We present the case of a 19-year-old man who suffered a penetrating injury to the brain with a large-calibre steel industrial prybar approximately 1 m long and 2.5 cm wide that was retained in his ...cranium. The management of this type of injury is discussed, based on our experience with penetrating brain injuries with large-calibre retained objects, from initial presentation to surgical removal of the object to post-operative care. Additionally, given the similarities of the injuries suffered by our patient with those of Phineas Gage, we discuss the extensive lessons learned in treating this type of large-calibre injury.
In this patient, making the diagnosis of hyponatraemia secondary to excess water ingestion was straightforward.1 What was surprising was the severity of the hyponatraemia, given the relatively modest ...water intake and normal renal function. A normal kidney can produce urine with a concentration in the range 50 mOsm/kg to 1200 mOsm/kg.2 A normal diet generates approximately 1000 mOsm per day from dietary electrolytes and protein metabolism.3,4 With 1000 mOsm of solute to excrete, the kidney can clear between 0.8 L and 20 L of water without any change in serum osmolality. Thus, if a diet results in smaller amounts of solute being produced or if the kidney's ability to dilute the urine is impaired, proportionately less water can be excreted. In this situation, relatively modest water consumption may result in dilutional hyponatraemia. This patient would have been generating approximately 600 mOsm of solute from her diet.3 Furthermore, she was passing a sub-maximally dilute urine (147 mOsm/kg). Her maximum urine output would have been approximately 4 L per day. By drinking more water than she could excrete, she became dangerously hyponatraemic. She was fortunate to have suffered only mild symptoms.
Objective
Degeneration of chronically demyelinated axons is a major cause of irreversible neurological disability in multiple sclerosis (MS) patients. Development of neuroprotective therapies will ...require elucidation of the molecular mechanisms by which neurons and axons degenerate.
Methods
We report ultrastructural changes that support Ca2+‐mediated destruction of chronically demyelinated axons in MS patients. We compared expression levels of 33,000 characterized genes in postmortem motor cortex from six control and six MS brains matched for age, sex, and postmortem interval. As reduced energy production is a major contributor to Ca2+‐mediated axonal degeneration, we focused on changes in oxidative phosphorylation and inhibitory neurotransmission.
Results
Compared with controls, 488 transcripts were decreased and 67 were increased (p < 0.05, 1.5‐fold) in the MS cortex. Twenty‐six nuclear‐encoded mitochondrial genes and the functional activities of mitochondrial respiratory chain complexes I and III were decreased in the MS motor cortex. Reduced mitochondrial gene expression was specific for neurons. In addition, pre‐synaptic and postsynaptic components of GABAergic neurotransmission and the density of inhibitory interneuron processes also were decreased in the MS cortex.
Interpretation
Our data supports a mechanism whereby reduced ATP production in demyelinated segments of upper motor neuron axons impacts ion homeostasis, induces Ca2+‐mediated axonal degeneration, and contributes to progressive neurological disability in MS patients. Ann Neurol 2006
In the machining of Ti alloys, it is challenging to optimise the cutting tool life and process productivity. It is not a trivial task to find an efficient strategy to improve the tool life during ...machining of Ti alloys using surface engineered tooling. In the case of rough turning operation with strong built up edge formation we establish that it can be achieved through the application of self-lubricating TiB2 PVD coating. It has been shown that the application of a TiB2 coating results in tool life improvement by over 60% compared to the uncoated tool and over 70% compared to the TiAlN coated tool. Comprehensive characterization of the coated vs. uncoated cutting tool wear performance was performed using optical 3D imaging, SEM/EDX and XPS methods. Various micro-mechanical characteristics of the TiB2 coating were evaluated. It was determined that tool life improvement using the TiB2 coating is mostly related to the ability of the coating layer to provide self-lubrication effect and in this way, very efficiently dissipate frictional energy. The coating also exhibited less substrate exposure as it fails indicating better protection of the coated tool surface. This is of particular importance for machining of materials like Ti, which have strong sticking intensity. It has been demonstrated that the TiB2 coating combines beneficial micro-mechanical characteristics and self-lubricating properties due to the formation of B-O tribo-films on the tool surface under operation. These tribo-films serve as a liquid lubricant formed in-situ on the tool surface under the elevated temperature of cutting. The formation of liquid tribo-films is an effective way to address intensive adhesive interaction followed by built up edge formation at the tool/chip interface, which is typical for roughing operations during Ti machining.
