Initial Glucose Research Articles

Strategies to reduce the culture medium costs for a high‐yield and high‐selectivity bio‐based 2,3‐butanediol production

AbstractBio‐based 2,3‐butanediol (2,3‐BDO) production on a large scale depends on critical factors, such as culture medium, oxygen supply, pH and biosafety. In this study, three strategies for reducing culture medium costs were investigated: carbon/nitrogen (C/N) ratio; low‐cost nitrogen sources (crude yeast extract, brewer's yeast extract, corn steep liquor, urea, sodium nitrate, ammonium chloride, ammonium sulfate and dibasic ammonium phosphate); and microbial pH autoregulation. Batch fermentations were performed in a microaerobic environment using wild‐type and safe Paenibacillus peoriae NRRL BD 62. The yield and selectivity of 2,3‐BDO were used as control variables. A ratio between 2,3‐BDO production and glucose consumption (YP/S) of almost 80% and an optical purity of 87% levo‐2,3‐BDO, with no acetoin accumulation, were achieved in an NH4Cl‐based medium at C/N = 8.5 g/g and without external pH control, considering an initial glucose of 10 g/L. Based on Free on Board prices, a 63% savings in culture medium costs was achieved by replacing commercial yeast extract at pH 5. Validation assays with higher initial glucose concentrations showed a YP/S of 0.40 g/g and an optical levo‐/meso‐2,3‐BDO ratio of 1:0.8, with negligible acetoin accumulation. Therefore, the NH4Cl‐based medium at C/N = 8.5 g/g and without pH control was considered economically promising for high‐yield and high‐selectivity bio‐based 2,3‐BDO production.

6978 Traumatic Presentation Of A Pancreatic Neuroendocrine Tumor

Abstract Disclosure: C.J. Kahn: None. J. Mai: None. A.E. Cabrera: None. A.D. Anderson: None. D.H. Huynh: None. Background: Insulinomas are a subset of functional pancreatic neuroendocrine tumors associated with neuroglycopenic symptoms, fasting hypoglycemia, and rapid resolution of symptoms with glucose administration. Despite this classic presentation, patients often spend years undiagnosed before formal diagnosis and definitive management. Clinical Case: We report the case of a 37-year-old post-partum female with a history of gestational diabetes who presented to our trauma center after losing consciousness while driving and colliding with a utility pole. Emergency Medical Services reported seizure-like activity on the scene with altered sensorium. Her initial blood glucose level of 32 mg/dL improved to 100 mg/dL after 100 ml of 10% dextrose. Initial biochemical analysis obtained from the trauma bay demonstrated a negative serum ethanol level, negative urine toxicology and sulfonylurea level, and elevated C-peptide of 6.71 ng/mL. After stabilization, she underwent a 72-hour fasting test. At the 12-hour mark, she developed hypoglycemia (blood glucose 36 mg/dL) correlated with elevated insulin (28.8 mU/L), proinsulin (173.1 pmol/L), and C-peptide (7.86 ng/mL). Although an initial CT scan of the abdomen and pelvis did not demonstrate any pancreatic abnormalities, an abdominal MRI demonstrated a 13 mm lesion in the tail of the pancreas consistent with a pancreatic neuroendocrine tumor. She subsequently underwent a laparoscopic distal pancreatectomy during the same hospital admission and recovered expeditiously. Final pathology demonstrated a 10 by 15 mm, grade two, well-differentiated neuroendocrine tumor with negative margins. The specimen stained strongly positive for synaptophysin and chromogranin, consistent with the clinical diagnosis of insulinoma. During the patient's postoperative recovery, she had no further episodes of hypoglycemia and did not require insulin for post-pancreatectomy hyperglycemia. She was discharged home with a glucometer and a follow-up scheduled with endocrinology and general surgery. Conclusion: The presentation of patients with insulinomas can vary from vague, nonspecific symptoms to altered levels of consciousness placing patients in potentially lethal situations. Moreover, the insulin resistance experienced by pregnant patients may mask clinical manifestations of hypoglycemia during the peripartum period, making diagnosis more elusive for this population. A high index of suspicion along with prompt diagnosis, in this case, led to definitive surgical management, effectively preventing future traumatic incidents secondary to hypoglycemia. Reference: 1. Dobrindt EM, Mogl M, Goretzki PE, Pratschke J, Dukaczewska AK. Insulinoma in pregnancy (a case presentation and systematic review of the literature). Rare Tumors. 2021;13. doi:10.1177/2036361320986647 Presentation: 6/3/2024

