This study suggests that the new DCR parameters of the Corvis ST are able to detect early changes in biomechanics following CXL and those that are measurable before corneal shape modifications take place. Based on these results, the authors suggest the use of these metrics to assess the early efficacy of cross-linking. [J Refract Surg. 2017;33(12):840-846.].

Understanding process parameter interactions and their effects on mammalian cell cultivations is an essential requirement for robust process scale-up. Furthermore, knowledge of the relationship between the process parameters and the product critical quality attributes (CQAs) is necessary to satisfy quality by design guidelines. So far, mainly the effect of single parameters on CQAs was investigated. Here, we present a comprehensive study to investigate the interactions of scale-up relevant parameters as pH, pO2 and pCO2 on CHO cell physiology, process performance and CQAs, which was based on design of experiments and extended product quality analytics. The study used a novel control strategy in which process parameters were decoupled from each other, and thus allowed their individual control at defined set points. Besides having identified the impact of single parameters on process performance and product quality, further significant interaction effects of process parameters on specific cell growth, specific productivity and amino acid metabolism could be derived using this method. Concerning single parameter effects, several monoclonal antibody (mAb) charge variants were affected by process pCO2 and pH. N-glycosylation analysis showed positive correlations between mAb sialylation and high pH values as well as a relationship between high mannose variants and process pH. This study additionally revealed several interaction effects as process pH and pCO2 interactions on mAb charge variants and N-glycosylation pattern. Hence, through our process control strategy and multivariate investigation, novel significant process parameter interactions and single effects were identified which have to be taken into account especially for process scale-up.Electronic supplementary materialThe online version of this article (doi:10.1007/s00449-016-1693-7) contains supplementary material, which is available to authorized users.

Human colonic myofibroblasts can secrete large amounts of IL-6, IL-8, M-CSF and GM-CSF upon stimulation. The induction of IL-8, M-CSF and GM-CSF, but not of IL-6 secretion, is mediated mainly by NF-kappaB activation. The cytokine profile and the total amounts of cytokines released suggest that colonic myofibroblasts can play a role in leukocyte recruitment and during mucosal inflammation. They therefore have to be regarded as an important part of the mucosal immune system.

Compared with ICGA, current OCTA systems are less precise in capturing small vessels in CoNV complexes, and validation studies are needed for OCTA segmentation software. OCTA, however, complements ICGA by providing evidence of red blood cell flow, which together with depth information, may be helpful when planning treatment of CoNV.

To investigate a method for precision analysis to discriminate true corneal change from measurement imprecision in keratoconus (KC). Thirty patients with KC and 30 healthy controls were included. Coefficients of repeatability and limits of agreement (LOA) were compared using multiple measurements for inter-observer and inter-device agreement with the Pentacam HR, Orbscan IIz, and Tomey Casia SS-1000. Correlation of repeated measurements was evaluated using a linear mixed effect model (also called random effect model). A formula was derived for the theoretical expected change in precision and compared with measured change. Correlation between measurements from the same eye was small (R = 0.13). The 99.73% LOA (3 SD) of the mean of three measurements, provided better precision than 95% LOA (2 SD) of single cut-off values as expected from statistical theory for uncorrelated measurements for evidence of a significant change in corneal shape in patients with keratoconus. This enabled the determination of cut-off values for the detection of true change in corneal shape. The mean of three repeated measurements will provide better precision when there is minimal correlation. Three (rather than two) standard deviations provides a precise estimate of the LOA within or between observers and can be used as a reliable measure for identifying stage-independent corneal shape changes (progression) in keratoconus.

Summaryobjective To determine the extent of carnivore-transmitted parasitic zoonoses in a community in eastern Kazakhstan, a region where cystic echinococcosis (CE) re-emerged in recent years.methods Cross sectional ultrasound study of 3126 human subjects to determine the extent of human cystic and alveolar echinococcosis (AE). Blood samples were taken from each subject and analysed for antibodies against Echinococcus, Toxocara and Toxoplasma spp. Each subject was questioned about possible risk factors that might be associated with zoonotic transmission. Analysis employed a mixed modelling approach based on the results of the ultrasound study, the serological results and the results of the questionnaire. Bayesian techniques were employed to estimate diagnostic performance. A helminthological study of the local dog population was also undertaken.results A total of 23 subjects tested positive for CE on ultrasound and a further three individuals had strong serological evidence of infection. Another 24 reported treatment for CE. Ultrasound lesions or treatment for CE were associated with poverty. No ultrasound evidence of AE was found, but one individual had strong serological evidence of exposure to Echinococcus multilocularis. Toxoplasma seropositivity (16%; 504 individuals) increased with age. Household level Toxoplasma-seropositivity was associated with unsafe drinking water. Toxocara seropositivity (11%; 349 individuals) was more frequent in children and in individuals who disposed of dog faeces on the vegetable garden. A purgation study of dogs indicated that 13% of dogs in the community were infected with Echinococcus granulosus, 5% with E. multilocularis and 2% with Toxocara canis respectively.conclusions There is significant transmission of E. granulosus to humans in this community. Transmission may be associated with poverty. There is little evidence of E. multilocularis transmission to humans, despite the presence in the parasite in the domestic dog population. Toxoplasma is actively transmitted and there is evidence for transmission by the water supply. Children are at highest risk of exposure to Toxocara.

The shift from lactate production to consumption in CHO cell metabolism is a key event during cell culture cultivations and is connected to increased culture longevity and final product titers. However, the mechanisms controlling this metabolic shift are not yet fully understood. Variations in lactate metabolism have been mainly reported to be induced by process pH and availability of substrates like glucose and glutamine. The aim of this study was to investigate the effects of elevated pCO2 concentrations on the lactate metabolic shift phenomena in CHO cell culture processes. In this publication, we show that at elevated pCO2 in batch and fed‐batch cultures, the lactate metabolic shift was absent in comparison to control cultures at lower pCO2 values. Furthermore, through metabolic flux analysis we found a link between the lactate metabolic shift and the ratio of NADH producing and regenerating intracellular pathways. This ratio was mainly affected by a reduced oxidative capacity of cultures at elevated pCO2. The presented results are especially interesting for large‐scale and perfusion processes where increased pCO2 concentrations are likely to occur. Our results suggest, that so far unexplained metabolic changes may be connected to increased pCO2 accumulation in larger scale fermentations. Finally, we propose several mechanisms through which increased pCO2 might affect the cell metabolism and briefly discuss methods to enable the lactate metabolic shift during cell cultivations.

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