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1.
Plant Cell Environ ; 47(5): 1813-1833, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321806

RESUMO

Increasingly frequent and intense heatwaves threaten ecosystem health in a warming climate. However, plant responses to heatwaves are poorly understood. A key uncertainty concerns the intensification of transpiration when heatwaves suppress photosynthesis, known as transpiration-photosynthesis decoupling. Field observations of such decoupling are scarce, and the underlying physiological mechanisms remain elusive. Here, we use carbonyl sulphide (COS) as a leaf gas exchange tracer to examine potential mechanisms leading to transpiration-photosynthesis decoupling on a coast live oak in a southern California woodland in spring 2013. We found that heatwaves suppressed both photosynthesis and leaf COS uptake but increased transpiration or sustained it at non-heatwave levels throughout the day. Despite statistically significant decoupling between transpiration and photosynthesis, stomatal sensitivity to environmental factors did not change during heatwaves. Instead, midday photosynthesis during heatwaves was restricted by internal diffusion, as indicated by the lower internal conductance to COS. Thus, increased evaporative demand and nonstomatal limitation to photosynthesis act jointly to decouple transpiration from photosynthesis without altering stomatal sensitivity. Decoupling offered limited potential cooling benefits, questioning its effectiveness for leaf thermoregulation in xeric ecosystems. We suggest that adding COS to leaf and ecosystem flux measurements helps elucidate diverse physiological mechanisms underlying transpiration-photosynthesis decoupling.


Assuntos
Ecossistema , Transpiração Vegetal , Óxidos de Enxofre , Transpiração Vegetal/fisiologia , Folhas de Planta/fisiologia , Fotossíntese/fisiologia , Água/fisiologia
2.
Environ Sci Technol ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38344765

RESUMO

Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.

3.
Pediatr Transplant ; 28(1): e14584, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37470130

RESUMO

BACKGROUND: Pediatric heart transplantation (HT) continues to be limited by the shortage of donor organs, distance constraints, and the number of potential donor offers that are declined due to the presence of multiple risk factors. METHODS: We report a case of successful pediatric HT in which multiple risk factors were mitigated through a combination of innovative donor utilization improvement strategies. RESULTS: An 11-year-old, 25-kilogram child with cardiomyopathy and pulmonary hypertension, on chronic milrinone therapy and anticoagulated with apixaban, was transplanted with a heart from a Hepatitis C virus positive donor and an increased donor-to-recipient weight ratio. Due to extended geographic distance, an extracorporeal heart preservation system (TransMedics™ OCS Heart) was used for procurement. No significant bleeding was observed post-operatively, and she was discharged by post-operative day 15 with normal biventricular systolic function. Post-transplant Hepatitis C virus seroconversion was successfully treated. CONCLUSIONS: Heart transplantation in donors with multiple risk factor can be achieved with an integrative team approach and should be taken into consideration when evaluating marginal donors in order to expand the current limited donor pool in pediatric patients.


Assuntos
Transplante de Coração , Obtenção de Tecidos e Órgãos , Feminino , Humanos , Criança , Doadores de Tecidos , Coração , Fatores de Risco
4.
Int J Sport Nutr Exerc Metab ; : 1-9, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168457

RESUMO

OBJECTIVE: Micronutrient status, specifically vitamin D and iron, represent modifiable factors for optimizing military readiness. The primary purpose of this investigation was to determine associations between micronutrient deficiency (i.e., iron status and 25-hydroxy-vitamin D [25(OH)D]) and operationally relevant outcomes (i.e., skeletal health, musculoskeletal injury) at baseline and post-10 weeks of arduous military training. METHODS: A total of 227 (177 men, 50 women) Marine Officer Candidates School (OCS) candidates who completed OCS training with complete data sets were included in this analysis. Vitamin D and iron status indicators were collected at two timepoints, pre (baseline) and post OCS. Musculoskeletal outcomes at the mid- and proximal tibial diaphysis were assessed via peripheral quantitative computed tomography. RESULTS: Micronutrient status declined following OCS training in men and women and was associated with musculoskeletal outcomes including greater bone strength (strength strain index) at the mid-diaphysis site in those with optimal status (M = 38.26 mm3, SE = 15.59) versus those without (M = -8.03 mm3, SE = 17.27). In women (p = .037), endosteal circumference was greater in the deficient group (M = 53.26 mm, SE = 1.19) compared with the optimal group (M = 49.47 mm, SE = 1.31) at the proximal diaphysis. In men, greater baseline hepcidin concentrations were associated with an increased likelihood of suffering musculoskeletal injury during training. CONCLUSIONS: Vitamin D and iron status declined over the course of training, suggesting impaired micronutrient status. Differences in musculoskeletal outcomes by micronutrient group suggests optimal vitamin D and ferritin concentrations may exert beneficial effects on bone fatigability and fracture reduction during military training.

