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BACKGROUND AND PURPOSE: Healthcare is responsible for 5.4% of greenhouse gas emissions in the UK. Emissions in surgery is a relatively unexplored area; in particular, this hasn't yet been looked at as a whole in ENT in the UK. The purpose of the study was to quantify the amount of greenhouse gas (GHG) emission from a tonsillectomy and assess the proportion of each source's contribution. METHODS: Operational data from tonsillectomies performed at a large university teaching hospital in the UK were gathered and converted to global warming potential using established conversion factors and data from existing healthcare-focused carbon footprint studies. The domains considered were waste, pharmaceuticals, surgical instrument decontamination, transportation, consumables use and utilities. This study used a process-based carbon footprint approach based on the "Greenhouse Gas Protocol: Product Life Cycle Accounting and Reporting Standard". MAIN FINDINGS: The carbon footprint of a typical case was 41 kgCO2e which is equivalent to driving a car for approximately 150 miles. Consumables were responsible for 17% of this; 14% came from transport, 5.4% from decontamination, 4.8% from pharmaceuticals and 4% from waste. However, the largest GHG was from utilities, of which heating, ventilation and air conditioning was the overwhelming contributor. CONCLUSIONS: While the largest sources of GHG emissions require hospital-wide initiatives, there are aspects of consumables and waste streams we can improve on in ENT surgery. These include the use of disposable vs reusable instruments as well as increased availability and use of recycling waste streams in theatres. Additionally, this study provides a template that can be applied to other ENT procedures.
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Pegada de Carbono , Tonsilectomia , Pegada de Carbono/estatística & dados numéricos , Humanos , Gases de Efeito Estufa/análise , Reino UnidoRESUMO
It has been claimed that longitudinal field muon spin relaxation (LF-µSR) experiments on the organic semiconductor (OSC) tris-(8-hydroxyquinoline)aluminum(III) (Alq3) have measured electron hopping rates of â¼1012s-1, while density functional theory (DFT) calculations suggest that electron hopping between a muoniated radical and a neighboring molecule is energetically unfavorable and that the LF-µSR experiments were probing muoniated radicals with localized spin density. We have performed avoided level crossing muon spin resonance (ALC-µSR) and transverse field muon spin rotation (TF-µSR) measurements on Alq3 and 8-hydroxyquinoline (8hq), which is meant to model the muoniated radicals present in Alq3 when they are not in an OSC. These are supplemented by benchmarked DFT calculations. The ALC-µSR and TF-µSR spectra of 8hq and Alq3 are best explained by Mu adding to all six secondary carbons of the quinolate rings with roughly equal yields and localized spin density. There is no evidence in the TF-µSR spectrum of Alq3 for the formation of radicals with muon hyperfine coupling constants of 23 or 91 MHz as reported earlier by others. Our measurements support the view that there is localized spin density on the molecule to which Mu is covalently bound and the muon is not a passive probe in organic systems as it can be incorporated into radicals that have different electronic structures to the parent compounds. The muoniated radicals in Alq3 are more short-lived than in 8hq, which could be due to interactions with mobile electrons in the OSC, but with electron spin flip rates on the order of â¼107s-1.
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The human cutaneous circulation is an accessible and representative regional circulation for investigating mechanisms of microvascular dysfunction, a systemic disease process occurring early in the pathogenesis of atherosclerosis. Elevated concentrations of low-density lipoproteins ([LDL]) are highly atherogenic and independently associated with the severity of coronary atherosclerosis through their actions on the lectin-like oxidized LDL receptors (LOX-1). We hypothesized that cutaneous microvascular dysfunction, as measured by a decrement in endothelial nitric oxide- (NO-) dependent vasodilation during local heating, would be correlated with serum [LDL], oxidized [LDL], and soluble LOX-1 receptors [sLOX-1]. Intradermal microdialysis fibers were placed in the skin of 53 otherwise healthy men and women (aged 52±8 years) whose serum [LDL] ranged from 72 to 233 mg/dL. Skin blood flow was measured by laser Doppler flowmetry over a local forearm skin site as it was heated (42°C) to induce sustained local vasodilation. After flux plateaued, L-NAME was infused to block endothelial NO synthase in order to determine the NO-dependent portion of the vasodilatory response. Data were normalized to maximal cutaneous vascular conductance (CVC). NO-dependent vasodilation was reduced as a linear function of [LDL] (R(2)=0.303, p<0.001), oxidized [LDL] (R(2)=0.214, p<0.001), and [sLOX-1] (R(2)=0.259, p=0.026) but was unrelated to high-density lipoprotein (HDL) concentration (R(2)=0.003, p=0.68). Hypercholesterolemia-induced microvascular dysfunction is related to various LDL markers and involves a reduction in NO-dependent vasodilation that appears to be a progressive process measurable in the skin microcirculation.
