Growth Function Research Articles

Harnessing three-dimensional porous chitosan microsphere embedded with adipose-derived stem cells to promote nerve regeneration

BackgroundNerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects.MethodsIn vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats.ResultsCompared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration.ConclusionsThe ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.Graphical

Kelly Criterion Extension: Advanced Gambling Strategy

This article introduces an innovative extension of the Kelly criterion, which has traditionally been used in gambling, sports wagering, and investment contexts. The Kelly criterion extension (KCE) refines the traditional capital growth function to better suit dynamic market conditions. The KCE improves the traditional approach to accommodate the complexities of financial markets, particularly in stock and commodity trading. This innovative method focuses on crafting strategies based on market conditions and player actions rather than direct asset investments, which enhances its practical application by minimizing risks associated with volatile investments. This paper is structured to first outline the foundational concepts of the Kelly criterion, followed by a detailed presentation of the KCE and its advantages in practical scenarios, including a case study on its application to blackjack strategy optimization. The mathematical framework and real-world applicability of the KCE are thoroughly discussed, demonstrating its potential to bridge the gap between theoretical finance and actual trading outcomes.

Age, growth, and mortality of Blackfin Tuna in the Gulf of Mexico

AbstractObjectiveAn otolith‐based aging approach was used to evaluate age and growth relationships, sexual dimorphism in growth, and derive mortality estimates for Blackfin Tuna Thunnus atlanticus in the Gulf of Mexico (GOM).MethodsBlackfin Tuna (n = 395) were sampled from recreational fisheries and aged from 0 to 13 years, representing an increase over previous estimates of longevity for the species.ResultRapid growth was exhibited during the first two years of life, and the Richards growth function provided a better fit (L∞ = 907 mm, k = 0.112 /year, a = 1.05, b = 0.25) to the data compared with the von Bertalanffy growth model (L∞ = 824 mm, k = 0.365/year, t0 = −0.96). Sexual dimorphism in growth was observed, with males (907 mm) reaching a larger L∞ than females (857 mm), and otolith mass was a strong predictor of age in both sexes. Estimated instantaneous total (Z = 0.532/year) and natural (M = 0.467 year) mortality rates for Blackfin Tuna in the GOM were low relative to previous estimates in the southwestern Atlantic, where fishing mortality (F) is likely much higher.ConclusionResults represent critical baseline estimates of size‐at‐age, longevity, and natural mortality for Blackfin Tuna at relatively low levels of exploitation that can be used to inform future assessments.

Modeling the growth curve in ducks: a sinusoidal model as an alternative to classical nonlinear models

The present study aimed to apply a sinusoidal model to duck body weight records in order to introduce it to the field of poultry science. Using 8 traditional growth functions as a guide (Bridges, Janoschek, logistic, Gompertz, Von Bertalanffy, Richards, Schumacher, and Morgan), this study looked at how well the sinusoidal equation described the growth patterns of ducks. By evaluating statistical performance and examining model behavior during nonlinear regression curve fitting, models were compared. The data used in this study came from 3 published articles reporting 1) body weight records of Kuzi ducks aged 1 to 70 d, 2) body weight records for Polish Peking ducks aged 1 to 70 d, and 3) average body weight of Peking ducks aged 1 to 42 d belonging to 5 different breeds. The general goodness-of-fit of each model to the various data profiles was assessed using the adjusted coefficient of determination, root mean square error, Akaike's information criterion (AIC), and Bayesian information criterion. All of the models had adjusted coefficient of determination values that were generally high, indicating that the models generally fit the data well. Duck growth dynamics are accurately described by the chosen sinusoidal equation. The sinusoidal equation was found to be one of the best functions for describing the age-related changes in body weight in ducks when the growth functions were compared using the goodness-of-fit criteria. To date, no research has been conducted on the use of sinusoidal equations to describe duck growth development. To describe the growth curves for a variety of duck strains/lines, the sinusoidal function employed in this study serves as a suitable substitute for conventional growth functions.

