Cerebral net uptake of lactate contributes to neurological injury after experimental cardiac arrest in rabbits.

During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Experimental study. Experimental laboratory. Male New-Zealand rabbits. Animals were surgically instrumented and randomly divided into five groups receiving short infusion duration of either lactate or pyruvate or a pre-cardiac arrest infusion of oxamate (an inhibitor of the lactate dehydrogenase) or injection of fluorocitrate (an inhibitor of astrocytic tricarboxylic acid), or Saline (lactate, pyruvate, Oxa, FC and Control groups, respectively). After randomization, animals were submitted to 10 min of ventricular fibrillation and subsequent resuscitation. All animals were then either followed during 4 h, for the evaluation of the cerebral net uptake and concentrations of metabolites by microdialysis (n = 6 in each experimental group, n = 12 in control group), or during 48 h for the evaluation of their neurological outcome (n = 7 in each groups and n = 14 in control group). Cardiac arrest was associated with a dramatic increase in cerebral net uptake of lactate during 120 min after resuscitation, which was increased by lactate or pyruvate administration. This was associated with an increase in the mean neurological dysfunction score (66.7 ± 4.7, 79.0 ± 4.5 vs 57.7 ± 1.5 in Lactate, Pyruvate and Control group respectively) at 48 h after cardiac arrest. Oxamate and FC administration were associated with a lower lactate cerebral uptake after cardiac arrest and with an improvement of the neurological recovery (28.85 ± 9.4, 23.86 ± 6.2 vs 57.7 ± 1.5 in Oxa, FC and Control group respectively). After cardiac arrest, immediate isotonic lactate or pyruvate administration is deleterious. Pre-cardiac arrest LDH inhibition was potently neuroprotective in this setting.

Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy disproportionately affects low- and middle-income countries, where ≈96% of affected infants reside. The current standard of care, therapeutic hypothermia, is frequently ineffective in this setting, likely because injury may be occurring earlier during labor. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal caffeine administration in near-term lambs following global ischemic injury to support the development of earlier treatment strategies targeting the fetus in utero as well as the infant postnatally. METHODS: Ewes were randomly assigned to receive either 1 g IV caffeine citrate or placebo before delivery and placental transport assessed. Near-term lambs (141-143 days) of both sexes were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Lambs that received caffeine in utero also received 20 mg/kg IV caffeine citrate following resuscitation and 10 mg/(kg·d) IV for 2 days. An additional cohort received 60 mg/kg followed by 30 mg/(kg·d) (low dose versus high dose) postnatally. Biochemical, histological, and neurological outcome measures in lambs were assessed over a 6-day period. RESULTS: Perinatal caffeine administration demonstrated excellent placental transport kinetics and was well tolerated with lamb plasma levels comparable to those targeted in neonates with apnea of prematurity. Caffeine administration resulted in a systemic immunomodulatory effect, evidenced by significant reductions in proinflammatory IP-10 levels. Treated lambs demonstrated improved neurodevelopmental outcomes, while histological analysis revealed that caffeine reduced gray matter injury and attenuated inflammation in the cingulate and parasagittal cortex. This neuroprotective effect was greater and via a different mode of action than we previously reported for azithromycin. A higher caffeine dosing regimen demonstrated significant toxicity. CONCLUSIONS: Perinatal caffeine administration is well tolerated, attenuates systemic and brain inflammation, and contributes to improvements in histological and neurological outcomes in an ovine model of neonatal hypoxic-ischemic encephalopathy.

The association of gene polymorphisms of adenosine and dopamine receptors with the response to caffeine citrate treatment in infants with apnea of prematurity: a prospective nested case-control study.