8814 Concordance in Defining Diabetes Remission: A Comparative Analysis of HbA1c, eA1c, and FPG Criteria After One Year of Digital Twin (DT) Intervention

Abstract Disclosure: P. Shamanna: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. M. Thajudeen: None. A. Balasubramanian: None. S.R. Joshi: None. Introduction: This study investigates the concordance among HbA1c, estimated A1c (eA1c), and fasting plasma glucose (FPG) remission criteria following one year of Digital Twin (DT) intervention. Understanding the agreement of these criteria in a cohort of 209 patients is critical for evaluating diabetes treatment efficacy. Methods: Diabetes remission was assessed in 209 patients after one year of DT intervention, using HbA1c, eA1c, and FPG criteria. Kappa values, along with sensitivity, specificity, and p-values, were calculated for concordance. Mean, standard deviation, and p-values for age, duration of diabetes, HbA1c, fasting plasma glucose, and eA1c were also computed. Results: The study revealed substantial agreement between HbA1c and eA1c criteria (Kappa: 0.751, indicating 'substantial' agreement), HbA1c and FPG criteria (Kappa: 0.703, indicating 'substantial' agreement), and eA1c and FPG criteria (Kappa: 0.719, indicating 'substantial' agreement), post one year of DT intervention. The average age of participants was 43.89 years (±8.72), with a diabetes duration of 3.65 years (±2.66). The initial HbA1c was 9.02% (±1.90), reducing to 6.00% (±0.67) at the end of the study. Initial and final fasting plasma glucose levels averaged 170.75 mg/dL (±61.11) and 109.33 mg/dL (±30.60), respectively. Remission rates were 72.73% for HbA1c, 75.60% for eA1c, and 71.29% for FPG. Conclusion: Our findings suggest that remission using either eA1c or FPG criteria can be reliably compared to the gold standard HbA1c criteria, with all showing 'substantial' agreement post one year of DT intervention. This high concordance, reflected in the statistically significant kappa values, highlights the effectiveness of eA1c and FPG criteria as robust tools in assessing diabetes remission alongside the HbA1c criteria. These insights are crucial for clinical practice and diabetes research, offering flexibility in evaluating patient outcomes. Presentation: 6/1/2024

