The COVID-19 pandemic does not fit into prevailing Post-traumatic Stress Disorder (PTSD) models, or diagnostic criteria, yet emerging research shows traumatic stress symptoms as a result of this ...ongoing global stressor. Current pathogenic event models focus on past, and largely direct, trauma exposure to certain kinds of life-threatening events. Yet, traumatic stress reactions to future, indirect trauma exposure, and non-Criterion A events exist, suggesting COVID-19 is also a traumatic stressor which could lead to PTSD symptomology. To examine this idea, we asked a sample of online participants (N = 1,040), in five western countries, to indicate the COVID-19 events they had been directly exposed to, events they anticipated would happen in the future, and other forms of indirect exposure such as through media coverage. We then asked participants to complete the Posttraumatic Stress Disorder Checklist-5, adapted to measure pre/peri/post-traumatic reactions in relation to COVID-19. We also measured general emotional reactions (e.g., angry, anxious, helpless), well-being, psychosocial functioning, and depression, anxiety, and stress symptoms. We found participants had PTSD-like symptoms for events that had not happened and when participants had been directly (e.g., contact with virus) or indirectly exposed to COVID-19 (e.g., via media). Moreover, 13.2% of our sample were likely PTSD-positive, despite types of COVID-19 "exposure" (e.g., lockdown) not fitting DSM-5 criteria. The emotional impact of "worst" experienced/anticipated events best predicted PTSD-like symptoms. Taken together, our findings support emerging research that COVID-19 can be understood as a traumatic stressor event capable of eliciting PTSD-like responses and exacerbating other related mental health problems (e.g., anxiety, depression, psychosocial functioning, etc.). Our findings add to existing literature supporting a pathogenic event memory model of traumatic stress.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Traumatic brain injury triggers neuroinflammation that may contribute to progressive neurodegeneration. We investigated patterns of recruitment of astrocytes and microglia to inflammation after brain ...trauma by firstly characterising expression profiles over time of marker genes following TBI, and secondly by monitoring glial morphologies reflecting inflammatory responses in a rat model of traumatic brain injury (i.e. the lateral fluid percussion injury). Gene expression profiles revealed early elevation of expression of astrocytic marker glial fibrillary acidic protein relative to microglial marker allograft inflammatory factor 1 (also known as ionized calcium-binding adapter molecule 1). Adult rat brains collected at day 7 after injury were processed for immunohistochemistry with allograft inflammatory factor 1, glial fibrillary acidic protein and complement C3 (marker of bad/disruptive astrocytic A1 phenotype). Astrocytes positive for glial fibrillary acidic protein and complement C3 were significant increased in the injured cortex and displayed more complex patterns of arbourisation with significantly increased bifurcations. Our observations suggested that traumatic brain injury changed the phenotype of microglia from a ramified appearance with long, thin, highly branched processes to a swollen amoeboid shape in the injured cortex. These findings suggest differential glial activation with astrocytes likely undergoing strategic changes in morphology and function. Whilst a detailed analysis is needed of temporal patterns of glial activation, ours is the first evidence of a role for the bad/disruptive astrocytic A1 phenotype in an open head model of traumatic brain injury.
This book critically examines the significance of gender, race and sexuality to wars waged by liberal states. Drawing on original field-research with British soldiers, it offers insights into how ...their everyday experiences are shaped by, and shape, a politics of gender, race and sexuality that not only underpins power relations in the military, but the geopolitics of wars waged by liberal states. Linking the politics of daily life to the international is an intervention into international relations (IR) and security studies because instead of overlooking the politics of the everyday, this book insists that it is vital to explore how geopolitical events and practices are co-constituted, reinforced and contested by it. By utilising insights from Michel Foucault, the book explores how shared and collectively mediated knowledge on gender, race and sexuality facilitates certain claims about the nature of governing in liberal states and about why and how such states wage war against 'illiberal' ones in pursuit of global peace and security. The book also develops post-structural work in international relations by urging scholars interested in the linguistic construction of geopolitics to consider the ways in which bodies, objects and architectures also reinforce particular ideas about war, identity and statehood.
Carrier mobility in doped conjugated polymers is limited by Coulomb interactions with dopant counterions. This complicates studying the effect of the dopant's oxidation potential on carrier ...generation because different dopants have different Coulomb interactions with polarons on the polymer backbone. Here, dodecaborane (DDB)‐based dopants are used, which electrostatically shield counterions from carriers and have tunable redox potentials at constant size and shape. DDB dopants produce mobile carriers due to spatial separation of the counterion, and those with greater energetic offsets produce more carriers. Neutron reflectometry indicates that dopant infiltration into conjugated polymer films is redox‐potential‐driven. Remarkably, X‐ray scattering shows that despite their large 2‐nm size, DDBs intercalate into the crystalline polymer lamellae like small molecules, indicating that this is the preferred location for dopants of any size. These findings elucidate why doping conjugated polymers usually produces integer, rather than partial charge transfer: dopant counterions effectively intercalate into the lamellae, far from the polarons on the polymer backbone. Finally, it is shown that the IR spectrum provides a simple way to determine polaron mobility. Overall, higher oxidation potentials lead to higher doping efficiencies, with values reaching 100% for driving forces sufficient to dope poorly crystalline regions of the film.