5.
Eur J Contracept Reprod Health Care ; 29(1): 8-14, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38108091

RESUMO

PURPOSE: Oral contraceptives (OCs) are commonly used by female athletes raising concerns regarding the possible adverse effects of OCs on physical performance, musculoskeletal injuries, and bone density. We aimed to review all current studies on the physiological effects of OCs in physically active women. MATERIALS AND METHODS: A review of literature in electronic search in PubMed and Google Scholar databases from December 2002 to December 2022 using relevant keywords. The reference lists of the articles found eligible were also reviewed. RESULTS: Out of 344 articles in the initial database, 54 clinical studies were eligible for inclusion in our literature review. OCs are used by about two-thirds of female athletes. Current research suggests that OCs' effects on endurance performance and muscle strength are mostly reassuring. OCs do not seem to have a major negative impact on bone health or sports injuries. In fact, new data suggests that they may even significantly reduce the risk of anterior cruciate ligament (ACL) injury. CONCLUSIONS: OCs can be safely used by young female athletes, who may also benefit from better menstrual cycle control. OCs offer newly realised protection from ACL injuries. The use of OCs must be carefully individualised according to their preferences, expectations, and experience.


Hormonal contraception can be safely prescribed to active women. The International Olympic Committee advocates a new and wider definition for the 'athlete triad', where low energy availability presents a special challenge for these athletes. New data suggests that the use of oral contraceptives may protect against ACL injury.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos em Atletas , Humanos , Feminino , Contracepção Hormonal , Anticoncepcionais Orais , Ciclo Menstrual , Atletas , Traumatismos em Atletas/prevenção & controle , Lesões do Ligamento Cruzado Anterior/prevenção & controle
6.
Medicina (Kaunas) ; 60(7)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-39064456

RESUMO

Background and Objectives: Fibromyalgia syndrome (FMS) is defined as a chronic pain syndrome that is characterized by widespread pain, tenderness, and diffuse stiffness. In addition, neuropsychological symptoms such as fatigue, sleep disorders, poor mood, cognitive impairment, and headaches are often reported. Many reports have addressed the coexistence of affective disorders and anxiety with FMS, yet few have focused on its association with obsessive compulsive disorder (OCD). We investigated the occurrence of classical patterns of OCD in participants with FMS and assessed their effect on pain perception and functional impairment. Material and Methods: The research population included 37 patients diagnosed with FMS, treated at the Rheumatology Clinic in the Sheba Medical Center, Tel-Hashomer, Israel. We used validated questionnaires including a demographic questionnaire, a questionnaire on average and maximal pain intensity, the Eysenck Personality Questionnaire-Revised (EPQ-R), the Perceived Stress Scale, the Pain Catastrophizing Scale, the Pain Obsessive questionnaire, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Patients with FMS were found to have intrusive and obsessive thoughts regarding pain for several hours every day, causing a high degree of anxiety and high levels of pain, catastrophizing, and magnification, leading to helplessness and functional impairment. In total, 27% of the patients reported severe malfunction due to pain and pain ideation, and 49% demonstrated mild obsessive compulsive symptoms that were strongly correlated with pain intensity and functional impairment. Conclusions: Obsessive compulsive thinking patterns contribute to pain magnification and to the cognitive aspects of fibromyalgia syndrome.


