Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages) are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly ...activate NFkappaB in macrophages, causing enhanced release of proinflammatory cytokines (TNFalpha, IL-1beta, IL-6). Both adrenal-intact (AD+) and adrenalectomized (ADX) rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-beta-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine. The effects of upregulation of phagocyte-derived catecholamines were investigated in two models of acute lung injury (ALI). Increased levels of phagocyte-derived catecholamines were associated with intensification of the acute inflammatory response, as assessed by increased plasma leak of albumin, enhanced myeloperoxidase content in lungs, augmented levels of proinflammatory mediators in bronchoalveolar lavage fluids, and elevated expression of pulmonary ICAM-1 and VCAM-1. In adrenalectomized rats, development of ALI was enhanced and related to alpha(2)-adrenoceptors engagement but not to involvement of mineralocorticoid or glucocorticoid receptors. Collectively, these data demonstrate that catecholamines are potent inflammatory activators of macrophages, upregulating NFkappaB and further downstream cytokine production of these cells. In adrenalectomized animals, which have been used to further assess the role of catecholamines, there appears to be a compensatory increase in catecholamine generating enzymes and catecholamines in macrophages, resulting in amplification of the acute inflammatory response via engagement of alpha(2)-adrenoceptors.
Kīlauea Volcano’s 2018 lower East Rift Zone (LERZ) eruption produced exceptionally high lava effusion rates and record-setting SO
2
emissions. The eruption involved a diverse range of magmas, ...including primitive basalts sourced from Kīlauea’s summit reservoirs. We analyzed LERZ matrix glasses, melt inclusions, and host minerals to identify melt volatile contents and magma storage depths. The LERZ glasses and melt inclusions span nearly the entire compositional range previously recognized at Kīlauea. Melt inclusions in Fo
86-89
olivine from the main eruptive vent (fissure 8) underwent 70–170 °C cooling during transport in LERZ carrier melts, causing extensive post-entrapment crystallization and sulfide precipitation. Many of these melt inclusions have low sulfur (400–900 ppm) even after correction for sulfide formation. CO
2
and H
2
O vapor saturation pressures indicate shallow melt inclusion trapping depths (1–5 km), consistent with formation within Kīlauea’s Halemaʻumaʻu and South Caldera reservoirs. Many of these inclusions also have degassed δ
34
S values (− 1.5 to − 0.5‰). Collectively, these results indicate that some primitive melts experienced near-surface degassing before being trapped into melt inclusions. We propose that decades-to-centuries of repeated lava lake activity and lava drain-back during eruptions (e.g., 1959 Kīlauea Iki) recycled substantial volumes of degassed magma into Kīlauea’s shallow reservoir system. Degassing and magma recycling from the 2008–2018 Halemaʻumaʻu lava lake likely reduced the volatile contents of LERZ fissure 8 magmas, resulting in lower fountain heights compared to many prior Kīlauea eruptions. The eruption’s extreme SO
2
emissions were due to high lava effusion rates rather than particularly volatile-rich melts.
After intracerebral hemorrhage (ICH), brain edema commonly occurs and can cause death. Along with edema, there are significant alterations in the concentrations of key ions such as sodium, potassium, ...and chloride, which are essential to brain function. NKCC1, a cation-chloride cotransporter, is upregulated after brain damage, such as traumatic injury and ischemic stroke. NKCC1 brings sodium and chloride into the cell, possibly worsening ion dyshomeostasis. Bumetanide, a specific NKCC1 antagonist, blocks the transport of chloride into cells, and thus should attenuate the increases in chloride, which should lessen brain edema and improve neuronal functioning post-ICH, as with other injuries. We used the collagenase model of ICH to test whether bumetanide treatment for three days (vs. vehicle) would improve outcome. We gave bumetanide beginning at two hours or seven days post-ICH and measured behavioural outcome, edema, and brain ion content after treatment. There was some evidence for a minor reduction in edema after early dosing, but this did not improve behaviour or lessen injury. Contrary to our hypothesis, bumetanide did not normalize ion concentrations after late dosing. Bumetanide did not improve behavioural outcome or affect lesion volume. After ICH, bumetanide is safe to use in rats but does not improve functional outcome in the majority of animals.
