells, in addition to CD8+ T cells, were dispensable in the development of the HLH-like syndrome. In fact, no T or B cells were required for induction and propagation of HLH disease, as evidenced by the occurrence of cytomegalovirus-associated HLH in severe combined immunodeficient (SCID) mice. These data suggest that lymphocyte-independent mechanisms can underlie virus-associated secondary HLH, accentuating a clear distinction with primary HLH.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por Herpesviridae/imunologia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfócitos T Reguladores/imunologia , Animais , Infecções por Herpesviridae/complicações , Interferon gama/genética , Ativação Linfocitária , Depleção Linfocítica , Linfo-Histiocitose Hemofagocítica/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Muromegalovirus , Células Th1/imunologia
16.
Arch Pediatr ; 24(7): 600-606, 2017 Jul.
Artigo em Francês | MEDLINE | ID: mdl-28595829

RESUMO

Vascular anomalies (VAs) result from the defective development of the embryonic vascular system and feature dysplastic malformed vessels, which are not always apparent at birth. They do not regress over the patient's lifetime; they usually have commensurate growth during childhood and may worsen over time if not treated. VAs may cause chronic painful swelling, bleeding, functional deficits or vital structure obstruction. These patients' quality of life is usually impaired because of the chronicity and recurrence of the disease. We report on six cases of complicated VAs, refractory to current treatments, treated with rapamycin, an mTor inhibitor recently used in VAs.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Sirolimo/uso terapêutico , Malformações Vasculares/tratamento farmacológico , Adolescente , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto Jovem
17.
Allergy ; 72(5): 737-753, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27696462

RESUMO

BACKGROUND: Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics. AIM: We developed and characterized a robust, consistent, and reproducible mouse model of severe exacerbation of chronic allergic asthma. METHODS: Chronic allergic airway inflammation was induced following a house dust mite (HDM) sensitization protocol. HDM-sensitized mice and controls were infected with influenza virus A/X31 H3N2 and either or not treated with inhaled fluticasone propionate (FP), systemic corticosteroids (Pred), or anti-IL-5. Mice were killed at different time points after infection: Cellular accumulation and cytokines levels in the airways, PenH as a measure of airway hyper-responsiveness (AHR), and lung histology and viral replication were assessed. RESULTS: Infection with low-dose A/X31 H3N2 led to prolonged deterioration of lung function, aggravated mucus production, peri-vascular, peri-bronchial, and allergic inflammation that was unresponsive to inhaled corticosteroids, but responsive to systemic corticosteroids. The exacerbation was preceded at 14 h after virus exposure by a marked innate, but no Th2 and Th1 response subsequently followed by enhanced numbers of eosinophils, neutrophils, dendritic, and T cells into the lung lumen, parenchyma, and draining lymph nodes in HDM-sensitized mice. Anti-IL-5 treatment attenuated eosinophils and prevented the X31-induced exacerbation. CONCLUSIONS: Together, these findings indicate that an early innate response that involves eosinophils underlies the exacerbation. This model recapitulates all major features of severe asthma exacerbations and can serve to discern driving mechanisms and promote the development of novel therapeutics.


Assuntos
Asma/etiologia , Asma/patologia , Tolerância a Medicamentos , Imunidade Inata , Vírus da Influenza A , Interleucina-5/antagonistas & inibidores , Infecções por Orthomyxoviridae/complicações , Esteroides/farmacologia , Alérgenos/imunologia , Anfirregulina/biossíntese , Animais , Antiasmáticos/farmacologia , Anticorpos Monoclonais/farmacologia , Asma/tratamento farmacológico , Biópsia , Citocinas/biossíntese , Modelos Animais de Doenças , Progressão da Doença , Eosinófilos/imunologia , Eosinófilos/metabolismo , Fluticasona/farmacologia , Imunização , Masculino , Camundongos , Infecções por Orthomyxoviridae/virologia , Pyroglyphidae/imunologia , Carga Viral
18.
Ann Chir Plast Esthet ; 61(5): 480-497, 2016 Oct.
Artigo em Francês | MEDLINE | ID: mdl-27641115

RESUMO

Vascular anomalies, which are broadly identified as "angiomas", are rare entities and often unknown by the medical sphere. They are divided in two different categories which carry different prognosis and management: "vascular tumors" and "vascular malformations". Their precise identification is crucial and involves a good knowledge of the biological classification published by Mulliken and Glowacki and that has recently been updated by the International Society for the Study of Vascular Anomalies (ISSVA). Vascular tumors are benign, common, inborn or not and most of the time disappear with growth. Vascular malformations are always congenital and growth with the child. They can involve type of vessels solely or combined with others. A rheologic differentiation between slow and fast flow malformations is essential in order to characterize the seriousness of the lesion. Frequently, their diagnosis is clinically established and the anamnesis is conducted to answer three questions that are the time of revelation of the lesion ("When?"), its aspect ("What?") and its evolution ("How?"). Further investigations are usually not required but a non-invasive imaging technique such as Doppler ultrasound could be useful if a doubt exists. Surgery is not mandatory and must always be well thought because its consequences might be disastrous. It must be left to cosmetic sequelae of these lesions or to lesions that are totally resectable without causing any unacceptable deformation.


