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Bacterial arthritis and osteomyelitis are usually acute diseases, which in this way differ from the often insidious course of nonbacterial osteomyelitis; however, there is often an overlap both in less acute courses of bacterial illnesses and also in nonbacterial osteitis. The overlapping clinical phenomena can be explained by similar pathophysiological processes. In bacteria-related illnesses the identification of the pathogen and empirical or targeted anti-infectious treatment are prioritized, whereas no triggering agent is known for nonbacterial diseases. The diagnostics are based on the exclusion of differential diagnoses, clinical scores and magnetic resonance imaging (MRI). An activity-adapted anti-inflammatory treatment is indicated.
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OBJECTIVES: The study investigated the longitudinal association between physical activity and the risk of long COVID in patients who recovered from COVID-19 infection. STUDY DESIGN: We analyzed longitudinal data of the Prospective Study About Mental and Physical Health cohort, a prospective cohort study with adults living in Southern Brazil. METHODS: Participants responded to an online, self-administered questionnaire in June 2020 (wave 1) and June 2022 (wave 4). Only participants who self-reported a positive test for COVID-19 were included. Physical activity was assessed before (wave 1, retrospectively) and during the pandemic (wave 1). Long COVID was assessed in wave 4 and defined as any post-COVID-19 symptoms that persisted for at least 3 months after infection. RESULTS: A total of 237 participants (75.1% women; mean age [standard deviation]: 37.1 [12.3]) were included in this study. The prevalence of physical inactivity in baseline was 71.7%, whereas 76.4% were classified with long COVID in wave 4. In the multivariate analysis, physical activity during the pandemic was associated with a reduced likelihood of long COVID (prevalence ratio [PR]: 0.83; 95% confidence interval [CI]: 0.69-0.99) and a reduced duration of long COVID symptoms (odds ratio: 0.44; 95% CI: 0.26-0.75). Participants who remained physically active from before to during the pandemic were less likely to report long COVID (PR: 0.74; 95% CI: 0.58-0.95), fatigue (PR: 0.49; 95% CI: 0.32-0.76), neurological complications (PR: 0.47; 95% CI: 0.27-0.80), cough (PR: 0.40; 95% CI: 0.22-0.71), and loss of sense of smell or taste (PR: 0.43; 95% CI: 0.21-0.87) as symptom-specific long COVID. CONCLUSION: Physical activity practice was associated with reduced risk of long COVID in adults.
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COVID-19 , Síndrome Post Agudo de COVID-19 , Humanos , Adulto , Femenino , Masculino , COVID-19/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , Ejercicio FísicoRESUMEN
OBJECTIVES: This study aimed to examine the changes in depression and anxiety symptoms among Brazilian adults over 10 months of the COVID-19 pandemic. STUDY DESIGN/METHODS: The present study used data from wave 1 (June/July 2020) and wave 2 (December 2020/January 2021) of the Prospective Study About Mental and Physical Health (PAMPA) Cohort, a state-level, ambispective longitudinal study with adults from southern Brazil. The frequency of anxiety and depressive symptoms was assessed using the Hospital Anxiety and Depression Scale. Anxiety and depressive symptoms before social distancing were retrospectively assessed during wave 1. RESULTS: Most of the 674 participants were classified as non-symptomatic for depressive (85.0%) and anxiety symptoms (73.2%) before the COVID-19 pandemic. At wave 1, there were increases in symptoms of depression (7.6% [95% confidence interval [CI]: 7.2%, 8.1%]) and anxiety (9.1% [95% CI: 8.6%, 9.5%]). These decreased at wave 2 (depression: 6.9% [95% CI: 6.5%, 7.2%]; anxiety: 7.4% [95% CI: 7.1%, 7.8%]) although they were still elevated compared with pre-COVID (depression: 4.5% [95% CI: 4.2%, 4.8%]; anxiety: 5.8% [95% CI: 5.5%, 6.1%]). Adults living alone (b = 0.44 [95% CI: 0.07, 0.82]) had a faster trajectory in anxiety symptoms than their counterparts. Cohort members who were living alone (b = 0.24 [95% CI: 0.06, 0.42]) and with diagnosed chronic disease (0.32 [95% CI: 0.18, 0.46]) had a faster increase in depressive symptoms than their respective counterparts. Participants aged ≥60 years showed a slower trajectory of depressive (b = -0.46 [95% CI: -0.73, -0.18]) and anxiety (b = -0.61 [95% CI: -1.20, -0.02) symptoms. CONCLUSIONS: During 10 months of COVID-19, anxiety and depression symptoms improved but were still higher than before COVID-19.