BACKGROUND: To investigate the potential influence of adenosine and dopamine receptor genes polymorphisms in combination with clinical factors on the response of preterm infants to caffeine citrate treatment in apnea of prematurity (AOP). METHODS: A prospective nested case-control study enrolled 221 preterm infants with gestational age < 34 weeks. These infants were divided into the response (n = 160) and the non-response groups (n = 61). 22 single-nucleotide polymorphisms in adenosine and dopamine receptor genes were genotyped. The basic characteristics and clinical outcomes of the two groups were compared. Univariate logistic regression analysis was performed to evaluate the differences in genotype distribution between the groups. Multivariable logistic regression analysis was performed to identify independent risk and protective factors and develop a nomogram to predict caffeine citrate response in preterm infants. RESULTS: Preterm infants in the non-response group had lower gestational age, lower birth weight, longer periods of oxygen supplementation and caffeine citrate use, and higher incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), neonatal respiratory distress syndrome (NRDS), retinopathy of prematurity (ROP), and brain injury (P < 0.05 for all). The ADORA1 rs10920573, ADORA2B rs2015353, ADORA3 rs10776728, DRD3 rs7625282, and DRD3 rs6280 gene polymorphisms were associated with caffeine citrate response in preterm infants (PFDR < 0.05 for all). The ADORA1 rs10920573 CC (aOR, 3.51; 95% CI, 1.34-9.25) and DRD3 rs6280 CT genotypes (aOR, 3.19; 95% CI, 1.53-6.65) were independent risk factors for non-response, whereas greater gestational age (aOR, 0.631; 95% CI, 0.53-0.75) was an independent protective factor for response. The concordance index of the nomogram was 0.764 (95% CI, 0.687-0.842), and the calibration and decision curve analysis indicated the nomogram had excellent predict performance. CONCLUSIONS: Adenosine receptor gene and dopamine receptor gene polymorphisms influence caffeine citrate treatment response in AOP. By combining genetic and clinical variables, it is possible to predict the response to caffeine citrate treatment in preterm infants.

Astrocytes contribute to the functional differentiation of the hippocampal longitudinal axis during reward and aversion processing in the adult male rat.

This study aims to investigate whether glial cells, in particular putative astrocytes, contribute to functional distinctions between the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus. To evaluate this, we performed three different behavioral tasks (i.e., Morris water maze; MWM, Passive avoidance; PA, T-maze place preference; TPP) to determine whether the DH, IH, and VH are necessary for each task. Sensitivity of behavioral tasks was confirmed using lidocaine (2 %, 1 µl) reversible inactivation. Subsequently, we examined the effects of silencing astrocytes, using fluorocitrate (FC, 1 mM/1 µl), into the DH, IH, and VH on these tasks. The effects of drugs were examined separately. We observed that injection of FC into the DH resulted in a significant impairment in MWM performance. In contrast, while FC injections into the IH or VH did not prevent platform localization during the acquisition phase, rats showed difficulty recalling the target zone during the retrieval phase. In the PA test, FC injection into the VH impaired task learning and memory. During the acquisition phase, FC injection into the DH or IH did not differ from the control in the number of shocks; however, during retrieval, there was a significant decrease in the latency before entering the dark chamber. The TPP test performance was impaired by FC injection in the IH. In sum, we show that glial cells, especially astrocytes in specific functional regions of the hippocampus, play distinct roles in processing aversive and rewarding experiences and contribute to the functional organization of the hippocampal longitudinal axis.

Identification of candidate exposure biomarkers for acetyl tributyl citrate and acetyl triethyl citrate using suspect screening in human liver microsomes.

Acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) are increasingly used as alternatives to phthalates in various products, including food packaging, medical devices, and personal care items, raising concerns about their potential health impacts. This study aimed to investigate the in vitro human metabolism of ATBC and ATEC and identify potential exposure biomarkers applicable in human biomonitoring. Pooled human liver microsomes were utilized to conduct in vitro metabolism assays of deuterium labeled ATBC (ATBC-d3) and ATEC, and ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-qToF/MS) was employed for analysis. Suspect screening workflow and confidence level assignment were applied for metabolite identification. Time-course analysis revealed rapid metabolism of both compounds, with estimated apparent half-lives of approximately 5 min for ATBC-d3 and less than 15 min for ATEC. Eleven metabolites were identified for ATBC-d3 and six for ATEC. The predominant chemical reactions observed were carboxylic ester hydrolysis, deacetylation, and hydroxylation. Based on their abundance and specificity, MB1 (hydroxylated) and MB11 (hydrolyzed and hydroxylated) were proposed as candidate exposure biomarkers for ATBC, and ME1 (hydrolyzed and deacetylated) for ATEC. The identified metabolites and proposed sequences of kinetic process enhance our understanding of the fate of these compounds in the human body, potentially informing future toxicological assessments and guiding the development of more comprehensive human biomonitoring strategies.

