Microstructural Characterization of Additively Manufactured Metal Components Using Linear and Nonlinear Ultrasonic Techniques

Metal additive manufacturing (AM) is an innovative manufacturing technology that uses a high-power laser for the layer-by-layer production of metal components. Despite many achievements in the field of AM, few studies have focused on the nondestructive characterization of microstructures, such as grain size and porosity. In this study, various microstructures of additively manufactured metal components were characterized non-destructively using linear/nonlinear ultrasonic techniques. The contributions of this study are as follows: (1) presenting correlation analyses of various microstructures (grain size and texture, lack of fusion, and porosity) and ultrasonic properties (ultrasonic velocity, attenuation, and nonlinearity parameters), (2) development of nondestructive microstructural characterization techniques for additively manufactured components; and (3) exploring the potential for the online monitoring of AM processes owing to the nondestructive nature of the proposed technique. The performance of the proposed technique was validated using additively manufactured samples under varying laser beam speed conditions. The characteristics of the target microstructures characterized using the proposed technique were consistent with the results obtained using destructive optical microscopy and electron back-scattered diffraction methods.     

High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations

Type 1 citrullinemia (CTLN1) often presents as a hyperammonemic encephalopathy in the neonatal period, but it can also develop in the late-infantile period and in adults. In addition, some patients can be identified in the presymptomatic period by neonatal or family member screening. In this study, twenty Korean patients with CTLN1 (19 families) were examined; fourteen patients with neonatal-onset, three with late-onset, and three that were identified presymptomatically. The 13 patients with hyperammonemic encephalopathy received continuous venovenous hemofiltration (CVVH) or peritoneal dialysis (PD). Although the hyperammonemia was relieved more effectively in the six patients on CVVH than the seven on PD, most of these patients suffered from severe neurologic deficits. Recurrent hyperammonemic episodes (7 pts, 35%), recurrent and reversible acute hepatic dysfunction (5 pts, 25%), and focal cerebral infarction (2 pts, 10%) were noted. The neonates with hyperammonemic encephalopathy had extensive brain injuries at the onset of hyperammonemia, followed by encephalomalacia and brain atrophy at quite an early age. Genetic testing for the ASS1 gene revealed a different mutation spectrum from those of other ethnicities; Three common mutations, c.421-2A > G (37.8%), c.1128-6_1188dup67 (18.9%), and p.Gly324Ser (16.2%), accounted for 73% of the mutations. The poor outcome was expected in patients with the peak ammonia level at onset over 600 μmol/L, whose proportion was higher in the neonatal presentation group than in the presymptomatic/late presentation group. Our findings add to the current understanding of the ethnic diversity of CTLN1 from both clinical and genetic perspectives.     

Norepinephrine provides short-term neuroprotection against Aβ1–42 by reducing oxidative stress independent of Nrf2 activation

Pathophysiological evidence correlating locus ceruleus neuron loss with increased Alzheimer's disease pathology suggests that norepinephrine (NE) is neuroprotective. Here, we evaluated the effects of NE on amyloid-β (Aβ)1-42–induced neurotoxicity and determined how NE exerts its actions in human SK-N-SH neurons. NE protected SK-N-SH cells against Aβ1-42–induced neurotoxicity only after a 4-hour treatment. The ability of NE to reduce Aβ1-42–induced neurotoxicity was independent of the adrenoceptor signaling pathway. Notably, NE downregulated Aβ1-42–mediated increases in intracellular reactive oxygen species (ROS) production. However, NE did not affect Aβ1-42–induced activation of the nuclear factor erythroid 2–related factor 2 (Nrf2) redox signaling pathway, known to be involved in oxidative stress. Among the antioxidants tested, N-acetyl cysteine and glutathione, which are not only ROS scavengers but also thiol-reducing agents, mimicked the protective effects of NE. Consistently, Kelch-like ECH-associating protein 1 inhibitors, which activated the Nrf2 pathway, failed to decrease Aβ1-42–induced ROS generation and elicited no protection against Aβ1–42. Taken together, these findings suggest that NE could exert neuroprotective function against Aβ1–42 via redox cycling and reduction of intracellular oxidative stress regardless of downstream activation of the Nrf2 pathway.     

Possible pathophysiology of ketamine‐related cystitis and associated treatment strategies

Ketamine‐related cystitis is characterized by ketamine‐induced urinary frequency and bladder pain. It has become a serious problem in recent years. The most typical grossly pathological bladder change with ketamine related cystitis is a contracted bladder and bladder wall thickening. Ulcerative cystitis with an easily bleeding mucosa is a common cystoscopic finding. Microscopically, the urothelium is denuded and is infiltrated by inflammatory cells, such as mast cells and eosinophils. The pathogenesis of ketamine‐related cystitis is complicated and involves many different pathways. Past evidence suggests a direct toxic effect, bladder barrier dysfunction, neurogenic inflammation, immunoglobulin‐E‐mediated inflammation, overexpression of carcinogenic genes, abnormal apoptosis and nitric oxide synthase‐mediated inflammation contribute to the pathogenesis of ketamine‐related cystitis. The first step to managing ketamine‐related cystitis is always asking patients to cease ketamine. Medical treatment might be helpful in patients with early ketamine‐related cystitis and abstinence from ketamine. Several case studies showed that the intravesical installation of hyaluronic acid and intravesical injection of botulinum toxin type A were effective for symptom relief in selected patients. For patients with irreversible pathological change, such as contracted bladder, augmentation enterocystoplasty might be the only solution to increase bladder capacity and relieve intractable bladder pain.     

CA 125 levels in the preoperative assessment of advanced-stage uterine cancer

OBJECTIVE: The purpose of this study was too evaluate preoperative levels of CA 125 in for the prediction of advanced uterine cancer. STUDY DESIGN: We conducted a retrospective analysis of the correlation of preoperative CA 125 with grade, depth of invasion, lymph vascular space involvement, lymph node status, and stage. RESULTS: High CA 125 levels correlated with advanced-stage (P <.0001) and positive (P <.0001) lymph node status. High levels of CA 125 also correlated with the deepest myometrial invasion, the presence of lymph vascular space involvement, and the highest grade. Receiver-operator characteristic curves demonstrated that depth of invasion, lymph vascular space involvement, and grade accurately predicted advanced-stage disease 73%, 77% and 80% of the time, respectively. CA 125 levels, however, correctly predicted advanced stage 94% of the time. The sensitivity and specificity of a CA 125 cutoff level of 37 IU/mL were 95% and 90%, respectively, with a positive predictive value of 78% and a negative predictive value of 97%. CONCLUSION: CA 125 appears to be a significant independent predictor of positive lymph node status and the extrauterine spread of disease.     

Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions

Cytokines are hypothesized to play a central role in the pathophysiology of IgG-mediated hemolytic transfusion reactions (HTRs), and deeper understanding is required for improving therapy for these events. After establishing well-defined mouse models of HTRs, we tested whether cytokines were involved. Red blood cells (RBCs) from human glycophorin A transgenic (hGPA-Tg) or wild-type (WT) mice were transfused into non-Tg recipients passively immunized with monoclonal antibodies (Mabs). Only transfusions of incompatible RBCs induced IgG-mediated HTRs, exemplified by rapid clearance and hemoglobinuria. Very high plasma levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), and lower levels of tumor necrosis factor- (TNF-), were induced after incompatible transfusion. No significant changes in IL-10, IL-12, or interferon- (IFN-) levels were observed. The proinflammatory cytokines elaborated in this in vivo mouse model are also implicated in the systemic inflammatory response syndrome (SIRS) and confirm the hypothesis that cytokine storm occurs as a result of HTRs.