•TiB2 coating improves tool life during rough turning of Ti alloy with intensive buildup edge formation•This is mostly related to self-lubrication effect and better surface protection•Comprehensive characterization of TiB2 coating was performed•Generation of B-Ox tribo-films which are liquid at high temperatures of cutting minimises adhesive interaction at the tool/chip interface
With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to ...establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation.
Diverse and robust predator communities are important for effective prey suppression in natural and managed communities. Ants are ubiquitous components of terrestrial systems but their contributions ...to natural prey suppression is relatively understudied in temperate regions. Growing evidence suggests that ants can play a significant role in the removal of insect prey within grasslands, but their impact is difficult to separate from that of nonant predators. To test how ants may contribute to prey suppression in grasslands, we used poison baits (with physical exclosures) to selectively reduce the ant population in common garden settings, then tracked ant and nonant ground predator abundance and diversity, and removal of sentinel egg prey for 7 wk. We found that poison baits reduced ant abundance without a significant negative impact on abundance of nonant ground predators, and that a reduction in ant abundance decreased the proportion of sentinel prey eggs removed. Even a modest decrease (∼20%) in abundance of several ant species, including the numerically dominant Lasius neoniger Emery (Hymenoptera: Formicidae), significantly reduced sentinel prey removal rates. Our results suggest that ants disproportionately contribute to ground-based predation of arthropod prey in grasslands. Changes in the amount of grasslands on the landscape and its management may have important implications for ant prevalence and natural prey suppression services in agricultural landscapes.
Hard nano-multilayered TiAlCrN/NbN coatings on cemented carbide have shown promise in dry high speed machining applications involving repetitive contact, such as end milling of hardened H13 steel. In ...this study the fracture resistance of TiAlCrN/NbN coatings under repetitive dynamic high strain rate loading has been evaluated by the micro-scale impact test method. Although the fatigue mechanisms can vary with the ratio of coating thickness t to the indenter radius R, macro-scale tests of thin coatings using probe radii in the mm range are necessarily at low t/R. Micro-impact tests at higher t/R have been performed with a range of diamond indenter geometries (R = 8, 20, 100 μm) to investigate the role of varying t/R (0.03–0.375) on the deformation behaviour. With the largest radius probe there was no clear failure for the coatings or substrate under the test conditions. With the 8 and 20 μm radius probes the behaviour of the coatings was strongly load-dependent and they were more susceptible to impact-induced damage than the carbide substrate. As the load increased there was a change from coating to substrate dominated deformation behaviour as the stress field extended further into the substrate. At lower load the dominant fracture behaviour was coating fracture through ring cracking, radial cracking and chipping. At higher load chipping became less prevalent and break-up of the carbide substrate more extensive.
•Applied load and probe sharpness control deformation in micro-impact.•Damage can be tailored to affect coating, substrate or interface.•Ratio of coating thickness to probe radius influences deformation.•High t/R and lower load micro impacts generate damage within the coating.•Damage at lower load occurs by a three step process.
Traditionally, molecular mechanisms of pathogenesis for infectious agents were studied in cell culture or animal models but have limitations on the extent to which the resulting data reflect natural ...infection in humans. The COVID-19 pandemic has highlighted the urgent need to rapidly develop laboratory models that enable the study of host-pathogen interactions, particularly the relative efficacy of preventive measures. Recently, human and animal ex vivo tissue challenge models have emerged as a promising avenue to study immune responses, screen potential therapies and triage vaccine candidates. This approach offers the opportunity to closely approximate human disease from the perspective of pathology and immune response. It has advantages compared to animal models which are expensive, lengthy and often require containment facilities. Herein, we summarize some recent advances in the development of ex vivo tissue challenge models for COVID-19, HIV-1 and other pathogens. We focus on the contribution of these models to enhancing knowledge of host-pathogen interactions, immune modulation, and their value in testing therapeutic agents. We further highlight the advantages and limitations of using ex vivo challenge models and briefly summarize how the use of organoids provides a useful advancement over current approaches. Collectively, these developments have enormous potential for the study of infectious diseases.
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