Evaluation of the Newborn Screening Pilot for Sickle Cell Disease in Suriname Using the Non-Adoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) Framework.

The early detection of sickle cell disease (SCD) is vital to reduce mortality among affected children. Suriname currently lacks a newborn screening programme (NSP) for SCD. We performed a pilot programme to evaluate the scalability of such an initiative. Dried blood spots were collected from five birth centres and subjected to electrophoresis analysis. The programme scalability was evaluated using the non-adoption, abandonment, scale-up, spread, and sustainability framework. Challenges across six domains (illness, technology, value proposition, adopter system, organisation, and societal system), were categorised hierarchically as simple 😊, complicated 😐, or complex 😢. It has been proven that implementing programmes with mainly complicated challenges is difficult and those in mainly complex areas may be unachievable. SCD was detected in 33 of 5185 (0.64%) successfully screened newborns. Most of the domains were classified as simple or complicated. Disease detection and technology suitability for screening in Suriname were confirmed, with favourable parental acceptance. Only minor routine adjustment was required from the medical staff for programme implementation. Complex challenges included a reliance on external suppliers for technical maintenance, ensuring timely access to specialised paediatric care for affected newborns, and securing sustainable financial funding. Scaling up is challenging but feasible, particularly with a targeted focus on identified complex challenges.

Scale-Up of Coffea canephora Somatic Embryogenesis in Temporary Immersion System.

Somatic embryogenesis (SE) is a clear example of cellular totipotency. The SE of the genus Coffea has become a model for in vitro propagation for woody species and for the large-scale production of disease-free plants that provide an advantage for modern agriculture. Temporary immersion systems (TIS) are in high demand for the propagation of plants. The success of this type of bioreactor is based on the alternating cycles of immersion of the plant material in the culture medium, usually a few minutes, and the permanence outside the medium of the tissues for several hours. Some bioreactors are very efficient for propagating one species but not another. The efficiency of bioreactors depends on the species, the tissue used to propagate, the species' nutritional needs, the amount of ethylene produced by the tissue, and many more. In this protocol, we show how we produce C. canephora plants that are being taken to the field.

Conclusions and Perspectives on Plant Micropropagation in Temporary Immersion Systems.

In vitro propagation protocols that include temporary immersion systems are available for the most economically important plant species. However, these have not been established yet for multiple species. Having protocols validated by the scientific community guarantees the success of the mass production of commercial propagules. Besides, adequate TIS parameters should be established for each plant species to improve the efficiency of micropropagation processes. This book compiles basic and applied aspects of temporal immersion systems used for in vitro plant micropropagation, along with several detailed protocols already established, which may be used as a guide by those interested in this technique, including laboratory technicians, scientists, and other professionals.

Scaling up a home-visiting program for child development in Brazil: a comparative case studies analysis.

Background: In 2016, Brazil scaled up the Criança Feliz Program (PCF, from the acronym in Portuguese), making it one of the largest Early Childhood Development (ECD) programs worldwide. However, the PCF has not been able to achieve its intended impact. We aimed to identify barriers and facilitators to achieving the PCF implementation outcomes across the RE-AIM dimensions (Reach, Effectiveness or Efficacy, Adoption, Implementation and Maintenance) during the COVID-19 pandemic. Methods: This comparative case study analysis selected five contrasting municipalities based on population size, region of the country, implementation model, and length of time implementing the PCF. We conducted 244 interviews with PCF municipal team (municipal managers, supervisors, home visitors), families, and cross-sectoral professionals. A rapid qualitative analysis was used to identify themes across RE-AIM dimensions. Findings: Families' limited knowledge and trust in PCF goals were a barrier to its reach. While the perceived benefit of PCF on parenting skills and ECD enabled reach, the lack of referral protocols to address social needs, such as connecting food-insecure families to food resources, undermined effectiveness. Questions about whether the social assistance sector should be in charge of PCF challenged its adoption. Implementation barriers exacerbated by the COVID-19 pandemic included low salaries, temporary contracts, high turnover, infrequent supervision, lack of an effective monitoring system, and nonexistence or non-functioning multisectoral committees. The absence of institutionalized funding was a challenge for sustainability. Interpretation: Complex intertwined system-level barriers may explain the unsuccessful implementation of PCF. These barriers must be addressed for Brazil to benefit from the enormous reach of the PCF and the evidence-based nurturing care principles it is based upon. Funding: NIH/NICHD.

