Structure-guided drug design targeting Abl kinase: how structure and regulation can assist in designing new drugs.

The human protein Abelson kinase (Abl), a tyrosine kinase, plays a pivotal role in developing chronic myeloid leukemia (CML). Abl's involvement in various signaling pathways underscores its significance in regulating fundamental biological processes, including DNA damage responses, actin polymerization, and chromatin structural changes. The discovery of the Bcr-Abl oncoprotein, resulting from a chromosomal translocation in CML patients, revolutionized the understanding and treatment of the disease. The introduction of targeted therapies, starting with interferon-alpha and culminating in the development of tyrosine kinase inhibitors (TKIs) like imatinib, significantly improved patient outcomes. However, challenges such as drug resistance and side effects persist, indicating the necessity of research into novel therapeutic strategies. This review describes advancements in Abl kinase inhibitor development, emphasizing rational compound design from structural and regulatory information. Strategies, including bivalent inhibitors, PROTACs, and compounds targeting regulatory domains, promise to overcome resistance and minimize side effects. Additionally, leveraging the intricate structure and interactions of Bcr-Abl may provide insights into developing inhibitors for other kinases. Overall, this review highlights the importance of continued research into Abl kinase inhibition and its broader implications for therapeutic interventions targeting kinase-driven diseases. It provides valuable insights and strategies that may guide the development of next-generation therapies.

Mitochondrion genomes of seven species of the endangered genus Sporophila (Passeriformes: Thraupidae).

We announce the mitochondrial genomes of seven species of the genus Sporophila (S. bouvreuil, S. iberaensis, S. melanogaster, S. minuta, S. nigrorufa, S. pileata, and S. ruficollis) which were validated by comparative genomic and phylogenetic analysis with related species. The mitochondrial genomes of seven passerines of the genus Sporophila were assembled (three complete and four nearly complete genomes) and were validated by reconstructing phylogenetic relations within Thraupidae. The complete mitogenomes ranged from 16,781 bp in S. ruficollis to 16,791 bp in S. minuta. We identified a conserved genome composition within all mitogenomes with 13 protein-coding genes, 22 tRNAs and two rRNAs. We observed a bias in the nucleotide composition and six mutational hotspots in Sporophila mitogenomes. Our mitogenome-based phylogenetic tree has S. minuta, S. maximiliani and S. nigricollis as sister species of the remaining species in the genus. We present new mitogenome sequences for seven Sporophila species, providing new genomic resources that may be useful for research on the evolution, comparative genetics, and conservation of this threatened group.

Differences in DNA methylation status explain phenotypic variability in patients with 5p- syndrome.

Cri Du Chat syndrome, or 5p- syndrome, is characterized by a terminal or interstitial deletion on the short arm of chromosome 5 that causes variable clinical manifestations, including high-pitched cry in newborns, delayed growth, and global development. Different cytogenomic rearrangements, family history, and environmental factors may hinder the genotype-phenotype association. Thus, the phenotypic variability of this syndrome may not be limited only to variations in gene structure, such as deletions and duplications. It is possible that other mechanisms related to the activation or inactivation of promoters and/or exons of actively transcribed genes, such as DNA methylation are involved. Therefore, we studied the genome-wide methylation status profile of peripheral blood samples from fifteen patients with Cri du Chat Syndrome and nine control samples through the array method to look for Differentially Methylated Regions. We found that Differentially Methylated Regions outside the 5p region are mainly associated with regulating gene transcription, splicing, and chromatin remodeling. Most biological pathways are related to transcription, histone and chromatin binding, spliceosome and ribosomal complex, and RNA processing. Our results suggest that changes in the 5p region can cause an imbalance in other chromosomal regions capable of affecting gene modulation and thus explain the phenotypic differences in patients with 5p-.

Synthesis and Evaluation of New Phytotoxic Fluorinated Chalcones as Photosystem II and Seedling Growth Inhibitors.