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COVID-19 , Adulto , Ansiedad/epidemiología , Brasil/epidemiología , COVID-19/epidemiología , Depresión/epidemiología , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVES: This study aimed to identify the effects of different physical activities practised during the time period when COVID-19 social distancing measures were in place on the risk of subjective memory decline in adults. STUDY DESIGN: Retrospective cohort study. METHODS: Data from the Prospective Study about Mental and Physical Health (PAMPA), a state-level (Rio Grande do Sul, Brazil), online-based cohort study, were analysed. Respondents were asked to rate their memory before COVID-19 social distancing measures were implemented (retrospectively) and on the day that the survey was completed. Subjective memory decline was defined as a perceived worsening of memory function during COVID-19 social distancing compared with the pre-pandemic period. The types of physical activity practised before and during COVID-19 social distancing measures were assessed. RESULTS: Data from 2319 adults were included. Out-of-home endurance, muscle strengthening, combined endurance and muscle strengthening, and stretching activities reduced the risk of subjective memory decline during the pandemic. In terms of physical activities practised at home, only muscle strengthening did not protect against subjective memory decline. Participants who sustained any type of physical activity at home during the COVID-19 pandemic showed a reduced risk for subjective memory decline. CONCLUSIONS: Physical activity, regardless of the type of activity and location performed, during the time period when COVID-19 social distancing measures were in place can mitigate the effects of the pandemic on subjective memory decline.
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COVID-19 , Pandemias , Adulto , Estudios de Cohortes , Ejercicio Físico , Humanos , Trastornos de la Memoria , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVES: We aimed to compare the prevalence of depression and anxiety symptoms before and during the pandemic and identify factors associated with aggravated mental health symptoms. STUDY DESIGN: Retrospective cohort study. METHODS: We identified the proportion of normal, mild, moderate, and severe symptoms of depression and anxiety before and during the social distancing restrictions in adults from southern Brazil. An online, self-administered questionnaire was delivered for residents within the state of Rio Grande do Sul. Depressive and anxiety symptoms were examined by the Hospital Anxiety and Depression Scale. RESULTS: Most of the participants (n = 2314) aged between 31 and 59 years (54.2%), were women (76.6%), White (90.6%) with a university degree (66.6%). Moderate-to-severe symptoms of depression and anxiety were reported in 3.9% and 4.5% of participants, respectively, before COVID-19. During the pandemic (June-July, 2020), these proportions increased to 29.1% (6.6-fold increase) and 37.8% (7.4-fold increase), respectively. Higher rates of depressive and anxiety symptoms were observed among women, those aged 18-30 years, diagnosed with chronic disease and participants who had their income negatively affected by social restrictions. Remaining active or becoming physically active during social distancing restrictions reduced the probability of aggravated mental health disorders. CONCLUSIONS: Depressive and anxiety symptoms had a 6.6- and 7.4-fold increase since the COVID-19 pandemic. Public policies such as physical activity promotion and strategies to reduce the economic strain caused by this pandemic are urgently needed to mitigate the impact of the pandemic on mental health.