12599 Early Remission Of Chromosome 6 Q 24-related Neonatal Diabetes Mellitus

Abstract Disclosure: R. Pratibha: None. K. Dummula: None. Introduction: Chromosome 6q24 imprinting abnormalities represent the predominant cause of transient neonatal diabetes mellitus (TNDM), accounting for over two-thirds of cases with an estimated prevalence of 1 in 400,000. While remission typically manifests by 3 months of age, herein we detail a case of Chromosome 6q24-related TNDM exhibiting remission by 1.5 months of age. We share our clinical experience in managing this case without hypoglycemia and using C-Peptide levels as a monitoring tool to track the resolution. Case: A female infant, born at 36 weeks via elective C-section due to fetal growth restriction and oligohydramnios, was closely monitored in the nursery for potential hypoglycemia. Contrary to the expectation, she displayed escalating hyperglycemia, necessitating insulin infusion within 25 hours of birth. Apgar scores were 7 and 9, and the birth weight was 2095 g (6th percentile). Maternal history included impaired glucose tolerance in a previous pregnancy with borderline glucose tolerance during this gestation. The newborn physical exam was unremarkable except for mild macroglossia. Despite initial blood glucose (BG) of 52 mg/dl, it rose to 257 mg/dL by 16 hours. Insulin drip was started at 24 hours due to BG of 304 mg/dL. The monogenic diabetes panel obtained on day of life (DOL) #2 was negative; no acidosis was observed. The C- Peptide was low at 0.2 ng/ml. Insulin infusion was continued until DOL # 20. A trial of glyburide commenced on DOL #9 while on Insulin drip, yielded minimal response, prompting a transition to short-acting insulin for correction of hyperglycemia (>250 mg/dL). C-peptide level during sulfonylurea (SU) trial remained low (0.5 ng/mL). The infant required 2 to 3 corrections per day with 0.05 units of Lispro Insulin, with the last dose administered at 44 days. She did not receive any long-acting Insulin. As of her last follow-up at the endocrine clinic at 57 days of age, the infant is thriving well and has normal blood glucose levels. The 6q24 Methylation-MLPA study showed duplication of 6q24 on the paternally inherited chromosome 6. Significantly, she never encountered hypoglycemia during her hospital stay. The C-peptide increased to 0.8 ng/ml at DOL#37 and had normalized to 1.3 ng/mL by DOL#57 indicating remission of TNDM. Conclusion: 6q24-related TNDM may often be characterized by features such as small for gestational age (SGA), macroglossia, umbilical hernia, cardiac and renal abnormalities. Early presentation of hyperglycemia with this phenotype must prompt its diagnostic evaluation. Early resolution by 1.5 months as seen in our case is uncommon. Uniquely, we used C-peptide as a tracking tool to guide resolution and manage insulin therapy. Presentation: 6/3/2024

Avoiding overflow metabolite formation in Komagataella phaffii fermentations to enhance recombinant protein production

BackgroundKomagataella phaffii (K. phaffii), formerly known as Pichia pastoris, is a widely utilized yeast for recombinant protein production. However, due to the formation of overflow metabolites, carbon yields may be reduced and product recovery becomes challenging. This study investigates the impact of oxygen availability, different glucose concentrations and feeding strategies on overflow metabolite formation and recombinant protein production in K. phaffii.ResultsHigh glucose concentrations in batch fermentation, as applied in literature, lead to substantial ethanol accumulation, adversely affecting biomass yield and product formation. Increasing dissolved oxygen setpoints does not significantly reduce ethanol formation, indicating that glucose surplus, rather than oxygen availability, drives overflow metabolism. Decreasing the initial glucose concentration to 5 g/L and adapting the feeding strategy of the fed-batch phase, effectively mitigates overflow metabolite formation, improving biomass yield by up to 9% and product concentration by 40% without increasing process time.ConclusionsThese findings underscore the importance of a suitable glucose-feeding strategy in K. phaffii fermentation processes and highlight the detrimental effects of overflow metabolites on productivity. By optimizing carbon source utilization, it is possible to enhance fermentation efficiency and recombinant protein production with K. phaffii.

Pattern recognition of drying lysozyme–glucose droplets using machine learning classifiers

Out-of-equilibrium processes, such as sessile droplet drying, often result in distinctive macroscopic residual patterns in systems containing molecules, proteins, and colloids. Protein–glucose mixtures are particularly effective models for studying the behavior of complex fluids containing biomolecules. This study investigates the drying patterns of lysozyme droplets with varying initial glucose concentrations. Without glucose, the crack patterns are chaotic and dispersed throughout the droplet. Interestingly, cracks predominantly form around the droplet edges at intermediate glucose concentrations, while the deposits become uniform and crack-free at high glucose concentrations. To understand and classify the unique patterns related to the initial compositional changes, we developed an automated pattern recognition pipeline. We used two methods for analyzing images captured throughout the drying process. The first method involved extracting statistical textural parameters from the images as quantitative features for machine learning classifiers. The second method utilized a neural network-based classifier to directly classify the images, achieving an accuracy of 97%. The results demonstrate the effectiveness of using images from the entire drying process, not just the final images, for pattern classification. This approach may be useful in gaining a fundamental understanding of unique crack pattern that emerge when glucose is added to a protein solution.