The development of novel phytotoxic compounds has been an important aim of weed control research. In this study, we synthesized fluorinated chalcone derivatives featuring both electron-donating and electron-withdrawing groups. These compounds were evaluated both as inhibitors of the photosystem II (PSII) electron chain as well as inhibitors of the germination and seedling growth of Amaranthus plants. Chlorophyll a (Chl a) fluorescence assay was employed to evaluate their effects on PSII, while germination experiments were conducted to assess their impact on germination and seedling development. The results revealed promising herbicidal activity for (E)-3-(4-bromophenyl)-1-(4-fluorophenyl)prop-2-en-1-one (7 a) and (E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one (7 e). Compounds 7 a and 7 e exhibited a reduction in Chl a parameters associated with performance indexes and electron transport per reaction center. This reduction suggests a decrease in PSII activity, attributed to the blockage of electron flow at the quinone pool. Molecular docking analyses of chalcone derivatives with the D1 protein of PSII revealed a stable binding conformation, wherein the carbonyl and fluorine groups interacted with Phe265 and His215 residues, respectively. Additionally, at a concentration of 100 µM, compound 7 e demonstrated pre- and post-emergent herbicidal activity, resulting in a reduction of the seed germination index, radicle and hypocotyl lengths of Amaranthus weeds.

Antimicrobial metabolites produced by endophytic fungi associated with the leaves of Vochysia divergens.

Investigation of the endophytic fungi Nigrospora sphaerica, Nigrospora oryzae, and Pseudofusicoccum stromaticum MeOH fractions isolated from the leaves of Vochysia divergens, a medicinal species from the Brazilian Pantanal, led to the identification of five compounds, namely a new compound (1E,8Z)-10,11-dihydroxy-5,5,8-trimethyl-4-oxocycloundeca-1,8-diene-1-carbaldehyde (1) and four known compounds: 5-methylmellein (2), sclerone (3), daldinone A (4), and lasiodiplodin (5). All compounds were identified using spectroscopic methods, and 1 was corroborated with mass spectrometry, while the known compounds were compared with data in the literature. The relative configuration of compound 1 was determined based on theoretical conformational studies as well as the J experimental values between the hydroxymethyne hydrogens. The antimicrobial activity of the compounds was evaluated. Promising results were obtained for compounds 2, 4, and 5 since they inhibited the bacterium Pseudomonas aeruginosa, an opportunistic pathogen, suggesting the potential of these microorganisms as a source of new antibacterial agents.

Effects of in-house and commercial extracts of the allergenic mite Tyrophagus putrescentiae on murine and human cell responses.

Mites are among the major sources of domestic and occupational allergens worldwide, and continuous exposure to these allergens leads to chronic airway inflammation. One of the most allergenic species is the storage mite Tyrophagus putrescentiae (Schrank). Protein extracts are produced from this mite for tests that help the clinical diagnosis (via prick test), treatment, and monitoring of disease progression in patients who had positive results for allergic reactions. Therefore, the aim of the present study was to evaluate the cell viability of RAW 264.7 and L929 cells when exposed to in-house raw protein extracts of T. putrescentiae compared to a commercial product, as well as quantify TNF-α secretion by RAW 264.7. Additionally, this study quantified the effect of these extracts in IgE secretion in total blood of people affected by this mite. The study found similarity between the in-house extract and the commercial extract as they had equivalent TNF-α secretion. Additionally, viabilities of RAW 264.7 and L929 exposed to the in-house extract were compatible with viabilities of cells exposed to the commercial extract, with no cytotoxicity at the concentrations tested. Results corroborated the hypothesis that the extract produced in-house would be equivalent to the commercial extract in allergic patients when the IgE was quantified. This study is the first to show the cytotoxicity of T. putrescentiae extracts, and to provide a quantitative analysis of TNF-α and IgE.

Secondary prevention in coronary artery disease: development and content validity of educational messages for mobile phones.

OBJECTIVE: To identify information needs of patients with coronary artery disease and develop and validate the content of educational messages for mobile phones for these patients. METHOD: The study was carried out in three phases: 1) Identification of information needs in relation to coronary artery disease of patients hospitalized for an acute coronary event; 2) Development of templates containing text and pictures about the disease and treatment; 3) Content validity analysis of template evidence through the assessment of 10 experts. Templates were considered validated when the Content Validity Ratio (CVR) was equal to or greater than 0.80. RESULTS: A total of 67 patients were included, and all the information that emerged about the disease was classified as important to very important. Thirty templates were developed (heart function, recommendations on nutrition and exercise, treatments and medications, and clinical signs related to the disease and risk factor control), and the CVR obtained was greater than 0.80. CONCLUSION: All information needs were categorized by patients as important or very important. The templates were developed and validated considering content and design.

Checklist of the fish fauna of the Munim River Basin, Maranhão, north-eastern Brazil.

