Search Results (9)

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is characterised by unexplained intense pruritus during pregnancy. While serum bile acid (BA) is the standard diagnostic marker for ICP, we explored the potential of serum calprotectin as an alternative diagnostic marker for ICP. Methods: Leftover serum specimens with known serum BA levels, collected from non-pregnant women and pregnant women with an ICP, were used to measure serum calprotectin levels using the Human calprotectin L1/S100-A8/A9 ELISA kit. Results: Serum calprotectin levels were measured in 79 pregnant women with ICP (median [interquartile range] 28 year; serum BA 20 [13.7–35.7] μMol/L; calprotectin159 pg/mL [122.2–212.3]); 43 pregnant women without ICP (age 28 years; serum BA 3.6 [2.1–5.8] μMol/L; calprotectin 146.5 pg/mL [75.8–194.8]), and 59 non-pregnant women (age 28 years; serum BA 3.5 [1.6–5.1 μMol/L; calprotectin 82.4 pg/mL [48.8–137.2]). Compared to non-pregnant women, calprotectin levels were significantly elevated among pregnant women with (p < 0.001) or without ICP (p = 0.01). Calprotectin levels were comparable between pregnant women with and without ICP (p = 0.15). The areas under the ROC curve, to differentiate the presence and absence of ICP, were 0.940 (0.903–0.977; p < 0.001) and 0.681 (0.604–0.759; p < 0.001) for BA and calprotectin, respectively. Conclusions: Serum calprotectin is raised in pregnant women regardless of the presence or absence of ICP and had an inferior diagnostic performance for ICP compared to BA. This information is crucial for understanding the challenges in ICP diagnosis and the limitations of serum calprotectin as an alternative marker. Full article

Ablative composites serve as sacrificial materials, protecting underlying materials from high-temperature environments by endothermic reactions. These materials undergo various phenomena, including thermal degradation, pyrolysis, gas generation, char formation, erosion, gas flow, and different modes of heat transfer (such as conduction, convection, and radiation), all stemming from these endothermic reactions. These phenomena synergize to form a protective layer over the underlying materials. Carbon, with its superb mechanical properties and various available forms, is highlighted, alongside phenolics known for good adhesion and fabric ability and elastomers valued for flexibility and resilience. This study focuses on recent advancements in carbon-and-phenolic and carbon-and-elastomeric composites, considering factors such as erosion speed; high-temperature resistance; tensile, bending, and compressive strength; fiber–matrix interaction; and char formation. Various authors’ calculations regarding the percentage reduction in linear ablation rate (LAR) and mass ablation rate (MAR) are discussed. These analyses inform potential advancements in the field of carbon/phenolic and carbon/elastomeric ablative composites. Full article

Gas-enhanced oil recovery (EOR) through huff-n-puff (HnP) is an important method of recovering oil from fracture-stimulated reservoirs. HnP productivity is hampered by fracture channeling, leading to early gas breakthroughs and gas losses. To mitigate these issues, foam-generating surfactants have been developed as a method of reducing injected gas phase mobility and increasing oil recovery. This work investigates foam generation and propagation by a proprietary surfactant blend in high-temperature, high-pressure, high-permeability, and high-shear conditions that simulate the environment of a proppant-packed fracture. Bulk foam tests confirmed the aqueous stability and foaming viability of the surfactant at the proposed conditions. Through several series of floods co-injecting methane gas and the surfactant solution through a proppant pack at residual oil saturation, the effects of several injection parameters on apparent foam viscosity were investigated. The foam exhibited an exceptionally high transition foam quality (>95%) and strong shear-thinning behavior. The foam viscosity also linearly decreased with increasing pressure. Another flood series conducted in an oil-free proppant pack showed that swelling of residual oil had no effect on the apparent foam viscosity and was not the reason for the inversely linear pressure dependency. An additional flood series with nitrogen as the injection gas was completed to see if the hydrophobic attraction between the methane and surfactant tail was responsible for the observed pressure trend, but the trend persisted even with nitrogen. In a previous study, the dependence of foam viscosity on pressure was found to be much weaker with a different foaming surfactant under similar conditions. Thus, a better understanding of this important phenomenon requires additional tests with a focus on the effect of pressure on interfacial surfactant adsorption. Full article