Exploring the influencing factors of non-insulin drug prescriptions in discharged patients with type 1 diabetes.

The aim of this study was to evaluate the admission indicators and characteristics of individuals diagnosed with type 1 diabetes (T1D) to ascertain potential impact on the choice of glucose control therapy after discharge. A total of 398 eligible T1D patients were selected. We conducted multivariable logistic regression analysis to determine the independent influence of predictors on the selection of glucose control therapy after discharge. To explore the influencing factors of different subgroups, we additionally performed subgroup analyses based on gender and age. Our study revealed that body mass index (BMI) was noteworthy influence factor for prescription of insulin and non-insulin antidiabetic drug (NIAD prescription) in T1D patients of general population [OR = 1.109 (1.033-1.195), p = 0.006], male [OR = 1.166 (1.040-1.318), p = 0.011] and individuals below the age of 30 years [OR = 1.146 (1.020-1.301), p = 0.028]. Diastolic blood pressure (DBP) was a protective factor for NIAD prescription in the general population [OR = 0.971 (0.949-0.992), p = 0.008] and women [OR = 0.955 (0.923-0.988), p = 0.008]. The other risk factor of NIAD prescription in men was dyslipidemia [OR = 4.824 (1.442-22.246), p = 0.020]. Pulse pressure [OR = 1.036 (1.007-1.068), p = 0.016] constituted an additional risk factor of NIAD prescription among individuals below the age of 30 years. The risk factors of NIAD prescription for people aged 30 to 50 years were length of stay [OR = 1.097 (1.014-1.196), p = 0.026] and initial blood glucose [OR = 1.078 (1.007-1.168), p= 0.047]. In the case of individuals aged above 50 years, physicians exhibited a higher tendency to prescribe supplementary non-insulin medications to men [OR = 9.385 (1.501-87.789), p = 0.029]. We identified notable factors that influence discharge prescriptions in patients with T1D. In order to enhance the treatment outcome for the patient, clinicians ought to have a special focus on these indicators or factors.

The Role of Secreted Frizzled-Related Protein 5 (Sfrp5) in Overweight and Obesity in Childhood and Adolescence.

Background/Objective: Secreted frizzled-related protein 5 (Sfrp5) is an anti-inflammatory adipokine that has been implicated in the pathophysiology of obesity and its metabolic complications. Despite the fact that numerous studies have been carried out in adults, limited data on Sfrp5 exist for youth, especially in relation to overweight and obesity. Methods: In our study, we assessed the concentrations of Sfrp5, total oxidative (TOS) and antioxidative (TAS) status, high-sensitivity C-reactive protein (hs-CRP), and several cytokines (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-12, TNF-α) in 120 children and adolescents (mean age ± SE: 11.48 ± 0.25 years; 48 prepubertal, 72 pubertal; 74 males and 46 females) before and 1 year after the implementation of a personalized, structured, lifestyle intervention program of healthy diet, sleep, and physical exercise. Results: Based on the body mass index (BMI), participants were categorized as having morbid obesity (n = 63, 52.5%), obesity (n = 21, 17.5%), overweight (n = 22, 18.33%), or normal BMIs (n = 14, 11.67%), based on the International Obesity Task Force (IOTF) cut-off points. Following the 1-year lifestyle intervention program, a significant improvement in anthropometric measurements (BMI, BMI-z score, diastolic blood pressure, WHR, and WHtR), body-composition parameters, hepatic enzymes, lipid profile, inflammation markers, and the insulin-sensitivity profile (HbA1C, HOMA index) was observed in all subjects. Sfrp5 decreased in subjects with obesity (p < 0.01); however, it increased significantly (p < 0.05) in patients with morbid obesity. Linear regression analysis indicates that TNF-α and systolic blood pressure were the best positive predictors and hs-CRP was the best negative predictor for Sfpr5 concentration at initial assessment and glucose concentration for ΔSfrp5, while TNF-α and TAS were the best positive predictors for Sfpr5 concentration at annual assessment. Conclusions: These results indicate that Sfrp5 is associated with severe obesity and is increased following weight loss in children and adolescents with morbid obesity. It is also related to metabolic homeostasis, as well as inflammation and oxidative status.

