Evaluation and clinical application of a bracketing calibration-based isotope dilution liquid chromatography-tandem mass spectrometry candidate reference measurement procedure for serum theophylline.

A candidate reference measurement procedure (RMP) for serum theophylline via isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. With a single-step precipitation pretreatment and a 6-min gradient elution, the method achieved baseline separation of theophylline and its analogs on a C18-packed column. A bracketing calibration method was used to ensure repeatable signal intensity and high measurement precision. The intra-assay and inter-assay imprecisions were 1.06%, 0.84%, 0.72% and 0.47%, 0.41%, 0.25% at concentrations of 4.22 µg/mL (23.40 µmol/L), 8.45 µg/mL (46.90 µmol/L), and 15.21 µg/mL (84.43 µmol/L), respectively. Recoveries ranged from 99.35 to 102.34%. The limit of detection (LoD) was 2 ng/mL, and the lowest limit of quantification (LLoQ) was 5 ng/mL. The linearity range extended from 0.47 to 60 µg/mL (2.61-333.04 µmol/L). No ion suppression and carry-over (< 0.68%) were observed. The relative bias for this candidate RMP that participated in 2023 External Quality Control for Reference Laboratories (RELA) conducted by the International Federation of Clinical Chemistry (IFCC) was within a range of 0.17 to 0.93%. Furthermore, two clinical immunoassay systems were compared with this candidate RMP, demonstrating good correlations. The results of the Trueness Verification Plan indicate significant differences among routine systems, highlighting the need for standardization efforts. The developed candidate RMP for serum theophylline serves as a precise reference baseline for standardizing clinical systems and assigning values to reference materials.

Establishment and clinical application of a candidate reference measurement procedure for quantification of urinary vanillylmandelic acid and homovanillic acid using ID-LC-MS/MS method.

Neuroblastoma (NB), an embryonic tumor of the autonomous nervous system, poses a significant threat to the health and lives of children. Accurate measurement of vanillylmandelic acid (VMA) and homovanillic acid (HVA) in human urine is crucial for screening and diagnosis of NB. Although various laboratories have developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect VMA and HVA, the comparability between the results obtained from different laboratories and methods was poor. The absence of reference method for VMA and HVA hinders the standardization of their measurements. Therefore, a candidate reference measurement procedure (cRMP) based on isotope dilution LC-MS/MS (ID-LC-MS/MS) for the detection of VMA and HVA in human urine was established. Urine samples were spiked with VMA-d3 and HVA-d5 as internal standards and extracted using a protein precipitation method. The cRMP exhibited desirable precision with the total imprecision below 5 %. The accuracy of this cRMP was demonstrated by the high analytical recovery (98.64 % - 102.22 % and 98.41 % - 100.97 % for VMA and HVA, respectively), and comparability between different reference systems. The limit of detection for HVA and VMA were 15.625 ng/mL and 3.906 ng/mL, respectively; the quantification limits were 62.5 ng/mL and 7.813 ng/mL, respectively, which can meet the clinical detection requirements. The linear range was from 78.125 ng/mL to 20 µg/mL. Specificity evaluations showed no corresponding interference from structurally similar analogs. In conclusion, we have established a cRMP based on ID-LC-MS/MS for the measurement of VMA and HVA in urine samples, demonstrating well-defined method performance including accuracy, precision, and specificity. This newly established cRMP is suitable for routine assay standardization and evaluation of clinical samples. Furthermore, this method has the potential to significantly enhance the diagnostic accuracy for neuroblastoma.

Revealing mechanisms of NH3 and N2O emissions reduction in the rapid bio-drying of food waste: Insights from organic nitrogen composition and microbial activity.