The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop

Animal longevity is a function of global vital organ functionality and, consequently, a complex polygenic trait. Yet, monogenic regulators controlling overall or organ-specific ageing exist, owing their conservation to their function in growth and development. Here, by using pathway analysis combined with wet-biology methods on several dynamic timelines, we identified Hnf1a as a novel master regulator of the maturation and ageing in the adult pancreatic islet during the first year of life. Conditional transgenic mice bearing suboptimal levels of this transcription factor in the pancreatic islets displayed age-dependent changes, with a profile echoing precocious maturation. Additionally, the comparative pathway analysis revealed a link between Hnf1a age-dependent regulation and immune signaling, which was confirmed in the ageing timeline of an overly immunodeficient mouse model. Last, the global proteome analysis of human islets spanning three decades of life largely backed the age-specific regulation observed in mice. Collectively, our results suggest a novel role of Hnf1a as a monogenic regulator of the maturation and ageing process in the pancreatic islet via a direct or indirect regulatory loop with immune signaling.

Pregnancy-Related Disorders and Intrauterine Impaired Lung Development

Various pregnancy-related disorders are known to affect fetal lung development negatively. During pregnancy, chronic nutrition and/or oxygen limitation is known to impede lung maturation and induce airway and lung abnormalities. Structural abnormalities and reduced lung function may be evident immediately after birth, persist, or develop with age. The expansion of the fetal lung, fetal breath movements, fetal lung growth, alveolarization, blood-air barrier, extracellular matrix (ECM), airways, surfactant system, and lung immune function are all affected by nutritional limitations during pregnancy. Gestational hypoxia disrupts fetal lung development, which manifests as morphological and functional pulmonary abnormalities. Additionally, intrauterine growth restriction (IUGR), preeclampsia (PE), exposure to air pollution, and smoking are known to interfere with embryonic lung development. Birth defects, such as bronchopulmonary dysplasia, as well as chronic obstructive pulmonary disease (COPD), can be caused by abnormalities in pregnancy. Adequate nutrition, avoidance of smoking, and watchful monitoring and intervention during pregnancy should be promoted to prevent chronic lung disease of the newborn, child, and adult.

Employing Genomic Tools to Explore the Molecular Mechanisms behind the Enhancement of Plant Growth and Stress Resilience Facilitated by a Burkholderia Rhizobacterial Strain.

The rhizobacterial strain BJ3 showed 16S rDNA sequence similarity to species within the Burkholderia genus. Its complete genome sequence revealed a 97% match with Burkholderia contaminans and uncovered gene clusters essential for plant-growth-promoting traits (PGPTs). These clusters include genes responsible for producing indole acetic acid (IAA), osmolytes, non-ribosomal peptides (NRPS), volatile organic compounds (VOCs), siderophores, lipopolysaccharides, hydrolytic enzymes, and spermidine. Additionally, the genome contains genes for nitrogen fixation and phosphate solubilization, as well as a gene encoding 1-aminocyclopropane-1-carboxylate (ACC) deaminase. The treatment with BJ3 enhanced root architecture, boosted vegetative growth, and accelerated early flowering in Arabidopsis. Treated seedlings also showed increased lignin production and antioxidant capabilities, as well as notably increased tolerance to water deficit and high salinity. An RNA-seq transcriptome analysis indicated that BJ3 treatment significantly activated genes related to immunity induction, hormone signaling, and vegetative growth. It specifically activated genes involved in the production of auxin, ethylene, and salicylic acid (SA), as well as genes involved in the synthesis of defense compounds like glucosinolates, camalexin, and terpenoids. The expression of AP2/ERF transcription factors was markedly increased. These findings highlight BJ3's potential to produce various bioactive metabolites and its ability to activate auxin, ethylene, and SA signaling in Arabidopsis, positioning it as a new Burkholderia strain that could significantly improve plant growth, stress resilience, and immune function.