The GNE-associated V727M mutation is one of the most prevalent ethnic founder mutations in the Asian HIBM cohort; however, its role in inducing disease phenotype remains largely elusive. In this study, the function of this hotspot mutation was profoundly investigated. For this, V727M mutation-specific altered expression profile and potential networks were explored. The relevant muscular disorder-specific in vivo studies and patient data were further analyzed, and the key altered molecular pathways were identified. Our study found that the GNEV727M mutation resulted in a deregulated lincRNA profile, the majority of which (91%) were associated with a down-regulation trend. Further, in silico analysis of associated targets showed their active role in regulating Wnt, TGF-β, and apoptotic signaling. Interestingly, COL6a3 was found as a key target of these lincRNAs. Further, GSEA analysis showed HIBM patients with variable COL6A3 transcript levels have significant alteration in many critical pathways, including epithelial-mesenchymal-transition, myogenesis, and apoptotic signaling. Interestingly, 12 of the COL6A3 coexpressed genes also showed a similar altered expression profile in HIBM. A similar altered trend in COL6A3 and coexpressed genes were found in in vivo HIBM disease models as well as in multiple other skeletal disorders. Thus, the COL6A3-specific 13 gene signature seems to be altered in multiple muscular disorders. Such deregulation could play a pivotal role in regulating many critical processes such as extracellular matrix organization, cell adhesion, and skeletal muscle development. Thus, investigating this novel COL6A3-specific 13 gene signature provides valuable information for understanding the molecular cause of HIBM and may also pave the way for better diagnosis and effective therapeutic strategies for many muscular disorders. Full article

(i) Background: ChAdOx1 nCoV-19 (Covishield^®) vaccine is widely used in India. We studied the Covishield^® induced antibody response and its durability among health care workers (HCWs) (ii) Method: HCWs received two doses (0.5 mL) four weeks apart. Blood specimens, collected before each dose, day (D)60, D150 and D270 after second dose, were tested for anti-spike antibody (ASAb) titre and neutralising antibody (%) (NAb) using Elecsys Anti-SARS-CoV-2 S (Roche) and SARS-CoV-2 NAb ELISA Kit (Invitrogen), respectively. Data are expressed as proportions and median (interquartile range) and compared using non-parametric (iii) Result: Among 135 HCWs (83 males; age 45 (37–53); 36 had pre-existing ASAb), 29 (21.5%) acquired COVID-19 after 60 (39–68) days of vaccination. ASAb titre before second dose and at D60, D150, D270 were 77.2 (19.4–329.4), 512 (114.5–9212), 149 (51.6–2283) and 2079 (433.9–8644) U/mL, respectively. Compared to those without pre-existing ASAb, titres were significantly higher before second dose (5929 vs. 41, p < 0.001), D60 (3395 vs. 234, p = 0.007) and D150 (1805 vs. 103, p < 0.001) in participants with pre-existing ASAb; NAb were also higher (80 vs. 18, p < 0.001) before second dose. Between those who acquired infection or not after vaccination, ASAb titres were comparable before second dose (77 vs. 78, p = 0.362) but significantly higher at D60 (14,019 vs. 317, p < 0.001) and D150 (2062 vs. 121, p = 0.002) in the former group, though NAb percentage were higher at D60 (87 vs. 27, p < 0.001) and D150 (79 vs. 25, p = 0.007) only (iv) Conclusions: Covishield^® induces a higher antibody titre in those with pre-existing ASAb. The vaccine induced antibody starts falling 5 months after vaccination. Full article

Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care. A wealth of information about mAbs regarding their structure, stability, post-translation modifications, and the relationship between modification and function has been reported. Yet, substantial resources are still required throughout development and commercialization to have appropriate control strategies to maintain consistent product quality, safety, and efficacy. A typical feature of mAbs is charge heterogeneity, which stems from a variety of modifications, including modifications that are common to many mAbs or unique to a specific molecule or process. Charge heterogeneity is highly sensitive to process changes and thus a good indicator of a robust process. It is a high-risk quality attribute that could potentially fail the specification and comparability required for batch disposition. Failure to meet product specifications or comparability can substantially affect clinical development timelines. To mitigate these risks, the general rule is to maintain a comparable charge profile when process changes are inevitably introduced during development and even after commercialization. Otherwise, new peaks or varied levels of acidic and basic species must be justified based on scientific knowledge and clinical experience for a specific molecule. Here, we summarize the current understanding of mAb charge variants and outline risk-based control strategies to support process development and ultimately commercialization. Full article