The effect of dopant redox potential on the chemical doping of conjugated polymers is studied using dodecaborane dopants whose potential can be tuned at constant size and shape. The 2‐nm dodecaborane clusters preferentially intercalate into the polymer crystalline lamellae, and the doping efficiency increases with redox potential. The isolation of the counteranion from the hole leads to improved carrier mobility.
Using a novel microfluidic chamber that allows the isolation of axons without contamination by nonaxonal material, we have for the first time purified mRNA from naive, matured CNS axons, and ...identified the presence of >300 mRNA transcripts. We demonstrate that the transcripts are axonal in nature, and that many of the transcripts present in uninjured CNS axons overlap with those previously identified in PNS injury-conditioned DRG axons. The axonal transcripts detected in matured cortical axons are enriched for protein translational machinery, transport, cytoskeletal components, and mitochondrial maintenance. We next investigated how the axonal mRNA pool changes after axotomy, revealing that numerous gene transcripts related to intracellular transport, mitochondria and the cytoskeleton show decreased localization 2 d after injury. In contrast, gene transcripts related to axonal targeting and synaptic function show increased localization in regenerating cortical axons, suggesting that there is an increased capacity for axonal outgrowth and targeting, and increased support for synapse formation and presynaptic function in regenerating CNS axons after injury. Our data demonstrate that CNS axons contain many mRNA species of diverse functions, and suggest that, like invertebrate and PNS axons, CNS axons synthesize proteins locally, maintaining a degree of autonomy from the cell body.
Abstract Objective To assess and characterize the temporal variation in ovarian cancer incidence and mortality by age within countries in the Americas, Europe, Asia, and Oceania. Methods/Materials ...Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in the United States (U.S.) were used to assess ovarian cancer incidence rates (1998–2008) and mortality rates, (1988–2007 for 12-month survival, 1988–2006 for 24-month survival, and 1988–2003 for 60-month survival), stratified by age at diagnosis. Data from GLOBOCAN were used to calculate country-specific incidence rates for 2010 and 2020 and case-fatality rates for 2010. Results A statistically significant decrease in Annual Percent Change (APC) of ovarian cancer incidence was observed in the U.S. for all women (− 1.03%), among women who were diagnosed at < 65 years of age (− 1.09%) and among women who were diagnosed at ≥ 65 years of age (− 0.95%). There was a statistically significant increase in the observed APC for survival at 12-months (0.19%), 24-months (0.58%), and 60-months (0.72%) for all women; however, 5-year survival for advanced stage (III or IV) disease was low at less than 50% for women < 65 years and less than 30% for women ≥ 65 years. Global results showed a wide range in ovarian cancer incidence rates, with China exhibiting the lowest rates and the Russian Federation and the United Kingdom exhibiting the highest rates. Conclusions Ovarian cancer survival has shown modest improvement from a statistical perspective in the U.S. However, it is difficult to ascertain how clinically relevant these improvements are at the population or patient level.
One of the most effective ways to tune the electronic properties of conjugated polymers is to dope them with small‐molecule oxidizing agents, creating holes on the polymer and molecular anions. ...Undesirably, strong electrostatic attraction from the anions of most dopants localizes the holes created on the polymer, reducing their mobility. Here, a new strategy utilizing a substituted boron cluster as a molecular dopant for conjugated polymers is employed. By designing the cluster to have a high redox potential and steric protection of the core‐localized electron density, highly delocalized polarons with mobilities equivalent to films doped with no anions present are obtained. AC Hall effect measurements show that P3HT films doped with these boron clusters have conductivities and polaron mobilities roughly an order of magnitude higher than films doped with F4TCNQ, even though the boron‐cluster‐doped films have poor crystallinity. Moreover, the number of free carriers approximately matches the number of boron clusters, yielding a doping efficiency of ≈100%. These results suggest that shielding the polaron from the anion is a critically important aspect for producing high carrier mobility, and that the high polymer crystallinity required with dopants such as F4TCNQ is primarily to keep the counterions far from the polymer backbone.
Chemical doping of conjugated polymers produces polarons via charge transfer. The counterions produced using traditional small‐molecule dopants are proximal to the polaron and thus limit polaron mobility due to Coulomb attraction. A boron cluster‐based dopant that shields the charge on the counterion from the polaron is designed. This allows the creation of nearly 100% free polarons with high mobility.