Inevitably, aerobic biological treatment processes generate emissions of ammonia (NH3) and greenhouse gas (GHGs) emissions, especially nitrous oxide (N2O). The rapid bio-drying process (RBD) for food waste (FW) alleviates issues arising from its substantial growth. However, its emissions of NH3 and N2O remain unknown, and the correlation with nitrogen components in the substrate remains unclear, significantly impeding its widespread adoption. Here, the nitrogen loss and its mechanisms in RBD were investigated, and the results are as follows: The total emission of NH3 and N2O were1.42 and 1.16 mg/kg FW (fresh weight), respectively, achieving a 98 % reduction compared to prior studies. Structural equation modeling demonstrates that acid ammonium nitrogen (AN) decomposition chiefly generates NH3 in compost (p < 0.001). Strong correlation (p < 0.001) exists between amino acid nitrogen (AAN) and AN. In-depth analysis of microbial succession during the process reveals that the enrichment of Brevibacterium, Corynebacterium, Dietzia, Fastidiosipila, Lactobacillus, Mycobacterium, Peptoniphilus, and Truepera, are conducive to reducing the accumulation of AN and AAN in the substrate, minimizing NH3 emissions (p < 0.05). While Pseudomonas, Denitrobacterium, Nitrospira, and Bacillus are identified as key species contributing to N2O emissions during the process. Correlation analysis between physicochemical conditions and microbial succession in the system indicates that the moisture content and NO3- levels during the composting process provide suitable conditions for the growth of bacteria that contribute to NH3 and N2O emissions reduction, these enrichment in RBD process minimizing NH3 and N2O emissions. This study can offer crucial theoretical and data support for the resource utilization process of perishable organic solid waste, mitigating NH3 and GHGs emissions.

Cardiovascular disease and preventive care service utilization among midlife adults: The roles of diagnosis and depression.

Objectives: Secondary preventive care is important for monitoring the progression of cardiovascular disease (CVD). However, the factors that promote secondary prevention were not well understood. This study addressed this gap by investigating the impact of CVD diagnosis on preventive care utilization among midlife adults. Given the high prevalence of depression among this population, it further examined whether depression interacted with CVD diagnosis to affect preventive care utilization. Methods: The study sample included 6,222 midlife adults from six waves of the National Longitudinal Survey of Youth 1979 (NLSY79) collected between 2006 and 2016. Multiple logistic regressions were conducted to examine the relationship between a CVD diagnosis and each of the five types of preventive care utilization: influenza vaccinations, electrocardiography (EKG) and screening for high blood pressure, cholesterol, and blood sugar. Depression was then added to examine its possible moderation effect. Results: The results showed that midlife adults with a CVD diagnosis were more likely to utilize all five types of preventive care services. EKG, the most relevant preventive care type with CVD diagnosis, had the largest strength of likelihood. Depression strengthened the relationship between a CVD diagnosis and the utilization of blood pressure tests, but it showed no associations with other four types of preventive care utilization. Conclusions: The study findings indicate that a CVD diagnosis could serve as an opportunity for promoting secondary preventive care utilization. Future research needs to explore how a CVD diagnosis affects different population groups, and further explore the roles of depression.

Photoreversible Aggregation of the Biliprotein Containing the First and Second GAF Domains of a Cyanobacteriochrome All2699 in Nostoc sp. PCC7120.

As plant photoreceptors, phytochromes are capable of detecting red light and far-red light, thereby governing plant growth. All2699 is a photoreceptor found in Nostoc sp. PCC7120 that specifically responds to red light and far-red light. All2699g1g2 is a truncated protein carrying the first and second GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domains of All2699. In this study, we found that, upon exposure to red light, the protein underwent aggregation, resulting in the formation of protein aggregates. Conversely, under far-red light irradiation, these protein aggregates dissociated. We delved into the factors that impact the aggregation of All2699g1g2, focusing on the protein structure. Our findings showed that the GAF2 domain contains a low-complexity (LC) loop region, which plays a crucial role in mediating protein aggregation. Specifically, phenylalanine at position 239 within the LC loop region was identified as a key site for the aggregation process. Furthermore, our research revealed that various factors, including irradiation time, temperature, concentration, NaCl concentration, and pH value, can impact the aggregation of All2699g1g2. The aggregation led to variations in Pfr concentration depending on temperature, NaCl concentration, and pH value. In contrast, ΔLC did not aggregate and therefore lacked responses to these factors. Consequently, the LC loop region of All2699g1g2 extended and enhanced sensory properties.

Risk Compensation After Initiation of Daily Oral Pre-exposure Prophylaxis Among Sexual and Gender Minorities in Nigeria.