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Lipoproteínas LDL/sangue , Microcirculação/fisiologia , Receptores Depuradores Classe E/sangue , Pele/irrigação sanguínea , Idoso , Aterosclerose , LDL-Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Hipercolesterolemia/metabolismo , Fluxometria por Laser-Doppler/métodos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Pele/patologia , Temperatura , Fatores de Tempo , VasodilataçãoRESUMO
Cytokine receptor subunits are released from cells in a regulated manner and circulate in soluble forms at concentrations that are orders of magnitude greater than the concentrations of the cytokines themselves. The purpose of this study was to determine if the circulating concentrations of soluble receptor subunits for interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) might serve as early indicators of vascular dysfunction independent of the traditional cardiovascular disease (CVD) risk factors in women. Healthy women, aged 20-50 years (n = 36), were assessed for circulating concentrations of the cytokines IL-1ß, IL-6 and TNFα and the soluble cytokine receptor subunits interleukin-1 receptor type I (sIL-1RI), sIL-1RII, sIL-6Rα, glycoprotein 130 (s-gp130), soluble TNF receptor type 1 (sTNFR1), and sTNFR2, along with traditional CVD risk factors. Cytokine receptor subunit expression on mononuclear cells and the release of these subunits in vitro were also determined. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) were assessed by ultrasonography and Doppler probes. Circulating sIL-6Rα correlated negatively with FMD (r = -0.56, p = 0.007) independent of age and other CVD risk factors. Circulating sTNFR1 correlated positively with cfPWV (r = 0.60, p = 0.002). TNFR1 receptor expression on monocytes correlated positively with cIMT (r = 0.51, p = 0.004). Plasma concentrations of IL-1ß, IL-6 and TNFα were not significantly associated with FMD, cIMT or cfPWV. These data suggest that the receptors for IL-6 and TNFα, rather than the cytokines themselves, may be better indicators of early vascular changes that are associated with CVD.
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Doenças Cardiovasculares/sangue , Receptores de Interleucina-6/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Espessura Intima-Media Carotídea , Citocinas/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso , Receptores de Citocinas/sangue , Receptores de Interleucina-1/sangue , Fatores de Risco , Solubilidade , Rigidez Vascular , Adulto JovemRESUMO
BACKGROUND: External ventricular drain (EVD)-associated infections have a negative impact on healthcare cost and patient outcomes. Practice variation in EVD management may place patients at increased risk for EVD-associated infection. This project aimed to evaluate the impact of implementing an interprofessional evidence-based EVD bundle of care on reduction of EVD-related ventriculitis rates. METHODS: An interprofessional team developed an evidence based EVD care bundle and order set to eliminate practice inconsistencies. Standardization of EVD equipment and optimization of the electronic health record occurred. Education and competency validation were completed with neurosurgical providers and nurses. Interprofessional rounds occur weekly for observation, recognition, and in-the-moment education. RESULTS: A pre/post intervention design was used to show that the rate of EVD-associated ventriculitis decreased from 8.8 per reported EVD days in 2019 to 0 per reported EVD days in 2021 after implementation of the EVD care bundle. CONCLUSION: Through an interprofessional team approach, reduction in EVD-associated infection rates is feasible with implementation of an evidence based EVD care bundle.