Glutamatergic and purinergic transmitters and astrocyte modulation in the synaptic transmission in the NTS of rats exposed to short-term sustained hypoxia.

There is evidence that astrocytes modulate synaptic transmission in the nucleus tractus solitarius (NTS) interacting with glutamatergic and purinergic mechanisms. Here, using in situ working heart-brainstem preparations, we evaluated the involvement of astrocyte and glutamatergic/purinergic neurotransmission in the processing of autonomic and respiratory pathways in the NTS of control and rats exposed to sustained hypoxia (SH). Baseline autonomic and respiratory activities and the responses to chemoreflex activation (KCN) were evaluated before and after microinjections of fluorocitrate (FCt, an astrocyte metabolic inhibitor), kynurenic acid, and pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS) (nonselective antagonists of glutamatergic and purinergic receptors) into the rostral aspect of the caudal commissural NTS. FCt had no effects on the baseline parameters evaluated but reduced the bradycardic response to chemoreflex activation in SH rats. FCt combined with kynurenic acid and PPADS in control rats reduced the baseline duration of expiration, which was attenuated after SH. FCt produced a large increase in PN frequency discharge in control rats, which was reduced after SH, indicating a reduction in the astrocyte modulation after SH. The data show that 1) the bradycardic component of the peripheral chemoreflex is reduced in SH rats after astrocytes inhibition, 2) the inhibition of astrocytes in the presence of double antagonists in the NTS affects the modulation of baseline duration of expiration in control but not in SH rats, and 3) the autonomic and respiratory responses to chemoreflex activation are mediated by glutamatergic and purinergic receptors in the rostral aspect of the caudal commissural NTS.NEW & NOTEWORTHY Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats.

Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6 J male mice were subjected to a diet containing ATHC for 12 weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies.

Polydiolcitrate-MoS2 Composite for 3D Printing Radio-Opaque, Bioresorbable Vascular Scaffolds.

Implantable polymeric biodegradable devices, such as biodegradable vascular scaffolds, cannot be fully visualized using standard X-ray-based techniques, compromising their performance due to malposition after deployment. To address this challenge, we describe a new radiopaque and photocurable liquid polymer-ceramic composite (mPDC-MoS2) consisting of methacrylated poly(1,12 dodecamethylene citrate) (mPDC) and molybdenum disulfide (MoS2) nanosheets. The composite was used as an ink with microcontinuous liquid interface production (µCLIP) to fabricate bioresorbable vascular scaffolds (BVS). Prints exhibited excellent crimping and expansion mechanics without strut failures and, importantly, with X-ray visibility in air and muscle tissue. Notably, MoS2 nanosheets displayed physical degradation over time in phosphate-buffered saline solution, suggesting the potential for producing radiopaque, fully bioresorbable devices. mPDC-MoS2 is a promising bioresorbable X-ray-visible composite material suitable for 3D printing medical devices, such as vascular scaffolds, that require noninvasive X-ray-based monitoring techniques for implantation and evaluation. This innovative biomaterial composite system holds significant promise for the development of biocompatible, fluoroscopically visible medical implants, potentially enhancing patient outcomes and reducing medical complications.

Development and application of a population pharmacokinetic model repository for caffeine dose tailoring in preterm infants.