Abstract Introduction Annual influenza vaccine coverage for young adults (including college students) remains low, despite a 2011 US recommendation for annual immunization of all people 6 months and ...older. College students are at high risk for influenza morbidity given close living and social spaces and extended travel during semester breaks when influenza circulation typically increases. We evaluated influenza vaccine uptake following an on-campus vaccine campaign at a large, public New York State university. Methods Consecutive students visiting the University Health Center were recruited for a self-administered, anonymous, written survey. Students were asked about recent influenza vaccination, barriers to influenza vaccination, and willingness to get vaccinated to protect other vulnerable individuals they may encounter. Frequencies and proportions were evaluated. Results Of 653 students approached, 600 completed surveys (92% response proportion); respondents were primarily female (61%) and non-Hispanic white (59%). Influenza vaccine coverage was low (28%). Compared to coverage among non-Hispanic white students (30%), coverage was similar among Hispanic (30%) and other race/ethnicity students (28%) and lowest among non-Hispanic black students (17%). Among the unvaccinated, the most commonly selected vaccination barriers were “Too lazy to get the vaccine” (32%) and “Don’t need the vaccine because I’m healthy” (29%); 6% of unvaccinated students cited cost as a barrier. After being informed that influenza vaccination of young, healthy people can protect other vulnerable individuals (e.g., infants, elderly), 71% of unvaccinated students indicated this would increase their willingness to get vaccinated. Conclusions Influenza vaccine uptake among college students is very low. While making vaccine easily obtained may increase vaccine uptake, college students need to be motivated to get vaccinated. Typically healthy students may not perceive a need for influenza vaccine. Education about vaccinating healthy individuals to prevent the spread of influenza to close contacts, such as vulnerable family members, may provide this motivation to get vaccinated.
Less than a year after the 2018 Kīlauea caldera collapse and eruption, water appeared in newly deepened Halemaʻumaʻu crater. The lake—unprecedented in the written record—grew to a depth of ∼50 m ...before lava from the December 2020 eruption boiled it away. Surface water heightened concerns of potential phreatic or phreatomagmatic explosions but also offered a new means of possibly identifying eruption precursors. The U.S. Geological Survey Hawaiian Volcano Observatory (HVO) monitored the lake via direct visual observation, webcams, thermal imaging, colorimetry, and laser rangefinders. HVO also employed uncrewed aircraft systems to sample the water and measure near‐lake gas composition. The lake's δD and δ18O indicate a groundwater source with substantial evaporation. The initial sample had a salinity (total dissolved solids concentration) of 71,000 mg/L and was rich in sulfate (∼53,000 mg/L), iron (∼500 mg/L), and magnesium (∼10,000 mg/L). Subsequent samples were slightly more dilute. The water's pH (∼4), δ34S (+4.3‰), and surface temperatures (up to 85°C) suggest, rather than significant scrubbing of magmatic volatiles, leaching of basalt and reactions with sulfate minerals resulted in high concentrations of sulfate and other solutes. Thermodynamic modeling and precipitate mineralogy indicate that water composition was controlled by iron oxidation and sulfate dissolution. Although the lake exhibited no detectable precursors before the next eruption, and phreatic or phreatomagmatic explosions did not materialize, our multi‐parameter approach to monitoring yielded an enhanced understanding of the hydrologic, geologic, and magmatic conditions that led to the formation of the unique and short‐lived lake.
Plain Language Summary
In 2019, ponded water was spotted within Kīlauea Volcano's summit crater—the first water body in the crater in written history. The presence of a crater lake was important, as it increased the chance of hazardous, explosive eruptions once Kīlauea resumed eruptive activity. However, the lake provided a new way to keep an eye on Kīlauea; other volcanic lakes have changed temperature, color, or chemistry, or even boiled away, before eruptions. We monitored Kīlauea's lake with various methods, including water sampling via drone. Data showed that the lake was fed by groundwater, not rainwater; the lake was acidic, but less so than most acid volcanic lakes; and the lake was not absorbing large amounts of volcanic gas directly. Instead, the lake's chemistry was controlled by reactions with rocks and sulfur‐bearing minerals in and near the crater. Ultimately, no changes to the lake were detected before the next eruption, most likely because of the nature of magma at Kīlauea, which is different from that at most volcanoes with crater lakes. The water lake also did not cause the eruption to be explosive, as lava merely flowed into the lake from above rather than being injected vigorously into the lake from beneath.
Key Points
Kīlauea Volcano's summit water lake was sampled three times to track any potential geochemical precursors to eruption
The lake was fed by groundwater and its chemistry was controlled by leaching of host basalt, iron oxidation, and sulfate dissolution
No precursory changes to the lake or phreatic activity occurred, likely owing to the nature of basaltic magma and eventual dike location
Repeated short‐term deployments of seismic, infrasound, video, and gas‐emission instruments at Fuego volcano, Guatemala have revealed three types of very long period (VLP) events associated with ...conduit sealing, pressure accumulation, and release. In 2008, ash‐rich explosions issued from a vent on the western flank and produced one type of VLP (Type 1). Impulsive, bomb‐rich explosions from the summit vent in 2009 produced a shorter period VLP (Type 2), but also generated ash release. Type 3 VLP events occurred during ash‐free exhalations from the summit in 2008 and had waveform shapes similar to Type 2 events. Weak infrasound records for Type 1 explosions compared to Type 2 suggest lower pressures and higher magma porosity for Type 1. Type 3 events correlate with spikes in SO2 emission rate and are driven by partial sealing and rapid release of ash‐free gas at the summit vent. Variations in the VLP period may provide a new tool for monitoring conditions within the conduit.