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Ansiedad/epidemiología , COVID-19/psicología , Depresión/epidemiología , Salud Mental/estadística & datos numéricos , SARS-CoV-2 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/etiología , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/etiología , Brasil/epidemiología , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/prevención & control , Estudios de Cohortes , Depresión/etiología , Femenino , Humanos , Renta , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Prevalencia , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
We investigate a regime of parametric amplification in which the pump and signal waves are spectrally separated by only a few hundreds of GHz frequency - therefore resulting in a sub-THz frequency idler wave. Operating in this regime we find an optical parametric amplifier (OPA) behavior which is highly dissimilar to conventional OPAs. In this regime, we observe multiple three-wave mixing processes occurring simultaneously which results in spectral cascading around the pump and signal wave. Via numerical simulations, we elucidate the processes at work and show that cascaded optical parametric amplification offers a pathway toward THz-wave generation beyond the Manly-Rowe limit and toward the generation of high-energy, sparse frequency-combs.
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This study aimed to evaluate the waste cooking oil (WCO) hydrolysis in ultrasonic system using lipase as catalyst. Lipase was produced by the fungus Aspergillus niger via solid state fermentation (SSF) using canola meal as substrate. Prior to the hydrolysis reaction, the lipase behavior when subjected to ultrasound was evaluated by varying the temperature of the ultrasonic bath, the exposure time and the equipment power. Having optimized the treatment on ultrasound, the WCO hydrolysis reaction was carried out by evaluating the oil:water ratio and the lipase concentration. For a greater homogenization of the reaction medium, a mechanical stirrer at 170rpm was used. All steps were analyzed by experimental design technique. The lipase treatment in ultrasound generated an increase of about 320% in its hydrolytic activity using 50% of ultrasonic power for 25min. at 45°C. The results of the experimental design conducted for ultrasound-assisted hydrolysis showed that the best condition was using an oil:water ratio of 1:3 (v:v) and enzyme concentration of 15% (v/v), generating 62.67µmol/mL of free fatty acids (FFA) in 12h of reaction. Thus, the use of Aspergillus niger lipase as a catalyst for hydrolysis reaction of WCO can be considered as a possible pretreatment technique of the oil in order to accelerate its degradation.
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Biocatálisis , Culinaria , Lipasa/metabolismo , Aceites/química , Ondas Ultrasónicas , Residuos , Aspergillus niger/enzimología , HidrólisisRESUMEN
A cryogenically cooled, bulk Yb:YAG, four-pass amplifier delivering up to 250 W average power at 100 kHz repetition rate is reported. The 2.5 mJ amplified optical pulses show a sub-20 ps duration before temporal compression and a spectrum supporting a transform-limited duration of 3.6 ps. The power instabilities were measured to be <0.5% rms over 30 min at full power, and the spatial intensity profile showed a flat-top distribution and near diffraction-limited beam quality. This compact amplifier is an ideal source for pumping either near-IR or mid-IR optical parametric chirped pulse amplifiers.
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X-ray crystallography is one of the main methods to determine atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes consisting of hundred-thousands of atoms that constitute the macromolecular machinery of life. Life is not static, and unravelling the structure and dynamics of the most important reactions in chemistry and biology is essential to uncover their mechanism. Many of these reactions, including photosynthesis which drives our biosphere, are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by optical spectroscopy, enabled by ultrafast laser technology, but they reduce the vast complexity of the process to a few reaction coordinates. In the AXSIS project at CFEL in Hamburg, funded by the European Research Council, we develop the new method of attosecond serial X-ray crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology like energy conversion processes. For that purpose, we develop a compact, fully coherent, THz-driven atto-second X-ray source based on coherent inverse Compton scattering off a free-electron crystal, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals. This highly synergistic project starts from a completely clean slate rather than conforming to the specifications of a large free-electron laser (FEL) user facility, to optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. A multidisciplinary team formed by laser-, accelerator,- X-ray scientists as well as spectroscopists and biochemists optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. Ultimately, the new capability, attosecond serial X-ray crystallography and spectroscopy, will be applied to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis.
