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We report the case of a 15-year-old boy with a de novo chromosomal deletion in the 12q13.13 region, presenting with congenital hand difference. This case emphasizes the clinical significance of recognizing such genetic anomalies and their implications.
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Maximizing product quality attributes by optimizing process parameters and performance attributes is a crucial aspect of bioprocess chromatography process design. Process parameters include but are not limited to bed height, eluate cut points, and elution pH. An under-characterized chromatography process parameter for protein A chromatography is process temperature. Here, we present a mechanistic understanding of the effects of temperature on the protein A purification of a monoclonal antibody (mAb) using a commercial chromatography resin for batch and continuous counter-current systems. A self-designed 3D-printed heating jacket controlled the 1 mL chromatography process temperature during the loading, wash, elution, and cleaning-in-place (CIP) steps. Batch loading experiments at 10, 20, and 30 °C demonstrated increased dynamic binding capacity (DBC) with temperature. The experimental data were fit to mechanistic and correlation-based models that predicted the optimal operating conditions over a range of temperatures. These model-based predictions optimized the development of a 3-column temperature-controlled periodic counter-current chromatography (TCPCC) and were validated experimentally. Operating a 3-column TCPCC at 30 °C led to a 47% increase in DBC relative to 20 °C batch chromatography. The DBC increase resulted in a two-fold increase in productivity relative to 20 °C batch. Increasing the number of columns to the TCPCC to optimize for increasing feed concentration resulted in further improvements to productivity. The feed-optimized TCPCC showed a respective two, three, and four-fold increase in productivity at feed concentrations of 1, 5, and 15 mg/mL mAb, respectively. The derived and experimentally validated temperature-dependent models offer a valuable tool for optimizing both batch and continuous chromatography systems under various operating conditions.
Assuntos
Anticorpos Monoclonais , Distribuição Contracorrente , Proteína Estafilocócica A , Temperatura , Proteína Estafilocócica A/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Distribuição Contracorrente/métodos , Cromatografia de Afinidade/métodos , Cricetulus , Células CHO , AnimaisRESUMO
The self-assembly and surface adsorption of glycerol monooleate (GMO) in n-dodecane are studied using a combination of experimental and molecular dynamics simulation techniques. The self-assembly of GMO to form reverse micelles, with and without added water, is studied using small-angle neutron scattering and simulations. A large-scale simulation is also used to investigate the self-assembly kinetics. GMO adsorption onto iron oxide is studied using depletion isotherms, neutron reflectometry, and simulations. The adsorbed amounts of GMO, and any added water, are determined experimentally, and the structures of the adsorbed films are investigated using reflectometry. Detailed fitting and analysis of the reflectometry measurements are presented, taking into account various factors such as surface roughness, and the presence of impurities. The reflectometry measurements are complemented by molecular dynamics simulations, and good consistency between both approaches is demonstrated by direct comparison of measured and simulated reflectivity and scattering length density profiles. The results of this analysis are that in dry systems, GMO adsorbs as self-assembled reverse micelles with some molecules adsorbing directly to the surface through the polar head groups, while in wet systems, the GMO is adsorbed onto a thin layer of water. Only at high surface coverage is some water trapped inside a reverse-micelle structure; at lower surface coverages, the GMO molecules associate primarily with the water layer, rather than self-assemble.
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Purpose: Low-dose-rate (LDR) brachytherapy in young men remains controversial amongst urologists due to their concerns regarding long-term biochemical control and treatment-related toxicities. The purpose of this study was to evaluate the treatment outcomes of men under 60 years of age who underwent LDR brachytherapy with iodine-125 (125I) for clinically localized low- to intermediate-risk prostate cancer. Material and methods: All consecutive patients with clinically localized prostate cancer treated at our institution from 2003 to 2016 with 125I monotherapy were included in the study. Prescription dose was 145.0 Gy modified peripheral loading (MPD). All patients were assessed for biochemical progression-free survival using Phoenix definition (nadir +2 ng/ml), clinical progression-free survival, overall survival (OS), and any associated treatment toxicity. Results: A total of 161 patients were included, with a median follow-up of 6.8 years (range, 3-14.54 years). Median age at implant was 57 years (range, 53-59 years). Mean prostate specific antigen (PSA) level at diagnosis was 4.43 ng/ml (SD = 2.29). Majority of men had low-risk prostate cancer (70.2%). Biochemical progression-free survival at 8 years was 94% for the entire cohort. Median PSA at 4 years was 0.169 (IQR, 0.096-0.360), with 45% of patients having a PSA greater than 0.2. OS was 96.9%, with 5 deaths reported but only one was secondary to prostate cancer. Late grade > 2 genitourinary toxicities were reported in 18 patients (11.2%). Three patients (1.9%) developed secondary cancers, all considered unrelated to their LDR brachytherapy. Conclusions: With excellent long-term treatment outcomes and minimal associated toxicities, our results showed that LDR brachytherapy can be an effective treatment of choice in younger men.