Neutrophil-mediated secondary tissue injury underlies acute respiratory distress syndrome (ARDS) and progression to multi-organ-failure (MOF) and death, processes linked to COVID-19-ARDS. This ...secondary tissue injury arises from dysregulated neutrophils and neutrophil extracellular traps (NETs) intended to kill pathogens, but instead cause cell-injury. Insufficiency of pleiotropic therapeutic approaches delineate the need for inhibitors of dysregulated neutrophil-subset(s) that induce subset-specific apoptosis critical for neutrophil function-shutdown. We hypothesized that neutrophils expressing the pro-survival dual endothelin-1/VEGF-signal peptide receptor, DEspR, are apoptosis-resistant like DEspR+ cancer-cells, hence comprise a consequential pathogenic neutrophil-subset in ARDS and COVID-19-ARDS. Here, we report the significant association of increased peripheral DEspR+CD11b+ neutrophil-counts with severity and mortality in ARDS and COVID-19-ARDS, and intravascular NET-formation, in contrast to DEspR- neutrophils. We detect DEspR+ neutrophils and monocytes in lung tissue patients in ARDS and COVID-19-ARDS, and increased neutrophil RNA-levels of DEspR ligands and modulators in COVID-19-ARDS scRNA-seq data-files. Unlike DEspR- neutrophils, DEspR+CD11b+ neutrophils exhibit delayed apoptosis, which is blocked by humanized anti-DEspR-IgG4
antibody, hu6g8, in ex vivo assays. Ex vivo live-cell imaging of Rhesus-derived DEspR+CD11b+ neutrophils showed hu6g8 target-engagement, internalization, and induction of apoptosis. Altogether, data identify DEspR+CD11b+ neutrophils as a targetable 'rogue' neutrophil-subset associated with severity and mortality in ARDS and COVID-19-ARDS.
Throughout history, the yeast
has played a central role in human society due to its use in food production and more recently as a major industrial and model microorganism, because of the many genetic ...and genomic tools available to probe its biology. However,
has proven difficult to engineer to expand the carbon sources it can utilize, the products it can make, and the harsh conditions it can tolerate in industrial applications. Other yeasts that could solve many of these problems remain difficult to manipulate genetically. Here, we engineered the thermotolerant yeast
to create a new synthetic biology platform. Using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats with Cas9)-mediated genome editing, we show that wild isolates of
can be made heterothallic for sexual crossing. By breeding two of these mating-type engineered
strains, we combined three complex traits-thermotolerance, lipid production, and facile transformation with exogenous DNA-into a single host. The ability to cross
strains with relative ease, together with CRISPR-Cas9 genome editing, should enable engineering of
isolates with promising lipid production at temperatures far exceeding those of other fungi under development for industrial applications. These results establish
as a synthetic biology platform comparable to
, with naturally more robust traits that hold potential for the industrial production of renewable chemicals.
The yeast
grows at high temperatures and on a wide range of carbon sources, making it a promising host for industrial biotechnology to produce renewable chemicals from plant biomass feedstocks. However, major genetic engineering limitations have kept this yeast from replacing the commonly used yeast
in industrial applications. Here, we describe genetic tools for genome editing and breeding
strains, which we use to create a new thermotolerant strain with promising fatty acid production. These results open the door to using
as a versatile synthetic biology platform organism for industrial applications.
Multiple myeloma is a cancer of plasma cells that often leads to complications including osteolytic bone lesions, nephropathy and neuropathy. Multiple myeloma is only one etiology of many cancer pain ...conditions that may necessitate interventional pain treatment when refractory to multimodal medications. Notably, local anesthetic systemic toxicity is a rare but life-threatening complication of local anesthetic administered for these interventions.
A 50-60-year-old woman presented with multiple myeloma complicated by chronic bone pain and in an acute pain crisis. A fluoroscopic-guided L4-5 epidural catheter was placed with clinical doses of bupivacaine for comfort to undergo MRI of the spine. Soon after, she became tachycardic, tachypneic and hypoxic requiring non-invasive positive pressure airway support. As this respiratory distress was attributed to a large pleural effusion, a pigtail catheter was inserted in the intensive care unit with submaximally dosed lidocaine infiltration. She then developed a left bundle branch block followed by cardiovascular collapse minimally responsive to high-dose inotrope and vasopressor support. Lipid emulsion was started with dramatic therapeutic response and recovery to baseline. A CT of the thoracolumbar spine showed worsening extensive lytic lesions throughout all vertebral bodies and ribs from diffuse myeloma.
Patients with oncologic lesions focal to the thoracolumbar spine may be at higher risk for local anesthetic systemic toxicity from palliative epidurals due to increased cancer-related angiogenesis. Likewise, local anesthetic infiltration for procedures near any malignant sites could have a similar risk and may require lower initial fractionated dosages with increased vigilance.
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