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We report the fabrication and visible laser operation of Pr,Mg:SrAl12O19 waveguides. Waveguiding structures were created by focusing the radiation of a femtosecond Ti:sapphire laser into bulk material. Guiding losses were determined to be as low as 0.12 dB cm(-1) at 632.8 nm. By employing a frequency-doubled optically pumped semiconductor laser, waveguide laser operation was realized at wavelengths of 525.3, 644.0, and 724.9 nm with output powers as high as 36, 1065, and 504 mW, respectively. To the best of our knowledge this is the first demonstration of green laser operation in a Pr(3+)-doped crystalline waveguide laser.
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In this Letter, we report on laser operation of Pr3+,Mg2+:SrAl12O19 pumped by a frequency-doubled optically pumped semiconductor laser. By employing a V-type cavity, we demonstrate cw laser operation at room temperature in the green spectral range in a doped oxide host for the first time to the best of our knowledge. Furthermore, efficient laser operation was realized in the orange, red, and deep red spectral range with output powers exceeding 1.1 W at emission wavelengths of 643.6 and 724.4 nm.
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We report on the first results of diode pumped laser operation of Pr3+:LaF3 in a quasi continuous wave (qcw) mode with average output powers of up to 80.0 mW (≈ 161.3 mW qcw) and a maximum slope efficiency of 37% at 719.8 nm. Furthermore it was possible to operate the laser at 537.1 nm and 635.4 nm and to tune the emission wavelength from 609 nm to 623 nm. The pump source was an InGaN laser diode with a maximum output power of 1 W at a central emission wavelength of 442 nm.
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Láseres de Estado Sólido , Análisis Espectral/instrumentación , Diseño de Equipo , Análisis de Falla de EquipoAsunto(s)
Antibióticos Antineoplásicos/farmacología , Benzoquinonas/farmacología , Lactamas Macrocíclicas/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasias Experimentales/dietoterapia , Animales , Antibióticos Antineoplásicos/uso terapéutico , Benzoquinonas/uso terapéutico , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Humanos , Lactamas Macrocíclicas/uso terapéutico , Leucemia Mieloide Aguda/metabolismo , Ratones , Neoplasias Experimentales/metabolismoRESUMEN
BACKGROUND: Disruption of circadian rhythms has been associated with obesity in children and adolescents, and with hypertension in adults, in industrialized populations. OBJECTIVE: We examined cross-sectional associations between sleep duration or television viewing and obesity and blood pressure in Brazilian adolescents. DESIGN: The sample consisted of 4452 adolescents aged 10-12 years participating in a prospective birth cohort study in Pelotas, Brazil. Sleep duration and television viewing were determined through questionnaires. Obesity was assessed using international cut-offs for body mass index (BMI), and body fatness by skinfold thicknesses. Blood pressure was measured using a validated monitor. RESULTS: Short sleep duration was associated with increased BMI, skinfolds, systolic blood pressure, activity levels and television viewing. Each hour of sleep reduced BMI by 0.16 kg/m(2) (s.e. 0.04), and was associated with odds ratio for obesity of 0.86 (s.e. 0.04), both P<0.001. Television viewing was associated with increased BMI and skinfolds, and increased blood pressure. The effects of sleep duration and television viewing on obesity were independent of one another. Their associations with blood pressure were mediated by body fatness. CONCLUSIONS: Both short sleep duration and increased television viewing were associated with greater body fatness, obesity and higher blood pressure, independently of physical activity level. These associations were independent of maternal BMI, identified in other studies as the strongest predictor of childhood obesity. Our study shows that behavioural factors associated with metabolic risk in industrialized populations exert similar deleterious effects in a population undergoing nutritional transition and suggest options for public health interventions.
