Alveolar epithelial cells of lung fibrosis patients are susceptible to severe virus-induced injury.

Patients with pulmonary fibrosis (PF) often experience exacerbations of their disease, characterised by a rapid, severe deterioration in lung function that is associated with high mortality. Whilst the pathobiology of such exacerbations is poorly understood, virus infection is a trigger. The present study investigated virus-induced injury responses of alveolar and bronchial epithelial cells (AECs and BECs, respectively) from patients with PF and age-matched controls (Ctrls). Air-liquid interface (ALI) cultures of AECs, comprising type I and II pneumocytes or BECs were inoculated with influenza A virus (H1N1) at 0.1 multiplicity of infection (MOI). Levels of interleukin-6 (IL-6), IL-36γ and IL-1ß were elevated in cultures of AECs from PF patients (PF-AECs, n = 8-11), being markedly higher than Ctrl-AECs (n = 5-6), 48 h post inoculation (pi) (P<0.05); despite no difference in H1N1 RNA copy numbers 24 h pi. Furthermore, the virus-induced inflammatory responses of PF-AECs were greater than BECs (from either PF patients or controls), even though viral loads in the BECs were overall 2- to 3-fold higher than AECs. Baseline levels of the senescence and DNA damage markers, nuclear p21, p16 and H2AXγ were also significantly higher in PF-AECs than Ctrl-AECs and further elevated post-infection. Senescence induction using etoposide augmented virus-induced injuries in AECs (but not viral load), whereas selected senotherapeutics (rapamycin and mitoTEMPO) were protective. The present study provides evidence that senescence increases the susceptibility of AECs from PF patients to severe virus-induced injury and suggests targeting senescence may provide an alternative option to prevent or treat the exacerbations that worsen the underlying disease.

Impact of Beam Shape on Print Accuracy in Digital Light Processing Additive Manufacture.

Photopolymerization-based additive manufacturing requires selectively exposing a feedstock resin to ultraviolet (UV) light, which in digital light processing is achieved either using a digital micromirror device or a digital mask. The minimum tolerances and resolution for a multilayer process are separate for resolution through the Z-axis, looking through the thickness of a printed part, and resolution in the XY-axes, in the plane of the printed layer. The former depends wholly on the rate of attenuation of the incident UV light through the material relative to the mechanical motion of the build layer, while the latter is determined by a two-dimensional pattern of irradiance on the resin formed by the digital micromirror device or the digital mask. The size or the spacing of elements or pixels of this digital mask is frequently given by manufacturers as the "resolution" of the device, however, in practice the achievable resolution is first determined by the beam distribution from each pixel. The beam distribution is, as standard, modeled as a two-parameter Gaussian distribution but the key parameters of peak intensity and standard deviation of the beam are hidden to the user and difficult to measure directly. The ability of models based on the Gaussian distribution to correctly predict the polymerization of printed features in the microscale is also typically poor. In this study, we demonstrate an alternative model of beam distribution based on a heavy-tailed Lorentzian model, which is able to more accurately predict small build areas for both positive and negative features. We show a simple calibration method to derive the key space parameters of the beam distribution from measurements of a single-layer printed model. We propose that the standard Gaussian model is insufficient to accurately predict a print outcome as it neglects higher-order terms, such as beam skew and kurtosis, and in particular failing to account for the relatively heavy tails of the beam distribution. Our results demonstrate how the amendments to the beam distribution can avoid errors in microchannel formation, and better estimates of the true XY-axes resolution of the printer. The results can be used as the basis for voxel-based models of print solidification that allow software prediction of the photopolymerization process.

A randomised crossover trial of five cryocompression devices' ability to reduce skin temperature of the knee.

BACKGROUND: The application of cold and pressure to the knee is a common part of post-operative rehabilitation. Skin temperature should be reduced to within 10-15 °C to optimise the therapeutic benefits of cryocompression. The purpose of this study was to investigate the ability of five different cryocompression devices to reduce skin temperature to within this therapeutic range. MATERIALS AND METHODS: 32 healthy adult participants (mean (SD): age 26.3 (7.9) years; BMI 24.8 (2.7) kg/m2; 20 males) were recruited for this randomised crossover study. Skin temperature was measured 20 mm distal to the patella using a k-type thermocouple every five minutes during a 30-minute treatment with one of five different cryocompression devices (Physiolab S1, GameReady, Cryo/Cuff, VPulse, and a Gel Wrap). Changes in skin temperature over time were compared to baseline within and between conditions. A subjective rating of comfort was also recorded for each device. RESULTS: The Physiolab S1 and GameReady devices caused significantly lower skin temperatures compared to the VPulse, Gel Wrap, and Cryo/Cuff after 30 minutes (p<0.05). 87-96% reported a positive comfort rating for the Physiolab S1, VPulse, Cryo/Cuff and Gel Wrap, whereas 53% of participants reported a positive comfort rating for the GameReady. CONCLUSIONS: Only the Physiolab S1 and GameReady devices reduced skin temperature of the knee to within the target range of 10-15 °C. The Physiolab S1 was reportedly more comfortable than the GameReady. Clinicians should be aware of the performance differences of different cryocompression devices to understand which is most likely to provide an effective dose of cold therapy to a joint.