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Infecções Relacionadas a Cateter , Ventriculite Cerebral , Humanos , Ventriculite Cerebral/epidemiologia , Ventriculite Cerebral/prevenção & controle , Ventriculite Cerebral/etiologia , Infecções Relacionadas a Cateter/etiologia , Centros de Traumatologia , Estudos Retrospectivos , Drenagem/efeitos adversosRESUMO
Elevated serum concentrations of follicle-stimulating hormone (FSH) are associated with diminished bone density in women, beginning years before menopause and the decline in estradiol. We hypothesized that FSH promotes development of myeloid cells toward the bone-resorbing osteoclast phenotype. This was tested by isolating peripheral blood mononuclear cells from nine healthy adults, incubating them in the presence of FSH at three different concentrations spanning the physiological range, and then measuring the expression of receptor activator for NF-κB (RANK, a surface marker for osteoclasts) on CD14(+) cells by flow cytometry. In the absence of FSH, 3.3±0.5% of the cells expressed high levels of the receptor (RANK(high)). Increasing concentrations of FSH caused a biphasic dose-response, with a maximal (1.5-fold) increase in RANK(high) cells achieved with 50 mIU/ml FSH (P=0.02). Cytokines that influence development of osteoclasts were also measured in culture supernatants: macrophage colony stimulating factor (M-CSF), osteoprotegerin (OPG) and tumor necrosis factor-α (TNFα) concentrations were not significantly influenced by FSH, whereas RANK-ligand was undetectable. This study supports the concept that the elevated circulating concentrations of FSH during perimenopause may contribute to the increased rate of bone loss by promoting the development of osteoclast precursor cells.
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Hormônio Foliculoestimulante Humano/farmacologia , Monócitos/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Adulto , Feminino , Citometria de Fluxo , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Osteoprotegerina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Recent studies have indicated that follicle-stimulating hormone (FSH) promotes bone loss. The present study tested the hypothesis that FSH enhances the activity of bone-resorbing cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6], either by inducing their secretion or by altering their receptor expression. Thirty-six women between the ages of 20 and 50 were assessed for bone mineral density (BMD), reproductive hormone, cytokine ligand and soluble receptor concentrations, and surface expression of cytokine receptors on monocytes. In addition, isolated mononuclear cells were incubated in vitro with exogenous FSH. Univariate regression analyses indicated that BMD was inversely related to serum FSH (r = -0.29 to -0.51, P = 0.03-0.001, depending upon the skeletal site). Physical activity and body composition were also identified as significant factors by multiple regressions. Exogenous FSH induced isolated cells to secrete IL-1beta, TNF-alpha, and IL-6 in proportion to the surface expression of FSH receptors on the monocytes. Endogenous (serum) FSH concentrations correlated with the circulating concentrations of these cytokines. None of these individual cytokines was related to BMD, but the IL-1beta to IL-1 receptor antagonist (IL-1Ra) ratio was inversely related to BMD (r = -0.53, P = 0.002) in all but the most physically active women, who had significantly lower expression of IL-1 type I receptors relative to type II (decoy receptors, P = 0.01). Physical activity also correlated positively with secretion of inhibitory soluble IL-1 receptors (r = 0.53, P = 0.003). Moreover, IL-1Ra correlated strongly with percent body fat (r = 0.66, P < 0.0001). These results indicate that BMD is related to FSH concentration, physical activity, and body composition. Although each of these factors likely has direct effects on bone, the present study suggests that each may also influence BMD by modulating the activity of the osteoresorptive cytokine IL-1beta.
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Envelhecimento/fisiologia , Densidade Óssea/fisiologia , Hormônio Foliculoestimulante Humano/sangue , Fase Folicular/fisiologia , Interleucina-1beta/sangue , Adulto , Composição Corporal , Células Cultivadas , Estradiol/sangue , Feminino , Citometria de Fluxo , Hormônio Foliculoestimulante Humano/farmacologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/metabolismo , Leptina/sangue , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Atividade Motora , Receptores de Interleucina-1/metabolismo , Análise de Regressão , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Muon spin spectroscopic measurements were made on atactic low-molecular-weight (LMW) (1.3 kg mol-1) and high-molecular-weight (HMW) (202 kg mol-1) polystyrene. Muoniated cyclohexadienyl radicals, which are formed by muonium addition to the phenyl side groups, are used as local probes of bulk dynamics. Muon spin relaxation is caused by the secondary γ-relaxation process, which involves motion of the phenyl rings, and is sensitive to the glass transition. The activation energy of the γ-relaxation process in the rubbery state is 0.60(2) eV in the HMW sample and 0.37(3) eV in the LMW sample.
