The mechanical and architectural properties of the three-dimensional (3D) tissue microenvironment can have large impacts on cellular behavior and phenotype, providing cells with specialized functions ...dependent on their location. This is especially apparent in macrophage biology where the function of tissue resident macrophages is highly specialized to their location. 3D bioprinting provides a convenient method of fabricating biomaterials that mimic specific tissue architectures. If these printable materials also possess tunable mechanical properties, they would be highly attractive for the study of macrophage behavior in different tissues. Currently, it is difficult to achieve mechanical tunability without sacrificing printability, scaffold porosity, and a loss in cell viability. Here, we have designed composite printable biomaterials composed of traditional hydrogels nanofibrillar cellulose (cellulose) or methacrylated gelatin (gelMA) mixed with porous polymeric high internal phase emulsion (polyHIPE) microparticles. By varying the ratio of polyHIPEs to hydrogel, we fabricate composite hydrogels that mimic the mechanical properties of the neural tissue (0.1–0.5 kPa), liver (1 kPa), lungs (5 kPa), and skin (10 kPa) while maintaining good levels of biocompatibility to a macrophage cell line.
Abstract Paralabral cysts are an increasingly recognized cause of suprascapular nerve (SSN) impingement, often causing insidious weakness in the rotator cuff. Compression at the suprascapular notch ...is often due to the presence of a SLAP tear and leads to pain, weakness, and atrophy of both the supraspinatus and infraspinatus muscles. Compression of the SSN at the spinoglenoid notch leads to weakness and atrophy of the infraspinatus only. Arthroscopic decompression of cysts with repair of labral pathology is typically performed in a sublabral fashion, which may make visualization of the extent of the cyst difficult and places the SSN at increased risk. With any approach, an intimate knowledge of the anatomy of the SSN is vital to safe decompression. We present a surgical technique for decompression of paralabral cysts using an intra-articular transcapsular approach. This approach maximizes visualization and efficiency and reduces possible damage to the SSN.
The arbuscular mycorrhizal (AM) fungal symbiosis is widely hypothesized to have promoted the evolution of land plants from rootless gametophytes to rooted sporophytes during the mid-Palaeozoic ...(480-360 Myr, ago), at a time coincident with a 90% fall in the atmospheric CO(2) concentration (CO(2)(a)). Here we show using standardized dual isotopic tracers ((14)C and (33)P) that AM symbiosis efficiency (defined as plant P gain per unit of C invested into fungi) of liverwort gametophytes declines, but increases in the sporophytes of vascular plants (ferns and angiosperms), at 440 p.p.m. compared with 1,500 p.p.m. CO(2)(a). These contrasting responses are associated with larger AM hyphal networks, and structural advances in vascular plant water-conducting systems, promoting P transport that enhances AM efficiency at 440 p.p.m. CO(2)(a). Our results suggest that non-vascular land plants not only faced intense competition for light, as vascular land floras grew taller in the Palaeozoic, but also markedly reduced efficiency and total capture of P as CO(2)(a) fell.
Many people with multiple sclerosis (MS) have spasticity, generally in the lower limbs, but this symptom is complex and multidimensional and therefore difficult to characterize.
MS spasticity may be ...influenced by moderators, triggers, modifiers, and treatment, all of which can affect objective measures and the subjective experience of spasticity.
MS spasticity can have physical, functional, social, and emotional/psychological impacts as well as long-term consequences that can affect rehabilitation and ultimately reduce health-related quality of life for people with MS.
Given that people with MS may view spasticity differently than their rehabilitation providers, providers should ask patients about their spasticity, including their moderators, triggers, modifiers, experience, impacts, long-term consequences, and effects on quality of life.
This conceptual model provides a framework to improve clinician-patient dialogue, research, and rehabilitation for MS spasticity.
Spasticity is common in multiple sclerosis (MS), often leading to functional limitations and disability. We developed a conceptual model of spasticity in MS integrating expert opinion, recent literature, and experiences of clinicians and people with MS spasticity.
A conceptual model was developed based on a targeted literature review of articles published between 2014 and 2019, followed by input from clinicians, then input from participants with MS spasticity. Multidisciplinary experts on spasticity provided guidance at each step.