Advanced Computational Analysis of Cobalt-Based Superalloys through Crystal Plasticity.

This study introduces an advanced computational method aimed at accelerating continuum-scale processes using crystal plasticity approaches to predict mechanical responses in cobalt-based superalloys. The framework integrates two levels, namely, sub-grain and homogenized, at the meso-scale through crystal plasticity finite element (CPFE) platforms. The model is applicable across a temperature range from room temperature up to 900 °C, accommodating various dislocation mechanisms in the microstructure. The sub-grain level explicitly incorporates precipitates and employs a dislocation density-based constitutive model that is size-dependent. In contrast, the homogenized level utilizes an activation energy-based constitutive model, implicitly representing the γ' phase for efficiency in computations. This level considers the effects of composition and morphology on mechanical properties, demonstrating the potential for cobalt-based superalloys to rival nickel-based superalloys. The study aims to investigate the impacts of elements including tungsten, tantalum, titanium, and chromium through the homogenized constitutive model. The model accounts for the locking mechanism to address the cross-slip of screw dislocations at lower temperatures as well as the glide and climb mechanism to simulate diffusions at higher temperatures. The model's validity is established across diverse compositions and morphologies, as well as various temperatures, through comparison with experimental data. This advanced computational framework not only enables accurate predictions of mechanical responses in cobalt-based superalloys across a wide temperature range, but also provides valuable insights into the design and optimization of these materials for high-temperature applications.

Exploring the feasibility of a gambling harm screening model in general practice and community service settings in Fairfield: a pilot study.

BACKGROUND: Gambling is a growing public health issue in Australia. However, limited research has examined the role of primary health care and social services in routine screening for gambling harm in Australia. This research aimed to explore the enablers and barriers to implementing a co-designed gambling screening model in Fairfield, New South Wales - an area with high gambling expenditure. METHODS: A co-designed gambling screening and referral model for GP and community-based organisations was implemented in Fairfield in 2020. Follow-up interviews were conducted with nine health care professionals who implemented the screening in 130 patients. Thematic analysis generated key barriers and enablers for implementation of this model. RESULTS: Key enablers for the screening model implementation included structural factors (alignment of the screening model with current work), process factors and staffing factors (staff empowerment). However, we also noted process factors as a barrier to implementation, particularly the referral pathway following screening. Other barriers included social and structural factors, such as the complexity of gambling harm and project funding. CONCLUSIONS: Embedding routine screening in primary and community care settings can play a role in treating, reducing and preventing gambling-related harm, and reducing stigma in Fairfield and beyond. Additionally, screening models such as this provide health systems with clear evidence on the level of gambling harm in their community (particularly important in culturally and linguistically diverse communities who are underrepresented in research). This evidence is important for addressing system-level drivers of harm and advocating for political reform to reduce the impact of gambling on communities.

Coupled membranes: a mechanism of frequency filtering and transmission in the field cricket ear evidenced by micro-computed tomography, laser Doppler vibrometry and finite element analysis.

Many animals employ a second frequency filter beyond the initial filtering of the eardrum (or tympanal membrane). In the field cricket ear, both the filtering mechanism and the transmission path from the posterior tympanal membrane (PTM) have remained unclear. A mismatch between PTM vibrations and sensilla tuning has prompted speculations of a second filter. PTM coupling to the tracheal branches is suggested to support a transmission pathway. Here, we present three independent lines of evidence converging on the same conclusion: the existence of a series of linked membranes with distinct resonant frequencies serving both filtering and transmission functions. Micro-computed tomography (µ-CT) highlighted the 'dividing membrane (DivM)', separating the tracheal branches and connected to the PTM via the dorsal membrane of the posterior tracheal branch (DM-PTB). Thickness analysis showed the DivM to share significant thinness similarity with the PTM. Laser Doppler vibrometry indicated the first of two PTM vibrational peaks, at 6 and 14 kHz, originates not from the PTM but from the coupled DM-PTB. This result was corroborated by µ-CT-based finite element analysis. These findings clarify further the biophysical source of neuroethological pathways in what is an important model of behavioural neuroscience. Tuned microscale coupled membranes may also hold biomimetic relevance.

A case study of ileal metaplasia and neoplasia in a patient with an ileal-rectal anatomosis / Um caso de estudo de metaplasia ileal e neoplasia em paciente com anastomose ileal-retal

ABSTRACT A clear link between ulcerative colitis and the formation of dysplasia and neoplasia has been described. This increased risk remains even after subtotal colectomy and ileo-rectal anastomosis, necessitating life-long surveillance of the remaining ano-rectum. This case study highlights the importance in long-term follow up in this population, including proximal to the anastomosis as dysplastic changes can occur in the distal ileum.

RESUMO Uma ligação clara entre colite ulcerativa e a formação de displasia e neoplasia tem sido descrita. Ese risco aumentado permanece mesmo após colectomia subtotal e ileo-retal, necesitando de uma vigilância ao longo da vida do ano-recto restante. Este caso de estudo realça a importância no acompanhamento a longo prado dessa população, incluindo áqueles próximos à anastomose já que podem ocorrer alteraçoes displásicas no íleo distal.