BACKGROUND: Considerable interindividual variability for the pharmacokinetics of caffeine in preterm infants has been demonstrated, emphasizing the importance of personalized dosing. This study aimed to develop and apply a repository of currently published population pharmacokinetic (PopPK) models of caffeine in preterm infants to facilitate model-informed precision dosing (MIPD). RESEARCH DESIGN AND METHODS: Literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases. Relevant publications were screened, and their quality was assessed. PopPK models were reestablished to develop the model repository. Covariate effects were evaluated and the concentration-time profiles were simulated. An online simulation and calculation tool was developed as an instance. RESULTS: Twelve PopPK models were finally included in the repository. Preterm infants' age and body size, especially the postnatal age and current weight, were identified as the most clinically critical covariates. Simulated blood concentration-time profiles across these models were comparable. Caffeine citrate-dose regimen should be adjusted according to the age and body size of preterm infants. The developed online tool can be used to facilitate clinical decision-making. CONCLUSIONS: The first developed repository of PopPK models for caffeine in preterm infants has a wide range of potential applications in the MIPD of caffeine.

Small Charged Molecule-Mediated Fibrillar Mineralization: Implications for Ectopic Calcification.

Numerous small biomolecules exist in the human body and play roles in various biological and pathological processes. Small molecules are believed not to induce intrafibrillar mineralization alone. They are required to work in synergy with noncollagenous proteins (NCPs) and their analogs, e.g. polyelectrolytes, for inducing intrafibrillar mineralization, as the polymer-induced liquid-like precursor (PILP) process has been well-documented. In this study, we demonstrate that small charged molecules alone, such as sodium tripolyphosphate, sodium citrate, and (3-aminopropyl) triethoxysilane, could directly mediate fibrillar mineralization. We propose that small charged molecules might be immobilized in collagen fibrils to form the polyelectrolyte-like collagen complex (PLCC) via hydrogen bonds. The PLCC could attract CaP precursors along with calcium and phosphate ions for inducing mineralization without any polyelectrolyte additives. The small charged molecule-mediated mineralization process was evidenced by Cryo-TEM, AFM, SEM, FTIR, ICP-OES, etc., as the PLCC exhibited both characteristic features of collagen fibrils and polyelectrolyte with increased charges, hydrophilicity, and density. This might hint at one mechanism of pathological biomineralization, especially for understanding the ectopic calcification process.

The regulating mechanisms of Triton X-100 affected oxidation of PAHs in site soil aggregates using sodium citrate assisted Fe2+-persulfate.

Here, we present a first investigation of the inhibition mechanism of surfactant Triton X-100 (TX-100) on the oxidation degradation of polycyclic aromatic hydrocarbons (PAHs) in site soil aggregates using sodium citrate assisted Fe2+-activated persulfate (SC/Fe2+/PS). First, TX-100 was not only competed the adsorption sites of soil aggregates with PS, but also consumed PS, which inhibit the PAHs remediation rate in the TX-100 elution followed by the SC/Fe2+/PS oxidation system from 55.6 % in the oxidation system to 50.3 %. Furthermore, in the oxidation followed by elution system, PAHs was adsorbed on the iron minerals produced during the oxidation, which would be form a bound PAHs that was difficult to react with PS, and then re-eluted to the soil by the TX-100. Additionally, it was found that the oxidative and the elution efficiency of PAHs exhibited negative correlations with aggregate particle sizes. Finally, soil microorganism communities were more strongly changed by SC/Fe2+/PS oxidation and PAHs concentration than that of TX-100 elution, with obvious alterations bacteria than fungi, the effects of SC/Fe2+/PS and PAHs concentration on microorganism communities were opposite. This study provided a proof of regulating mechanisms for the site soil remediation using surfactants combined with the iron-PS system.

Physicochemical characterization of the metamorphosis of film-forming formulations of betamethasone-17-valerate.