Pre-exposure prophylaxis (PrEP) use may be associated with risk compensation. We enrolled and provided PreP to sexual and gender minorities (SGM) in Abuja, Nigeria between April 2018 and May 2019. Behavioral information and samples for urogenital and anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections (STIs) were collected at baseline. Blood samples for PrEP assay and self-reported adherence were collected at three-monthly follow-up visits. STIs were detected using Aptima Combo2 assay. We estimated the odds ratios (ORs) of PCR-diagnosed bacterial STIs and self-reported behavioral outcomes (condomless anal intercourse [CAI] and concurrent sexual relationships) with conditional logistic regression. Of 400 SGM who initiated PrEP, 206 were eligible for analysis, and had a median age of 24 years (IQR 22-27). In multivariable analysis, participants in the PrEP period had decreased odds of CAI (adjusted OR: 0.49, 95% CI 0.28, 0.84). PrEP use was not associated with risk compensation.

Metabolomics-Based Effects of a Natural Product on Remyelination After Cerebral Ischemia Injury Via GABABR-pCREB-BDNF Pathway.

BACKGROUND: Yi-Qi-Tong-Luo Granules (YQTLs) is a natural compound of Traditional Chinese Medicine authorized by China Food and Drug Administration (CFDA). These granules are employed in the convalescent stage of cerebral infarction and render notable clinical efficacy. This study aims to uncover the underlying mechanisms of YQTLs on remyelination after cerebral ischemia injury. MATERIALS AND METHODS: We established cerebral ischemia model in rats using microsphere-induced multiple cerebral infarction (MCI). We evaluated the pharmacological effects of YQTLs on MCI rats, through Morri's water maze test, open field test, hematoxylin and eosin staining, and glycine silver immersion. We employed liquid chromatography mass spectrometry metabolomics to identify differential metabolites. Enzyme-linked immunosorbent assay was utilized to measure the release of neurotrophins, while immunofluorescence staining was used to assess oligodendrocyte precursor cells differences and myelin regeneration. We used Western blotting to validate the protein expression of remyelination-associated signaling pathways. RESULTS: YQTLs significantly improves cognitive function following cerebral ischemia injury. Pathological tissue staining revealed that YQTLs administration inhibits neuronal denaturation and neurofibrillary tangles. We identified 141 differential metabolites among the sham, MCI, and YQTLs-treated MCI groups. Among these metabolites, neurotransmitters were identified, and notably, gamma-aminobutyric acid (GABA) showed marked improvement in the YQTLs group. The induction of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and PDGFAA, upregulation of olig2 and MBP expression, and promotion of remyelination were evident in YQTLs-treated MCI groups. Gamma-aminobutyric acid B receptors (GABABR), pERK/extracellular regulated MAP kinase, pAKT/protein kinase B, and pCREB/cAMP response element-binding were upregulated following YQTLs treatment. CONCLUSION: YQTLs enhance the binding of GABA to GABABR, thereby activating the pCREB/BDNF signaling pathway, which in turn increases the expression of downstream myelin-associated proteins and promotes remyelination and cognitive function.

Comparison of three rapid diagnostic tests for bloodstream infections using Benefit-risk Evaluation Framework (BED-FRAME).

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 positive blood cultures were collected from the University of Maryland Medical Center. The RDTs were compared by their sensitivities, time-to-results, hands-on time, and BED-FRAME analysis. The overall sensitivity of all platforms compared to culture results from monomicrobial-positive blood cultures was 88.3%. However, the three RDTs differed in their accuracy for identifying Gram-positive bacteria, Gram-negative bacteria, and yeast. Time-to-results for FLAT MS, Sepsityper, and BioFire BCID2 were all approximately one hour. Hands-on times for FLAT MS, Sepsityper, and BioFire BCID2 were 10 (±1.3), 40 (±2.8), and 5 (±0.25) minutes, respectively. BED-FRAME demonstrated that each RDT had utility at different pathogen prevalence and relative importance. BED-FRAME is a useful tool that can used to determine which RDT is best for a healthcare center.

Probable rivaroxaban-induced erythema multiforme in children: A case report.