Assuntos
Fibromialgia , Transtorno Obsessivo-Compulsivo , Humanos , Fibromialgia/psicologia , Fibromialgia/complicações , Fibromialgia/fisiopatologia , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/complicações , Inquéritos e Questionários , Israel/epidemiologia , Medição da Dor/métodos , Catastrofização/psicologia , Ansiedade/psicologia , Ansiedade/complicações , Ansiedade/etiologia
7.
Psychol Med ; 53(7): 2936-2945, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35469587

RESUMO

BACKGROUND: Obsessive-compulsive symptoms (OCS) are commonly associated with clozapine treatment but are frequently overlooked by clinicians despite their potential impact on patients' quality of life. In this study, we explored whether OCS severity impacted subjective wellbeing and general functioning, independently of depressive and psychotic symptoms. METHODS: We used anonymised electronic healthcare records from a large cohort of patients who were treated with clozapine and assessed annually for OCS, wellbeing, general functioning, and psychopathology using standardised scales as part of routine clinical practice. We used statistical mixed linear model techniques to evaluate the longitudinal influence of OCS severity on wellbeing and general functioning. RESULTS: A total of 184 patients were included, with 527 face-to-face assessments and 64.7% evaluated three or more times. Different linear mixed models demonstrated that OCS in patients treated with clozapine were associated with significantly worse wellbeing scores, independently of depression and psychotic symptoms, but OCS did not impair general functioning. Obsessional thinking and hoarding behaviour, but not compulsions, were significantly associated with the impact on wellbeing, which may be attributable to the ego-syntonic nature of the compulsions. CONCLUSIONS: Given the frequent occurrence of OCS and their negative impact on wellbeing, we encourage clinicians to routinely assess and treat OCS in patients who are taking clozapine.


Assuntos
Antipsicóticos , Clozapina , Transtorno Obsessivo-Compulsivo , Esquizofrenia , Humanos , Clozapina/efeitos adversos , Antipsicóticos/efeitos adversos , Esquizofrenia/epidemiologia , Estudos Longitudinais , Qualidade de Vida , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Escalas de Graduação Psiquiátrica , Comorbidade
8.
J Asthma ; 60(6): 1227-1236, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36282045

RESUMO

OBJECTIVE: Primary antibody deficiencies (PAD) are an underestimated comorbidity in asthma and its treatment could improve disease control. METHODS: a retrospective cohort of asthmatics, affected by IgG subclass deficiency or unclassified antibody deficiency and treated with low-dose intravenous immunoglobulin replacement therapy (IRT) was recruited. Demographic and clinical data, chest CT scan, blood eosinophils, atopy, chronic oral corticosteroid (OCS) therapy were evaluated at baseline. Asthma exacerbations, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI) and asthma-related hospitalizations were assessed after one and two years of IRT. RESULTS: 57 moderate-to-severe asthmatics were enrolled, mostly affected by T2 low asthma (39/57, 68.4%). After one year, IRT was effective in improving, irrespective of bronchiectasis, atopy, eosinophils and PAD type: 1) trough IgG (826.9 ± 221.3 vs 942.2 ± 195.1 mg/dl; p < 0.0001) and IgG subclasses (IgG1 355.4 ± 88.4 vs 466.7 ± 122.3, p < 0.0001; IgG2 300.1 ± 130.1 vs 347.6 ± 117.3, p < 0.0005) serum levels. 2) asthma exacerbations (6.4 ± 4.1 vs 2.4 ± 1.9, p < 0.0001), LRTI (4.3 ± 3.9 vs 1.3 ± 1.5, p < 0.0001) and hospitalization rate (0.26 ± 0.7 vs 0.05 ± 0.2, p < 0.01). These results persisted after 2 years of therapy. Estimated mean cumulative OCS exposure was reduced by 4500 mg over the 2-year period. CONCLUSIONS: low-dose IRT is effective in improving asthma control and lessening OCS burden in asthmatics affected by PAD.


Assuntos
Asma , Doenças da Imunodeficiência Primária , Infecções Respiratórias , Humanos , Asma/tratamento farmacológico , Asma/epidemiologia , Estudos Retrospectivos , Comorbidade , Imunoglobulina G
9.
Scand Cardiovasc J ; 57(1): 2267804, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37822186