Key PointsVariations in very‐long‐period earthquakes are related to eruption styleA class of very‐long‐period earthquakes is clearly related to gas emissionVLPs may inform about conditions within the conduit
•Three months of aerobic exercise training (AET) improves fitness in PD patients.•Effects of AET on cognitive and motor skills in PD were evaluated concurrently.•Some executive functions and ...procedural learning capacity improved after AET.•AET can be used as a non-pharmacological intervention to improve functioning in PD.
Background: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson’s disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. Objective: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. Methods: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12weeks). Exercise prescription started at 20min (+5min/week up to 40min) based on participant’s maximal aerobic power. Before and after AET, EF tests assessed participants’ inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. Results: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. Conclusion: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.
The two guard cells of a stoma are produced by a single symmetric division just before terminal differentiation. Recessive mutations in the FOUR LIPS (FLP) gene abnormally induce at least four guard ...cells in contact with one another. These pattern defects result from a persistence of precursor cell identity that leads to extra symmetric divisions at the end of the cell lineage. FLP is likely to be required for the correct timing of the transition from cell cycling to terminal differentiation. FLP encodes a two-repeat (R2R3) MYB protein whose expression accumulates just before the symmetric division. A paralogous gene, MYB88, overlaps with FLP function in generating normal stomatal patterning. Plants homozygous for mutations in both genes exhibit more severe defects than flp alone, and transformation of flp plants with a genomic MYB88 construct restores a wild-type phenotype. Both genes compose a distinct and relatively basal clade of atypical R2R3 MYB proteins that possess an unusual pattern of amino acid substitutions in their putative DNA binding domains. Our results suggest that two related transcription factors jointly restrict divisions late in the Arabidopsis thaliana stomatal cell lineage.
There are currently no effective treatments to halt the muscle breakdown in Duchenne muscular dystrophy (DMD), although genetic-based clinical trials are being piloted. Most of these trials have as ...an endpoint the restoration of dystrophin in muscle fibers, hence requiring sufficiently well-preserved muscle of recruited patients. The choice of the muscles to be studied and the role of noninvasive methods to assess muscle preservation therefore require further evaluation.
We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD >8 years, using muscle MRI. In a subgroup of 15 patients we correlated the muscle MRI findings with the histology of open extensor digitorum brevis (EDB) muscle biopsies. Muscle MRI involvement was assigned using a scale 0-4 (normal-severe).
In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius > soleus) was most severely affected; the anterior compartment (tibialis anterior/posterior, popliteus, extensor digitorum longus) least affected. Muscle MRI showed EDB involvement that correlated with the patient's age (p = 0.055). We show a correlation between the MRI and EDB histopathologic changes, with MRI 3-4 grades associated with a more severe fibro-adipose tissue replacement. The EDB was sufficiently preserved for bulk and signal intensity in 18/22 wheelchair users aged 10-16.6 years.
This study provides a detailed correlation between muscle histology and MRI changes in DMD and demonstrates the value of this imaging technique as a reliable tool for the selection of muscles in patients recruited into clinical trials.
To describe the course, complications, and prognosis of Ullrich congenital muscular dystrophy (UCMD), with special reference to life-changing events, including loss of ambulation, respiratory ...insufficiency, and death.
Review of the case notes of 13 patients with UCMD, aged 15 years or older at last visit, followed up at a tertiary neuromuscular centre, London, UK, from 1977 to 2007. Data collected were age at onset of symptoms, presenting symptoms, mobility, contractures, scoliosis, skin abnormalities, respiratory function, and feeding difficulties.
The mean age at onset of symptoms was 12 months (SD 14 months). Eight patients (61.5%) acquired independent ambulation at a mean age of 1.7 years (SD 0.8 years). Nine patients (69.2%) became constant wheelchair users at a mean age of 11.1 years (SD 4.8 years). Three patients continued to ambulate indoors with assistance. Forced vital capacity (FVC) values were abnormal in all patients from age 6 years. The mean FVC (% predicted) declined at a mean rate of 2.6% (SD 4.1%) yearly. Nine patients (69.2%) started noninvasive ventilation at a mean age of 14.3 years (SD 5.0 years). Two patients died of respiratory insufficiency.
In Ullrich congenital muscular dystrophy (UCMD), the decline in motor and respiratory functions is more rapid in the first decade of life. The deterioration is invariable, but not always correlated with age or severity at presentation. This information should be of help to better anticipate the difficulties encountered by patients with UCMD and in planning future therapeutic trials in this condition.
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