Effects of dietary fermented Saccharomyces cerevisiae extract (Hilyses) supplementation on growth, hematology, immunity, antioxidants, and intestinal health in Nile tilapia

This study investigated the effects of dietary supplementation with the product Hilyses on growth performance, feed utilization, nutrient composition, hematological parameters, serum biochemistry, immune function, antioxidant status, and digestive enzyme activity in juvenile Nile tilapia (Oreochromis niloticus, initial body weight 4.24 ± 0.01 g). The fish were fed diets supplemented with Hilyses at concentrations of 0, 1, 2, or 3 g/kg for a period of 8 weeks. The results showed that supplementation with Hilyses at levels up to 2 g/kg diet significantly improved final body weight, weight gain, specific growth rate, feed efficiency ratio, protein efficiency ratio, apparent protein utilization, and energy utilization compared to the control diet without Hilyses. Carcass crude protein content and moisture were significantly higher in Hilyses-fed groups, while crude lipid content decreased at the 3 g/kg supplementation level. Hilyses supplementation enhanced various hematological parameters, including increased red blood cell count, total leukocyte count, hemoglobin concentration, hematocrit, and mean corpuscular volume. Serum biochemistry and immune function markers like total protein, albumin, complement component C3, IgM, and IgG were significantly elevated in the 2 and 3 g/kg Hilyses groups. Antioxidant enzyme activities (catalase, glutathione peroxidase, total superoxide dismutase) were enhanced, and lipid peroxidation was reduced, in the 2 g/kg Hilyses group. Digestive enzyme activities, particularly protease and lipase, were also improved with Hilyses supplementation. Histological examination showed reduced lipid deposition in the liver and increased branching of intestinal villi at the 2 g/kg Hilyses level. Overall, these results indicated that dietary Hilyses supplementation at 2 g/kg diet optimizes growth, feed utilization, nutrient composition, hematology, immunity, antioxidant status, and digestive function in juvenile Nile tilapia.

A traits-based approach to assess aquaculture’s contributions to food, climate change, and biodiversity goals

Aquaculture has the potential to support a sustainable and equitable food system in line with the United Nations Sustainable Development Goals (SDG) on food security, climate change, and biodiversity (FCB). Biological diversity amongst aquaculture organisms can drive diverse contributions to such goals. Existing studies have assessed the performance of a limited number of taxa in the general context of improving aquaculture production, but few explicitly consider the biological attributes of farmed aquatic taxa at the FCB nexus. Through a systematic literature review, we identify key traits associated with FCB and evaluate the potential of aquaculture to contribute to FCB goals using a fuzzy logic model. The majority of identified traits are associated with food security, and two-thirds of traits linked with food security are also associated with climate change or biodiversity, revealing potential co-benefits of optimizing a single trait. Correlations between FCB indices further suggest that challenges and opportunities in aquaculture are intertwined across FCB goals, but low mean FCB scores suggest that the focus of aquaculture research and development on food production is insufficient to address food security, much less climate or biodiversity issues. As expected, production-maximizing traits (absolute fecundity, the von Bertalanffy growth function coefficient K, macronutrient density, maximum size, and trophic level as a proxy for feed efficiency) highly influence a species’ FCB potential, but so do species preferences for environmental conditions (tolerance to phosphates, nitrates, and pH levels, as well as latitudinal and geographic ranges). Many highly farmed species that are typically associated with food security, especially finfish, score poorly for food, climate, and biodiversity potential. Algae and mollusc species tend to perform well across FCB indices, revealing the importance of non-fish species in achieving FCB goals and potential synergies in integrated multi-trophic aquaculture systems. Overall, this study provides decision-makers with a biologically informed assessment of desirable aquaculture traits and species while illuminating possible strategies to increase support for FCB goals. Our findings can be used as a foundation for studying the socio-economic opportunities and barriers for aquaculture transitions to develop equitable pathways toward FCB-positive aquaculture across nuanced regional contexts.

Genome-wide identification of bZIP transcription factors and their expression analysis in Platycodon grandiflorus under abiotic stress.