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Presión Sanguínea/fisiología , Países en Desarrollo , Obesidad/etiología , Privación de Sueño , Televisión , Adolescente , Brasil , Niño , Ritmo Circadiano , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Actividad Motora , Oportunidad Relativa , Estudios Prospectivos , Riesgo , Grosor de los Pliegues CutáneosRESUMEN
In this paper, we report the deposition of graphite multilayer containing nitrogen covering nanometric nickel particles. In-situ photoelectron emission spectroscopy (XPS) reveals the presence of nitrogen in the carbon layer covering the nickel particles. The field emission properties of the structures are reported. Atomic force microscopy displays regular domelike structures. Raman spectroscopy shows the characteristic frequencies associated with graphite and disordered structures. High-resolution transmission electron microscopy confirms the presence of multiwall well-organized graphite layers covering the nickel particles. Disorder increases on increasing nitrogen content. The samples were prepared in-situ by depositing first a few atomic layers of nickel and subsequent islands formation by thermal annealing. Then, an argon ion beam bombards an ultrapure carbon target and simultaneously the growing film is assisted with a second low-energy nitrogen ion beam (ion beam assisted deposition).
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Carbono/química , Microscopía Electrónica de Transmisión , Nanoestructuras/química , Nitrógeno/química , Argón/química , Grafito/química , Calor , Iones , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Níquel/química , Oxidación-Reducción , Silicio/química , Espectrometría por Rayos X , Espectrometría RamanRESUMEN
The removal of damaged myelin is central to repair after injury to axons and in autoimmune demyelinating diseases. Complement receptor 3 (CR3/MAC-1) plays a major role in mediating the phagocytosis of damaged myelin by macrophages and microglia. We studied the modulation (inhibition and augmentation) of CR3/MAC-1 mediated myelin phagocytosis by mAbs that bind to distinct epitopes of subunits alphaM and beta2 of CR3/MAC-1. mAb M1/70 anti-alpha(M) and mAb 5C6 anti-alpha(M) inhibited, whereas mAb M18/2 anti-beta2 augmented myelin phagocytosis. This mAb-induced modulation of myelin phagocytosis occurred in the presence and absence of active complement. Inhibition induced by M1/70 or 5C6 did not add when the two were combined. Combining M1/70 or 5C6 with M18/2 reduced the augmentation induced by M18/2 alone. CR3/MAC-1-mediated myelin phagocytosis may thus be subjected to modulation between efficient and inefficient functional/activation states. These observations and conclusions may offer an explanation for the observed discrepancy between efficient myelin phagocytosis in experimental allergic encephalomyelitis and inefficient myelin phagocytosis after injury to CNS axons, although in both instances macrophages/microglia express CR3/MAC-1.
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Antígeno de Macrófago-1/metabolismo , Macrófagos/inmunología , Vaina de Mielina/inmunología , Vaina de Mielina/metabolismo , Fagocitosis/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Epítopos/inmunología , Antígeno de Macrófago-1/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Regeneración Nerviosa/inmunologíaRESUMEN
Injury and demyelinating diseases result in the disruption of the myelin sheath that surrounds axons in the nervous system. The removal of degenerating myelin by macrophages and microglia is central to repair mechanisms that follow. The efficiency of myelin removal depends on magnitudes and rates of myelin phagocytosis and degradation. In the present study we test whether environmental conditions within a tissue can control patterns of myelin removal. We document that macrophages that are recruited to the same tissue but by distinct inflammatory stimuli differ in their ability to phagocytose and degrade myelin. These observations may apply to the nervous system where different pathological conditions that involve distinct inflammatory stimuli may induce different functional states in microglia and macrophages.