Photobioreactor configurations in cultivating microalgae biomass for biorefinery.

Microalgae, highly prized for their protein, lipid, carbohydrate, phycocyanin, and carotenoid-rich biomass, have garnered significant industrial attention in the context of third-generation (3G) biorefineries, seeking sustainable alternatives to non-renewable resources. Two primarily cultivation methods, open ponds and closed photobioreactors systems, have emerged. Open ponds, favored for their cost-effectiveness in large-scale industrial production, although lacking precise environmental control, contrast with closed photobioreactors, offering controlled conditions and enhanced biomass production at the laboratory scale. However, their high operational costs challenge large-scale deployment. This review comprehensively examines the strength, weakness, and typical designs of both outdoor and indoor microalgae cultivation systems, with an emphasis on their application in terms of biorefinery concept. Additionally, it incorporates techno-economic analyses, providing insights into the financial aspects of microalgae biomass production. These multifaceted insights, encompassing both technological and economic dimensions, are important as the global interest in harnessing microalgae's valuable resources continue to grow.

LED-irradiated photo-Fenton process on pollutant removal: outcomes, trends, and limitations.

This manuscript critically reviews the state of the art on the application of photo-Fenton processes irradiated by light-emitting diode arrays (LED) with a focus on the removal of contaminants of emerging concern (CEC) from aqueous matrices. LEDs are clean, low-cost radiation sources with longer lifespan compared to mercury lamps. This study covers the influence of LED sources, wavelengths, and dose upon CEC removal, and the potential for disinfection, abatement of antibiotic-resistant bacteria (ARB), and genes (ARG). The bibliographic search was performed in Scopus database using keyword combinations and resulted in a portfolio containing 52 relevant articles published between 2010-2023. According to reviewed papers, LED photoreactor design has evolved in the past decade aiming to improve CEC degradation in aqueous matrices while reducing construction and operation costs, and energy consumption. Among several reactors (annular, fluidized bed, parallel plate, wireless, pathway systems, and microreactor) surveyed for their performance and scalability, LED chips and strips are particularly suitable for application due to their wide emission angle (≈120°) and small size (mm2), which allow for, respectively, efficient illumination coverage and flexible arrangement and design. LED microreactors are very efficient in the degradation of contaminants and scalable with reduced area requirements. Although most studies were performed in synthetic solutions and at laboratory scale, the externally LED irradiated cylindrical reactor was successful for application in full-scale municipal water treatment plants. Future studies should focus on evaluating CEC removal in wastewater using scalable devices for continuous operation of solar photo-Fenton at night.

In Vitro Conversion of Coffea spp. Somatic Embryos in SETIS™ Bioreactor System.

Somatic embryogenesis (SE) is an excellent example of mass plant propagation. Due to its genetic variability and low somaclonal variation, coffee SE has become a model for in vitro propagation of woody species, as well as for large-scale production of vigorous plants that are advantageous to modern agriculture. The success of the large-scale propagation of an embryogenic system is dependent on the development, optimization, and transfer of complementary system technologies. In this study, two successful SE systems were combined with a SETIS™ bioreactor immersion system to develop an efficient and cost-effective approach for the in vitro development of somatic embryos of Coffea spp. This study used an efficient protocol for obtaining somatic embryos, utilizing direct and indirect SE for both C. canephora and C. arabica. Embryos in the cotyledonary stage were deposited in a bioreactor to complete their stage of development from embryo to plant with minimal manipulation. Following ten weeks of cultivation in the bioreactor, complete and vigorous plants were obtained. Different parameters such as fresh weight, length, number of leaves, and root length, as well as stomatal index and relative water content, were recorded. In addition, the survival rate and ex vitro development of plantlets during acclimatization was assessed. The best substrate combination was garden soil (GS), peat moss (PM), and agrolite (A) in a 1:1:0.5 ratio, in which the bioreactor-regenerated plants showed an acclimatization rate greater than 90%. This is the first report on the use of SETIS™ bioreactors for the in vitro development of somatic embryos in Coffea spp., providing a technology that could be utilized for the commercial in vitro propagation of coffee plants. A link between research and innovation is necessary to establish means of communication that facilitate technology transfer. This protocol can serve as a basis for the generation and scaling of different species of agroeconomic importance. However, other bottlenecks in the production chains and the field must be addressed.