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Knockout (KO) of IL-6 has been shown to attenuate ANG II hypertension, and mineralocorticoid receptors (MR) have been reported to contribute to the increase in IL-6 during acute ANG II infusion. This study determined whether that MR action is sustained with chronic ANG II infusion and whether it plays a role in mediating ANG II hypertension. ANG II infusion (90 ng/min) increased plasma IL-6 from 1.6 +/- 0.6 to 22.7 +/- 2.2 and 19.9 +/- 3.2 pg/ml on days 7 and 14, respectively, and chronic MR blockade with spironolactone attenuated that only at day 7 (7.2 +/- 2.2 pg/ml). ANG II increased MAP (19 h/day with telemetry) approximately 40 mmHg, but in ANG II+spironolactone mice (25 or 50 mg*kg(-1)*day(-1)), mean arterial pressure (MAP) was not significantly different despite a tendency for lower pressure the first 6 days. To isolate further the mineralocorticoid link to IL-6 and blood pressure, DOCA-salt hypertension was induced in IL-6 KO and wild-type (WT) mice. Plasma IL-6 increased from 4.1 +/- 1.7 to 34.5 +/- 7.0 pg/ml by day 7 of DOCA treatment in the WT mice but was back to control levels by day 14. An IL-6 bioassay using the murine B9, B-cell hybridoma cell line demonstrated that plasma IL-6 measurements reflected actual IL-6 bioactivity. The hypertension was not different and virtually superimposable in WT vs. IL-6 KO mice, averaging 145 +/- 2 and 144 +/- 3 mmHg, respectively. Both experiments confirm chronic stimulation of IL-6 by mineralocorticoids but show that it is transient. In addition, IL-6 was not required for mineralocorticoid hypertension. This suggests that aldosterone contributes to the increase in plasma IL-6 in the early stage of ANG II hypertension but that the blood pressure actions of IL-6 in that model are linked most likely to ANG II rather than aldosterone.
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Aldosterona/metabolismo , Pressão Sanguínea , Hipertensão/metabolismo , Interleucina-6/metabolismo , Angiotensinas/administração & dosagem , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Desoxicorticosterona , Modelos Animais de Doenças , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/fisiopatologia , Bombas de Infusão Implantáveis , Infusões Subcutâneas , Interleucina-6/sangue , Interleucina-6/deficiência , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Espironolactona/farmacologia , Fatores de TempoRESUMO
Animal studies have identified monocyte chemoattractive protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) as critical mediators of arterial diameter enlargement in response to chronic increases in blood flow (arteriogenesis). Furthermore, cellular studies have shown that the shear stresses resulting from increased blood flow stimulate synthesis of MCP-1, which in turn stimulates synthesis of VEGF. The purpose of this study was to determine if these mechanisms are evident in healthy women. Resting femoral artery diameter and blood flow, lean leg mass, MCP-1 and VEGF concentrations, and aerobic capacity were measured in 34 healthy women along with plasma concentrations of lipids associated with cardiovascular disease risk. Femoral artery diameter was independently related to metabolically active (lean) leg mass (b=0.41, P=0.008) and aerobic capacity (b=0.45, P=0.004). Plasma MCP-1 correlated negatively with the ratio of femoral artery diameter to lean leg mass (b=-0.42, P=0.009) and positively with serum triglycerides (b=0.46, P=0.005). Plasma VEGF exhibited similar correlations and strongly correlated with MCP-1 (R=0.92, P<0.0001). The results indicate that circulating MCP-1 and VEGF concentrations are associated with both arteriogenic and atherogenic stimuli in healthy women.