Background: The Maranhão State harbours great fish diversity, but some areas are still undersampled or little known, such as the Munim River Basin in the northeast of the State. This lack of knowledge is critical when considering anthropogenic impacts on riverine systems especially in the face of major habitat destruction. These pressing threats mean that a comprehensive understanding of diversity is critical and fish checklists extremely relevant. Therefore, the present study provides a checklist of the fish species found in the Munim River Basin, Maranhão State, north-eastern Brazil, based on collected specimens. New information: A total of 123 species were recorded for the Munim River Basin, with only two non-native species, Oreochromisniloticus and Colossomamacropomum, showing that the fish assemblage has relatively high ecological integrity. In addition, 29 species could not be identified at the species level, indicating the presence of species that are probably new to science in the Basin. A predominance of species belonging to the fish orders Characiformes and Siluriformes, with Characidae being recovered as the most species-rich family (21 species) agrees with the general pattern for river basins in the Neotropical Region. The total fish diversity was estimated by extensive fieldwork, including several sampling gears, carried out in different seasons (dry and rainy) and exploring different environments with both daily and nocturnal sampling, from the Basin's source to its mouth. A total of 84 sites were sampled between 2010 and 2022, resulting in 12 years of fieldwork. Fish assemblages were distinct in the Estuary and Upper river basin sections and more similar in the Lower and Middle sections indicating environmental filtering processes. Species were weakly nested across basin sections, but unique species were found in each section (per Simpsons Index). High variability of species richness in the Middle river basin section is likely due to microhabitat heterogeneity supporting specialist fish communities.

ACL reconstruction associated with lateral extra-articular tenodesis with shared femoral tunnel

Recently, the anterolateral ligament has gained attention in knee surgery for its ability to improve rotational stability in ACL reconstructions. However, the lateral extra-articular tenodesis (LET) procedure, which involves creating a femoral tunnel using the modified Lemaire technique, presents a risk of overlapping with the femoral tunnel used in the ACL reconstruction. This can lead to complications and limit the success of the surgery. To avoid these issues without needing additional fixation, we describe an easily reproducible surgical technique in which a single femoral tunnel is shared for both ACL reconstruction and LET using the iliotibial tract

Recientemente, el ligamento anterolateral ha ganado atención en la cirugía de rodilla por su capacidad para mejorar la estabilidad rotacional en las reconstrucciones del LCA. Sin embargo, el procedimiento de tenodesis lateral extraarticular (TLE), que implica la creación de un túnel femoral utilizando la técnica modificada de Lemaire, presenta un riesgo de solapamiento con el túnel femoral utilizado en la reconstrucción del LCA. Esto puede provocar complicaciones y limitar el éxito de la cirugía. Para evitar estos problemas, sin necesidad de una fijación adicional, describimos una técnica quirúrgica fácilmente reproducible en la que se comparte un solo túnel femoral tanto para la reconstrucción del LCA como para LET utilizando el tracto iliotibial

Prevalence of migraine in patients with fibromyalgia / Prevalência de enxaqueca em pacientes com fibromialgia

Objective: To evaluate the prevalence of migraine in patients with fibromyalgia and the impacts of these comorbidities on the daily life of patients. Methods: Questionnaires were applied to fibromyalgia patients. The questionnaires were applied through a Google forms application link and in person, printed. We used FIQ, PHQ-9, and ID migraine. And for patients with a positive ID migraine, we applied the Midas subsequently. Results: Seventy fibromyalgia patients were recruited, age of 47.31 ± 14.5 years. Sixty-five (92.86%) were female and 5 (7.14%) were male. We obtained a prevalence of 60% (n = 42) of migraine associated with fibromyalgia. Among the analyzed variables, severity of depression (p = 0.007), aggregate severity of depression (p = 0.004), and impact of fibromyalgia (p = 0.008) were significantly associated. Among the migraine patients, the vast majority, 34/42 (80.95%), were classified as having severe disability. Conclusion: There is a high prevalence of migraine in patients with fibromyalgia that has an associated impact on patients' lives, which makes clinical and psychosocial management of these patients necessary.