Following topical application of a dermatological product, the loss (by evaporation and/or absorption through the skin) of volatile excipients will alter the composition of the formulation remaining on the tissue. This so-called metamorphosis impacts the concentration of the drug in the residual vehicle, (potentially) its physical form therein and, as a result, its uptake into and subsequent permeation through the skin. This research aimed to characterise - using primarily confocal Raman microspectroscopy - the metamorphosis of film-forming formulations of betamethasone-17-valerate (at different loadings) comprised of hydroxypropyl cellulose (film-forming agent), triethyl citrate (plasticizer) and ethanol (solvent). Dissolved and crystalline drug in the films were identified separately by their different characteristic Raman frequencies (1666 cm-1 and 1659 cm-1, respectively). These Raman measurements, as well as optical imaging, confirmed corticosteroid crystallisation in the residual films left after ethanol evaporation when drug concentration exceeded the saturation limit. In vitro release tests of either sprayed or pipette-deposited films into either aqueous or ethanolic receptor solutions revealed drug release kinetics dominated by the residual film post-metamorphosis. In particular, the rate and extent of drug release depends on the concentration of dissolved drug in the residual film, which is limited by drug saturation unless supersaturation occurs. For the simple films examined here, supersaturation was not detected and the solubility limit of drug in the films was sufficient to sustain drug release at a constant flux from the saturated films through a thin silicone elastomer membrane into an aqueous receptor solution for 30 h. Flux values were âˆ¼ 1 µg cm-2h-1 from saturated residual films independent of the amount of crystallized drug present. Flux from subsaturated films was reduced by an amount that was consistent with the lower degree of saturation.

Soluble Salts in Processed Cheese Prepared with Citrate- and Phosphate-Based Calcium Sequestering Salts.

In this study, the protein and salts distribution (Ca, P, Na and Mg) in processed cheese (PC) samples prepared with 180 or 360 mEq/kg of the calcium sequestering salts (CSS) disodium phosphate (DSP), disodium pyrophosphate (DSPP), sodium hexametaphosphate (SHMP) and trisodium citrate (TSC) was studied. For this purpose, a water-soluble extract (WSE) of PC samples was prepared. All PC samples contained 45-46% moisture, 26-27% fat and 20-21% protein and had a pH of 5.2 or 5.7. Ultracentrifugation slightly reduced the protein content of the WSE of PC, indicating that most protein in the WSE was non-sedimentable. At equal concentration of CSS, the protein content of the WSE was higher for PC at pH 5.7 compared to PC at pH 5.2. Approximately 55-85% of the Ca and P in the WSE of samples was 10 kDa-permeable for PC prepared with DSPP and SHMP. This suggests that the formation of non-permeable Ca-polyphosphate-casein complexes. For PC prepared with TSC, >90% of Ca in the WSE was 10 kDa-permeable, indicating that micellar disruption arises from sequestration of micellar Ca. These results indicate that the WSE method is an appropriate method to understand how salts present in PC are distributed. However, the WSE and ultracentrifugal supernatant of the WSE can include both soluble and protein-associated salts. Therefore, determining levels of salts in 10 kDa permeate of ultracentrifugal supernatant of the WSE is most appropriate.

Simultaneous determination of total homocysteine, methionine, methylmalonic acid and 2-methylcitric acid in dried blood spots by ultra-performance liquid chromatography-tandem mass spectrometry.

Homocysteine, methionine, methylmalonic acid and 2-methylcitric acid are clinically relevant markers in the methionine, propionate, and cobalamin metabolism. This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously determining total homocysteine, methionine, methylmalonic acid and 2-methylcitric acid in dried blood spots. Three 3.2 mm discs were punched from each calibrator, quality control, and sample dried blood spot into a 96-well U-plate. Each sample was spiked with internal standards and extracted. Then the supernatant was transferred to another 96-well U-plate. After nitrogen drying, the dried residues were reconstituted, centrifuged, and the resulting supernatant was transferred to another 96-well plate for analysis. The method was performed using UPLC-MS/MS within 3 min, validated according to guidance documents, and applied to 72 samples from confirmed patients with methionine, propionate, and cobalamin metabolism disorders. The UPLC-MS/MS method provided satisfactory separation of the four analytes. The R2 values were ≥ 0.9937 for all analytes. The recoveries ranged from 94.17 to 114.29 %, and the coefficients of variation for intraday and interday precision were 0.19 % to 5.23 % and 1.02 % to 6.89 %, respectively. No significant carry-over was detected for the four analytes, and most of confirmed samples exhibited biomarker patterns characteristic of the relevant disorders. A simple and fast UPLC-MS/MS method was successfully developed, validated, and applied to clinical samples for the simultaneous determination of total homocysteine, methionine, methylmalonic acid, and 2-methylcitric acid in dried blood spots.

