Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the ...experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.
Embryonic stem (ES) cell‐derived neural lineage cells were transplanted into the spinal cord 9 days after injury. The results of this study provide the first evidence that cellular support for axonal ...outgrowth through the glial scar may be a property of the nerve glial antigen 2 (NG2)‐positive cell, suggesting that various cell types expressing NG2 might stimulate axonal growth even after the acute phase of spinal cord injury is over.
The glial scar resulting from spinal cord injury is rich in chondroitin sulfate proteoglycan (CSPG), a formidable barrier to axonal regeneration. We explored the possibility of breaching that barrier by first examining the scar in a functional in vitro model. We found that embryonic stem cell‐derived neural lineage cells (ESNLCs) with prominent expression of nerve glial antigen 2 (NG2) survived, passed through an increasingly inhibitory gradient of CSPG, and expressed matrix metalloproteinase 9 (MMP‐9) at the appropriate stage of their development. Outgrowth of axons from ESNLCs followed because the migrating cells sculpted pathways in which CSPG was degraded. The degradative mechanism involved MMP‐9 but not MMP‐2. To confirm these results in vivo, we transplanted ESNLCs directly into the cavity of a contused spinal cord 9 days after injury. A week later, ESNLCs survived and were expressing both NG2 and MMP‐9. Their axons had grown through long distances (>10 mm), although they preferred to traverse white rather than gray matter. These data are consistent with the concept that expression of inhibitory CSPG within the injury scar is an important impediment to regeneration but that NG2+ progenitors derived from ESNLCs can modify the microenvironment to allow axons to grow through the barrier. This beneficial action may be partly due to developmental expression of MMP‐9. We conclude that it might eventually be possible to encourage axonal regeneration in the human spinal cord by transplanting ESNLCs or other cells that express NG2.
Brothers volcano, located on the Kermadec arc north of New Zealand, hosts two geochemically distinct hydrothermal systems. The NW Caldera and Upper Cone hydrothermal fields exhibit distinct fluid ...compositions that are significantly influenced by seawater and magmatic volatiles, respectively. In this study, we present trace metal chemistry and sulfur isotope compositions of pyrite within hydrothermally altered volcanic rocks recovered from drill cores at depths of up to 429 m below the seafloor collected during the International Ocean Discovery Program’s Expedition 376. Magmatic volatile-influenced alteration resulting in pyrophyllite ± natroalunite assemblages occurs at the Upper Cone and at the NW Caldera below 189 m. At the NW Caldera, a later seawater-derived hydrothermal fluid overprints magmatic volatile alteration forming chlorite-rich alteration. Pyrite at the Upper Cone is fine-grained, euhedral and enriched in Cu, As, Sb, Pb and Pt and has an average δ
34
S composition of − 5.5 ± 2.9‰ (1σ,
n
= 32). In contrast, pyrite associated with pyrophyllite-rich alteration at the older NW Caldera site is coarse-grained, subhedral and has higher Co, Se, Te, and Bi contents but a comparable average δ
34
S value of -4.8 ± 5.5‰ (1σ,
n
= 26). The difference in trace metal content between pyrite from pyrophyllite ± natroalunite assemblages at the NW Caldera and Upper Cone site indicates a change in the trace metal enrichment signature of pyrite with the age of the hydrothermal system. Pyrite from chlorite-rich alteration (NW Caldera) is depleted in Cu, Te and Bi relative to all magmatic volatile-influenced pyrite but has a similar average δ
34
S composition of − 4.6 ± 3.5‰ (1σ,
n
=
20
). The similarity in trace metal enrichment signature and average δ
34
S composition of pyrite, regardless of associated alteration mineral assemblage shows that the initial magmatic volatile trace metal signature and sulfur isotope composition of pyrite is preserved during fluid overprinting. The lower content of Cu, Te, and Bi in pyrite from chlorite-rich alteration confirms the importance of seawater-derived hydrothermal fluids in metal mobilization and consequent formation of hydrothermal precipitates at the seafloor.
ABSTRACT
Introduction: Therapeutic trials in Duchenne muscular dystrophy (DMD) often exclude non‐ambulatory individuals. Here we establish optimal and reliable assessments in a multicenter trial. ...Methods: Non‐ambulatory boys/men with DMD (N = 91; 16.7 ± 4.5 years of age) were assessed by trained clinical evaluators. Feasibility (percentage completing task) and reliability intraclass correlation coefficients (ICCs) between morning and afternoon tests were measured. Results: Forced vital capacity (FVC), assessed in all subjects, showed a mean of 47.8 ± 22% predicted (ICC 0.98). Brooke Upper Extremity Functional Rating (Brooke) and Egen Klassifikation (EK) scales in 100% of subjects showed ICCs ranging from 0.93 to 0.99. Manual muscle testing, range of motion, 9‐hole peg test, and Jebsen‐Taylor Hand Function Test (JHFT) demonstrated varied feasibility (99% to 70%), with ICCs ranging from 0.99 to 0.64. We found beneficial effects of different forms of corticosteroids for the Brooke scale, percent predicted FVC, and hand and finger strength. Conclusions: Reliable assessment of non‐ambulatory boys/men with DMD is possible. Clinical trials will have to consider corticosteroid use. Muscle Nerve 51: 522–532, 2015
Chronic neuropathic pain is a debilitating disease process associated with several medical disorders. Different from pain caused by inflammation, neuropathic pain is a diffuse pain disorder often ...found to be recalcitrant to the limited medical treatments available. Intractable nerve pain may benefit from other therapies capable of longer-lasting pain coverage or greater efficacy. A growing number of reports have emerged suggesting a role for stem cells as a cellular delivery source with neuroprotective agents opposing the effects of nerve damage. Here, the authors review the current experimental therapies examining the use of stem cells for the treatment of neuropathic pain disorders.