From an interventional study to a national scale-up: lessons learned from the Malakit strategy at the French Guiana-Suriname border.

Scaling-up an experimental intervention is always a challenge. On the border between French Guiana, Brazil and Suriname, an interventional study demonstrated the effectiveness of distributing self-diagnosis and self-treatment kits (Malakits) to control malaria in mobile and hard-to-reach populations. Its integration into the Suriname's National Malaria Elimination Plan after a 2-year experiment faced numerous challenges, including human resources to cope with the additional workload of coordinators and to maintain the motivation of community health workers. The economic recession in Suriname, the Covid pandemic, and logistical issues also hampered the scale-up. Finally, thanks to the commitment of stakeholders in Suriname and French Guiana, the integration of Malakit distribution into the Surinamese national programme was proved possible.

Using lessons learnt from key stakeholders to increase support for scaling the Reach Up Early Childhood Parenting program.

Introduction: Sustainable implementation of early childhood programs requires resources, materials and methods that are adaptable, scalable and feasible for delivery through multiple sectors. Additional or modified program resources may be required to meet emerging needs, as programs go to scale. An active and effective monitoring, evaluation and learning (MEL) process may enable programs to be responsive to demands. The Reach Up: Early Childhood Parenting program, is designed primarily for disadvantaged children under 4 years of age in low- and middle-income countries (LMICs) to promote their development through playful caregiver interactions. The curriculum, training manuals and other materials and resources support implementers in the adaptation of the intervention, implementation, workforce training, monitoring and evaluation. This paper reports on how data collected from key informants drove modifications to program processes, materials and resources. Methods: We conducted in-depth interviews with 14 key informants (including program managers, lead trainers, academics, consultants and workforce personnel) on their experiences with Reach Up across 15 LMICs where the program has been implemented. We also reviewed written records generated from (i) structured small group discussions at a Knowledge Exchange meeting of 31 Reach Up partners and (ii) notes from working groups formed at the meeting and tasked to continue working post-meeting to find solutions to support ongoing implementation. The transcripts from the in-depth interviews and the meeting records were analysed using thematic analysis with a mixture of pre-defined categories and data-driven sub-themes. Results: The main findings indicated that there was a need to: (i) develop advocacy and communication resources and materials to aid prospective implementers and other stakeholders, to make decisions for implementation, (ii) revise and/or add to the content and format of the curriculum and add content in the training and other supporting manuals and (iii) enhance the training process. Conclusion: The feedback from the key global partners informed the development of new knowledge materials, resources and processes and modifications to existing program materials and resources. These will help to support advocacy, ongoing implementations, and the process of transitioning the Reach Up early childhood intervention to scale.

Optimization and scale up of the enzymatic hydrolysis of Californian red worm protein (Eiseniafoetida).

Although the best-known use of the different species of earthworm is the production of organic fertilizer, they can also be considered a rich source of biologically and pharmacologically-active compounds, for use in the treatment of various diseases. In recent decades, with the development of biochemical technologies, research on the pharmaceutical effects of compounds extracted from different species of earthworms has begun. Enzymatic hydrolysis is the most common and widely used technique for producing bioactive hydrolysates, because it uses moderate operating conditions, with a certain specificity for the substrate. In the present study, the objective was to optimize and scale up the enzymatic hydrolysis of Eisenia foetida protein to obtain peptides with biological activity. The substrate characterization was carried out according to AOAC, a response surface design was performed for the optimization of the enzymatic hydrolysis and then the scaling was performed by means of dimensional analysis. The results show that the major component of the paste is protein, 65% of which is albumin, and the absence of pathogenic microorganisms was also found. Regarding optimization, it was found that the optimal hydrolysis conditions are achieved with pH = 8.5; temperature = 45 °C; amount of substrate = 125 g and volume of enzyme = 1245µL. For the scaling, 4 dimensionless pi-numbers were calculated which describe the process with no statistically significant differences between the model and the prototype; it can be concluded that the enzymatic hydrolysate of Eisenia foetida presents high values of antioxidant activity evaluated by different methodologies.

