Stroke increases ischemia-related decreases in motor unit discharge rates

Following stroke, hyperexcitable sensory pathways, such as the group III/IV afferents that are sensitive to ischemia, may inhibit paretic motor neurons during exercise. We quantified the effects of whole leg ischemia on paretic vastus lateralis motor unit firing rates during submaximal isometric contractions. Ten chronic stroke survivors (>1 yr poststroke) and 10 controls participated. During conditions of whole leg occlusion, the discharge timings of motor units were identified from decomposition of high-density surface electromyography signals during repeated submaximal knee extensor contractions. Quadriceps resting twitch responses and near-infrared spectroscopy measurements of oxygen saturation as an indirect measure of blood flow were made. There was a greater decrease in paretic motor unit discharge rates during the occlusion compared with the controls (average decrease for stroke and controls, 12.3 ± 10.0% and 0.1 ± 12.4%, respectively; P < 0.001). The motor unit recruitment thresholds did not change with the occlusion (stroke: without occlusion, 11.68 ± 5.83%MVC vs. with occlusion, 11.11 ± 5.26%MVC; control: 11.87 ± 5.63 vs. 11.28 ± 5.29%MVC). Resting twitch amplitudes declined similarly for both groups in response to whole leg occlusion (stroke: 29.16 ± 6.88 vs. 25.75 ± 6.78 Nm; control: 38.80 ± 13.23 vs 30.14 ± 9.64 Nm). Controls had a greater exponential decline (lower time constant) in oxygen saturation compared with the stroke group (stroke time constant, 22.90 ± 10.26 min vs. control time constant, 5.46 ± 4.09 min; P < 0.001). Ischemia of the muscle resulted in greater neural inhibition of paretic motor units compared with controls and may contribute to deficient muscle activation poststroke. NEW & NOTEWORTHY Hyperexcitable inhibitory sensory pathways sensitive to ischemia may play a role in deficient motor unit activation post stroke. Using high-density surface electromyography recordings to detect motor unit firing instances, we show that ischemia of the exercising muscle results in greater inhibition of paretic motor unit firing rates compared with controls. These findings are impactful to neurophysiologists and clinicians because they implicate a novel mechanism of force-generating impairment poststroke that likely exacerbates baseline weakness

Roaring high and low: composition and possible functions of the Iberian stag's vocal repertoire

We provide a detailed description of the rutting vocalisations of free-ranging male Iberian deer (Cervus elaphus hispanicus, Hilzheimer 1909), a geographically isolated and morphologically differentiated subspecies of red deer Cervus elaphus. We combine spectrographic examinations, spectral analyses and automated classifications to identify different call types, and compare the composition of the vocal repertoire with that of other red deer subspecies. Iberian stags give bouts of roars (and more rarely, short series of barks) that are typically composed of two different types of calls. Long Common Roars are mostly given at the beginning or at the end of the bout, and are characterised by a high fundamental frequency (F0) resulting in poorly defined formant frequencies but a relatively high amplitude. In contrast, Short Common Roars are typically given in the middle or at the end of the bout, and are characterised by a lower F0 resulting in relatively well defined vocal tract resonances, but low amplitude. While we did not identify entirely Harsh Roars (as described in the Scottish red deer subspecies (Cervus elaphus scoticus), a small percentage of Long Common Roars contained segments of deterministic chaos. We suggest that the evolution of two clearly distinct types of Common Roars may reflect divergent selection pressures favouring either vocal efficiency in high pitched roars or the communication of body size in low-pitched, high spectral density roars highlighting vocal tract resonances. The clear divergence of the Iberian red deer vocal repertoire from those of other documented European red deer populations reinforces the status of this geographical variant as a distinct subspecies

Pedogenic pathways and deep weathering controls on soil organic carbon in Pacific Northwest forest soils

Characterizing the distribution and dynamics of organic carbon in soil is critical for quantifying changes in the global carbon cycle. In particular, weathering controls on near-surface and deep (>1 m) soil organic carbon (SOC) dynamics have been proposed but limited data prevents us from predicting SOC over topographically complex landscapes and quantifying how changes in climate and perturbations, such as wildfire or land management, influence SOC stocks. To advance our understanding of how weathering alters soil geochemistry and influences SOC storage, we synthesize previous data with a new analysis of the Siuslaw River soil chronosequence from terraces in the Oregon Coast Range, a region that harbors the richest SOC inventories in the continental US. We analyze how the relationships between soil geochemistry, physical properties, and SOC storage vary with weathering status and pathways across soils that span 0.041 to 990 kyr and vary in depth from 1 m to >10 m. To distinguish the key properties and processes influencing SOC storage at different depths, we break our analysis into three depth intervals: 0–30, 30–100, and >100 cm. Our results suggest that the processes that control SOC stocks vary systematically with time and depth owing to weathering impacts on soil properties and pedogenic development. At 30 kyr we observe a peak in SOC stock in the top 100 cm coincident with a peak in oxalate extractable Al and Fe concentrations, representing secondary poorly crystalline minerals, which is consistent with previous studies. We also observe a decline in shallow SOC stock for >30 kyr soils as poorly crystalline minerals are replaced by more stable crystalline forms and soils become clay dominated. At 120 kyr, SOC below 100 cm starts to contribute significantly to the total SOC profile inventory and by 990 kyr, this fraction composes >40% of the total SOC stock. Taken together, our results indicate that total SOC stock increases with soil age as the increased intensity of bedrock weathering deepens the critical zone, creating accommodation space for deep SOC storage. These findings reveal the intimate link between poorly crystalline minerals and SOC and suggest that systematic analysis of soil development in the critical zone provides a first-order constraint on SOC stocks