Introduction: Data are limited on antibody response to the ChAdOx1 nCoV-19 vaccine (AZD1222; Covishield^®) in cirrhosis. We studied the antibody response following two doses of the ChAdOx1 vaccine, given 4–12 weeks apart, in cirrhosis. Methods: Prospectively enrolled, 131 participants (71% males; age 50 (43–58); alcohol-related etiology 14, hepatitis B 33, hepatitis C 46, cryptogenic 21, autoimmune 9, others 8; Child–Turcott–Pugh class A/B/C 52/63/16). According to dose intervals, the participants were grouped as ≤6 weeks (group I), 7–12 weeks (group II), and 13–36 weeks (group III). Blood specimens collected at ≥4 weeks after the second dose were tested for anti-spike antibody titre (ASAb; positive ≥ 0.80 U/mL) and neutralizing antibody (NAb; positive ≥20% neutralization) using Elecsys Anti-SARS-CoV-2 S (Roche) and SARS-CoV-2 NAb ELISA Kit (Invitrogen), respectively. Data are expressed as number (proportion) and median (interquartile range) and compared using non-parametric tests. Results: Overall, 99.2% and 84% patients developed ASAb (titre 5440 (1719–9980 U/mL)) and NAb (92 (49.1–97.6%)), respectively. When comparing between the study groups, the ASAb titres were significantly higher in group II than in group I (2613 (310–7518) versus 6365 (2968–9463), p = 0.027) but were comparable between group II and III (6365 (2968–9463) versus 5267 (1739–11,653), p = 0.999). Similarly, NAb was higher in group II than in group I (95.5 (57.6–98.0) versus 45.9 (15.4–92.0); p < 0.001), but not between the groups II and III (95.5 (57.6–98.0) versus 92.4 (73.8–97.5); p = 0.386). Conclusion: Covishield^® induces high titres of ASAb and NAb in cirrhosis. A higher titre is achieved if two doses are given at an interval of more than six weeks. Full article

Kidney transplant recipients (KTRs) are at a much higher risk of complications and death following COVID-19 and are poor vaccine responders. The data are limited on the immune response to Covishield^® in KTRs. We prospectively recruited a cohort of 67 KTRs aged >18 between April 2021 and December 2021. Each participant was given two intramuscular doses of Covishield^®, each of 0.5 mL, at an interval of 12 weeks. A blood specimen of 5.0 mL was collected from each participant at two points within a few days before administering the first dose of the vaccine and at any time between 4–12 weeks after administering the second dose. The sera were tested for anti-RBD antibody (ARAb) titre and neutralising antibody (NAb). An ACE2 competition assay was used as a proxy for virus neutralization. According to the prior COVID-19 infection, participants were grouped as (i) group A: prior symptomatic COVID-19 infection, (ii) group B: prior asymptomatic COVID-19 infection as evidenced by detectable ARAb in the prevaccination specimen, (iii) Group C: no prior infection with COVID-19, (iv) group D: Unclassified, i.e., participants had no symptoms suggestive of COVID-19, but their prevaccination specimen was not available for ARAb testing before vaccination. Fifty of sixty-seven participants (74.6%) provided paired specimens (group A 14, group B 27, and group C 9) and 17 participants (25.4%) provided only postvaccination specimens (group D). In the overall cohort (n = 67), 91% and 77.6% of participants developed ARAb and NAb, respectively. Their ARAb titre and NAb proportion were 2927 (520–7124) U/mL and 87.9 (24.4–93.2) %, respectively. Their median ARAb titre increased 65.6 folds, from 38.2 U/mL to 3137 U/mL. Similarly, the proportion of participants with NAb increased from 56% to 86%, and the NAb proportion raised 2.7 folds, from 23% to 91%. A comparison of vaccine response between the study groups showed that all those with or without prior COVID-19 infection showed a significant rise in ARAb titre (p < 0.05) and NAb proportion (p < 0.05) after the two doses of vaccine administration. The median value of folds rise in anti-RBD and NAb between groups A and B were comparable. Hence, ARAb is present in more than 3/4th of KTRs before the ChAdOx1 vaccine in India. The titer of ARAb and the proportion of NAb significantly increased after the two doses of the ChAdOx1 vaccine in KTRs. Full article

The nucleating effect of silk fibroin nano-disc (SFN) on the crystallization behavior of poly(L-lactic acid) (PLLA) was investigated by simultaneous synchrotron small- and wide-angle X-ray scattering measurements. For the isothermal crystallization at 110 °C from the melt, the induction period of the PLLA specimens containing 1% SFN was reduced compared to that of the neat specimens, indicating the acceleration of the nucleation of PLLA. The final degree of crystallinity was also increased, and the crystallization half-time was decreased, which indicates that the overall crystallization process was accelerated. Furthermore, the final value of the crystallite size (the lateral size of the crystalline lamella) was slightly lower for the specimens containing 1% SFN than that for the PLLA neat specimen, although the crystallites started growing much earlier. However, it was found that there was no effect of SFN on the growth rate of the crystallite size. The lamellar thickening process was also accelerated with a clear overshooting phenomenon with the inclusion of 1% SFN. As for the polymorphism, the α’ phase is dominant with about 96%, but a small amount of the α phase (4%) is found to exist. It was found that the SFN can also accelerate the formation of the minor α phase as well as the major α’ phase. Full article