Stress hyperglycemia ratio and its influence on mortality in elderly patients with severe community-acquired pneumonia: a retrospective study

BackgroundCommunity-acquired pneumonia (CAP) is a significant health issue among the elderly, with severe cases (SCAP) having high mortality rates. This study assesses the predictive significance of the stress hyperglycemia ratio (SHR) in elderly SCAP patients and its impact on outcomes in both diabetic and non-diabetic patients.Methods and materialsThis retrospective study included 406 SCAP patients aged 65 or older from the Second People’s Hospital of Lianyungang (January 2020 to December 2023). Data collected included demographics, medical history, vital signs, and lab results. SHR was calculated from initial blood glucose and estimated average glucose (HbA1c). Statistical analyses, including Cox regression and Kaplan-Meier analysis, evaluated SHR’s impact on mortality. Mediation models explored the effects of neutrophil-lymphocyte ratio (NLR) and SHR.ResultsThe 28-day mortality rate was 21.67%. Deceased patients had higher age, Charlson Comorbidity Index, procalcitonin, NLR, glucose, and SHR levels compared to survivors (P < 0.05). Both SHR and NLR significantly increased mortality risk, particularly in non-diabetic patients. Combining NLR and SHR improved ROC AUC to 0.898, with 89.80% sensitivity and 81.10% specificity. Kaplan-Meier analysis showed higher cumulative survival for SHR < 1.14, regardless of diabetes status (P < 0.05). NLR mediated 13.02% of the SHR-survival relationship, while SHR mediated 14.06% of the NLR-survival relationship.ConclusionElevated SHR is a significant mortality risk factor in elderly SCAP patients, independent of diabetes status. Stringent glucose control and careful monitoring of SHR may improve outcomes in elderly patients with acute respiratory conditions.

Macroparticle-enhanced morphology engineering of Cordyceps sinensis for high glucose fermentation to optimize the production of bioactive exopolysaccharides

Cordyceps sinensis is widely known for its therapeutic properties. Enhancing the yield of exopolysaccharides (EPS), which is crucial for its medicinal efficacy, is a major challenge. In this study, we applied high initial glucose concentrations with talc particles to enhance EPS production and assessed the cell morphology, intracellular biochemical reactants, and bioactivity contribution of glycoproteins. The use of 150 g/L glucose and 10 g/L 2000 mesh talc increased the EPS yield by 1.8-fold to 4.21 g/L. The addition of talc regulated cell morphology, facilitated the entry of oxygen molecules into the cells to produce a large amount of ATP for polysaccharide synthesis, and altered the cell wall structure to facilitate the secretion of EPS. Moreover, environmental stress resulted in a notable increase in intracellular reactive oxygen species levels, which can potentially enhance cell membrane permeability and promote EPS synthesis. Furthermore, the highest protein content in crude EPS corresponded to the maximum activation of alcohol dehydrogenase (ADH) of 44.2 %, suggesting a mechanistic relationship between the proteins and polysaccharides in the glycoproteins that influence the activation of ADH. These findings elucidate the intricate interplay between fermentation conditions and EPS production and provide new avenues for optimizing the fermentation process of CS-HKI to enhance its therapeutic applications.

Implementation of a Macroporous Polyhydroxyethylmethacrylate Cryogel-Based Mini-Bioreactor System to Improve Monoclonal Antibody Production.

