MODELAMIENTO DE LA TRANSFERENCIA DE CALOR Y MASA (AGUA) EN UN BIORREACTOR DE CHAROLAS PARA FERMENTACION EN MEDIO SOLIDO

In this paper we developed a mathematical model for predicting temperature and moisture content profiles in the bed of a tray bioreactor for so lid-state fermentation (SSF). For this purpose we developed heat and mass (wat er) balances which considered the main mechanisms of heat and mass transfer in the fermentation bed. These ba lances were used to estimate the heat and mass (water) transfer co efficients. Bioreaction was also proposed for substrate consumption, biomass generation, CO 2 and water. Stoichiometric balances were carried out to describe the growth of microorganisms. We used two strains, Aspergillus niger AT for fermentations (runs) on substrate- support (70%, wheat bran; 30%, soybean meal) and Aspergillus niger C28B25 for fermentations on inert support (perlite). In the runs on s ubstrate-support, CO 2 production and fermentation bed temperature (no data storage) were on-line measured and initial and final moisture content of fermentation bed, water ac tivity, pH and enzyme activity phytase were off-line measured. In the r uns on inert support, CO 2 production and fermentation bed temperature (both data storage), were measured and at regular time intervals, moisture, water activity, pH, enzymatic activity of invertase, biomass concentr ation, substrate concentration were off-line measured. The online measurement of CO 2 production in the process was important because from these data, we estimated metabolic water generation, biomass and metabolic heat generation using the proposed bioreactions. Ordinary differential equations obtained fr om the water and energy balances allowed predictions of temperature and moisture cont ent profiles in the fermentation bed of tray bioreactor. The system of or dinary differential equations was solved using the algorithm "Runge-Kutta.Fehlberg (RKF56) Polymath ® so ftware version 6.0. Integral mass and energy balances made possible to estimate the coeffici ents of heat and mass transfer (water) during the growth of microorganisms, which were used later in the mathematical model proposed. The profiles predictions obtaine d with the model for temperature and moisture content in fermentation bed, showed good fit compared with the experimental data for different operating conditions in the tray bioreactor. As a strategy for removing metabolic heat from the bed of fermentation the use of a fan system is proposed to change the air flow cond itions in the bioreactor headspace (air space within the bioreactor that is not within the matrix of the substrate), the variations caused by internal forced air circulation we re defined by the Reynolds number (NRe). The effect of the NRe and fermentation bed height (o peration variables) on the va riables described above were evaluated. This study was conducted in both support-substrate as inert support. In the studies with substrate support and inert support carried out was found that the increase in bed height leads to higher accumulation of heat in the fermentation bed affecting negatively to the enzyme activities. The increase in the NRe had a positive effect in heat removal, improving the enzyme activities, however, must be found an optimum value, since the use of high values of NRe causes drying of fermentation bed that affect adversely the enzyme activities.En este trabajo se construyó un modelo matemático para la predi cción de los perfiles de temperatura y contenido de humedad en el lecho de un biorreactor de charolas para fermentación en medio sólido (FMS). Para este propósito se desarrollaron balances de calor y masa (agua) que consideraron los principales mecanismos de transferencia de calor y masa en el lecho de fermentación. Estos balances fueron empleados para estimar los coeficientes de transferencia de calor y masa (agua). También se propusieron biorreacciones de consumo de sustrato y generación de biomasa, CO 2 y agua, se llevaron a cabo los balances estequiométricos para describir el crecimiento de los microorganismos. Se emplearon dos cepas, Aspergillus niger AT para las ferment aciones (corridas) en soporte-sustrato (70% salvado de trigo, 30% harina de soya) y Aspergillus niger C28B25 para las fermentaciones en soporte iner te (agrolita). En las corridas en soporte-sustrato se midió en línea la producción de CO2 y la temperatura (sin almacenamiento de datos) y fuera de línea los valores iniciales y finales del contenido de humedad de lecho de fermentación, actividad de agua, pH y actividad enzimática de la fitasa. En las corridas en soporte inerte, se midió en línea la producción de CO 2 y la temperatura (ambas con almacenamiento de datos), y fuera de línea y a intervalos regulares de tiempo la hu medad, la actividad de agua, pH, actividad enzimática de la invertasa, concentración de biomasa producida, concen tración de sustrato consumido. La medición en línea del CO 2 resultó importante en el pr oceso ya que a partir de estos datos se estimó la generación de agua metabólica, producción de biomasa y generación de calor metabólico empleando las biorreacciones propuestas. Las ecuaciones diferenciales or dinarias obtenidas de los balances de agua y energía permitieron realizar la predicción de los perfiles de temperatura y del contenido de humedad del lecho en el biorreactor de charolas. El si stema de ecuaciones diferenciales ordinarias fue resuelto usando el algoritmo “Runge-Kutta.F ehlberg (RKF56) del software Polymath® Versión 6.0. Los balances integrales de materia y energía permitieron estimar los coeficientes de transferencia de calor y masa (agua) durante el crecimiento del microorganismo, los cuales fueron usados posteriormente en el modelo matemático propuesto. Las predicciones de los perfiles de temperatura y humedad en el lecho de fermentación realizadas con el modelo, en comparación con los datos experimentales, mostraron buen ajuste para diferentes condiciones de operación en el biorreactor de charolas. Como estrategia para la remoción del calor metabólico del lecho de fermentación se propuso el empleo de un sistema de ventilador es, para cambiar las condiciones de flujo del aire en el “headspace” (nombre con que se designa al espacio de aire dentro del biorreactor que no está dentro de la matriz del sustrato) del biorreactor, las variac iones provocadas por la circulación interna forzada del aire fueron definidas por medio del número de Reynolds (NRe). Se evaluó el efecto del NRe y la altura del lecho de fermentación (variables de operación) sobre las variables medidas mencionadas anteriormente. Lo anterior se realizó para los estudios tanto en soporte-sustrato como en soporte inerte. En los estudios con soporte-sustrato y con s oporte inerte se observó que el aumento en la altura del lecho provoca mayor acumulación de calor en el lecho de fermentación que afectó negativamente las actividades enzimáticas. El aumento en el NRe tuvo un efecto positivo en la re moción de calor, mejorando las actividades enzimáticas, sin embargo, debe encontrarse un valor óptimo, ya que emplear altos valores del NRe ocasiona secado del lecho de ferm entación afectando negativamente la actividad enzimática