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Quimiocina CCL2/sangue , Artéria Femoral/anatomia & histologia , Artéria Femoral/fisiologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Feminino , Humanos , Perna (Membro)/anatomia & histologia , Perna (Membro)/irrigação sanguínea , Aptidão FísicaRESUMO
BACKGROUND: It is currently unclear whether reductions in adiposity mediate the improvements in vascular health that occur with aerobic exercise. The purpose of this longitudinal study of 13 healthy women (33 +/- 4 years old) was to determine whether 14 weeks of aerobic exercise would alter functional measures of vascular health, namely resting aortic pulse wave velocity (aPWV, an index of arterial stiffness), femoral artery diameter (D(FA)), and femoral artery blood flow (BF(FA)) independent of changes in adiposity. METHODS: Aerobic fitness was assessed as VO2peak normalized to fat-free mass, and adiposity (percent body fat) was determined by dual energy x-ray absorptiometry. Serum concentrations of proteins associated with risk for cardiovascular disease, including C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and leptin, were also measured. Subjects cycled for 50 minutes, 3 times per week. RESULTS: Aerobic fitness normalized to fat-free mass increased 6% (P = 0.03) whereas adiposity did not change. Resting D(FA) increased 12% (P < 0.001) and resting shear rate decreased 28% (P = 0.007). Aortic PWV, and serum sICAM-1, CRP and leptin did not change with training. CONCLUSION: Significant reductions in adiposity were not necessary for aerobic exercise training to bring about improvements in aerobic fitness and arterial remodeling. Peripheral arterial remodeling occurred without changes in central arterial stiffness or markers of inflammation.
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The purpose of this study was to determine if P-selectin, an adhesion molecule involved in the transendothelial movement of leukocytes, might also have a direct influence on the function of cells that come into contact with it. Human peripheral blood mononuclear cells were incubated on immobilized P-selectin or a control substrate (bovine serum albumin, BSA) and stimulated with bacterial lipopolysaccharide (LPS). After 24 h, the concentrations of proinflammatory cytokines in the supernatants of LPS-stimulated cells incubated on P-selectin were <50% of those produced by cells incubated on BSA (interleukin-1beta: P=0.001, tumor necrosis factor-alpha: P=0.004, and interferon-gamma : P=0.026). In contrast, cells incubated on P-selectin produced 74% more of the anti-inflammatory cytokine interleukin-10 than cells incubated on BSA (P=0.013). Neither P-selectin nor BSA stimulated cytokine production in the absence of LPS. Thus, P-selectin modulated the cytokine secretion of peripheral blood mononuclear cells in a coordinated manner that reduced the inflammatory potential of the cells.
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Anti-Inflamatórios/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Selectina-P/farmacologia , Células Cultivadas , Humanos , Interferon gama/metabolismo , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Leucócitos Mononucleares/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This investigation sought to determine if P-selectin-mediated mechanisms contributed to macrophage localization in damaged muscle, an essential process for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P-selectin glycoprotein ligand-1 (sPSGL-1) at 5, 50, or 200 microg/mouse or with 100 microl vehicle alone, and then, lengthening contractions were induced in hindlimb plantar-flexor muscles. The contractions caused fiber damage in soleus muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post-injury and substantial accumulation of CD11b+ mononuclear cells in the extracellular matrix up to 7 days post-injury. sPSGL-1 treatment caused a dose-dependent decrease in the number of regenerating fibers (P=0.021), as determined by developmental myosin heavy chain (dMHC) expression. This expression was reduced 93% at 7 days post-injury by the highest dose of sPSGL-1, which had no significant influence on intrafiber or extracellular accumulation of cells expressing CD11b, a general marker for phagocytic cells. Additional mice were injected i.v. with 20 microg anti-P-selectin or isotype-control immunoglobulin G and were then subjected to lengthening contractions as before. At 7 days post-injury, soleus muscles from anti-P-selectin-treated mice contained 48% fewer mononuclear cells that bound ER-BMDM1 (P=0.019), a marker for mature macrophages and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared with muscles from isotype-injected, control mice. The number of CD11b+ cells was not significantly different between groups. The results are consistent with the concept that P-selectin is involved in the recruitment, maturation, and/or activation of cells that are critical for muscle fiber regeneration.