Monoclonal antibodies (mAbs) are pioneers in the diagnosis and treatment of many diseases, such as cancer, asthma, poisoning, viral infections, etc. As the market value of mAbs increases in the biopharma industry, the demand for high quantities is met by upscaled production using bioreactor systems. Thus, disposable, porous matrices called cryogels have gained the primary focus for adherent support in the proliferation of hybridoma cells. In this study, a gelatin-immobilized polyhydroxyethylmethacrylate-based cryogel material (disc-shaped, 9 mL bed volume) was synthesized, and a mini-bioreactor set up developed for culturing hybridoma cells to produce mAbs continuously. The hybridoma clone, 1B4A2D5, secreting anti-human serum albumin monoclonal antibodies, was immobilized in the cryogel matrix (2 discs, 18 mL bed volume). The hybridoma cells were attached to the matrix within 12 h after inoculation, and the cells were in the lag phase for seven days, where they were secreted mAb into the circulation medium. During the initial exponential phase, the glucose consumption, lactic acid production, and mAb production were 3.36 mM/day, 3.67 mM/day, and 55.61 µg/mL/day, respectively. The medium was refreshed whenever the glucose in the media went below 50% of the initial glucose concentration. The cryogenic reactor was run continuously for 25 days, and the mAb concentration reached a maximum on the 17th day at 310.59 µg/mL. The cumulative amount of mAbs produced in 25 days of running was 246 µg/mL, 7.7 times higher than the mAbs produced from T-flask batch cultivation. These results demonstrate that the developed polyhydroxyethylmethacrylate-based cryogel reactor can be used efficiently for continuous mAb production.

Admission Blood Glucose Associated with In-Hospital Mortality in Critically III Non-Diabetic Patients with Heart Failure: A Retrospective Study.

Heart failure (HF) is a primary public health issue associated with a high mortality rate. However, effective treatments still need to be developed. The optimal level of glycemic control in non-diabetic critically ill patients suffering from HF is uncertain. Therefore, this study examined the relationship between initial glucose levels and in-hospital mortality in critically ill non-diabetic patients with HF. A total of 1159 critically ill patients with HF were selected from the Medical Information Mart for Intensive Care-III (MIMIC-III) data resource and included in this study. The association between initial glucose levels and hospital mortality in seriously ill non-diabetic patients with HF was analyzed using smooth curve fittings and multivariable Cox regression. Stratified analyses were performed for age, gender, hypertension, atrial fibrillation, CHD with no MI (coronary heart disease with no myocardial infarction), renal failure, chronic obstructive pulmonary disease (COPD), estimated glomerular filtration rate (eGFR), and blood glucose concentrations. The hospital mortality was identified as 14.9%. A multivariate Cox regression model, along with smooth curve fitting data, showed that the initial blood glucose demonstrated a U-shape relationship with hospitalized deaths in non-diabetic critically ill patients with HF. The turning point on the left side of the inflection point was HR 0.69, 95% CI 0.47-1.02, p = 0.068, and on the right side, HR 1.24, 95% CI 1.07-1.43, p = 0.003. Significant interactions existed for blood glucose concentrations (7-11 mmol/L) (p-value for interaction: 0.009). No other significant interactions were detected. This study demonstrated a U-shape correlation between initial blood glucose and hospital mortality in critically ill non-diabetic patients with HF. The optimal level of initial blood glucose for non-diabetic critically ill patients with HF was around 7 mmol/L.

The Effect of Healthy Boba Pearl Drink on Post-Prandial Glucose

This study was a randomized controlled trial using a repeated experimental design with a pre-test and a post-test control group. The study subjects were women of childbearing age, aged 20‒30 years, with no diagnosed chronic diseases and with baseline fasting blood glucose levels less than 125 mg/dL. Participants were randomly assigned to treatment and control groups. The treatment group received 350 mL of healthy boba drink, while the control group received 350 mL of commercial boba drink. The healthy boba drink was made by mixing 67 mL of fresh milk, 133 mL of soy milk, 1 g of stevia sweetener, 100 g of red dragon fruit, and 40 g of healthy boba pearls. It contained 215 kcal of energy, 8.82 g of protein, 8.90 g of fat, 30.78 g of carbohydrate, and 1,808 g of fiber. Each group had an initial fasting blood glucose levels measurement before the intervention, and postprandial glucose levels were measured at the end of the intervention (one time of intervention). The collected data were analyzed univariately to analyze the effect of treatment on postprandial glucose using the independent t-test. The result indicated that the subjects in the treatment group and 96.2% of the subjects in the control group had fasting glucose levels less than 126 mg/dL. Both participants in the control and treatment groups had postprandial glucose levels less than 200 mg/dL. The mean glucose level was 89.49 mg/dL in the treatment group and 92.57 mg/dL in the control group. The study results showed that the treatment group that consumed the healthy boba drink had a lower average postprandial glucose level than the control group. The statistical test results showed that there was a significant effect of healthy boba drink consumption on postprandial glucose levels in the treatment group (p&lt;0.000). It is concluded that the healthy boba drink intervention had a significant effect (p&lt;0.000) on lowering blood glucose by 5.82 mg/dL after the initial treatment. The results of this study are a major first step for future work to develop a healthier boba drink.

