Abstract
Context
Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated.
Case report
A 46-year-old ...woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 µg/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone.
Discussion
We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19.
Conclusion
Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.
Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between ...anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.
Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.
Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.
Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.
Microstructures and a microstructural, columnar architecture as well as mechanical behavior of as-fabricated and processed INCONEL alloy 625 components produced by additive manufacturing using ...electron beam melting (EBM) of prealloyed precursor powder are examined in this study. As-fabricated and hot-isostatically pressed (“hipped”) at 1393 K (1120 °C) cylinders examined by optical metallography (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive (X-ray) spectrometry (EDS), and X-ray diffraction (XRD) exhibited an initial EBM-developed
γ
″ (bct) Ni
3
Nb precipitate platelet columnar architecture within columnar 200 textured
γ
(fcc) Ni-Cr grains aligned in the cylinder axis, parallel to the EBM build direction. Upon annealing at 1393 K (1120 °C) (hot-isostatic press (HIP)), these precipitate columns dissolve and the columnar,
γ
, grains recrystallized forming generally equiaxed grains (with coherent {111} annealing twins), containing NbCr
2
laves precipitates. Microindentation hardnesses decreased from ~2.7 to ~2.2 GPa following hot-isostatic pressing (“hipping”), and the corresponding engineering (0.2 pct) offset yield stress decreased from 0.41 to 0.33 GPa, while the UTS increased from 0.75 to 0.77 GPa. However, the corresponding elongation increased from 44 to 69 pct for the hipped components.
Nickel-based superalloys are known for their high-temperature performance regarding oxidation, creep and fatigue resistance. For this reason, they are widely used as structural components in the ...aerospace industry. However, because of these properties, they are difficult to machine, and normally a rigorous control of the surface integrity and residual stresses are required to avoid structural premature failures. Residual stresses are present in all mechanical components regardless of the manufacturing process applied, and they are either of thermal or mechanical origins. In machining several variables affect the residual stresses, but the tool quality is one that is most influential. The present work studies the influence of the wear of coated cemented carbide tools on the surface integrity of Inconel 718 alloy in the face milling process. Tools with different stages of wear were tested under finishing, roughing, and moderate machining conditions. During milling tests, the machining forces and cutting temperatures were monitored, the latter by two different techniques, using a thermal camera and with J-type thermocouples welded on the workpiece surface close to the cutting region. The surface roughness, microhardness, and residual stresses were measured after each machining test. The results showed that there is a close relationship between the tool wear and the residual stresses that varied from compressive to tensile stresses – the latter being of thermal origin. A direct relationship between tool wear and machining forces and cutting temperature were also observed.
•The artificially produced tool wear types had a significant influence on the machinability.•The cutting temperatures were correlated with the residual stresses in the workpiece.•The cutting conditions significantly influenced the hardness of the machined surface.
In this paper, we examine prospects for the manufacture of patient-specific biomedical implants replacing hard tissues (bone), particularly knee and hip stems and large bone (femoral) intramedullary ...rods, using additive manufacturing (AM) by electron beam melting (EBM). Of particular interest is the fabrication of complex functional (biocompatible) mesh arrays. Mesh elements or unit cells can be divided into different regions in order to use different cell designs in different areas of the component to produce various or continually varying (functionally graded) mesh densities. Numerous design elements have been used to fabricate prototypes by AM using EBM of Ti-6Al-4V powders, where the densities have been compared with the elastic (Young) moduli determined by resonant frequency and damping analysis. Density optimization at the boneimplant interface can allow for bone ingrowth and cementless implant components. Computerized tomography (CT) scans of metal (aluminium alloy) foam have also allowed for the building of Ti-6Al-4V foams by embedding the digital-layered scans in computer-aided design or software models for EBM. Variations in mesh complexity and especially strut (or truss) dimensions alter the cooling and solidification rate, which alters the -phase (hexagonal close-packed) microstructure by creating mixtures of / (martensite) observed by optical and electron metallography. Microindentation hardness measurements are characteristic of these microstructures and microstructure mixtures (/) and sizes.
► Relative stiffness versus relative density measurements for reticulated mesh and stochastic open cellular copper were shown to follow the Gibson–Ashby foam model. ► Microstructures for the mesh ...struts and foam ligaments illustrated a propensity of copper oxide precipitates which provided structural hardness and strength. ► These components, fabricated by electron beam melting, exhibit interesting prospects for specialized, complex heat-transfer devices.
Cu reticulated mesh and stochastic open cellular foams were fabricated by additive manufacturing using electron beam melting. Fabricated densities ranged from 0.73
g/cm
3 to 6.67
g/cm
3. The precursor Cu powder contained Cu
2O precipitates and the fabricated components contained arrays of Cu
2O precipitates and interconnected dislocation microstructures having average spacings of ∼2
μm, which provide hardness values ∼75% above commercial Cu products. Plots of stiffness (Young's modulus) versus density and relative stiffness versus relative density were in very close agreement with the Gibson–Ashby model for open cellular foams. These open cellular structure components exhibit considerable potential for novel, complex, multi-functional electrical and thermal management systems, especially complex, monolithic heat exchange devices.
Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance ...of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.
Ti–6Al–4V open cellular foams were fabricated by additive manufacturing using electron beam melting (EBM). Foam models were developed from CT-scans of aluminum open cellular foams and embedded in CAD ...for EBM. These foams were fabricated with solid cell structures as well as hollow cell structures and exhibit tailorable stiffness and strength. The strength in proportion to the measured microindentation hardness is as much as 40% higher for hollow cell (wall) structures in contrast to solid, fully dense EBM fabricated components. Plots of relative stiffness versus relative density were in good agreement with the Gibson–Ashby model for open cellular foam materials. Stiffness or Young's modulus values measured using a resonant frequency-damping analysis technique were found to vary inversely with porosity especially for solid cell wall, open cellular structure foams. These foams exhibit the potential for novel biomedical, aeronautics, and automotive applications.
Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and ...several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation.
Communicated by Ramaswamy H. Sarma
Cubic Nitride Boron (CBN) tools are generally used for machining harder alloys such as hardened high Cr steels, titanium and nickel alloys. The tools are expected to withstand the heat and pressure ...developed when machining at higher cutting conditions because of their high hardness and melting point. This paper evaluates the performance of different CBN tool grades in finish turning Ti–6Al–4V (IMI 318) alloy at high cutting conditions, up to 250
m
min
−1, with various coolant supplies. Tool wear, failure modes, cutting and feed forces and surface roughness of machined surfaces were monitored and used to access the performance of the cutting tools. Comparative trials were carried out with uncoated carbide tools when machining at a speed of 150
m
min
−1. Test results show that the performance of CBN tools, in terms of tool life, at the cutting conditions investigated is poor relative to uncoated carbide tools, as expected and often, reported due probably to rapid notching and excessive chipping of the cutting edge associated with a relatively high diffusion wear rate that tends to weaken the bond strength of the tool substrate. An increase in the CBN content of the cutting tool also led to a reduction in tool life when machining at the cutting conditions investigated.
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