Objetivo: Avaliar a prevalência de enxaqueca em pacientes com fibromialgia e os impactos dessas comorbidades no cotidiano dos pacientes. Métodos: Questionários foram aplicados a pacientes com fibromialgia. Os questionários foram aplicados por meio de link de aplicativo Google Forms e presencialmente, impressos. Usamos FIQ, PHQ-9 e enxaqueca ID. E para pacientes com enxaqueca ID positiva, aplicamos o Midas posteriormente. Resultados: Foram recrutados 70 pacientes com fibromialgia, idade de 47,31 ± 14,5 anos. Sessenta e cinco (92,86%) eram do sexo feminino e 5 (7,14%) do sexo masculino. Obtivemos uma prevalência de 60% (n = 42) de enxaqueca associada à fibromialgia. Entre as variáveis ​​analisadas, a gravidade da depressão (p = 0,007), a gravidade agregada da depressão (p = 0,004) e o impacto da fibromialgia (p = 0,008) foram significativamente associadas. Entre os pacientes com enxaqueca, a grande maioria, 34/42 (80,95%), foi classificada como portadora de incapacidade grave. Conclusão: Existe uma elevada prevalência de enxaqueca em pacientes com fibromialgia que tem impacto associado na vida dos pacientes, o que torna necessário o manejo clínico e psicossocial destes pacientes.

Binding Properties of Photosynthetic Herbicides: Photosynthetic Activity and Molecular Docking Approach towards 1,4-Dihydropyridines Derivatives.

In the current work, we describe the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives via Hantzsch multicomponent reaction and their evaluation as photosystem II (PSII) inhibitors through chlorophyll a fluorescence bioassay. Among all the compounds tested, 1,1'-(2,4,6-trimethyl-1,4-dihydropyridine-3,5-diyl)bis(ethan-1-one) (4b) showed best results, reducing the parameters performance index on absorption basis (PIabs ) and electron transport per reaction center by 61 % and 49 %, respectively, as compared to the control. These results indicate the inhibitory activity of PSII over the electron transport chain. Additionally, a molecular docking approach using the protein D1 (PDB code 4V82) was performed in order to assess the structure-activity relationship among the 1,4-DHP derivatives over the PSII, which revealed that both, size of the group at position 4 and the carbonyl groups at the dihydropyridine ring are important for the ligand's interaction, particularly for the hydrogen-bonding interaction with the residues His215, Ser264, and Phe265. Thus, the optimization of these molecular features is the aim of our research group to extend the knowledge of PSII electron chain inhibitors and the establishment of new potent bioactive molecular scaffolds.

Scale-Up of Capsular Polysaccharide Production Process by Haemophilus influenzae Type b Using kLa Criterion.

Polyribosyl-ribitol-phosphate (PRP) from Haemophilus influenzae type b (Hib) is an active immunizing molecule used in the production of the vaccine against H. influenzae, and industrial production could contribute to satisfying a world demand especially in developing countries. In this sense, the aim of this study was to establish a scale-up process using the constant oxygen mass transfer coefficient (kLa) such as the criterion for production of PRP in three different sizes of bioreactor systems. Three different kLa values (24, 52 and 80 h-1) were evaluated in which the biological influence in a 1.5 L bioreactor and 52 h-1 was selected to scale-up the production process until a 75 L pilot-scale bioreactor was achieved. Finally, the fed-batch phase was started under a dissolved oxygen concentration (pO2) at 30% of the saturation in the 75 L bioreactor to avoid oxygen limitation; the performance of production presented high efficiency (9.0 g/L DCW-dry cell weight and 1.4 g/L PRP) in comparison with previous scale-up studies. The yields, productivity and kinetic behavior were similar in the three-size bioreactor systems in the batch mode indicating that kLa is possible to use for PRP production at large scales. This process operated under two stages and successfully produced DCW and PRP in the pilot scale and could be beneficial for future bioprocess operations that may lead to higher production and less operative cost.

Holocene climate changes explain the spatial pattern in genetic diversity in populations of Cyperus papyrus from Southeast Africa wetlands.

Wetlands are one of the most threatened ecosystems in the world because more than 70% of the area worldwide has been lost since 1900. Wetland plant species rely greatly on water for seeds and propagules, which may lead to a downstream unidirectional dispersal and accumulation of genetic diversity downstream. However, several species show no support for unidirectional genetic diversity, revealing the complexity of population dynamics and gene flow in wetlands. Here, we used microsatellite loci to address how the past demographic dynamics shaped the contemporary spatial pattern in genetic diversity and population structure of Cyperus papyrus in wetlands of Southeast Africa. Using spatially explicit analysis and coalescent modelling, we found no support for unidirectional dispersal. Instead, we found higher genetic diversity in populations upstream than downstream in the river basin. We also found high admixture among populations, most likely due to connections between adjacent river basins during sporadic floods, and ongoing gene flow due to bird-mediated seed dispersal. Our results suggest stepping-stone migration due to strong isolation-by-distance, but not necessarily unidirectional. Moreover, the past demographic dynamics in the Holocene shaped the current pattern of genetic diversity and structure, leading to higher genetic diversity in populations upstream the Zambezi river basin. Our results also point to the very low genetic diversity of C. papyrus populations in Southeast Africa and the need for management and conservation strategies to guarantee the long-term persistence of the species in the region.