Optimizing the Production of gp145, an HIV-1 Envelope Glycoprotein Vaccine Candidate and Its Encapsulation in Guanosine Microparticles.

We have developed a pipeline to express, purify, and characterize HIV envelope protein (Env) gp145 from Chinese hamster ovary cells, to accelerate the production of a promising vaccine candidate. First in shake flasks, then in bioreactors, we optimized the growth conditions. By adjusting the pH to 6.8, we increased expression levels to 101 mg/L in a 50 L bioreactor, nearly twice the previously reported titer value. A battery of analytical methods was developed in accordance with current good manufacturing practices to ensure a quality biopharmaceutical. Imaged capillary isoelectric focusing verified proper glycosylation of gp145; dynamic light scattering confirmed the trimeric arrangement; and bio-layer interferometry and circular dichroism analysis demonstrated native-like properties (i.e., antibody binding and secondary structure). MALDI-TOF mass spectrometry was used as a multi-attribute platform for accurate mass determination, glycans analysis, and protein identification. Our robust analysis demonstrates that our gp145 product is very similar to a reference standard and emphasizes the importance of accurate characterization of a highly heterogeneous immunogen for the development of an effective vaccine. Finally, we present a novel guanosine microparticle with gp145 encapsulated and displayed on its surface. The unique properties of our gp145 microparticle make it amenable to use in future preclinical and clinical trials.

Scale-up and fed-batch cultivation strategy for the enhanced co-production of microbial lipids and carotenoids using renewable waste feedstock.

Agro-industrial by-product valorization as a feedstock for the bioproduction of high-value products has demonstrated a feasible alternative to handle the environmental impact of waste. Oleaginous yeasts are promising cell factories for the industrial production of lipids and carotenoids. Since oleaginous yeasts are aerobic microorganisms, studying the volumetric mass transfer (kLa) could facilitate the scale-up and operation of bioreactors to grant the industrial availability of biocompounds. Scale-up experiments were performed to assess the simultaneous production of lipids and carotenoids using the yeast Sporobolomyces roseus CFGU-S005 and comparing the yields in batch and fed-batch mode cultivation using agro-waste hydrolysate in a 7 L bench-top bioreactor. The results indicate that oxygen availability in the fermentation affected the simultaneous production of metabolites. The highest production of lipids (3.4 g/L) was attained using the kLa value of 22.44 h-1, while higher carotenoid accumulation of 2.58 mg/L resulted when agitation speed was increased to 350 rpm (kLa 32.16 h-1). The adapted fed-batch mode in the fermentation increased the production yields two times. The fatty acid profile was affected according to supplied aeration and after the fed-batch cultivation mode. This study showed the scale-up potential of the bioprocess using the strain S. roseus in the obtention of microbial oil and carotenoids by the valorization of agro-industrial byproducts as a carbon source.

Norfloxacin Cocrystals: Mechanochemical Synthesis and Scale-up Viability Through Solubility Studies.

Cocrystals are recognized as one of the most efficient approaches to improve aqueous solubility of Biopharmaceutical Classification System, BCS, classes II and IV drugs. Cocrystal discovery and the establishment of experimental conditions suitable for scale-up purposes are some of the main challenges in cocrystal investigation. In this work, the investigation of mechanochemical synthesis of norfloxacin cocrystals with picolinic and isonicotinic acids is performed, leading to the discovery of two new cocrystals of this important BCS class IV antibiotic, which were characterized through thermal, spectral and diffractometric analysis. Norfloxacin apparent aqueous solubility using the cocrystals is also presented, with higher values being obtained for all the investigated systems when compared to the pure drug. Norfloxacin has 3 polymorphs and several solvents/hydrates, which represents a challenge for obtaining pure cocrystal forms from solvent crystallization. This challenge was successfully overcome in this work, as experimental conditions to obtain the pure cocrystals (the new ones and also norfloxacin-nicotinic acid and norfloxacin-saccharin) were established using Crystal16 equipment. This is a crucial step to envisage future scale-up procedures and therefore a valuable information for the pharmaceutical industry.