RESUMO

The standard Conventional Cold Storage (CCS) during heart transplantation procurement is associated with time-dependent ischemic injury to the graft, which is a significant independent risk factor for post-transplant early morbidity and mortality - especially when cold ischemic time exceeds four hours. Since 2018, Rigshospitalet (Copenhagen, Denmark) has been utilising ex vivo perfusion (Organ Care System, OCS) in selected cases. The objective of this study was to compare the short-term clinical outcomes of patients transplanted with OCS compared to CCS. Methods: This retrospective single-centre study was based on consecutive patients undergoing a heart transplant between January 2018 and April 2021. Patients were selected for the OCS group when the cold ischemic time was expected to exceed four hours. The primary outcome measure was six-month event-free survival. Results: In total, 48 patients were included in the study; nine were transplanted with an OCS heart. The two groups had no significant differences in baseline characteristics. Six-month event-free survival was 77.8% [95% CI: 54.9-100%] in the OCS group and 79.5% [95% CI: 67.8-93.2%] in the CCS group (p = 0.91). While the OCS group had a median out-of-body time that was 183 min longer (p < 0.0001), the cold ischemic time was reduced by 51 min (p = 0.007). Conclusion: In a Scandinavian setting, our data confirms that utilising OCS in heart procurement allows for a longer out-of-body time and a reduced cold ischemic time without negatively affecting safety or early post-transplant outcomes.


Assuntos
Transplante de Coração , Humanos , Transplante de Coração/efeitos adversos , Doadores de Tecidos , Estudos Retrospectivos , Preservação de Órgãos/efeitos adversos , Perfusão/efeitos adversos
10.
Int J Mol Sci ; 24(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36768778

RESUMO

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Interleucina-5 , Estudos Retrospectivos , Receptores de Interleucina-5/metabolismo
11.
New Phytol ; 235(5): 1729-1742, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35478172

RESUMO

Carbonyl sulfide (COS) has emerged as a multi-scale tracer for terrestrial photosynthesis. To infer ecosystem-scale photosynthesis from COS fluxes often requires knowledge of leaf relative uptake (LRU), the concentration-normalized ratio between leaf COS uptake and photosynthesis. However, current mechanistic understanding of LRU variability remains inadequate for deriving robust COS-based estimates of photosynthesis. We derive a set of closed-form equations to describe LRU responses to light, humidity and CO2 based on the Ball-Berry stomatal conductance model and the biochemical model of photosynthesis. This framework reproduces observed LRU responses: decreasing LRU with increasing light or decreasing humidity; it also predicts that LRU increases with ambient CO2 . By fitting the LRU equations to flux measurements on a C3 reed (Typha latifolia), we obtain physiological parameters that control LRU variability, including an estimate of the Ball-Berry slope of 7.1 without using transpiration measurements. Sensitivity tests reveal that LRU is more sensitive to photosynthetic capacity than to the Ball-Berry slope, indicating stomatal response to photosynthesis. This study presents a simple framework for interpreting observed LRU variability and upscaling LRU. The stoma-regulated LRU response to CO2 suggests that COS may offer a unique window into long-term stomatal acclimation to elevated CO2 .


Assuntos
Dióxido de Carbono , Ecossistema , Fotossíntese/fisiologia , Folhas de Planta/fisiologia , Estômatos de Plantas/fisiologia , Óxidos de Enxofre
12.
Respir Res ; 23(1): 45, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246123

RESUMO

BACKGROUND: Long-term use of oral corticosteroids (OCS) is associated with a risk of adverse events and comorbidities. As such, a goal in assessing the efficacy of biologics in severe asthma is often to monitor reduction in OCS usage. Importantly, however, OCS dose reductions must be conducted without loss of disease control. MAIN BODY: Herein, we describe the development of OCS-sparing study methodologies for biologic therapies in patients with asthma. In particular, we focus on four randomized, placebo-controlled, parallel-group studies of varying sizes (key single-center study [n = 20], SIRIUS [n = 135], ZONDA [n = 220], VENTURE [n = 210]) and one open-label study (PONENTE [n = 598]), which assessed the effect of asthma biologics (mepolizumab, benralizumab or dupilumab) on OCS use using predefined OCS-tapering schedules. In particular, we discuss the evolution of study design elements in these studies, including patient eligibility criteria, the use of tailored OCS dose reduction schedules, monitoring of outcomes, the use of biomarkers and use of repetitive assessments of adrenal function during OCS tapering. CONCLUSION: Taken together, these developments have improved OCS-sparing asthma studies in recent years and the lessons learned may help with optimization of further OCS-sparing studies, and potentially clinical practice in the future.