The Basic Leucine Zipper (bZIP) transcription factors (TFs) family is among of the largest and most diverse gene families found in plant species, and members of the bZIP TFs family perform important functions in plant developmental processes and stress response. To date, bZIP genes in Platycodon grandiflorus have not been characterized. In this work, a number of 47 PgbZIP genes were identified from the genome of P. grandiflorus, divided into 11 subfamilies. The distribution of these PgbZIP genes on the chromosome and gene replication events were analyzed. The motif, gene structure, cis-elements, and collinearity relationships of the PgbZIP genes were simultaneously analyzed. In addition, gene expression pattern analysis identified ten candidate genes involved in the developmental process of different tissue parts of P. grandiflorus. Among them, Four genes (PgbZIP5, PgbZIP21, PgbZIP25 and PgbZIP28) responded to drought and salt stress, which may have potential biological roles in P. grandiflorus development under salt and drought stress. Four hub genes (PgbZIP13, PgbZIP30, PgbZIP32 and PgbZIP45) mined in correlation network analysis, suggesting that these PgbZIP genes may form a regulatory network with other transcription factors to participate in regulating the growth and development of P. grandiflorus. This study provides new insights regarding the understanding of the comprehensive characterization of the PgbZIP TFs for further exploration of the functions of growth and developmental regulation in P. grandiflorus and the mechanisms for coping with abiotic stress response.

Enhancing Selenium Accumulation in Rhodotorula mucilaginosa Strain 6S Using a Proteomic Approach for Aquafeed Development.

It is known that selenium (Se) is an essential trace element, important for the growth and other biological functions of fish. One of its most important functions is to contribute to the preservation of certain biological components, such as DNA, proteins, and lipids, providing protection against free radicals resulting from normal metabolism. The objective of this study was to evaluate and optimize selenium accumulation in the native yeast Rhodotorula mucilaginosa 6S. Sodium selenite was evaluated at different concentrations (5-10-15-20-30-40 mg/L). Similarly, the effects of different concentrations of nitrogen sources and pH on cell growth and selenium accumulation in the yeast were analyzed. Subsequently, the best cultivation conditions were scaled up to a 2 L reactor with constant aeration, and the proteome of the yeast cultured with and without sodium selenite was evaluated. The optimal conditions for biomass generation and selenium accumulation were found with ammonium chloride and pH 5.5. Incorporating sodium selenite (30 mg/L) during the exponential phase in the bioreactor after 72 h of cultivation resulted in 10 g/L of biomass, with 0.25 mg total Se/g biomass, composed of 25% proteins, 15% lipids, and 0.850 mg total carotenoids/g biomass. The analysis of the proteomes associated with yeast cultivation with and without selenium revealed a total of 1871 proteins. The results obtained showed that the dynamic changes in the proteome, in response to selenium in the experimental medium, are directly related to catalytic activity and oxidoreductase activity in the yeast. R. mucilaginosa 6S could be an alternative for the generation of selenium-rich biomass with a composition of other nutritional compounds also of interest in aquaculture, such as proteins, lipids, and pigments.

Pulsed DPOAEs in serial measurements : Combined analysis paradigm of simultaneously occurring changes in hearing thresholds and DPOAEs. German version

To date, there is no consensus on how to standardize the assessment of ototoxicity in serial measurements. For the diagnosis of damage to the cochlear amplifier, measurement methods are required that have the highest possible test-retest reliability and validity for detecting persistent damage. Estimated distortion-product thresholds (LEDPT) based on short-pulse distortion-product otoacoustic emission (DPOAE) level maps use individually optimal DPOAE stimulus levels and allow reliable quantitative estimation of cochlea-related hearing loss. Hearing thresholds were estimated objectively using LEDPT and subjectively using modified Békésy tracking audiometry (LTA). Recordings were performed seven times within threemonths at 14frequencies (f2 = 1-14 kHz) in 20ears (PTA4 (0.5-4 kHz) < 20 dB HL). Reconstruction of the DPOAE growth behavior as afunction of the stimulus levels L1, L2 was performed on the basis of 21DPOAE amplitudes. Anumerical fit of anonlinear mathematical function to the three-dimensional DPOAE growth function yielded LEDPT for each stimulus frequency. For the combined analysis, probability distributions of hearing thresholds (LTA, LEDPT), DPOAE levels (LDP), and combinations thereof were determined. LTA and LEDPT each exhibited atest-retest reliability with amedian of absolute differences (AD) of 3.2 dB and 3.3 dB, respectively. Combining LEDPT, LDP, and LTA into asingle parameter yielded asignificantly smaller median AD of 2.0 dB. It is expected that an analysis paradigm based on acombination of LEDPT, suprathreshold LDP, and fine-structure-reduced LTA would achieve higher test performance (sensitivity and specificity), allowing reliable detection of pathological or regenerative changes in the outer hair cells.

The protective effects of Lactobacillus SNK-6 on growth, organ health, and intestinal function in geese exposed to low concentration Aflatoxin B1

Aflatoxin B1 (AFB1) is a prevalent mycotoxin present in feed ingredients. In this study, we investigated the effects of Lactobacillus salivarius (L. salivarius) on the Landes geese exposed to AFB1. The 300 one-day-old Landes geese were randomly divided into five groups: The control group received a basic diet, while the other groups were fed a basic diet supplemented with 10 μg/kg AFB1, 10 μg/kg AFB1+ 4*108 cfu/g L. salivarius, 50 μg/kg AFB1, and 50 μg/kg AFB1 + 4*108 cfu/g L. salivarius for 63 d. Results showed that high level AFB1 exposure significantly decreased final BW and ADG, increased feed/gain ratio (F/G) and liver index (P < 0.05). L. salivarius improved levels of IL-1, IL-6, and IL-12 under low level of AFB1 exposure (P < 0.05), along with similar trends observed in serum IgA, IgG, IgM, T3, T4, TNF-ɑ, and EDT (P < 0.05). AFB1 exposure reduced jejunum villus high and villus high/crypt depth ratio, and suppressed expression of ZO-1, Occludin, and Claudin-1 mRNA, and significant improved with L. salivarius supplementation under low level AFB1 exposure (P < 0.05). AFB1 significantly increased expression levels of TLR3 and NF-kB1, with supplementation of L. salivarius showing significant improvement under low AFB1 exposure (P < 0.05). Cecal microbiota sequencing revealed that under low level AFB1 exposure, supplementation with L. salivarius increased the abundance of Bacteroidetes and Lactococcus. In summary, supplementation with 4*108 cfu/g L. salivarius under 10 μg/kg AFB1 exposure improved growth performance and immune capacity, enhanced jejunum morphology, reduced liver inflammation, altered the cecal microbial structure, and positively affected the growth and development of geese.

#2374 Long-term clinical outcomes in pediatric patients with primary nephrogenic insipidus

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, and there is a paucity of studies assessing long-term clinical outcomes in affected individuals. This study aims to evaluate the long-term clinical outcomes, encompassing growth and kidney function, in pediatric patients with NDI. Method This multicenter retrospective study included forty-nine children diagnosed with NDI. The medical records of these patients were retrospectively reviewed, and a linear mixed model was employed to analyze variations in growth and kidney function with increasing age. Results Mutations in the AVPR2 and AQP2 genes were identified in 40 (81.6%) and 4 (8.2%) patients, retrospectively, while pathogenic variants were either not found or not tested in 5 (10.2%) patients. The median ages at diagnosis and the last follow-up were 0.41 (interquartile ranges (IQR) 0.12−0.64) years and 9.97 (IQR 2.42−18.66) years, respectively. Thiazide treatment was administered to all patients, with 43 (87.8%) and 14 (28.6%) patients also receiving amiloride and indomethacin, respectively, in conjunction with thiazide. Our analysis using linear mixed models revealed significant changes in growth including height, weight, and body mass index (BMI) with increasing age. The estimated marginal means (EMM) for height Z score decreased from −0.114 (95% confidence interval (CI) −0.507 to 0.279) at diagnosis to −1.464 (95% CI −1.880 to −1.048) at 2 years of age, subsequently increasing to −0.706 (95% CI −1.186 to −0.225) at 14 years of age (P &amp;lt; 0.001). The height Z score at 19 year of age is −0.899 (95% CI −1.434 to −0.365), significantly lower than those at diagnosis (P = 0.038). The EMM for weight Z score increased from −1.580 (95% CI −2.009 to −1.149) at one year of age to 0.760 (95% CI 0.170 to 1.350) at 19 years of age, exhibiting a steady increase (P &amp;lt; 0.001). The EMM for BMI Z score demonstrated a consistent increase after age of 2 years (P &amp;lt; 0.001), which were −0.326 (95% CI −0.835 to 0.182) at 2 years of age and 1.210 (95% CI 0.602 to 1.817) at 19 years of age. The proportion of obesity increased from 3.2% at 3 years of age to 33.3% at 19 years of age. The EMM for estimated glomerular filtration rate (eGFR) consistently increased from 82.8 (95% CI 75.2 to 90.3) mL/min/m2 to 100.8 (95% CI 88.9 to 112.7) mL/min/m2. Although eGFR less than 60 mL/min/m2 is not present, the eGFR less than 90 mL/min/m2 is 47.5% at last follow up. Conclusion At the end of growth, the height Z score is low, and the proportion of obesity is high. To improve the growth pattern, clinicians need to monitor nutritional status and establish nutritional support during follow-up in patients with NDI. Since mild decreased kidney function developed in half, patients with NDI need long-term follow-up evaluation for kidney function.

#2746 Long-term benefits in dRTA patients treated with Sibnayal®, a prolonged-release combination of potassium bicarbonate and citrate: 6-year results

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disease, either inherited or acquired, characterized by an hyperchloremic metabolic acidosis leading to negative effects on growth, bone metabolism and kidney function, and hearing impairment. Sibnayal®, an oral twice-daily fixed and prolonged-release combination of potassium bicarbonate and potassium citrate3, is registered in the indication of dRTA, whatever the genetic or acquired form, in patients aged 1 year and older. Both efficacy and good tolerability profile of Sibnayal® versus alkali Standard of Care (SoC) were demonstrated in the short-term in children and adults dRTA patients (B21CS study1). B22CS study2 is the long-term follow-up study with safety profile as main objective and evaluation of the impact on the long-term complications as secondary or exploratory objectives. Method Thirty patients with genetic dRTA, previously enrolled in B21CS study, were followed-up for six years on average in a multicenter open-label extension trial (B22CS) to evaluate long-term impact of Sibnayal® on safety and efficacy on metabolic acidosis control, renal function, bone remodeling and growth. Tubular damages and kidney function were assessed by bicarbonatemia, kalemia, eGFR (CKiDU25 formula), nephrocalcinosis (paired-t-test) and urinary pH (UpH) (symmetry test). Bone remodeling was assessed with spine bone mineral density (BMD) Z-score (paired t-test, McNemar-test) from baseline to end of follow-up (EoF) and bone alkaline phosphatase (bALP) until M48. Growth was assessed by Z-score of height, weight, and body mass index (BMI) (paired t-test). Results Thirty patients (24 children, 6 adults), median age 10.6 (2-21) years, with inherited dRTA were included in B22CS study (mean study duration of 5.8 ± 1.3 years). Only 20% of patients reported at least one treatment related adverse event, mainly of gastro-intestinal type, which resolved without study treatment discontinuation. Bicarbonatemia was maintained stable in the normal range over the study duration (22.0 ± 3.2 mmol/L at baseline and 22.6 ± 2.5 mmol/L at EoF, p = NS). Kalemia was also maintained in the normal range (3.8 ± 0.5 mmol/L at baseline and 3.7 ± 0.4 mmol/L at EoF, p = NS). UpH was maintained between 7 and 8 in 70% of patients and when UpH was superior to 8 there was no impact on ACCP crystals presence (47% of patients at baseline versus 35.3% at EoF, p = NS). Nephrocalcinosis was reported in 89% of patients at baseline and in 93% at EoF (p = NS). Glomerular filtration rate remained stable all over the follow-up, eGFR was 105.2 ± 16.9 mL/min/1.73 m2 at baseline versus 103.9 ± 19.9 mL/min/1.73 m2 at EoF (p = NS). Bone metabolism was improved as spine BMD Z-score significantly increased from baseline (−1.1 ± 1.0) to EoF (−0.8 ± 0.9), p = 0.0053. In addition, 88% of patients had a spine BMD Z-score in the normal range (&amp;gt; -2SD) at EoF versus 71% of patients at baseline (p = NS). bALP Z-score was in normal range at baseline versus M48 (0.9 ± 2.22 at baseline vs 0.7 ± 1.3 at M48, p = NS). Growth was improved as Z-score for height significantly increased from baseline to EoF (p = 0.0323) while both Z-scores for weight and BMI were stable (p = NS). Conclusion These data confirm the long-term good tolerability profile and efficacy of Sibnayal® in the management of metabolic acidosis, in patients with dRTA. Sibnayal® showed a preventive effect on metabolic acidosis long-term complications in this population.

Population pharmacokinetics and dose rationale for aciclovir in term and pre-term neonates with herpes.

Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CLCR) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CLCR and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CLCR), suggesting different dosing requirement for pre-term neonates.

Investigating The Importance of Vaccines and Childhood Nutrition on Improving Maternal and Child Health

T Maternal and child health remains a critical global concern, with significant efforts directed towards improving outcomes. This paper undertakes a comprehensive review to elucidate the pivotal roles of vaccines and childhood nutrition in enhancing maternal and child health. Vaccines are recognized as one of the most effective public health interventions, substantially reducing the burden of infectious diseases among both mothers and children. Through immunization, mothers are safeguarded against potentially life-threatening infections during pregnancy, consequently reducing maternal morbidity and mortality rates. Additionally, childhood vaccination programs play a crucial role in preventing various communicable diseases, thereby ensuring the well-being of infants and young children. Concomitantly, childhood nutrition emerges as a cornerstone of maternal and child health. Adequate nutrition during pregnancy is paramount for fetal development and maternal well-being, mitigating the risks of complications such as low birth weight and preterm birth. Furthermore, early childhood nutrition profoundly influences growth, cognitive development, and immune function, laying the foundation for optimal health outcomes throughout life. Addressing malnutrition in all its forms is imperative, encompassing not only undernutrition but also the rising challenges of overweight and obesity, which pose significant health risks. Moreover, the synergistic effects of vaccines and proper nutrition are evident in promoting maternal and child health. Immunization efficacy can be augmented by ensuring adequate nutritional status, as malnutrition can compromise immune responses and vaccine effectiveness. Conversely, vaccines protect against infectious diseases that can exacerbate malnutrition, thus fostering a positive cycle of health improvement. However, challenges such as vaccine hesitancy, inadequate healthcare infrastructure, and socioeconomic disparities persist, hindering the full realization of these interventions' potential.

Structure-Based Virtual Screening, ADMET Properties Prediction and Molecular Dynamics Studies Reveal Potential Inhibitors of Mycoplasma pneumoniae HPrK/P.