Assuntos
Procedimentos de Cirurgia Plástica , Malformações Vasculares/cirurgia , Neoplasias Vasculares/cirurgia , Criança , Granuloma Piogênico/cirurgia , Hemangioma/cirurgia , Humanos
19.
BMC Genomics ; 17: 655, 2016 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27538394

RESUMO

BACKGROUND: Previously, several long non-coding RNAs (lncRNAs) were characterized as regulators in phosphate (Pi) starvation responses. However, systematic studies of novel lncRNAs involved in the Pi starvation signaling pathways have not been reported. RESULTS: Here, we used a genome-wide sequencing and bioinformatics approach to identify both poly(A) + and poly(A)- lncRNAs that responded to Pi starvation in Arabidopsis thaliana. We sequenced shoot and root transcriptomes of the Arabidopsis seedlings grown under Pi-sufficient and Pi-deficient conditions, and predicted 1212 novel lncRNAs, of which 78 were poly(A)- lncRNAs. By employing strand-specific RNA libraries, we discovered many novel antisense lncRNAs for the first time. We further defined 309 lncRNAs that were differentially expressed between P+ and P- conditions in either shoots or roots. Through Gene Ontology enrichment of the associated protein-coding genes (co-expressed or close on the genome), we found that many lncRNAs were adjacent or co-expressed with the genes involved in several Pi starvation related processes, including cell wall organization and photosynthesis. In total, we identified 104 potential lncRNA targets of PHR1, a key regulator for transcriptional response to Pi starvation. Moreover, we identified 16 candidate lncRNAs as potential targets of miR399, another key regulator of plant Pi homeostasis. CONCLUSIONS: Altogether, our data provide a rich resource of candidate lncRNAs involved in the Pi starvation regulatory network.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Fosfatos/metabolismo , RNA Longo não Codificante/genética , Análise de Sequência de RNA/métodos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Biologia Computacional/métodos , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Raízes de Plantas/genética , Plântula/genética
20.
J Med Case Rep ; 10(1): 179, 2016 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-27334918

RESUMO

BACKGROUND: Giant cell arteritis typically involves the temporal arteries, but can involve other cranial arteries. Temporal artery biopsy is the mainstay for the diagnosis of giant cell arteritis; however, biopsy may be problematic if giant cell arteritis involves other cranial arteries that are inaccessible for sampling. In these situations, magnetic resonance angiography is a useful, non-invasive adjunctive method in the diagnosis of giant cell arteritis. In this case report, we describe a case of giant cell arteritis involving only the occipital artery which was revealed by magnetic resonance angiography. CASE PRESENTATION: A 67-year-old Caucasian man was admitted to our hospital with a 4-week history of malaise, fever, and mild occipital headaches. There were no other positive findings on physical examination. Laboratory studies were remarkable for normocytic anemia, raised inflammatory markers, and mildly deranged liver function tests. To exclude intracranial pathology, he underwent a cranial magnetic resonance imaging with gadolinium, which demonstrated a thickened wall and mural enhancement of his right occipital artery, consistent with giant cell arteritis. His temporal arteries were normal. His occipital arteries were not accessible for biopsy and he was commenced on high-dose prednisolone (60 mg daily). His symptoms resolved completely after a week of glucocorticoid steroid treatment and he was well on 5 mg of prednisolone once a day on follow-up. CONCLUSION: While magnetic resonance angiography may not replace the need for biopsy, it may have a diagnostic role in suspected giant cell arteritis, such as when the involved arteries are inaccessible for biopsy.


Assuntos
Anti-Inflamatórios/toxicidade , Arterite de Células Gigantes/patologia , Testes de Função Hepática/métodos , Angiografia por Ressonância Magnética , Prednisolona/uso terapêutico , Artérias Temporais/patologia , Idoso , Febre/etiologia , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Cefaleia/etiologia , Humanos , Masculino , Artérias Temporais/diagnóstico por imagem , Resultado do Tratamento
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