Assuntos
Asma/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Asma/fisiopatologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
13.
Respir Res ; 23(1): 36, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183167

RESUMO

BACKGROUND: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. METHODS: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. RESULTS: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. CONCLUSIONS: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Eosinófilos/patologia , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
14.
Cell Mol Life Sci ; 78(17-18): 6087-6104, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34296319

RESUMO

Different types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in bone homeostasis. MGCs are formed by cell-to-cell fusion, and most types have been observed in pathological conditions, especially in infectious and non-infectious chronic inflammatory contexts. The precise role of the different MGCs and the mechanisms that govern their formation remain poorly understood, likely due to their heterogeneity. First, we will introduce the main populations of MGCs derived from the monocyte/macrophage lineage. We will then discuss the known molecular actors mediating the early stages of fusion, focusing on cell-surface receptors involved in the cell-to-cell adhesion steps that ultimately lead to multinucleation. Given that cell-to-cell fusion is a complex and well-coordinated process, we will also describe what is currently known about the evolution of F-actin-based structures involved in macrophage fusion, i.e., podosomes, zipper-like structures, and tunneling nanotubes (TNT). Finally, the localization and potential role of the key fusion mediators related to the formation of these F-actin structures will be discussed. This review intends to present the current status of knowledge of the molecular and cellular mechanisms supporting multinucleation of myeloid cells, highlighting the gaps still existing, and contributing to the proposition of potential disease-specific MGC markers and/or therapeutic targets.


Assuntos
Adesão Celular , Células Gigantes/metabolismo , Células Mieloides/metabolismo , Podossomos/metabolismo , Células Gigantes/citologia , Humanos , Integrinas/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Células Mieloides/citologia , Células Mieloides/ultraestrutura , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteogênese , Receptores Imunológicos/metabolismo
15.
J Asthma ; 58(4): 448-458, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31928102

RESUMO

OBJECTIVE: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes. However, long-term OCS use is associated with several comorbidities that may decrease health-related quality of life, worsen prognosis, and should ideally require monitoring and management. In this review, we discuss the adverse effects of OCS use, the OCS-sparing effect of biologics in severe asthma, and the need for optimal referral pathways to ensure the best outcomes for those at-risk asthma patients. DATA SOURCES: PubMed. STUDY SELECTION: Studies with results on the OCS-sparing effect of biologics in adult severe asthma were selected. RESULTS: Chronic and intermittent OCS use in asthma is associated with considerable adverse effects in asthma. Omalizumab, mepolizumab, benralizumab, and dupilumab reduce the need for OCS in severe asthma, while also reducing the exacerbation rate and improving several patient-related outcomes. CONCLUSION: Targeted biologic therapies have revolutionized the treatment of uncontrolled severe asthma by reducing or even eliminating the need for OCS and improving other major outcomes. Novel agents are now rapidly increasing the therapeutic armamentarium, but additional efforts are needed to optimize referral pathways in order to ensure sustainable access to these therapies.


Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Preparações de Ação Retardada , Humanos , Encaminhamento e Consulta , Índice de Gravidade de Doença
16.
J Asthma ; 58(4): 514-522, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31859541

RESUMO

OBJECTIVE: Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year and decreases oral corticosteroid (OCS) use after 28 weeks for patients with severe, uncontrolled eosinophilic asthma. We assessed whether these effects on OCS reduction are sustained for up to an additional year of treatment while maintaining an acceptable safety profile. METHODS: Data on OCS maintenance dosage were collected for adult patients with baseline blood eosinophil counts ≥150 cells/µL treated with add-on benralizumab 30 mg (every 4 [Q4W] or 8 weeks [Q8W; first three doses Q4W]) from the 28-week ZONDA study and were integrated with results from the predefined 56-week adult completion phase of the BORA extension study. Efficacy and safety were summarized descriptively. RESULTS: For patients receiving benralizumab Q8W, the median daily OCS dosage reduction of 75% from baseline to end of treatment achieved in ZONDA was sustained at the end of the BORA extension period (median 67% reduction from baseline). This was estimated to result in a median cumulative OCS dosage of 2.98 g over the 1.5-year period for patients receiving benralizumab Q8W compared with 5.74 g if these patients had remained on their baseline OCS dosages prior to benralizumab initiation. All adverse event rates were similar between the BORA extension and ZONDA periods, with no new or unexpected safety findings. CONCLUSION: This benralizumab 1.5-year integrated analysis demonstrates that OCS reductions and safety were maintained with further follow up and supports long-term use of benralizumab for patients with severe, uncontrolled eosinophilic asthma.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/fisiopatologia , Quimioterapia Combinada , Eosinófilos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
17.
Antonie Van Leeuwenhoek ; 114(5): 497-506, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33661468

RESUMO

A Gram-stain-negative, light yellow pigmented, non-motile and aerobic bacterial strain, designated HHU E2-1 T, was isolated from a surface seawater sample. The 16S rRNA gene sequence analysis indicated that HHU E2-1 T shared the highest sequence similarity to the type strain Qipengyuania gaetbuli DSM 16225 T (96.90%), which belongs to the family Erythrobacteraceae. Combined phylogeny of 288 single-copy orthologous gene clusters, analysis of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH), average amino acid identity (AAI) and evolutionary distances suggested that HHU E2-1 T can be considered as a member of the genus Altererythrobacter based on the recently proposed standard for defining genera of Erythrobacteraceae. Strain HHU E2-1 T grew at 15-35 °C and pH 5.0-8.0, with optimum growth at 28 °C and pH 7.0. Tolerance to NaCl was up to 4% (w/v) with optimum growth in 2-3% NaCl. The major fatty acids (> 10%) were C18:1ω7c11-methyl, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and summed feature 8 (C18:1ω7c and/or C18:1ω6c). The predominant isoprenoid quinone was ubiquinone-10. The genomic G + C content was 57.40%. On the basis of the phenotypic, phylogenetic and chemotaxonomic characterizations, HHU E2-1 T represents a novel species of the genus Altererythrobacter, for which the name Altererythrobacter flava sp. nov. is proposed. The type strain is HHU E2-1 T (= CGMCC 1.17394 T = KCTC 72835 T = MCCC 1K04226T).


Assuntos
Fosfolipídeos , Água do Mar , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
18.
Sensors (Basel) ; 21(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34372197

RESUMO

As the railway overhead contact system (OCS) is the key component along the high-speed railway, it is crucial to detect the quality of the OCS. Compared with conventional manual OCS detection, the vehicle-mounted Light Detection and Ranging (LiDAR) technology has advantages such as high efficiency and precision, which can solve the problems of OCS detection difficulty, low efficiency, and high risk. Aiming at the contact cables, return current cables, and catenary cables in the railway vehicle-mounted LiDAR OCS point cloud, this paper used a scale adaptive feature classification algorithm and the DBSCAN (density-based spatial clustering of applications with noise) algorithm considering OCS characteristics to classify the OCS point cloud. Finally, the return current cables, catenary cables, and contact cables in the OCS were accurately classified and extracted. To verify the accuracy of the method presented in this paper, we compared the experimental results of this article with the classification results of TerraSolid, and the classification results were evaluated in terms of four accuracy indicators. According to statistics, the average accuracy of using this method to extract two sets of OCS point clouds is 99.83% and 99.89%, respectively; the average precision is 100% and 99.97%, respectively; the average recall is 99.16% and 99.42%, respectively; and the average overall accuracy is 99.58% and 99.69% respectively, which is overall better than TerraSolid. The experimental results showed that this approach could accurately and quickly extract the complete OCS from the point cloud. It provides a new method for processing railway OCS point clouds and has high engineering application value in railway component detection.

19.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281184

RESUMO

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.


Assuntos
Corticosteroides/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Administração Oral , Antiasmáticos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
20.
Sensors (Basel) ; 20(8)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32326438

RESUMO

The overhead contact system (OCS) is a critical railway infrastructure for train power supply. Periodic inspections, aiming at acquiring the operational condition of the OCS and detecting problems, are necessary to guarantee the safety of railway operations. One of the OCS inspection means is to analyze data of point clouds collected by mobile 2D LiDAR. Recognizing OCS components from the collected point clouds is a critical task of the data analysis. However, the complex composition of OCS makes the task difficult. To solve the problem of recognizing multiple OCS components, we propose a new deep learning-based method to conduct semantic segmentation on the point cloud collected by mobile 2D LiDAR. Both online data processing and batch data processing are supported because our method is designed to classify points into meaningful categories of objects scan line by scan line. Local features are important for the success of point cloud semantic segmentation. Thus, we design an iterative point partitioning algorithm and a module named as Spatial Fusion Network, which are two critical components of our method for multi-scale local feature extraction. We evaluate our method on point clouds where sixteen categories of common OCS components have been manually labeled. Experimental results show that our method is effective in multiple object recognition since mean Intersection-over-Unions (mIoUs) of online data processing and batch data processing are, respectively, 96.12% and 97.17%.

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