In this review, we have documented some current research trends in rodent models of spinal cord injury. We have also catalogued the treatments used in studies published between October 2002 and ...November 2003, with special attention given to studies in which treatments were delayed for at least 4 days after injury.
Most spinal cord injury studies are performed with one of three general injury models: transection, compression, or contusion. Although most treatments are begun immediately after injury, a growing number of studies have used delayed interventions. Mice and the genetic tools they offer are gaining in popularity. Some researchers are setting their sights beyond locomotion, to issues more pressing for people with spinal cord injury (especially bladder function and pain).
Delayed treatment protocols may extend the window of opportunity for treatment of spinal cord injury, whereas continued progress in the prevention of secondary cell death will reduce the severity of new cases. The use of mice will hopefully accelerate progress towards useful regeneration in humans. Researchers must improve cross-study comparability to allow balanced decisions about potentially useful treatments.
Profiling gene expression in endothelial cells advances the understanding of normal vascular physiology and disease processes involving angiogenesis. However, endothelial cell purification has been ...challenging because of the difficulty of isolating cells and their low abundance. Here we examine gene expression in endothelial cells freshly isolated from lung capillaries after in vivo labeling with fluorescent cationic liposomes and purification by fluorescence-activated cell sorting (FACS). Of the 39,000 genes and expressed sequence tags evaluated on custom oligonucleotide arrays, 555 were enriched in endothelial cell fraction. These included familiar endothelial cell-associated genes such as VEGF, VEGF receptor (VEGFR)-1, VEGFR-2, angiopoietin-2, Tie1, Tie2, Edg1 receptor, VE-cadherin, claudin 5, connexin37, CD31, and CD34. Also enriched were genes in semaphorin/neuropilin (Sema3c and Nrp1), ephrin/Eph (ephrin A1, B1, B2, and EphB4), delta/notch (Hey1, Jagged 2, Notch 1, Notch 4, Numb, and Siah1b), and Wingless (Frizzled-4 and Tle1) signaling pathways involved in vascular development and angiogenesis. Expression of representative genes in alveolar capillary endothelial cells was verified by immunohistochemistry. Such expression reflects features that endothelial cells of normal lung capillaries have in common with embryonic and growing blood vessels. About half of the enriched genes, including exostosin 2, lipocalin 7, phospholipid scramblase 2, pleckstrin 2, protocadherin 1, Ryk, scube 1, serpinh1, SNF-related kinase, and several tetraspanins, had little or no previous association with endothelial cells. This approach can readily be used to profile genes expressed in blood vessels in tumors, chronic inflammation, and other sites in which endothelial cells avidly take up cationic liposomes.
We aimed to systematically review the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis (UC).
A literature ...search to April 2011 was performed to identify all randomized trials studying UFH or LMWH use in patients with UC. The Cochrane Risk of Bias Tool was used to assess study quality.
LMWH administered subcutaneously showed no benefit over placebo for any outcome, including clinical remission, and clinical, endoscopic, or histological improvement. High-dose LMWH administered via an extended colon-release tablet demonstrated benefit over placebo for clinical remission (odds ratio OR 2.73; 95% confidence interval CI 1.32-5.67; P = 0.007), clinical improvement (OR 2.99; 95% CI 1.30-6.87; P = 0.01), and endoscopic improvement (OR 2.25; 95% CI 1.01-5.01; P = 0.05) but not endoscopic remission or histologic improvement. LMWH was not beneficial when added to standard therapy for clinical remission, clinical improvement, endoscopic remission, or endoscopic improvement. One study examining UFH versus corticosteroids for the treatment of severe UC demonstrated the inferiority of UFH for clinical improvement. More patients assigned to UFH had rectal hemorrhage as an adverse event.
LMWH administered by extended colon-release tablets may be effective for the treatment of active UC. This benefit needs to be confirmed by further randomized controlled studies. The same benefits were not seen when LMWH was administered subcutaneously at lower doses. There is no evidence to support the use of UFH for the treatment of active UC.
Functional electrical stimulation (FES) can restore control and offset atrophy to muscles after neurological injury. However, FES has not been considered as a method for enhancing CNS regeneration. ...This paper demonstrates that FES dramatically enhanced progenitor cell birth in the spinal cord of rats with a chronic spinal cord injury (SCI). A complete SCI at thoracic level 8/9 was performed on 12 rats. Three weeks later, a FES device to stimulate hindlimb movement was implanted into these rats. Twelve identically-injured rats received inactive FES implants. An additional control group of uninjured rats were also examined. Ten days after FES implantation, dividing cells were marked with bromodeoxyuridine (BrdU). The “cell birth” subgroup (half the animals in each group) was sacrificed immediately after completion of BrdU administration, and the “cell survival” subgroup was sacrificed 7 days later. In the injured “cell birth” subgroup, FES induced an 82–86% increase in cell birth in the lumbar spinal cord. In the injured “cell survival” subgroup, the increased lumbar newborn cell counts persisted. FES doubled the proportion of the newly-born cells which expressed nestin and other markers suggestive of tripotential progenitors. In uninjured rats, FES had no effect on cell birth/survival. This report suggests that controlled electrical activation of the CNS may enhance spontaneous regeneration after neurological injuries.
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