Comparative transcriptomics analysis-guided metabolic engineering of Yarrowia lipolytica for improved erythritol and fructooligosaccharides production

Currently, fructooligosaccharides (FOS) are converted from sucrose by purified enzymes or fungal cells, but these methods are costly and time-consuming. Here, the optimal fermentation conditions for strain E326 were determined through fermentation optimization: initial glucose 200 g/L, NaCl 25 g/L, inoculum volume 20 %, dissolved oxygen 20–30 %, pH 3, and glucose feeding concentration 100 g/L, which increased erythritol titer by 1.5 times. The co-expression of HGT1 and APC11 genes alleviated the erythritol synthesis stagnation, shorten the fermentation time by 16.7 %, and increased the erythritol productivity by 17.2 %. The episomal plasmids based on yeast mitochondrial replication origins (mtORIs) were constructed to surface display fructosyltransferase, effectively utilizing waste yeast cells generated during erythritol fermentation. Under the conditions of 60℃ and pH 6, the FOS yield reached 65 %, which to our best of knowledge is so-far the highest yield of FOS obtained. These findings will contribute to the industrial production of erythritol and FOS.

Production of Ganodiesel from the biomass of Ganoderma lucidum in air-L-shaped bioreactor (ALSB)

The increasing need for alternative and sustainable energy sources, prompted by the depletion of fossil fuels and the rise in greenhouse gas emissions, has generated attention towards exploring fast-growing filamentous fungi as a potential bioenergy source. This study aimed to optimize Ganoderma lucidum production for elevated biomass and lipid yields in submerged liquid fermentation. The optimization involved varying initial pH, glucose concentration, and agitation rate using response surface methodology (RSM) with central composite design (CCD). Glucose concentration and initial pH significantly influenced biomass production, while agitation rate had an insignificant effect. For lipid production, glucose concentration, initial medium pH, and agitation rate were identified as significant factors. The optimized conditions (initial pH 6, 50 g/L glucose concentration, and 113.42 rpm) were validated in 500 mL shake flasks and a 3 L Air-L-Shaped Bioreactor (ALSB). Shake flask results showed 8.33 g/L of biomass and 2.17 % of lipid, while the ALSB system produced 5.32 g/L of biomass and 2.35 % lipid. The obtained Ganoderma lucidum mycelial lipid underwent acid-catalysed transesterification to produce biodiesel, which was subjected to several tests to comply ASTM and EN standards. This study serves as a valuable reference for future biodiesel applications through the optimization of Ganoderma lucidum biomass and lipid production.

Adaptation of Saccharomyces to High Glucose Concentrations and Its Impact on Growth Kinetics of Alcoholic Fermentations.

Prior adaptation of Saccharomyces cerevisiae to the fermentation medium ensures its implantation and success in alcoholic fermentations. Fermentation kinetics can be characterized with mathematical models to objectively measure the success of adaptation and growth. The study aims at assessing and comparing two pre-culture procedures using, respectively, one or two adaptation steps, analyzing the impact of different initial glucose concentrations on the fermentation profiles of S. cerevisiae cultures, and assessing the performance of three predictive growth models (Buchanan's, modified Gompertz, and Baranyi and Roberts models) under varied initial glucose concentrations. We concluded that both protocols produced S. cerevisiae pre-cultures with similar viability and biomass increase, which suggests that short protocols may be more cost-effective. Furthermore, the study highlights the need of inoculating a high S. cerevisiae population to minimize the depletion of dissolved oxygen in the medium and to ensure that glucose is predominantly directed toward the ethanol formation at early fermentative steps. This study shows that the relationship between kinetic parameters is model-dependent, which hinders inter-study comparisons and stresses the need for standardized growth models. We advocate for the generalized use of confidence intervals of the kinetic parameters to facilitate objective inter-study comparisons.