Key concepts of the integrated spasticity conceptual model included: moderators; triggers; modifiers; treatment; objective manifestations; subjective experience; physical, functional, social, and emotional/psychological impacts; and long-term consequences. Participants with MS spasticity most frequently endorsed spasms, tightness, and pain as descriptors of spasticity. Some participants with MS spasticity had difficulty distinguishing spasticity from other MS symptoms (e.g. muscle weakness). Some triggers, emotional/psychological impacts, and long-term consequences of spasticity reported by participants with MS spasticity were not previously identified in the published literature.
This conceptual model of spasticity, integrating published literature with the experience of clinicians, people with MS spasticity, and experts, demonstrates the complex, multidimensional nature of MS spasticity. This model may be used to improve clinician-patient dialogue, research, and patient care.
The decision to treat a suspected case of pertussis with antibiotics is usually based on a clinical diagnosis rather than waiting for laboratory confirmation. The current guideline focuses on making ...the clinical diagnosis of pertussis-associated cough in adults and children.
The American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on findings from a systematic review that was recently published on the topic; final grading was reached by consensus according to Delphi methodology. The systematic review was carried out to answer the Key Clinical Question: In patients presenting with cough, how can we most accurately diagnose from clinical features alone those who have pertussis-associated cough as opposed to other causes of cough?
In adults, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 4 clinical features: paroxysmal cough, post-tussive vomiting, inspiratory whooping, and absence of fever. Both paroxysmal cough and absence of fever had high sensitivity (93.2% 95% CI, 83.2-97.4 and 81.8% 95% CI, 72.2-88.7, respectively) and low specificity (20.6% 95% CI, 14.7-28.1 and 18.8% 95% CI, 8.1-37.9). Inspiratory whooping and posttussive vomiting had a low sensitivity (32.5% 95% CI, 24.5-41.6 and 29.8% 95% CI, 18.0-45.2) but high specificity (77.7% 95% CI, 73.1-81.7 and 79.5% 95% CI, 69.4-86.9). In children, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 1 clinical feature in children (0-18 years): posttussive vomiting. Posttussive vomiting in children was only moderately sensitive (60.0% 95% CI, 40.3-77.0) and specific (66.0% 95% CI, 52.5-77.3).
In adults with acute (< 3 weeks) or subacute (3-8 weeks) cough, the presence of whooping or posttussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children with acute (< 4 weeks) cough, posttussive vomiting is suggestive of pertussis but is much less helpful as a clinical diagnostic test. Guideline suggestions are made based upon these findings and conclusions.
Platelets have a pathophysiologic role in the ischemic microvascular environment of acute coronary syndromes. In comparison with platelet activation in normal healthy conditions, less attention is ...given to mechanisms of platelet activation in diseased states. Platelet function and mechanisms of activation in ischemic and reactive oxygen species-rich environments may not be the same as in normal healthy conditions. Extracellular regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase family member activated in hypoxic, reactive oxygen species-rich environments and in response to receptor-signaling mechanisms. Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells after ischemia. We present evidence that platelets express ERK5 and that platelet ERK5 has an adverse effect on platelet activation via selective receptor-dependent and receptor-independent reactive oxygen species-mediated mechanisms in ischemic myocardium.
Using isolated human platelets and a mouse model of myocardial infarction (MI), we found that platelet ERK5 is activated post-MI and that platelet-specific ERK5(-/-) mice have less platelet activation, reduced MI size, and improved post-MI heart function. Furthermore, the expression of downstream ERK5-regulated proteins is reduced in ERK5(-/-) platelets post-MI.
ERK5 functions as a platelet activator in ischemic conditions, and platelet ERK5 maintains the expression of some platelet proteins after MI, leading to infarct expansion. This demonstrates that platelet function in normal healthy conditions is different from platelet function in chronic ischemic and inflammatory conditions. Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment.
