Scleroderma is a chronic, progressive autoimmune disease that often presents with multiorgan involvement. Cardiac manifestations are common and include microvascular coronary artery disease, ...conduction abnormalities, autonomic insufficiency, and pericardial effusions. Although rare, pericardial effusions may progress and lead to cardiac tamponade. Patients diagnosed with scleroderma can be further prognosticated based on the presence of serologic scleroderma-specific antibodies. The anti-RNA polymerase III autoantibody (anti-RNAP3) is associated with an aggressive subtype of scleroderma. Looking at the current literature, no association has been reported between anti-RNAP3 and the development of cardiac tamponade in patients with underlying scleroderma. We discuss a unique case of a patient with scleroderma who was found to be anti-RNAP3 positive and signs of cardiac tamponade. This case illustrates the importance of an expeditious diagnosis and timely interventions to treat cardiac tamponade. Additionally, we share a rare but important association between anti-RNAP3 and the formation of tamponade physiology in scleroderma.
Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo ...human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46-48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer's) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.
Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. ...Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse.
Neural oscillations as important information carrier in the brain, are increasingly interpreted as transient bursts rather than as sustained oscillations. Short (<150 ms) bursts of beta-waves (15-30 ...Hz) have been documented in humans, monkeys and mice. These events were correlated with memory, movement and perception, and were even suggested as the primary ingredient of all beta-band activity. However, a method to measure these short-lived events in real-time and to investigate their impact on behaviour is missing. Here we present a real-time data analysis system, capable to detect short narrowband bursts, and demonstrate its usefulness to increase the beta-band burst-rate in rats. This neurofeedback training induced changes in overall oscillatory power, and bursts could be decoded from the movement of the rats, thus enabling future investigation of the role of oscillatory bursts.
The use of functional nanomaterials is a common strategy to improve the mechanical and electrochemical properties of silicon anodes for secondary lithium‐ion cells. Here, we report the preparation of ...a structurally stable composite material with a unique morphology comprising small‐size silicon particles and especially branched carbonaceous nanofibers and the analysis of its cycling performance by galvanostatic measurements. This two‐phase composite was obtained from pyrolysis of blended silicon/cyanamide powders. The conversion of cyanamide to turbostratic carbon, rather than graphitic carbon nitride, was unexpected and appears to be catalyzed by accidental iron nanoparticles. Although the carbon content after pyrolysis was only about 7 %, half‐cells using electrodes containing the silicon/carbon composite outperformed other silicon‐based anode materials tested herein in terms of cyclability. After 300 cycles, they delivered two times higher capacity (>1.7 A h gsilicon−1 at C/10 and >0.5 A h gsilicon−1 at 1C in the 600–30 mV range when operated in constant current mode) than cells of similar loading with pristine silicon particles. The average fade rate per cycle was around 0.1 % between the 10th and 300th cycles, which is notable considering that the electrode structure and composition have not yet been optimized for battery applications.
Long live the battery: A structurally stable anode nanocomposite with a unique morphology comprising silicon particles of average size ≤50 nm and especially branched carbonaceous fibers synthesized by pyrolysis of silicon/cyanamide blends is presented. This new two‐phase material has promising properties toward next generation lithium‐ion batteries.
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