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Músculos/fisiologia , Selectina-P/fisiologia , Regeneração/fisiologia , Animais , Antígeno CD11b/fisiologia , Movimento Celular/fisiologia , Leucócitos Mononucleares/fisiologia , Masculino , Camundongos , Músculos/lesões , Fatores de TempoRESUMO
Synaptic plasticity is often explored as a form of unsupervised adaptation in cortical microcircuits to learn the structure of complex sensory inputs and thereby improve performance of classification and prediction. The question of whether the specific structure of the input patterns is encoded in the structure of neural networks has been largely neglected. Existing studies that have analyzed input-specific structural adaptation have used simplified, synthetic inputs in contrast to complex and noisy patterns found in real-world sensory data. In this work, input-specific structural changes are analyzed for three empirically derived models of plasticity applied to three temporal sensory classification tasks that include complex, real-world visual and auditory data. Two forms of spike-timing dependent plasticity (STDP) and the Bienenstock-Cooper-Munro (BCM) plasticity rule are used to adapt the recurrent network structure during the training process before performance is tested on the pattern recognition tasks. It is shown that synaptic adaptation is highly sensitive to specific classes of input pattern. However, plasticity does not improve the performance on sensory pattern recognition tasks, partly due to synaptic interference between consecutively presented input samples. The changes in synaptic strength produced by one stimulus are reversed by the presentation of another, thus largely preventing input-specific synaptic changes from being retained in the structure of the network. To solve the problem of interference, we suggest that models of plasticity be extended to restrict neural activity and synaptic modification to a subset of the neural circuit, which is increasingly found to be the case in experimental neuroscience.
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Muscle damage resulting from eccentric exercise provides a useful model of oxyradical-induced injury and can be used to examine age-related responses to oxidative stress. Sixteen young (26.4 +/- 3.3 years) and 16 older (71.1 +/- 4.0 years) healthy men were randomly assigned to 1000 IU/d vitamin E or placebo for 12 weeks and ran downhill for 45 min at 75% VO(2)max, once before and following supplementation. Blood samples were obtained before (baseline) and immediately postexercise (0 h), and at 6, 24, and 72 h postexercise to determine antioxidant status, muscle damage, lipid peroxidation, and DNA damage. Following exercise, young and older men experienced similar increases in serum creatine kinase (CK), F(2alpha)-isoprostanes (iPF(2alpha); p <.001) and malondialdehyde (MDA; p <.01), although iPF(2alpha) peaked at 72 h postexercise and MDA peaked at 0 h. Oxygen Radical Absorbance Capacity (ORAC) decreased at 72 h (p <.01) and correlated with the rise in iPF(2alpha), MDA, and CK in the young men (p <.05). Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) was unaffected by exercise. Vitamin E decreased peak CK in young men, while in older men it decreased resting levels of iPF(2alpha) and suppressed the 24 h postexercise increases in iPF(2alpha) (p <.05). Thus, vitamin E supplementation induced modest changes eccentric exercise-induced oxidative stress, although differentially between the young and older subjects, while age had no direct influence on these responses among this group of physically fit subjects.
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Envelhecimento/fisiologia , Antioxidantes/farmacologia , Biomarcadores/análise , Desoxiguanosina/análogos & derivados , Exercício Físico , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatina Quinase/sangue , Desoxiguanosina/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , F2-Isoprostanos/metabolismo , Humanos , Peroxidação de Lipídeos , Masculino , Malondialdeído/metabolismo , Músculo Esquelético/metabolismo , OxirreduçãoRESUMO
This investigation examined the influence of hormone replacement therapy on plasma leptin concentrations in postmenopausal women and sought to determine if a relationship existed between plasma leptin, the thermoregulatory cytokine interleukin-1 (IL-1), and basal body temperature. Twenty-two women (54-71 years of age) were studied: eight were not taking hormone replacement, seven took oral estrogen only, and seven took oral estrogen plus progestin. Morning oral temperature, plasma leptin concentration, and mononuclear cell secretion of IL-1beta, IL-1 receptor antagonist (IL-1Ra), and soluble IL-1 receptor type II (sIL-1RII) were measured. Plasma leptin concentrations were not affected by hormone replacement therapy, but were inversely related to years since menopause (R = -0.48, P = 0.02) and were proportional to IL-1 activity (the balance of IL-1beta/IL-1Ra secretion, R = 0.69, P = 0.001). Moreover, morning oral temperature was positively related to plasma leptin (P = 0.03), after stratifying by progestin intake. These results support the concept that basal body temperature is regulated by a network of endocrine and immune mediators that are significantly influenced by age.