Plasticization mechanism of biobased plasticizers comprising polyethylene glycol diglycidyl ether-butyl citrate with both long and short chains on poly(lactic acid).

Polylactic acid (PLA), a biodegradable polymer with low flexibility, is commonly plasticized with small molecules like tributyl citrate (TBC) for film production. However, these plasticizers, which lack chemical bonds or strong intermolecular interactions with the matrix, tend to migrate to the film surface over time. Their inclusion often compromises material strength for flexibility, increasing elongation at break but reducing tensile strength. In this research, by combining citric acid with n-butanol (B) and poly(ethylene glycol) diglycidyl ether (E), we synthesized three plasticizers, namely TE3, TE2B1, and TE1B2, to enhance the flexibility of PLA. TE2B1 and TE1B2 are equipped with butyl ester groups that offer effective plasticizing effects. Additionally, the incorporation of long-chain alkyl featuring epoxy groups can boost the interaction with PLA. The results showed that the epoxy groups of the long-chain alkyl plasticizers can improve the elongation at break without compromising tensile strength significantly. The migration of plasticizer from PLA matrix can be reduced by strong interactions like chemical bonds, entanglements, and hydrogen bonding with PLA. TE1B2 demonstrated the best plasticizing effect. Adding 15 portions of TE1B2 and TBC separately increased PLA's elongation at break to 304 % and 242 %, with tensile strengths of 36.1 MPa and 22.3 MPa, respectively.

Quantitative evaluation of 67Ga-citrate scintigraphy in the management of nephritis.

In 67Ga-citrate scintigraphy (Ga-S), visual assessment is used by evaluating renal-uptake comparison with liver and spine and is simple and objective. We adopted the standardized uptake value (SUV) for 67Ga-citrate and proposed two quantitative indices, active nephritis volume (ANV) and total nephritis uptake (TNU). This study clarified the utility of new Ga-S-based quantitative indices in nephritis management. Before SUV measurement, the Becquerel calibration factor of 67Ga-citrate was obtained using a phantom experiment. Seventy patients who underwent SPECT/CT imaging were studied. SUV, ANV, and TNU were calculated using a quantitative analysis software for bone SPECT. SUVmean, ANV, and TNU were analyzed using the (1) threshold method (set 40%) and constant-value method for (2) vertebral SUVmax, and (3) vertebral SUVmean. ROC analysis was used to evaluate SUV, ANV, and TNU diagnostic abilities to distinguish nephritis presence and absence as well as interstitial nephritis (IN) and non-IN. The area under the curve (AUC) for nephritis presence or absence had a good value (0.80) for SUVmean (1), ANV (3), and TNU (3). The AUC for differentiation between IN and non-IN groups had a good value (0.80) for SUVmean (1). Thus, the new Ga-S-based quantitative indices were useful to evaluate nephritis and distinguish IN and non-IN.

Enhanced hydrolysis of waste activated sludge and recovery of volatile fatty acids: Performance and mechanistic analysis of synergistic treatment with sodium citrate and calcium oxide.

Anaerobic fermentation has emerged as a promising method of transforming waste activated sludge into high-value products (e.g., volatile fatty acids (VFAs)). This work developed sodium citrate (SC)-calcium oxide (CaO) pretreatment to accelerate the production of VFAs by enhancing sludge solubilization and disintegration of extracellular polymeric substances. The results showed that co-pretreatment with 0.25 g/g TSS of SC and 0.05 g/g TSS of CaO effectively boosted VFAs accumulation (5823.3 mg COD/L), which was 12.2 times higher than the Control group. SC-CaO pretreatment enhanced hydrolysis and acidogenesis by providing ample organic substrates, thereby promoting the growth of hydrolytic and acidogenic bacteria. Additionally, the fermentation broth resulting from co-pretreatment exhibited lower phosphorus concentration and higher biodegradability. Economic analysis confirmed that the combined pretreatment is cost-effective. This work provides a viable strategy for enhancing high-value product recovery from sludge.

Identification and quantification of acetyl tributyl citrate (ATBC) metabolites using human liver microsomes and human urine.