Outbreak caused by the SARS-CoV-2 Omicron variant in the psychiatric ward of a general hospital in Brazil.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. METHODS: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. RESULTS: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. CONCLUSIONS: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.

Comparative population genomics in Tabebuia alliance shows evidence of adaptation in Neotropical tree species.

The role of natural selection in shaping spatial patterns of genetic diversity in the Neotropics is still poorly understood. Here, we perform a genome scan with 24,751 probes targeting 11,026 loci in two Neotropical Bignoniaceae tree species: Handroanthus serratifolius from the seasonally dry tropical forest (SDTF) and Tabebuia aurea from savannas, and compared with the population genomics of H. impetiginosus from SDTF. OutFLANK detected 29 loci in 20 genes with selection signal in H. serratifolius and no loci in T. aurea. Using BayPass, we found evidence of selection in 335 loci in 312 genes in H. serratifolius, 101 loci in 92 genes in T. aurea, and 448 loci in 416 genes in H. impetiginosus. All approaches evidenced several genes affecting plant response to environmental stress and primary metabolic processes. The three species shared no SNPs with selection signal, but we found SNPs affecting the same gene in pair of species. Handroanthus serratifolius showed differences in allele frequencies at SNPs with selection signal among ecosystems, mainly between Caatinga/Cerrado and Atlantic Forest, while H. impetiginosus had one allele fixed across all populations, and T. aurea had similar allele frequency distribution among ecosystems and polymorphism across populations. Taken together, our results indicate that natural selection related to environmental stress shaped the spatial pattern of genetic diversity in the three species. However, the three species have different geographical distribution and niches, which may affect tolerances and adaption, and natural selection may lead to different signatures due to the differences in adaptive landscapes in different niches.

Effects of Anodal Transcranial Direct Current Stimulation on Training Volume and Pleasure Responses in the Back Squat Exercise Following a Bench Press.

ABSTRACT: Rodrigues, GM, Machado, S, Faria Vieira, LA, Ramalho de Oliveira, BR, Jesus Abreu, MA, Marquez, G, Maranhão Neto, GA, and Lattari, E. Effects of anodal transcranial direct current stimulation on training volume and pleasure responses in the back squat exercise following a bench press. J Strength Cond Res 36(11): 3048-3055, 2022-This study aimed to investigate the effects of anodal transcranial direct current stimulation (a-tDCS) on volume-load and pleasure responses in a back squat following a bench press. Twelve male subjects advanced in resistance training (RT) (age, 25.5 ± 4.4 years) completed 2 experimental trials in a counterbalanced crossover design: a-tDCS and sham conditions. The stimulus was applied over the left dorsolateral prefrontal cortex for 20 minutes using a 2-mA current intensity in a-tDCS condition and 1 minute of active stimulus in the sham condition. Immediately after stimulation, subjects performed the bench press followed by the back squat. The exercise protocol consisted of 3 sets of maximum repetitions at an intensity of 80% of 1 repetition maximum. The volume-load, perceived pleasure, and arousal responses were measured during the RT protocol. The results indicated that volume-load was higher in the a-tDCS condition than in the sham condition for both exercises ( p = 0.02), with large effect for the back squat ( p = 0.045; d = 0.96). The higher volume-load was obtained by increasing the number of repetitions across all sets for the bench press ( p ≤ 0.0001) and only in the first set for the back squat ( p = 0.01). The circumplex model analysis showed a higher pleasure in the bench press and a tendency toward a higher pleasure in the a-tDCS condition. Anodal tDCS may be used as an ergogenic resource for increasing the back squat volume after performing the bench press in resistance-trained male subjects.

