ABSTRACT
Introduction: Tobacco (Nicotiana tabacum) cv Bright Yellow-2 (BY-2) cell suspension cultures enable the rapid production of complex protein-based biopharmaceuticals but currently achieve low volumetric productivity due to slow biomass formation. The biomass yield can be improved with tailored media, which can be designed either by laborious trial-and-error experiments or systematic, rational design using mechanistic models, linking nutrient consumption and biomass formation. Methods: Here we developed an iterative experiment-modeling-optimization workflow to gradually refine such a model and its predictions, based on collected data concerning BY-2 cell macronutrient consumption (sucrose, ammonium, nitrate and phosphate) and biomass formation. Results and discussion: The biomass formation was well predicted by an unstructured segregated mechanistic Monod-type model as long as the nutrient concentrations did not approach zero (we omitted phosphate, which was completely depleted). Multi-criteria optimization for sucrose and biomass formation indicated the best tradeoff (in a Paretian sense) between maximum biomass yield and minimum process time by reducing the initial sucrose concentration, whereas the inoculation biomass could be increased to maximize the biomass yield or minimize the process time, which we confirmed in calibration experiments. The model became inaccurate at biomass densities > 8 g L-1 dry mass when sucrose was almost depleted. We compensated for this limitation by including glucose and fructose as sucrose hydrolysis products in the model. The remaining offset between the simulation and experimental data might be resolved by including intracellular pools of sucrose, ammonium, nitrate and phosphate. Overall, we demonstrated that iterative models can be used to systematically optimize conditions for bioreactor-based processes.
ABSTRACT
BACKGROUND: Chronic osteomyelitis (COM) causes major physical disability. In situations of limited resources and war zones, western world treatments are neither affordable nor sustainable. The International Committee of the Red Cross has established a COM treatment project in the Democratic Republic of Congo, with emphasis on affordability and sustainability. METHODS: One hundred and sixty-eight patients were treated for COM. The protocol focused on surgical excision of necrotic bone, physiotherapy and an open wound dressing method using granulated brown sugar. RESULTS: Seventy-one patients could be reviewed with a mean follow-up of 13.7 months (5-28 months). 46 patients (63.4%, 95% CI 52.5-75.6) had excellent/good results in terms of clinical cure of the infection, and 36 patients (50.7%, 95% CI 38.7-62.7) had seen excellent/good improvement in their functional status compared with before treatment. CONCLUSIONS: The above-mentioned treatment protocol has shown encouraging results: almost two-thirds of the patients had their infection clinically cured, and half the patients saw significant functional improvement.
Subject(s)
Disease Management , Osteomyelitis/therapy , Outcome Assessment, Health Care/statistics & numerical data , Red Cross , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Chronic Disease , Clinical Protocols , Debridement , Democratic Republic of the Congo , Dietary Sucrose/therapeutic use , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Osteonecrosis/surgery , Physical Therapy Modalities , Warfare , Wound Closure Techniques , Young AdultABSTRACT
Breast tuberculosis can confuse the clinician by its close resemblance to carcinoma or non-specific abscess, with obvious negative therapeutical implications. We present two cases, one mimicking a breast malignancy and the other being confused with non-specific abscess, to illustrate the misdiagnosis risks and diagnostic challenges.