One in 26 people develop epilepsy and in these temporal lobe epilepsy (TLE) is common. Many patients display a pattern of neuron loss called hippocampal sclerosis. Seizures usually start in the ...hippocampus but underlying mechanisms remain unclear. One possibility is insufficient inhibition of dentate granule cells. Normally parvalbumin‐immunoreactive (PV) interneurons strongly inhibit granule cells. Humans with TLE display loss of PV interneurons in the dentate gyrus but questions persist. To address this, we evaluated PV interneuron and bouton numbers in California sea lions (Zalophus californianus) that naturally develop TLE after exposure to domoic acid, a neurotoxin that enters the marine food chain during harmful algal blooms. Sclerotic hippocampi were identified by the loss of Nissl‐stained hilar neurons. Stereological methods were used to estimate the number of granule cells and PV interneurons per dentate gyrus. Sclerotic hippocampi contained fewer granule cells, fewer PV interneurons, and fewer PV synaptic boutons, and the ratio of granule cells to PV interneurons was higher than in controls. To test whether fewer boutons was attributable to loss versus reduced immunoreactivity, expression of synaptotagmin‐2 (syt2) was evaluated. Syt2 is also expressed in boutons of PV interneurons. Sclerotic hippocampi displayed proportional losses of syt2‐immunoreactive boutons, PV boutons, and granule cells. There was no significant difference in the average numbers of PV‐ or syt2‐positive boutons per granule cell between control and sclerotic hippocampi. These findings do not address functionality of surviving synapses but suggest reduced granule cell inhibition in TLE is not attributable to anatomical loss of PV boutons.
Sea lions with naturally occurring TLE display proportional losses of parvalbumin boutons and granule cells suggesting reduced inhibition is not attributable to loss of parvalbumin boutons.
ObjectiveThe objective of the current study was to compare the responses to different ex vivo immunogenic challenges between immune cells derived from metabolically healthy subjects with obesity and ...subjects with obesity and type 2 diabetes.Research design and methodsWe recruited 10 metabolically healthy subjects with obesity (Edmonton Obesity Staging System (EOSS) stage 0) and 9 subjects with obesity and type 2 diabetes (EOSS stage 2) aged between 21 years and 70 years and matched for body mass index. Peripheral blood mononuclear cells (PBMCs) were isolated and immune cell phenotypes and ex vivo cytokine production after phytohaemagglutinin (PHA, a T cell mitogen) stimulation were determined. Neutrophil oxidative burst activity was assessed in whole blood.ResultsPBMCs from subjects with stage 2 obesity produced significantly less interleukin (IL)-2, IL-6 and tumour necrosis factor α after PHA stimulation than PBMCs from subjects with stage 0 obesity (all, p<0.05). Subjects with stage 2 obesity also had higher proportions of cytotoxic T cells, activated helper T cells (CD4+CD278+) and inflammatory monocytes (CD14+CRTh2+, all p<0.05). Poststimulation, neutrophils from subjects with stage 2 obesity produced significantly more free radicals, were larger and more granular and had a lower stimulation index (all p<0.05).ConclusionsOur results suggest that compared with obese individuals metabolically healthy individuals with obesity and type 2 diabetes have an impaired neutrophil function and T cell response on challenge despite having a T cell population expressing more activation markers which may be partly responsible for the increased prevalence of infection reported in this population.
Ecosystem effects of invertebrate fisheries Eddy, Tyler D; Lotze, Heike K; Fulton, Elizabeth A ...
Fish and fisheries (Oxford, England),
January 2017, 2017-01-00, 20170101, Letnik:
18, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Since the 1950s, invertebrate fisheries catches have rapidly expanded globally to more than 10 million tonnes annually, with twice as many target species, and are now significant contributors to ...global seafood provision, export, trade and local livelihoods. Invertebrates play important and diverse functional roles in marine ecosystems, yet the ecosystem effects of their exploitation are poorly understood. Using 12 ecosystem models distributed worldwide, we analysed the trade‐offs of various invertebrate fisheries and their ecosystem effects as well as ecological indicators. Although less recognized for their contributions to marine food webs, our results show that the magnitude of trophic impacts of invertebrates on other species of commercial and conservation interest is comparable with those of forage fish. Generally, cephalopods showed the strongest ecosystem effects and were characterized by a strong top‐down predatory role. Lobster, and to a lesser extent, crabs, shrimp and prawns, also showed strong ecosystem effects, but at lower trophic levels. Benthic invertebrates, including epifauna and infauna, also showed considerable ecosystem effects, but with strong bottom‐up characteristics. In contrast, urchins, bivalves, and gastropods showed generally lower ecosystem effects in our simulations. Invertebrates also strongly contributed to benthic–pelagic coupling, with exploitation of benthic invertebrates impacting pelagic fishes and vice versa. Finally, on average, invertebrates produced maximum sustainable yield at lower levels of depletion (~45%) than forage fish (~65%), highlighting the need for management targets that avoid negative consequences for target species and marine ecosystems as a whole.
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