Humoral response after a BNT162b2 heterologous third dose of COVID-19 vaccine following two doses of BBIBP-CorV among healthcare personnel in Peru

Background: The inactivated virus vaccine, BBIBP-CorV, was principally distributed across low- and middle-income countries as primary vaccination strategy to prevent poor COVID-19 outcomes. Limited information is available regarding its effect on heterologous boosting. We aim to evaluate the immunogenicity and reactogenicity of a third booster dose of BNT162b2 following a double BBIBP-CorV regime. Methods: We conducted a cross-sectional study among healthcare providers from several healthcare facilities of the Seguro Social de Salud del Perú - ESSALUD. We included participants two-dose BBIBP-CorV vaccinated who presented a three-dose vaccination card at least 21 days passed since the vaccinees received their third dose and were willing to provide written informed consent. Antibodies were determined using LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin Inc., Stillwater, USA). Factors potentially associated with immunogenicity, and adverse events, were considered. We used a multivariable fractional polynomial modeling approach to estimate the association between anti-SARS-CoV-2 IgG antibodies’ geometric mean (GM) ratios and related predictors. Results: We included 595 subjects receiving a third dose with a median (IQR) age of 46 [37,54], from which 40% reported previous SARS-CoV-2 infection. The overall geometric mean (IQR) of anti-SARS-CoV-2 IgG antibodies was 8,410 (5,115 – 13,000) BAU/mL. Prior SARS-CoV-2 history and full/part-time in-person working modality were significantly associated with greater GM. Conversely, time from boosting to IgG measure was associated with lower GM levels. We found 81% of reactogenicity in the study population; younger age and being a nurse were associated with a lower incidence of adverse events. Conclusions: Among healthcare providers, a booster dose of BNT162b2 following a full BBIBP-CorV regime provided high humoral immune protection. Thus, SARS-CoV-2 previous exposure and working in person displayed as determinants that increase anti-SARS-CoV-2 IgG antibodies

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd

Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials

Background: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). Methods: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300). Findings: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). Interpretation: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD