Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature.

The effect of renal functional status on drug metabolism is a crucial consideration for clinicians when determining the appropriate dosage of medications to administer. In critically ill patients, there is often a significant increase in renal function, which leads to enhanced drug metabolism and potentially inadequate drug exposure. This phenomenon, known as augmented renal clearance (ARC), is commonly observed in pediatric critical care settings. The findings of the current study underscore the significant impact of ARC on the pharmacokinetics and pharmacodynamics of antimicrobial drugs in critically ill pediatric patients. Moreover, the study reveals a negative correlation between increased creatinine clearance and blood concentrations of antimicrobial drugs. The article provides a comprehensive review of ARC screening in pediatric patients, including its definition, risk factors, and clinical outcomes. Furthermore, it summarizes the dosages and dosing regimens of commonly used antibacterial and antiviral drugs for pediatric patients with ARC, and recommendations are made for dose and infusion considerations and the role of therapeutic drug monitoring. CONCLUSION:  ARC impacts antimicrobial drugs in pediatric patients. WHAT IS KNOWN: • ARC is inextricably linked to the failure of antimicrobial therapy, recurrence of infection, and subtherapeutic concentrations of drugs. WHAT IS NEW: • This study provides an updated overview of the influence of ARC on medication use and clinical outcomes in pediatric patients. • In this context, there are several recommendations for using antibiotics in pediatric patients with ARC: 1) increase the dose administered; 2) prolonged or continuous infusion administration; 3) use of TDM; and 4) use alternative drugs that do not undergo renal elimination.

Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin.

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1-15). Acetate of these derivatives were prepared (compounds 1a-15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

Skeleton Synthesis of a Plant-Derived Radioprotective Alkaloid Born to Produce a Novel Fused Heterocycle.

Alkaloids are a material treasure bestowed on humans by nature owing to their numerous biological activities. Orychophragine D, an alkaloid isolated from the seeds of Orychophragmus violaceus was identified as bearing a novel skeleton and proved to have an excellent radioprotective effect. Different from the common alkaloid structure, the main block of orychophragine D is constructed of an oxotriazine and an oxopiperazine, which are connected in parallel by a C-N bond. In this paper, a preparation method for the novel heterocycle skeleton of orychophragine D is proposed for the first time. N-Boc-L-serine was utilized as the original material to complete the preparation with 11 steps in a 13% overall yield. A hydroxyl group was established on the side chain of the skeleton as the reaction site for researchers to conduct further structural modification or derivatization.

Phytochemical Constituents from the Seeds of Capsella bursa-pastoris and Their Antioxidant Activities.

Phytochemical investigation of 70% EtOH extract of the seeds of Capsella bursa-pastoris led to the isolation of a new cyclobutane organic acid (1), and fourteen known compounds, including two organosulfur compounds (2, 3), two quinonoids (4, 5), five flavonoids (6-10), three sterols (11-13) and two other types (14, 15). The structures of the compounds were elucidated by extensive spectroscopic analyses as well as comparison of their spectroscopic data with those reported in the literature. The antioxidant capacities of all compounds and extractive fractions were evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging test and ferric reducing antioxidant power (FRAP) assay. Then the antioxidative substances were evaluated for their neuroprotective effects against H2O2-induced HT22 cell injury. The results indicated the strong scavenging ability to free radical of the extractive fractions and compounds 1-3, 8-10 and 13, and the ferric reducing antioxidant power of the extractive fractions and compounds 1-3, 8 and 10, which were close to or higher than that of the positive control trolox. The EtOAc fraction, n-BuOH fraction, and compounds 1, 3 and 8 can protect HT-22 cells from oxidative damage.

Statistical Challenges in Tracking the Evolution of SARS-CoV-2.

Genomic surveillance of SARS-CoV-2 has been instrumental in tracking the spread and evolution of the virus during the pandemic. The availability of SARS-CoV-2 molecular sequences isolated from infected individuals, coupled with phylodynamic methods, have provided insights into the origin of the virus, its evolutionary rate, the timing of introductions, the patterns of transmission, and the rise of novel variants that have spread through populations. Despite enormous global efforts of governments, laboratories, and researchers to collect and sequence molecular data, many challenges remain in analyzing and interpreting the data collected. Here, we describe the models and methods currently used to monitor the spread of SARS-CoV-2, discuss long-standing and new statistical challenges, and propose a method for tracking the rise of novel variants during the epidemic.

Absolute Configuration and Biological Evaluation of Novel Triterpenes as Possible Anti-Inflammatory or Anti-Tumor Agents.

Two new compounds, ardisiapunine B (1) and ardisiapunine C (2), were isolated from Ardisia lindleyana D. Dietr. Their structures were examined using HR-ESI-MS, IR, (1D, 2D) NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD calculation. It was found that the two new compounds belong to unusual oleanane-type triterpenes, with compound 1 bearing an acetal unit and a C-13-C-18 double bond, and compound 2 bearing a C-28 aldehyde group and a C-18-C-19 double bond. The anti-inflammatory properties of compounds 1 and 2 were tested on NO production and cellular morphology using RAW264.7 cells, and their anti-tumor properties were tested on cytotoxic activities, cellular morphology, cell apoptosis, and cell cycle. The results showed that compound 1 exhibited a potent cytotoxicity against HepG2 cell lines with an IC50 of 12.40 µM. Furthermore, it is possible that compound 1 inhibits cell proliferation by blocking the cell G2/M phase and promoting cell apoptosis. Compound 2 exhibited a potential anti-inflammatory activity by decreasing the production of NO in LPS-stimulated RAW264.7 cells. Comparative analysis of the structures of compounds 1 and 2 revealed that the acetal structure and double bond positions were the main differences between them, and these are presumed to be the main reasons for the extreme differences in their cytotoxicity and anti-inflammatory activities. From these new findings, two promising lead compounds were identified for the future development of potential anti-inflammatory or anti-tumor agents.

Endoscopic ultrasound-guided drainage to abdominal abscess: A systematic review and meta-analysis.

Background: Ultrasound (US)- or computed tomography-guided drainage for abdominal abscess is currently the first-line options for drainage, but both options have disadvantages. Patients without adequate windows for drainage mostly undergo surgical drainage. However, surgical drainage is invasive and expensive. Endoscopic US (EUS)-guided drainage is a minimally invasive alternative for abdominal abscess, but there is less consensus on its efficacy, safety and complications. This meta-analysis aims to evaluate EUS-guided drainage for abdominal abscess. Materials and Methods: We retrieved relevant papers on EUS-guided drainage for abdominal abscess from the PubMed, Cochrane Library, Web of Science and EMBASE databases. Each paper was reviewed, and data were extracted. We used R software version 3.6.3 to perform the meta-analysis. Fixed effects models were used for merging data. Results: A total of 11 papers met the inclusion criteria, with a total sample population of 264 patients. The meta-analysis showed that the pooled clinical success rate was 90% (95% confidence interval [CI], 0.85-0.95), the technical success rate was 99% (95% CI, 0.97-1.00) and the recurrence rate was 1% (95% CI, 0.00-0.03). Three studies reported the complications, including perforation, bleeding and stent migration; none of the other eight studies reported complications. There were no significant differences between subgroups. There was no publication bias in either the clinical or the technical success rates. Conclusions: This meta-analysis showed that EUS-guided drainage for abdominal abscess was effective and safe, with an excellent technical success rate. In addition, EUS-guided drainage could be used for abscesses with complex anatomy. Nevertheless, complications and stent type should be considered.

Amplitude-modulated continuous-wave laser rangefinder employing Bessel-Gauss beamforming.

We propose an amplitude-modulated continuous-wave laser rangefinder employing Bessel-Gauss beamforming. Our Bessel-Gauss beam was generated by a newly proposed doublet configuration, which is simple and low cost. Such a beam was propagated >2m with a mainlobe having the diameter <1mm. We have conducted proof-of-concept ranging experiments employing the amplitude-modulated continuous-wave scheme with the Bessel-Gauss beam and obtained ranging results of a measurement distance up to 2 m. To the best of our knowledge, this is the first attempt to apply zeroth-order Bessel-Gauss beamforming to laser rangefinders.

How to reduce dimension with PCA and random projections?

In our "big data" age, the size and complexity of data is steadily increasing. Methods for dimension reduction are ever more popular and useful. Two distinct types of dimension reduction are "data-oblivious" methods such as random projections and sketching, and "data-aware" methods such as principal component analysis (PCA). Both have their strengths, such as speed for random projections, and data-adaptivity for PCA. In this work, we study how to combine them to get the best of both. We study "sketch and solve" methods that take a random projection (or sketch) first, and compute PCA after. We compute the performance of several popular sketching methods (random iid projections, random sampling, subsampled Hadamard transform, CountSketch, etc) in a general "signal-plus-noise" (or spiked) data model. Compared to well-known works, our results (1) give asymptotically exact results, and (2) apply when the signal components are only slightly above the noise, but the projection dimension is non-negligible. We also study stronger signals allowing more general covariance structures. We find that (a) signal strength decreases under projection in a delicate way depending on the structure of the data and the sketching method, (b) orthogonal projections are slightly more accurate, (c) randomization does not hurt too much, due to concentration of measure, (d) CountSketch can be somewhat improved by a normalization method. Our results have implications for statistical learning and data analysis. We also illustrate that the results are highly accurate in simulations and in analyzing empirical data.

Compensating deep focusing distortion for femtosecond laser inscription of low-loss optical waveguides.

Various beam shaping approaches were examined to counter the negative influence of surface aberration arising when inscribing optical waveguides deeply inside of glass with a femtosecond laser. Aberration correction was found unable to completely recover the low-loss waveguide properties, prompting a comprehensive examination of waveguides formed with focused Gaussian-Bessel beams. Diverging conical phase fronts are presented as a hybrid means of partial aberration correction to improve insertion loss and a new, to the best of our knowledge, means of asymmetric beam shaping. In this way, low-loss waveguides are presented over shallow to deep writing depth (2.8 mm) where morphological and modal properties could be further tuned with conical phase front.

Four pairs of alkaloid enantiomers from Isatis indigotica Fortune Ex Land with neuroprotective effects against H2O2-induced SH-SY5Y cell injury.

In the current study, four pairs of new enantiomeric alkaloids (1a/1b-4a/4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively.

Correction: Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica fortune.

Correction for 'Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica fortune' by Si-Fan Liu et al., Org. Biomol. Chem., 2018, 16, 9430-9439.

Discovery of cycloneolignan enantiomers from Isatis indigotica Fortune with neuroprotective effects against MPP+-induced SH-SY5Y cell injury.

A pair of new cycloneolignan enantiomers (1a and 1b) were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated by extensive spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, MS/MS analysis, together with theoretical electronic circular dichroism (ECD) calculations. Compounds 1a and 1b were then evaluated for their neuroprotective effects against MPP+-induced SH-SY5Y cell injury. As a result, compounds 1a (77.64%) and 1b (78.62%) exhibited moderate neuroprotective activity at the concentration of 12.5 µM compared with that of MPP+ treated group (62.00% at 1 mM) by MTT assay. Furthermore, Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 10.99% and 9.31%, respectively.

Are perfluoroalkyl substances in water and fish from drinking water source the major pathways towards human health risk?

Due to potential adverse effects and bioaccumulation in biota and humans, perfluoroalkyl substances (PFASs) have raised wide attention in recent years. Ingestion is a vital pathway for PFASs to transmit to humans especially through water and fish. In present study, PFASs in water and fish from the drinking water source of Beijing in China were investigated. Three layers of water were collected in order to find the connection between concentrations of PFASs and depth of water, which showed no prominent correlation. PFASs in water from Miyun Reservoir with concentrations of 5.30-8.50 ng/L, were relatively lower compared with other reports on raw drinking water. Perfluorobutanoic acid (PFBA) and perfluorooctanoic acid (PFOA) were the dominant PFASs. In addition, six species of fish (including Cyprinus carpio, Carassius auratus, Erythroculter dabryi, Pseudohemiculter dispar, Hypophthalmichthys molitrix and Siniperca chuatsi) were analyzed, with concentrations of PFASs ranging from 1.70 to 14.32 ng/g wet weight (w.w.). Due to relatively stronger bioaccumulation potential, long chain perfluorinated carboxylates (PFCAs) and perfluorinated sulfonates (PFSAs) were detected with higher concentrations, especially perfluoroundecanoic acid (PFUdA) and perfluorodecanoic acid (PFDA). The estimated daily intake (EDI) of PFASs through drinking water and fish consumption were 0.20-0.34 and 3.44-12.61 ng/kg bw/day based on Exposure Factors Handbook of Chinese Population, respectively. In addition, the EDI of high-priority concern PFASs via pork, chicken and dust were also calculated, with value of 0.015-0.043, 0.003-0.013 and 0.074-0.390 ng/kg bw/day, respectively. The total EDI of PFOS and PFOA via diverse pathways were less than suggested tolerable daily intake (PFOS, 150 ng/kg bw/day; PFOA, 1500 ng/kg bw/day), indicating that the detected levels would not cause severe health effects on Beijing residents.

Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica Fortune.

Four pairs of new spiropyrrolizidine oxindole enantiomers (1a/1b-4a/4b) were isolated from the leaves of Isatis indigotica Fortune. Their structures and absolute configurations were elucidated by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD) and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Notably, all the isolated spiropyrrolizidine oxindoles are reported as natural products for the first time. The biosynthetic pathway of these unique structures was proposed to be formed by cycloaddition reaction. In addition, all the compounds were evaluated for their inhibitory effects on ß-amyloid aggregation by ThT assay, and the optically pure compounds 1a/1b and 2a/2b exhibited better Aß1-42 aggregation inhibition potency (85.8% and 73.6%, 71.5% and 75.8%, respectively) at a concentration of 20 µM, compared with the positive control curcumin (57.0%). The difference of the inhibitory pattern caused by chirality was also explained by molecular docking studies.

Antioxidant and anti-inflammatory neolignans from the seeds of hawthorn.

Seven new neolignans (1-2, 7-11) and five known compounds (3-6, 12) were isolated from the 70% EtOH extract of hawthorn seeds. Their structures were determined by spectroscopic analyses. The antioxidant and anti-inflammatory activities of all the isolates were investigated. Most of the isolates showed moderate radical scavenging activity in the DPPH assay and significant activities in the ABTS and FRAP assays. Furthermore, compounds 7-12 exhibited marked nitric oxide (NO) inhibition and compounds 1-4 had a potent necrosis factor-α (TNF-α) inhibitory effect. The results we obtained showed that hawthorn seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors.

The oral microbiome and oral and upper gastrointestinal diseases.

Background: Microbiomes are essential components of the human body, and their populations are substantial. Under normal circumstances, microbiomes coexist harmoniously with the human body, but disturbances in this equilibrium can lead to various diseases. The oral microbiome is involved in the occurrence and development of many oral and gastrointestinal diseases. This review focuses on the relationship between oral microbiomes and oral and upper gastrointestinal diseases, and therapeutic strategies aiming to provide valuable insights for clinical prevention and treatment. Methods: To identify relevant studies, we conducted searches in PubMed, Google Scholar, and Web of Science using keywords such as "oral microbiome," "oral flora, " "gastrointestinal disease, " without any date restrictions. Subsequently, the retrieved publications were subject to a narrative review. Results: In this review, we found that oral microbiomes are closely related to oral and gastrointestinal diseases such as periodontitis, dental caries, reflux esophagitis, gastritis, and upper gastrointestinal tumors (mainly the malignant ones). Oral samples like saliva and buccal mucosa are not only easy to collect, but also display superior sample stability compared to gastrointestinal tissues. Consequently, analysis of the oral microbiome could potentially serve as an efficient preliminary screening method for high-risk groups before undergoing endoscopic examination. Besides, treatments based on the oral microbiomes could aid early diagnosis and treatment of these diseases. Conclusions: Oral microbiomes are essential to oral and gastrointestinal diseases. Therapies centered on the oral microbiomes could facilitate the early detection and management of these conditions.

1. Various microbiomes exist in the oral cavity. 2. Under normal circumstances, oral microbes and human health coexist in harmony, once this balance is broken, it may cause a variety of diseases. 3. Oral microbiota are associated with upper digestive diseases, which are expected to be an effective triage for high-risk population before endoscopic screening.

The Effect of Carboxymethyl Cellulose Sodium on the Proofing Tolerance and Quality of Frozen Dough Steamed Bread.

This study investigated the effects of dough proofing degree (1.1, 1.3, 1.5, and 1.7 mL/g) and carboxymethyl cellulose sodium (CMC-Na) on the quality of frozen dough steamed bread (FDSB). As the dough proofing degree was increased from 1.1 to 1.7 mL/g, the specific volume of FDSB initially increased and then decreased, with the maximum at 1.3 mL/g, and then dramatically decreased at 1.5 and 1.7 mL/g, accompanied by a harder texture and secession of crust and crumb, which were the detrimental effects brought by over-proofing. The optimal amount of CMC-Na effectively alleviated the deterioration associated with over-proofing, and the proofing tolerance of FDSB was increased from 1.3 mL/g to 1.7 mL/g. Fermentation analysis showed that CMC-Na significantly improved the extensibility and gas-holding capacity of the dough by increasing the maximum height of the dough (Hm) and the emergence time (T1) of Hm. Frequency sweep tests indicated that CMC-Na improved the plasticity of proofed dough by increasing loss factor tan δ. Significant reductions were found in peak viscosity and complex modulus G* in pasting properties tests and temperature sweep measurements, respectively, suggesting that CMC-Na influenced starch gelatinization and dough stiffening during steaming, which promoted the extension of the network structure, thus facilitating gas expansion and diffusion. These property changes theoretically explained the improvement in the proofing tolerance of FDSB by CMC-Na.

Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.

AIMS: The purpose of this study was to investigate the role of DGUOK in the pro-gression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment. METHODS: We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was inves-tigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy. RESULTS: Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This ef-fect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in au-tophagy pathways. CONCLUSION: These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment.

The 3-year follow-up of a fully biodegradable implantable device closure for perimembranous ventricular septal defects in children using echocardiography.

Objects: The aim of this study was to investigate the morphologic changes of a novel fully biodegradable implantable device after closing a perimembranous ventricular septal defect (Pm-VSD) and to evaluate the effect of the occluder on the myocardial function in patients during a 3-year follow-up period. Methods: One-year, 2-year, and 3-year follow-ups were carried out after implantation with a total of 30 Pm-VSD patients who had successful closure by the fully biodegradable occluder. In total, 30 healthy children were enrolled as controls. At discharge and at every follow-up visit, the lengths of the left and right discs of the novel device were measured in the apical three- and four-chamber as well as short-axis views. At the end of the follow-up, using three-dimensional speckle-tracking conditions, the values of myocardial deformation, including global longitudinal strain, global circumferential strain, and global area strain, were acquired. Results: The fully bioabsorbable double-disc occluder gradually decreased over time and was eventually invisible under echocardiographic scanning during the follow-up (p < 0.05). At the end of the third year, there were no significant differences in the myocardial deformation parameters between the cases implanted with the novel devices and the controls; no significant differences were found between the basal segments of the ventricle septa and that of the left ventricle (LV) free wall among the patients who completed the Pm-VSD closure using the fully biodegradable occluder (p > 0.05). Conclusion: The novel fully biodegradable occluder is a safe, effective, and perfect alternative for the treatment of VSD. Echocardiography plays a crucial role in the follow-up of this new type of occluder implantation.