Mycoplasma pneumoniae pneumonia (MPP) is a frequent cause of community-acquired pneumonia (CAP) in children. The incidence of childhood pneumonia caused by M. pneumoniae infection has been rapidly increasing worldwide. M. pneumoniae is naturally resistant to beta-lactam antibiotics due to its lack of a cell wall. Macrolides and related antibiotics are considered the optimal drugs for treating M. pneumoniae infection. However, clinical resistance to macrolides has become a global concern in recent years. Therefore, it is imperative to urgently identify new targets and develop new anti-M. pneumoniae drugs to treat MMP. Previous studies have shown that deficiencies in HPrK/P kinase or phosphorylase activity can seriously affect carbon metabolism, growth, morphology, and other cellular functions of M. pneumoniae. To identify potential drug development targets against M. pneumoniae, this study analyzed the sequence homology and 3D structure alignment of M. pneumoniae HPrK/P. Through sequence and structure analysis, we found that HPrK/P lacks homologous proteins in the human, while its functional motifs are highly conserved in bacteria. This renders it a promising candidate for drug development. Structure-based virtual screening was then used to discover potential inhibitors among 2614 FDA-approved drugs and 948 bioactive small molecules for M. pneumoniae HPrK/P. Finally, we identified three candidate drugs (Folic acid, Protokylol and Gluconolactone) as potential HPrK/P inhibitors through molecular docking, molecular dynamics (MDs) simulations, and ADMET predictions. These drugs offer new strategies for the treatment of MPP.

Intestinal health of squab pigeons responded to parental dietary protein levels during breeding period

The objective of this study was to determine the effects of dietary crude protein (CP) levels on intestinal antioxidant status, tight junction proteins expression, and amino acids transporters levels in squabs. A total of 180 pairs of White King parent pigeons approximately 10 mo old were randomly assigned to 5 groups with 6 replications of 6 pairs of parental pigeons each, and were fed with 14, 15, 16, 17, and 18% CP diets for 46 d, respectively. Dietary increasing CP levels increased final body weight (linear and quadratic, P < 0.05), serum urea nitrogen (linear, P<0.05) and triglyceride levels (quadratic, P < 0.05), and reduced kidney relative weight (quadratic, P < 0.05) in squabs. Final body weight of squabs in the 18% CP diet group was higher than that of the 14, 15, and 16% CP diet groups (P < 0.05) but was similar to that of the 17% CP diet group (P > 0.05). Increasing dietary CP levels reduced intestinal malondialdehyde contents (linear and quadratic, P < 0.05) and jejunal total superoxide dismutase (T-SOD) activity (linear, P < 0.05), and enhanced (linear and quadratic, P<0.05) ileal catalase and T-SOD activities in squabs, and these effects were more prominent in the 17% CP diet group. Graded CP levels up-regulated the mRNA expression of intestinal zonula occludens 1 (linear, P < 0.05), solute carrier family 7 members 9 (linear, P < 0.05) and claudin 1 (CLDN1, linear and quadratic, P < 0.05), ileal CLDN3 and solute carrier family 6 members 14 (linear, P < 0.05) but lowered jejunal solute carrier family 6 member 14 (quadratic, P<0.05) mRNA expression in squabs. The effects of dietary CP levels on intestinal tight junction proteins expression were more apparent when its supplemental levels were 18%. These results suggested that increasing parental dietary CP levels ranged from 14 to 18% during breeding period improved growth and intestinal function of squabs, with its recommended level being 17%.

Pattern formation and delay-induced instability in a Leslie–Gower type prey–predator system with Smith growth function

In this article, we have investigated the spatiotemporal dynamics and delay-induced instability of a Leslie–Gower type prey–predator model under the influence of environmental toxicants with Smith growth function. This growth function is more realistic than logistic growth as it better describes the growth of the biological population. It has been used where the growth limitations are based on the proportion of available resources not utilized. A few works of Smith’s growth models are reported in the literature. Therefore, spatiotemporal dynamics and pattern formation with delay effect remain an exciting area of research, which motivates the present work. This work has studied two types of dynamical systems: (i) an ordinary differential temporal system with time delay and (ii) a reaction–diffusion system with time delay. The existence of equilibrium points and their stability conditions are discussed. Hopf bifurcation emerges in both proposed systems with respect to delay parameter. The stability and direction of Hopf bifurcation and delay–diffusion-driven instability have been investigated for the reaction–diffusion system. Numerical simulation is performed to support the analytical results and theorems. Moreover, the existence of Hopf and delay-induced instability are proved numerically. Interesting one-dimensional regular and irregular stripe patterns are obtained for increased values of the time delay parameter. Also, the presence of natural toxicants has a negative impact on the growth of prey–predator species.