LiQD Cornea: Pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation

Transplantation with donor corneas is the mainstay for treating corneal blindness, but a severe worldwide shortage necessitates the development of other treatment options. Corneal perforation from infection or inflammation is sealed with cyanoacrylate glue. However, the resulting cytotoxicity requires transplantation. LiQD Cornea is an alternative to conventional corneal transplantation and sealants. It is a cell-free, liquid hydrogel matrix for corneal regeneration, comprising short collagen-like peptides conjugated with polyethylene glycol and mixed with fibrinogen to promote adhesion within tissue defects. Gelation occurs spontaneously at body temperature within 5 min. Light exposure is not required-particularly advantageous because patients with corneal inflammation are typically photophobic. The self-assembling, fully defined, synthetic collagen analog is much less costly than human recombinant collagen and reduces the risk of immune rejection associated with xenogeneic materials. In situ gelation potentially allows for clinical application in outpatient clinics instead of operating theaters, maximizing practicality, and minimizing health care costs

Plastic ingestion is an underestimated cause of death for southern hemisphere albatrosses

Albatrosses are among the world’s most imperiled vertebrates, with 73% ofspecies threatenedwith extinction. Ingestion of plastic is awell-recognized threatamong threeNorth Pacific species, but lesser known in the southern hemisphere,where it is considered a minor threat. As plastic entering the ocean is increasingwhile albatross populations decline, the threat of ocean plastic to albatrosspopulations may be underestimated. We present case studies of 107 beach-castalbatrosses of twelve species, received by wildlife hospitals in Australia and NewZealand, and estimate plastic ingestion and mortality rates for albatrosses in thesouthern hemisphere. Ingested plastic was present in 5.6% of individuals, andthe cause of death in half of these cases. We estimate ingestion of plastic maycause 3.4–17.5% of nearshoremortalities and is worth consideration as a substantialthreat to albatross populations. We provide clinical findings and “checklist”methodologies for identifying potential cases of foreign-body gastrointestinalobstruction. We suggest practical policy responses, empowering decision makersto reduce albatross mortality from anthropogenic sources

Quantifying erosion rates and weathering pathways that maximize soil organic carbon storage

Primary minerals that enter soils through bedrock weathering and atmospheric deposition can generate poorly crystalline minerals (PCM) that preferentially associate with soil organic carbon (SOC). These associations hinder microbial decomposition and the release of CO₂ from soils to the atmosphere, making them a critical geochemical control on terrestrial carbon abundance and persistence. Studies that explore these relationships are typically derived from soil chronosequences that experience negligible erosion and thus do not readily translate to eroding landscapes. Here, we propose a theoretical framework to estimate steady-state PCM density and stocks for hilly and mountainous settings by coupling geochemical and geomorphic mass balance equations that account for soil production from bedrock and dust, soil erosion, PCM formation from weathering, and the transformation of PCMs into crystalline phases. We calculate an optimal erosion rate for maximum PCM abundance that arises because PCMs are limited by insufficient weathering at faster erosion rates and loss via “ripening” into more crystalline forms at slower erosion rates. The optimal erosion rate for modeled hilltop soil is modulated by reaction rate constants that govern the efficiency of primary mineral weathering and PCM ripening. By comparing our analysis with global compilations of erosion and soil production rates derived from cosmogenic nuclides, we show that landscapes with slow-to-moderate erosion rates may be optimal for harboring abundant PCM stocks that can facilitate SOC sequestration and limit turnover. Given the growing array of erosion-topography metrics and the widespread availability of high-resolution topographic data, our framework demonstrates how weathering and critical zone processes can be coupled to inform landscape prioritization for persistent SOC storage potential across a broad range of spatial and temporal scales

Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission

"Diffuse" gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived "average" spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S. Cheng and G. E. Romero. More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm

Tension-Compression Loading with Chemical Stimulation Results in Additive Increases to Functional Properties of Anatomic Meniscal Constructs

Objective: This study aimed to improve the functional properties of anatomically-shaped meniscus constructs through simultaneous tension and compression mechanical stimulation in conjunction with chemical stimulation. Methods: Scaffoldless meniscal constructs were subjected to simultaneous tension and compressive stimulation and chemical stimulation. The temporal aspect of mechanical loadingwas studied by employing two separate five day stimulation periods. Chemical stimulation consisted of the application of a catabolic GAG-depleting enzyme, chondroitinase ABC (C-ABC), and an anabolic growth factor, TGF-b1. Mechanical and chemical stimulation combinations were studied through a full-factorial experimental design and assessed for histological, biochemical, and biomechanical properties following 4 wks of culture. Results: Mechanical loading applied from days 10–14 resulted in significant increases in compressive, tensile, and biochemical properties of meniscal constructs. When mechanical and chemical stimuliwere combined significant additive increases in collagen per wet weight (4-fold), compressive instantaneous (3-fold) and relaxation (2-fold) moduli, and tensile moduli in the circumferential (4-fold) and radial (6-fold) directions were obtained. Conclusions: This study demonstrates that a stimulation regimen of simultaneous tension and compression mechanical stimulation, C-ABC, and TGF-b1 is able to create anatomic meniscus constructs replicating the compressive mechanica

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

BACKGROUND Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizu- mab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. METHODS In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approxi- mately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. RESULTS Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, –7.6 to 8.2; nominal P=0.94). CONCLUSIONS In this randomized trial involving hospitalized patients with severe Covid-19 pneu- monia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann–La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov num- ber, NCT04320615.