Utility of the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) in Pediatric Stevens-Johnson Syndrome Patients.

The Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) is a system that predicts in-hospital mortality for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). The system is widely utilized in adults but not pediatrics. We aim to determine the accuracy of the SCORTEN in pediatrics. A retrospective review of pediatric patients admitted to a verified pediatric burn center with SJS/TEN from 2008 to 2022 was performed. Twenty-four patients were analyzed. Ten patients had 0-1 SCORTEN risk factor, thirteen had 2 risk factors, and one had three risk factors. There was no relationship between initial BUN, bicarbonate, glucose, or initial heart rate on the length of intensive care unit (ICU) stay or ventilator days. Hospital length of stay and feeding tube days were positively related (p<0.001) along with length of stay and maximum total body surface areas (TBSA) (p<0.05 Hospital length of stay, ICU length of stay, and ventilator days were not statistically significant between those having 0-1 and 2 risk factors. This study suggests that the SCORTEN system is not useful for pediatrics and a different scoring system is needed, as SCORTEN overestimates mortality and does not have a relationship to outcome measures.

Neurological outcomes for patients meeting radiographic criteria for DEFUSE 3 and SELECT2

BackgroundThe DEFUSE 3 and SELECT2 thrombectomy trials included some patients with similar radiographic profiles, although the rates of good functional outcomes differed widely between the studies.ObjectiveTo report neurological outcomes for...

Persistent hypoglycemia in patients with liver cancer.

Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon. Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.

Alternative production of fucoxanthin and PUFAs using Chlorochromonas danica and Hibberdia magna, unicellular chrysophytes with different trophic modes

Ochrophyte microalgae attract attention from the applied phycology perspective, due to their ability to grow rapidly, engage variable trophic modes, and simultaneously produce high-value compounds such as xanthophyll carotenoids and polyunsaturated fatty acids. Unlike more often considered marine diatoms and haptophytes, unicellular chrysophytes may represent a reasonable freshwater alternative. In this work, we introduced two representatives: Chlorochromonas danica (Ochromonadales) and Hibberdia magna (Hibberdiales). We compared their ability to produce target compounds in mixotrophic and photoautotrophic modes, respectively. Both organisms had a similar temperature optima (18–22 °C), but light demands were much higher in the photoautotrophic H. magna. This work is the first report of fucoxanthin content and productivity by C. danica, showing that the presence of light enhanced the content of fucoxanthin 4.5-fold compared with darkness. For fucoxanthin productivity in the mixotrophic batch cultured C. danica, the optimal initial glucose dose was 10 g L−1. Culture medium supplemented with mineral nutrients resulted in an increase in biomass and fucoxanthin productivity of C. danica achieving the highest biomass productivity of 0.81 ± 0.06 g L−1 d−1. H. magna accumulated a maximum of 4.54 ± 0.04 mg g−1 DW of fucoxanthin, which was slightly more than the maximum value for C. danica of 3.99 ± 0.19 mg g−1 DW. However, due to the lower biomass productivity of H. magna, the maximal fucoxanthin productivities reached very similar values of 1.15 ± 0.05 and 1.16 ± 0.01 mg L d−1 in C. danica and H. magna, respectively. Both organisms had a relatively high fatty acid content, accounting for 17 % and 19 % of DW in C. danica and H. magna, respectively. H. magna had a higher level of polyunsaturated fatty acids, which were more diverse, longer, and more unsaturated. The potential for utilization of selected chrysophytes as producers in a multi-target biorefinery is discussed.