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Envelhecimento/metabolismo , Terapia de Reposição de Estrogênios , Leptina/sangue , Pós-Menopausa/metabolismo , Idoso , Envelhecimento/imunologia , Temperatura Corporal/fisiologia , Estrogênios/administração & dosagem , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/metabolismo , Pessoa de Meia-Idade , Pós-Menopausa/imunologia , Congêneres da Progesterona/administração & dosagem , Receptores de Interleucina-1/metabolismo , Receptores Tipo II de Interleucina-1 , Receptores para Leptina , Sialoglicoproteínas/metabolismoRESUMO
Circulating and tissue concentrations of pyrogenic cytokines, especially interleukin (IL)-1 beta, vary temporally through the menstrual cycle and pregnancy. The secretion of these cytokines in vitro by isolated human mononuclear cells is significantly influenced by exogenous gonadal steroids and gonadotropins. Reciprocally, cytokines influence gonadotropin secretion by the pituitary and steroidogenesis by the ovaries and testes. Several hypotheses have been advanced regarding the adaptive value of these interrelationships. Cytokine-induced synthesis of proteolytic enzymes and extracellular matrix proteins may be important for the tissue remodeling necessary for ovulation, implantation, and delivery. Tolerance of the fetal allograft may require downregulation of cytotoxic effector cells and reciprocal upregulation of humoral and nonspecific host defenses. The inhibitory influence of IL-1 beta on the luteinizing hormone surge may prevent inopportune conception, and the abortive influences of tumor necrosis factor-alpha and gamma interferon may terminate pregnancy during periods of infection.
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Citocinas/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Ovário/fisiologia , Testículo/fisiologia , Aborto Espontâneo/imunologia , Aborto Espontâneo/fisiopatologia , Feminino , Humanos , Tolerância Imunológica , Interleucina-1/fisiologia , Masculino , Ciclo Menstrual/fisiologia , GravidezRESUMO
Self-organization in biological nervous systems during the lifetime is known to largely occur through a process of plasticity that is dependent upon the spike-timing activity in connected neurons. In the field of computational neuroscience, much effort has been dedicated to building up computational models of neural plasticity to replicate experimental data. Most recently, increasing attention has been paid to understanding the role of neural plasticity in functional and structural neural self-organization, as well as its influence on the learning performance of neural networks for accomplishing machine learning tasks such as classification and regression. Although many ideas and hypothesis have been suggested, the relationship between the structure, dynamics and learning performance of neural networks remains elusive. The purpose of this article is to review the most important computational models for neural plasticity and discuss various ideas about neural plasticity's role. Finally, we suggest a few promising research directions, in particular those along the line that combines findings in computational neuroscience and systems biology, and their synergetic roles in understanding learning, memory and cognition, thereby bridging the gap between computational neuroscience, systems biology and computational intelligence.
Assuntos
Biologia Computacional , Simulação por Computador , Modelos Neurológicos , Redes Neurais de Computação , Plasticidade Neuronal , HumanosRESUMO
Reservoir computing provides a simpler paradigm of training recurrent networks by initialising and adapting the recurrent connections separately to a supervised linear readout. This creates a problem, though. As the recurrent weights and topology are now separated from adapting to the task, there is a burden on the reservoir designer to construct an effective network that happens to produce state vectors that can be mapped linearly into the desired outputs. Guidance in forming a reservoir can be through the use of some established metrics which link a number of theoretical properties of the reservoir computing paradigm to quantitative measures that can be used to evaluate the effectiveness of a given design. We provide a comprehensive empirical study of four metrics; class separation, kernel quality, Lyapunov's exponent and spectral radius. These metrics are each compared over a number of repeated runs, for different reservoir computing set-ups that include three types of network topology and three mechanisms of weight adaptation through synaptic plasticity. Each combination of these methods is tested on two time-series classification problems. We find that the two metrics that correlate most strongly with the classification performance are Lyapunov's exponent and kernel quality. It is also evident in the comparisons that these two metrics both measure a similar property of the reservoir dynamics. We also find that class separation and spectral radius are both less reliable and less effective in predicting performance.