Plasticizers are chemicals that make plastics flexible, and phthalates are commonly used. Due to the toxic effects of phthalates, there is increasing use of non-phthalate plasticizers like acetyl tributyl citrate (ATBC). ATBC has emerged as a safer alternative, yet concerns about its long-term safety persist due to its high leachability and potential endocrine-disrupting effects. This study aims to identify ATBC metabolites using human liver microsomes and suspect screening methods, and to explore potential urinary biomarkers for ATBC exposure. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we identified ATBC metabolites, including acetyl dibutyl citrate (ADBC), tributyl citrate (TBC), and dibutyl citrate (DBC). Urine samples from 15 participants revealed the presence of ADBC in 5, TBC in 11, and DBC in all samples, with DBC concentrations pointedly higher than the other metabolites. These metabolites show promise as biomarkers for ATBC exposure, though further validation with human data is required. Our results underscore the need for comprehensive studies on ATBC metabolism, exposure pathways, and urinary excretion to accurately assess human exposure levels.

A randomized prospective study comparing the effect of low-volume bowel preparations for colonoscopy preparation in China.

AIM: To evaluate the effect of sodium picosulfate/magnesium citrate (SPMC) and 3 L split-dose polyethylene glycol (PEG) with or without dimethicone on bowel preparation before colonoscopy. METHODS: In this multicenter, prospective, randomized, controlled study conducted from April 2021 to December 2021, consecutive adult patients scheduled for colonoscopy were prospectively randomized into four groups: SPMC, SPMC plus dimethicone, 3 L PEG, and 3 L PEG plus dimethicone. Primary endpoint was colon cleansing based on Boston Bowel Preparation Scale (BBPS). Secondary endpoints were bubble score, time to cecal intubation, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS: We enrolled 223 and 291 patients in SPMC and 3 L PEG group, respectively. The proportion with acceptable bowel cleansing, total BBPS score and cecal intubation time were similar in all four subgroups (p > 0.05). Patient-reported acceptability and tolerability was significantly greater in SPMC than 3 L PEG group (p < 0.001); adverse events were significantly lower in SPMC than latter group (p < 0.001). ADR in both groups was greater than 30%. CONCLUSION: SPMC had significantly higher acceptability and tolerability than 3 L PEG, however, was similar in terms of bowel-cleansing effect and cecal intubation time and hence can be used before colonoscopy preparation.

Efficacy and safety of same-day preparation with sodium picosulfate plus magnesium citrate on the day of colonoscopy for bowel preparation: Multicenter, single-arm, open-label study.

BACKGROUND AND AIM: Sodium picosulfate plus magnesium citrate (SP + MC) is a well-tolerated bowel preparation agent. However, Japan currently approves only two methods of taking SP + MC: the day-before and split-dose preparation, without approval of same-day preparations. This study aimed to evaluate the efficacy and safety of same-day SP + MC preparations. METHODS: This was a multicenter, single-arm, nonrandomized, open-label study. We enrolled 145 Japanese patients between June and December 2023. The patients received two sachets of SP + MC dissolved in 300 ml of water and 1200 mL or more of clear liquid on the day of colonoscopy. Bowel cleansing efficacy, adverse events (AEs), and patient satisfaction were evaluated. RESULTS: Of the enrolled patients, 137 underwent colonoscopy according to our protocol. Bowel preparation was adequate in 133 patients (97.1%). The mean total Boston Bowel Preparation Score was 8.3 ± 1.2. Five patients experienced AEs (3.6%): two (1.5%), abdominal pain; one (0.73%), ischemic enteritis; one (0.73%), vomiting or nausea; and one (0.73%), headache. All AEs were treated conservatively. None of the patients exhibited abnormal blood test results or clinical symptoms after receiving SP + MC. Regarding patient satisfaction, all patients were able to take SP + MC as directed; 136 (99.2%) expressed a preference for this bowel preparation for future colonoscopies. CONCLUSION: The same-day SP + MC preparation showed high bowel-cleansing efficacy and satisfaction in Japanese patients without serious AEs.