Highly water-soluble dapsone nanocrystals: Towards innovative preparations for an undermined drug.

Dapsone (DAP)is a dual-function drug substance; however, its limited water solubility may impair its bioavailability. Drug nanocrystals are an alternative to overcome this limitation. Herein, a DAP nanosuspension was prepared using adesign space approach aiming to investigate the influence of raw material properties and process parameters on the critical quality attributes of the drugnanocrystals. Optimized nanocrystals with 206.3 ± 6.7 nm using povacoat™ as stabilizer were made. The nanoparticles were characterized by dynamic light scattering, laser diffraction, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and saturation solubility. Compared to the raw material, the nanocrystals were 250-times smaller. Meanwhile, its crystalline state remained basically unchanged even after milling and drying. The nanosuspension successfully maintained its physical stability inlong-termandaccelerated stability studiesover, 4 and 3 months. Furthermore, toxicity studiesshowed low a toxicity at a20 mg/kg. As expected for nanocrystals, the size reduction improvedsaturation solubility3.78 times in water. An attempt to scale up from lab to pilot scale resulted nanocrystals of potential commercial quality. In conclusion, the present study describes the development of dapsone nanocrystals for treating infectious and inflammatory diseases. The nanocrystal formuation can be scaled up for commercial use.

New insight into the role of oxygen supply for surfactin production in bench-scale bioreactors using induced surface aeration.

Surfactin biosurfactant produced by Bacillus sp. has been studied, because it has enormous potential in several applications in the oil and cosmetics industry. The cultivation conditions for obtaining this bioproduct, however, still require attention, as, for example, parameters related to oxygen supply and consumption. In this study, different volumetric oxygen transfer coefficient (KLa) levels (0-11.56 h-1) were tested in bench-scale bioreactor for surfactin biosurfactant production by Bacillus velezensis H2O-1, using induced surface aeration. While conditions close to anaerobiosis showed insignificant production of surfactin, an intermediated KLa condition (4.24 h-1) generated the best surfactin concentration (579.6 mg L-1), with a volumetric productivity of 11.9 mg L-1 h-1. These results showed that the oxygen demand to produce surfactin is not high, being possible to use induced surface aeration strategy in bioreactors, minimizing foam formation. In addition, in all KLa conditions tested, surfactin homologues C14 and C15 had higher relative abundance. Nevertheless, the KLa parameter seems to have had minimal influence on affecting the relative abundances of surfactin homologues produced. Particularly noteworthy in this study is the possibility of producing surfactin using a low-cost and scale-up feasible aeration strategy, unlike the foam collection strategies developed in other studies to obtain this bioproduct.

Alternative activated/KOH adsorbent for phenol adsorption: experimental, industrial case study and mass transfer interpretation.

Removal of phenol from wastewater is essential to achieve permitted concentrations according to the recommendations of USEPA. The adsorption capacity of phenol in activated adsorbent with KOH of Enterolobium contortisiliquum (TAC) was evaluated at different temperatures. The Langmuir isotherm represented the equilibrium data of this study. Thermodynamic process was endothermic, spontaneous, and reversible. The mass transfer parameters ranged from KE 0.68 to 0.96 × 10-3 (cm s-1), Ds 8.95 to 14.35 × 10-9 (cm2 s-1), and Dp 5.023 × 10-8 (cm2 s-1). The PVSDM model represented the adsorption kinetics. Intraparticle diffusion limits the mass transfer process Biot > 100. The two-stage process minimized the total amount of TAC required to achieve the permitted specification of phenol concentration in wastewater from different industrial sectors. TAC showed significant performance in the removal of phenol from wastewater.

Volumetric Scale-Up of a Packed-Bed Ion-Exchange System to Extract Phytate from Thin Stillage.