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Inflamación/inmunología , Macrófagos Peritoneales/metabolismo , Vaina de Mielina/inmunología , Vaina de Mielina/metabolismo , Fagocitosis/inmunología , Animales , Adhesión Celular/efectos de los fármacos , Adhesión Celular/inmunología , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Inflamación/inducido químicamente , Antígeno de Macrófago-1/metabolismo , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Proteína Básica de Mielina/análisis , Proteína Básica de Mielina/inmunología , Proteína Básica de Mielina/metabolismo , Fagocitosis/efectos de los fármacosRESUMEN
The removal of degenerating myelin by phagocytosis is central to pathogenesis and repair in traumatized and diseased nervous system. Galectin-3/MAC-2 is a differentiation and activation marker of murine and human monocytes/macrophages/microglia. Galectin-3/MAC-2, along with MAC-1 that mediates myelin phagocytosis, marks an in vivo activation state in macrophages, which are involved in myelin degeneration and phagocytosis in injured mouse peripheral nerves. In contrast, high levels of MAC-1 but extremely low levels of Galectin-3/MAC-2 are expressed in vivo in injured CNS where myelin degeneration and phagocytosis progress extremely slowly. The present study was aimed at testing whether an activation state marked by Galectin-3/MAC-2 is present in vivo in the CNS of EAE mice concomitant with autoimmune induced myelin degeneration and phagocytosis. EAE was inflicted by mouse spinal cord homogenate. Demyelination was assessed by light microscopy and Galectin-3/MAC-2, MAC-1, and F4/80 expression by immunocytochemistry. We presently document that Galectin-3/MAC-2 expression is up regulated, along with MAC-1 and F4/80, in spinal cords and optic nerves of EAE mice in areas of demyelination and myelin degeneration, in myelin phagocytosing microglia and macrophages. Copolymer 1 (Glatiramer acetate) suppresses EAE, demyelination, and Galectin-3/MAC-2 expression. EAE pathogenesis thus involves a state of activation in microglia and macrophages characterized by the expression Galectin-3/MAC-2 along with MAC-1. Furthermore, the in vivo responses to injury and autoimmune challenge in the CNS differ in the activation pattern of microglia and macrophages with regard to Galectin-3/MAC-2 expression and the corresponding occurrence of myelin degeneration and phagocytosis.
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Antígenos de Diferenciación/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Nervio Óptico/metabolismo , Médula Espinal/metabolismo , Animales , Antígenos de Diferenciación/análisis , Cruzamientos Genéticos , Encefalomielitis Autoinmune Experimental/patología , Femenino , Galectina 3 , Humanos , Inmunohistoquímica , Antígeno de Macrófago-1/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Vaina de Mielina/patología , Degeneración Nerviosa , Nervio Óptico/patología , Fagocitosis , Médula Espinal/inmunología , Médula Espinal/patologíaRESUMEN
Wallerian degeneration (WD) is the inflammatory response of peripheral nerves to injury. Evidence is provided that granulocyte macrophage colony stimulating factor (GM-CSF) contributes to the initiation and progression of WD by activating macrophages and Schwann, whereas IL-10 down-regulates WD by inhibiting GM-CSF production. A significant role of activated macrophages and Schwann for future regeneration is myelin removal by phagocytosis and degradation. We studied the timing and magnitude of GM-CSF and IL-10 production, macrophage and Schwann activation, and myelin degradation in C57BL/6NHSD and C57BL/6-WLD/OLA/NHSD mice that display normal rapid-WD and abnormal slow-WD, respectively. We observed the following events in rapid-WD. The onset of GM-CSF production is within 5 h after injury. Production is steadily augmented during the first 3 days, but is attenuated thereafter. The onset of production of the macrophage and Schwann activation marker Galectin-3/MAC-2 succeeds that of GM-CSF. Galectin-3/MAC-2 production is up-regulated during the first 6 days, but is down-regulated thereafter. The onset of myelin degradation succeeds that of Galectin-3/MAC-2, and is almost complete within 1 week. IL-10 production displays two phases. An immediate low followed by a high that begins on the fourth day, reaching highest levels on the seventh. The timing and magnitude of GM-CSF production thus enable the rapid activation of macrophages and Schwann that consequently phagocytose and degrade myelin. The timing and magnitude of IL-10 production suggest a role in down-regulating WD after myelin is removed. In contrast, slow-WD nerves produce low inefficient levels of GM-CSF and IL-10 throughout. Therefore, deficient IL-10 levels cannot account for inefficient GM-CSF production, whereas deficient GM-CSF levels may account, in part, for slow-WD.