Secondary prevention in coronary artery disease: development and content validity of educational messages for mobile phones / Prevenção secundária na doença arterial coronariana: desenvolvimento e validade de conteúdo de mensagens educativas para celulares / Prevención secundaria en la enfermedad de las arterias coronarias: desarrollo y validez de contenido de mensajes educativos para teléfonos móviles

ABSTRACT Objective: To identify information needs of patients with coronary artery disease and develop and validate the content of educational messages for mobile phones for these patients. Method: The study was carried out in three phases: 1) Identification of information needs in relation to coronary artery disease of patients hospitalized for an acute coronary event; 2) Development of templates containing text and pictures about the disease and treatment; 3) Content validity analysis of template evidence through the assessment of 10 experts. Templates were considered validated when the Content Validity Ratio (CVR) was equal to or greater than 0.80. Results: A total of 67 patients were included, and all the information that emerged about the disease was classified as important to very important. Thirty templates were developed (heart function, recommendations on nutrition and exercise, treatments and medications, and clinical signs related to the disease and risk factor control), and the CVR obtained was greater than 0.80. Conclusion: All information needs were categorized by patients as important or very important. The templates were developed and validated considering content and design.

RESUMO Objetivo: Identificar as informações sobre necessidades de pacientes com doença arterial coronariana e desenvolver e validar o conteúdo de mensagens educativas para celulares para esses pacientes. Método: O estudo foi realizado em três fases: 1) Identificação das informações sobre necessidades em relação à doença arterial coronariana de pacientes internados por evento coronariano agudo; 2) Desenvolvimento de templates contendo textos e imagens sobre a doença e tratamento; 3) Análise da validade de conteúdo das evidências do template por meio da avaliação de 10 especialistas. Os templates foram considerados validados quando a Razão de Validade de Conteúdo (RVC) foi igual ou superior a 0,80. Resultados: Foram incluídos 67 pacientes, e todas as informações que surgiram sobre a doença foram classificadas como importantes a muito importantes. Foram desenvolvidos 30 templates (função cardíaca, recomendações de nutrição e exercícios, tratamentos e medicamentos, sinais clínicos relacionados à doença e controle de fatores de risco), e a RVC obtida foi superior a 0,80. Conclusão Todas as necessidades de informação foram categorizadas pelos pacientes como importantes ou muito importantes. Os templates foram desenvolvidos e validados considerando conteúdo e design.

RESUMEN Objetivo: Identificar las necesidades de información de los pacientes con enfermedad de las arterias coronarias y desarrollar y validar el contenido de mensajes educativos para teléfonos celulares para estos pacientes. Método: El estudio se realizó en tres fases: 1) Identificación de necesidades de información sobre enfermedad de las arterias coronarias en pacientes hospitalizados por evento coronario agudo; 2) Desarrollo de templates que contienen textos e imágenes sobre la enfermedad y el tratamiento; 3) Análisis de la validez de contenido de la evidencia del template a través de la evaluación de 10 expertos. Los templates se consideraron validadas cuando el Razón de Validez de Contenido (RVC) fue igual o superior a 0,80. Resultados: Se incluyeron 67 pacientes y toda la información que surgió sobre la enfermedad se clasificó como importante a muy importante. Se desarrollaron 30 templates (función cardiaca, recomendaciones de nutrición y ejercicio, tratamientos y medicamentos, signos clínicos relacionados con la enfermedad y control de factores de riesgo), y la RVC obtenida fue superior a 0,80. Conclusión: Todas las necesidades de información fueron categorizadas por los pacientes como importantes o muy importantes. Los templates fueron desarrollados y validados considerando contenido y diseño.

Scale-up of capsular polysaccharide production process by Haemophilus influenzae type b using kLa criterion

Polyribosyl-ribitol-phosphate (PRP) from Haemophilus influenzae type b (Hib) is an active immunizing molecule used in the production of the vaccine against H. influenzae, and industrial production could contribute to satisfying a world demand especially in developing countries. In this sense, the aim of this study was to establish a scale-up process using the constant oxygen mass transfer coefficient (kLa) such as the criterion for production of PRP in three different sizes of bioreactor systems. Three different kLa values (24, 52 and 80 h−1) were evaluated in which the biological influence in a 1.5 L bioreactor and 52 h−1 was selected to scale-up the production process until a 75 L pilot-scale bioreactor was achieved. Finally, the fed-batch phase was started under a dissolved oxygen concentration (pO2) at 30% of the saturation in the 75 L bioreactor to avoid oxygen limitation; the performance of production presented high efficiency (9.0 g/L DCW-dry cell weight and 1.4 g/L PRP) in comparison with previous scale-up studies. The yields, productivity and kinetic behavior were similar in the three-size bioreactor systems in the batch mode indicating that kLa is possible to use for PRP production at large scales. This process operated under two stages and successfully produced DCW and PRP in the pilot scale and could be beneficial for future bioprocess operations that may lead to higher production and less operative cost.