Phytate is the main form of phosphorus in corn ethanol coproducts and poses digestion issues in monogastric-animal feed. Extracting phytate as a commodity chemical will bring extra revenue to the corn ethanol industry and reduces potential phosphorus pollution from livestock waste management. We assessed a simplified scale-up approach of an ion-exchange separation system applied to extract phytate from thin stillage using volumetric parameters and simplifications of the van Deemter model. Thin stillage is one of the main byproducts generated on dry-grind corn-to-ethanol plants and accounts for the liquid portion of the bottom product generated in the ethanol distillation process. Thin stillage is rich in dissolved phytate, which served as the basis for an ion-exchange extraction system developed with a scalability factor of 50. Under the evaluated conditions, similar breakthrough profiles were obtained when similar Péclet and Stanton numbers were maintained for the scales studied, demonstrating that a simple and straightforward scale-up can be attained if special attention is given to maintaining both parameters as the basis of calculations of the plate numbers of ion-exchange columns.

Relation of shear stress and KLa on bikaverin production by Fusarium oxysporum CCT7620 in a bioreactor.

This study involved evaluating the effects of rotational impeller speed agitation (N) and specific air flow rate (Фair) on bikaverin production and on the growth of Fusarium oxysporum employing 11 bench-scale bioreactor assays. The results showed that the maximum bikaverin production (close to 300 mg L-1) was achieved after 48 h of fermentation in rice medium (20 g L-1 milled rice in water) at 28 °C with a volumetric oxygen transfer coefficient (KLa) and shear stress values of approximately 20 h-1 and 17 N m-2, respectively. We reached this combination of parameters using an N of 340 rpm and Фair of 0.935 vvm. These KLa and shear stress values can be used as references when upscaling this process. Thus, this study was important to demonstrate how the main parameters in bioreactors affect bikaverin production and it presented important indications for upscaling this bioprocess.

Formulation Process Analysis of a Virus-based Biopesticide to Control the Tomato leafminer Tuta absoluta

Abstract: Virus-based biopesticides are effective biocontrol agents of crop insect pests. Development of suitable formulations and production processes are necessary to obtain high-quality products easily adopted by farmers. A detailed unit operation study was carried out for the production process of a Phthorimaea operculella granulovirus-based biopesticide to control the tomato leafminer, Tuta absoluta, one of the most important pests affecting this crop. Physicochemical, microbiological, and insecticidal parameters were implemented in the process and applied to the finished product, and a scaling strategy was developed. A Quantitative Polymerase Chain Reaction (Q-PCR) technique was implemented to quantify viral concentrations in the active ingredient (5.34 ± 1.44 x109 Occlusion Bodies mL-1) and in the finished product (>1.6x109 OB mL-1), without contaminant interferences. The Q-PCR methodology was also useful to select the appropriate solid mixing time following Lacey´s mixing index (8 min). Factors and similarity principles influencing the liquid mixing process were identified in the scaling evaluation. Furthermore, the drying kinetics analysis enabled identifying a drying temperature of 35 °C, with an efficacy under controlled conditions higher than 97%. Contaminant concentration was lower than 1%, indicating controlled and aseptic formulation process conditions. A simple statistical method was used to estimate the reproducibility and repeatability of the parameters assessed in the finished product. These results enable to establish and extrapolate important parameters in the standardization, scale-up, and quality control for the granulovirus-based biopesticide.

Spark Plasma Sintering of Aluminum Nanocomposite Powders: Recent Strategy to Translate from Lab-Scale to Mass Production.

The aim of this paper focuses on presenting a recent study that describes the fundamental steps needed to effectively scale-up from lab to mass production parts produced from Al powders reinforced with 0.5 wt% of industrial multiwalled carbon nanotubes (MWCNTs), with mechanical and electrical conductivity properties higher that those measured at the lab scale. The produced material samples were produced via a Spark Plasma Sintering (SPS) process using nanocomposite aluminum powders elaborated with a planetary ball-mill at the lab scale, and high-volume attrition milling equipment in combination with controlled atmosphere sinter hardening furnace equipment, which were used to consolidate the material at the industrial level. Surprisingly, the electrical conductivity and mechanical properties of the samples produced with the reinforced nanocomposite Al powders were made with mass production equipment and were similar or higher than those samples fabricated using metallic powders prepared with ball-mill lab equipment. Experimental measurements show that the hardness and the electrical conductivity properties of the samples fabricated with the mass production Al powders are 48% and 7.5% higher than those of the produced lab samples. This paper elucidates the steps that one needs to follow during the mass production process of reinforced aluminum powders to improve the physical properties of metallic samples consolidated via the SPS process.