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991.
Adrenomedullin protects from experimental arthritis by down-regulating inflammation and Th1 response and inducing regulatory T cells 下载免费PDF全文
Rheumatoid arthritis is a chronic autoimmune disease of unknown etiology characterized by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. The present study proposes a new strategy for the treatment of arthritis: the administration of the immunomodulatory neuropeptide adrenomedullin. Treatment with adrenomedullin significantly reduced incidence and severity of collagen-induced arthritis, an experimental model of rheumatoid arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of adrenomedullin was associated with a striking reduction of the two deleterious components of the disease, ie, the Th1-driven autoimmune and inflammatory responses. Adrenomedullin also induced the generation and/or activation of efficient CD4+ CD25+ regulatory T cells in arthritis with capacity to suppress autoreactive response and restore immune tolerance, which could play a pivotal role in the therapeutic effect of adrenomedullin on experimental arthritis contributing to the restoration of immune tolerance. 相似文献
992.
Martinez-Santiesteban FM Swanson SD Noll DC Anderson DJ 《Physics in medicine and biology》2007,52(8):2073-2088
To improve the overall temporal and spatial resolution of brain mapping techniques, in animal models, some attempts have been reported to join electrophysiological methods with functional magnetic resonance imaging (fMRI). However, little attention has been paid to the image artefacts produced by the microelectrodes that compromise the anatomical or functional information of those studies. This work presents a group of simulations and MR images that show the limitations of wire microelectrodes and the potential advantages of silicon technology, in terms of image quality, in MRI environments. Magnetic field perturbations are calculated using a Fourier-based method for platinum (Pt) and tungsten (W) microwires as well as two different silicon technologies. We conclude that image artefacts produced by microelectrodes are highly dependent not only on the magnetic susceptibility of the materials used but also on the size, shape and orientation of the electrodes with respect to the main magnetic field. In addition silicon microelectrodes present better MRI characteristics than metallic microelectrodes. However, metallization layers added to silicon materials can adversely affect the quality of MR images. Therefore only those silicon microelectrodes that minimize the amount of metallic material can be considered MR-compatible and therefore suitable for possible simultaneous fMRI and electrophysiological studies. High resolution gradient echo images acquired at 2 T (TR/TE = 100/15 ms, voxel size = 100 x 100 x 100 microm3) of platinum-iridium (Pt-Ir, 90%-10%) and tungsten microwires show a complete signal loss that covers a volume significantly larger than the actual volume occupied by the microelectrodes: roughly 400 times larger for Pt-Ir and 180 for W, at the tip of the microelectrodes. Similar MR images of a single-shank silicon microelectrode only produce a partial volume effect on the voxels occupied by the probe with less than 50% of signal loss. 相似文献
993.
Lofrano-Porto A Barra GB Giacomini LA Nascimento PP Latronico AC Casulari LA da Rocha Neves Fde A 《The New England journal of medicine》2007,357(9):897-904
Selective luteinizing hormone deficiency due to mutations in the luteinizing hormone beta-subunit gene (LHB) is a rare cause of hypogonadism. We describe the clinical features of a consanguineous family in which three siblings, two men and one woman, had hypogonadism related to isolated luteinizing hormone deficiency. These subjects have a newly discovered homozygous mutation of a 5' splice site in LHB: IVS2+1G-->C. This mutation disrupts the splicing of messenger RNA (mRNA), generating a gross abnormality in the processing of the luteinizing hormone beta-subunit mRNA, which abrogates the secretion of luteinizing hormone. We also determined that the female phenotype of this LHB mutation is characterized by normal pubertal development, secondary amenorrhea, and infertility. 相似文献
994.
Cappelletti M Barth H Fregni F Spelke ES Pascual-Leone A 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,179(4):631-642
It has been widely argued that the intraparietal sulcus (IPS) is involved in tasks that evoke representations of numerical
magnitude, among other cognitive functions. However, the causal role of this parietal region in processing symbolic and non-symbolic
numerosity has not been established. The current study used repetitive Transcranial Magnetic Stimulation (rTMS) to the left
and right IPS to investigate the effects of temporary deactivations of these regions on the capacity to represent symbolic
(Arabic numbers) and non-symbolic (arrays of dots) numerosities. We found that comparisons of both symbolic and non-symbolic
numerosities were impaired after rTMS to the left IPS but enhanced by rTMS to the right IPS. A signature effect of numerical
distance was also found: greater impairment (or lesser facilitation) when comparing numerosities of similar magnitude. The
reverse pattern of impairment and enhancement was found in a control task that required judging an analogue stimulus property
(ellipse orientation) but no numerosity judgements. No rTMS effects for the numerosity tasks were found when stimulating an
area adjacent but distinct from the IPS, the left and right angular gyrus. These data suggest that left IPS is critical for
processing symbolic and non-symbolic numerosity; this processing may thus depend on common neural mechanisms, which are distinct
from mechanisms supporting the processing of analogue stimulus properties.
H. Barth and F. Fregni contributed equally to this study. 相似文献
995.
Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty 下载免费PDF全文
Gabriel Adan Araújo Leite Marciana Sanabria Marilia Martins Cavariani Janete Aparecida Anselmo‐Franci Patrícia Fernanda Felipe Pinheiro Raquel Fantin Domeniconi Wilma De Grava Kempinas 《Journal of applied toxicology : JAT》2018,38(6):914-929
The increase of obesity, bad eating habits and the lack of physical exercises are highly related to dyslipidemias. Rosuvastatin is a lipid‐lowering drug and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to evaluate the reproductive adverse effects on sexual maturity due to rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were randomly formed with newly weaned rats: control, whose rats received saline solution 0.9% and rosuvastatin at doses of 3 or 10 mg kg–1 day–1, administered orally by gavage, from postnatal day 21 until preputial separation (average of 45 days for controls and 49 days for statin‐treated animals), indicative of puberty onset. Male rats were maintained until sexual maturity and were killed on postnatal day 110. In the rosuvastatin‐treated groups, the results showed diminished follicle‐stimulating hormone, luteinizing hormone and testosterone concentrations, increased estradiol and prolactin concentrations, histopathologic alterations on testis and epididymis and decreased sperm quality. Moreover, statin‐exposed groups showed decreased expression of androgen receptor on testis and epididymis and lower expression of aquaporin‐9 on epididymal epithelium. In conclusion, administration of rosuvastatin to prepubertal male rats provoked long‐term hormonal deregulation and impaired reproduction at adulthood. 相似文献
996.
Miquel À. Mas Sebastià J. Santaeugènia Francisco J. Tarazona-Santabalbina Sara Gámez Marco Inzitari 《Journal of the American Medical Directors Association》2018,19(10):860-863
Objectives
To compare clinical outcomes in older patients with acute medical crises attended by a geriatrician-led home hospitalization unit (HHU) vs an inpatient intermediate-care geriatric unit (ICGU) in a post-acute care setting.Design
Quasi-experimental longitudinal study, with 30-day follow-up.Participants
Older patients with chronic conditions attended at the emergency department or day hospital for an acute medical crisis.Interventions
Patients were referred to geriatrician-led HHU or ICGU wards.Setting
An acute care hospital, an intermediate care hospital, and the community of an urban area in the North of Barcelona, in Southern Europe.Measurements
We compared health crisis outcomes (recovery from the acute health crisis, referral to an acute hospital, or death), length of stay, relative functional gain (RFG) at discharge, readmission to an acute care unit within 30 days of discharge, and mortality within 30 days of discharge.Results
We included 171 older adults (57 in the HHU and 114 in the ICGU) with complex conditions at risk of negative outcomes. At baseline, HHU patients were significantly younger and less likely to be cognitively impaired and referred from an emergency department. Most patients in both groups recovered from their health crises (91.2% in the HHU group vs 88.6% in the ICGU group, P = .79). No differences were found between the 2 groups in 30-day mortality (8.6% vs 9.6%, P = >.99). There was a trend toward lower 30-day readmission to an acute care unit in the HHU group (10.5% vs 19.3% in the ICGU group, P = .19). HHU patients had higher RFG (mean 0.75 days vs 0.51 in the ICGU group, P = .01), and a longer stay in the unit (9.7 vs 8.2 days in the ICGU group, P < .01).Conclusions
These preliminary results suggest that the geriatrician-led HHU seems effective in resolving acute medical crises in older patients with chronic disease. Patients attended by the HHU obtained better functional outcomes compared to those from the ICGU, although the groups did have some baseline differences. 相似文献997.
Dario Carradori Claudia Balducci Francesca Re Davide Brambilla Benjamin Le Droumaguet Orfeu Flores Alice Gaudin Simona Mura Gianluigi Forloni Lara Ordoñez-Gutierrez Francisco Wandosell Massimo Masserini Patrick Couvreur Julien Nicolas Karine Andrieux 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(2):609-618
Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ1-42 in the blood and promote its elimination through the “sink effect” and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ1-42. Treatment of AD-like transgenic mice with anti-Aβ1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD. 相似文献
998.
Unravelling residents’ and supervisors’ workplace interactions: an intersubjectivity study 下载免费PDF全文
Francisco M Olmos‐Vega Diana HJM Dolmans Carlos Guzmán‐Quintero Renée E Stalmeijer Pim W Teunissen 《Medical education》2018,52(7):725-735
Context
Successful engagement between residents and supervisors lies at the core of workplace learning, a process that is not exempt from challenge. Clinical encounters have unique learning potential as they offer opportunities to achieve a shared understanding between the resident and supervisor of how to accomplish a common goal. How residents and supervisors develop such a mutual understanding is an issue that has received limited attention in the literature. We used the ‘intersubjectivity’ concept as a novel conceptual framework to analyse this issue.Methods
We conducted a constructivist grounded theory study in an anaesthesiology department in Bogota, Colombia, using focus groups and field observations. Eleven residents of different training levels and 18 supervisors with varying years of teaching experience participated in the study. Through iterative data analysis, collection and constant comparison, we constructed the final results.Results
We found that residents and supervisors achieved a shared understanding by adapting to one another in the process of providing patient care. Continuous changes in the composition of resident–supervisor dyads exposed them to many procedural variations, to which they responded by engaging in various adaptation patterns that included compliance by residents with supervisors’ directions, negotiation by residents of supervisors’ preferences, and the sharing of decision making. In the process, the resident played an increasingly key role as a member of the supervisory dyad. Additionally, experiencing these adaptation patterns repeatedly resulted in the creation of a working repertoire: an attuned working code used by the members of each supervisory dyad to work together as a team.Conclusions
The development of shared understanding between residents and supervisors entailed experiencing diverse adaptation patterns which resulted in the creation of working repertoires. Seeing supervisory interactions as adaptation processes has essential theoretical and practical implications regarding workplace learning in postgraduate settings. Our findings call for further exploration to understand learning in postgraduate education as a social process.999.
1000.
Maria de Paula Caldas Gláucia Maria Bovi Ambrosano Francisco Haiter Neto 《Journal of applied oral science : revista FOB》2007,15(2):144-147