Background: Limited data exists on the use of rivaroxaban for the treatment of pediatric patients. This report presents a case of probable rivaroxaban-induced Erythema Multiforme in Children. Case Summary: A female patient aged 5.5 years with antiphospholipid syndrome (APS) was administered oral rivaroxaban tablets 2.5 mg twice a day for 16 days. Subsequently, the patient developed a slight itching sensation on both feet and buttocks without an apparent cause. The following day, erythema multiforme appeared across the body in a scattered pattern. The erythema presented higher than the skin surface and partially merged into areas of the skin. Following an increase in the extent and degree of the erythema, all oral medications were ceased. Treatment with dexamethasone sodium phosphate injection, mometasone furoate cream, and mucopolysaccharide polysulfate cream resulted in an improvement of erythema multiforme. The erythema diminished and did not deteriorate subsequent to changing from rivaroxaban tablets to warfarin sodium tablets, and receiving nadroparin calcium injection.

Muscarinic receptor agonist-induced ßPix binding to ß-catenin promotes colon neoplasia.

M3 muscarinic receptors (M3R) modulate ß-catenin signaling and colon neoplasia. CDC42/RAC guanine nucleotide exchange factor, ßPix, binds to ß-catenin in colon cancer cells, augmenting ß-catenin transcriptional activity. Using in silico, in vitro, and in vivo approaches, we explored whether these actions are regulated by M3R. At the invasive fronts of murine and human colon cancers, we detected co-localized nuclear expression of ßPix and ß-catenin in stem cells overexpressing M3R. Using immunohistochemistry, immunoprecipitation, proximity ligand, and fluorescent cell sorting assays in human tissues and established and primary human colon cancer cell cultures, we detected time-dependent M3R agonist-induced cytoplasmic and nuclear association of ßPix with ß-catenin. ßPix knockdown attenuated M3R agonist-induced human colon cancer cell proliferation, migration, invasion, and expression of PTGS2, the gene encoding cyclooxygenase-2, a key player in colon neoplasia. Overexpressing ßPix dose-dependently augmented ß-catenin binding to the transcription factor TCF4. In a murine model of sporadic colon cancer, advanced neoplasia was attenuated in conditional knockout mice with intestinal epithelial cell deficiency of ßPix. Expression levels of ß-catenin target genes and proteins relevant to colon neoplasia, including c-Myc and Ptgs2, were reduced in colon tumors from ßPix-deficient conditional knockout mice. Targeting the M3R/ßPix/ß-catenin axis may have therapeutic potential.

Identification of Copper Metabolism Related Biomarkers, Polygenic Prediction Model, and Potential Therapeutic Agents in Alzheimer's Disease.

BACKGROUND: The underlying pathogenic genes and effective therapeutic agents of Alzheimer's disease (AD) are still elusive. Meanwhile, abnormal copper metabolism is observed in AD brains of both human and mouse models. OBJECTIVE: To investigate copper metabolism-related gene biomarkers for AD diagnosis and therapy. METHODS: The AD datasets and copper metabolism-related genes (CMGs) were downloaded from GEO and GeneCards database, respectively. Differentially expressed CMGs (DE-CMGs) performed through Limma, functional enrichment analysis and the protein-protein interaction were used to identify candidate key genes by using CytoHubba. And these candidate key genes were utilized to construct a prediction model by logistic regression analysis for AD early diagnosis. Furthermore, ROC analysis was conducted to identify a single gene with AUC values greater than 0.7 by GSE5281. Finally, the single gene biomarker was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in AD clinical samples. Additionally, immune cell infiltration in AD samples and potential therapeutic drugs targeting the identified biomarkers were further explored. RESULTS: A polygenic prediction model for AD based on copper metabolism was established by the top 10 genes, which demonstrated good diagnostic performance (AUC values). COX11, LDHA, ATOX1, SCO1, and SOD1 were identified as blood biomarkers for AD early diagnosis. 20 agents targeting biomarkers were retrieved from DrugBank database, some of which have been proven effective for the treatment of AD. CONCLUSIONS: The five blood biomarkers and copper metabolism-associated model can differentiate AD patients from non-demented individuals and aid in the development of new therapeutic strategies.

The clinical efficacy of ozone combined with steroid in the treatment of discogenic low back pain: a randomized, double-blinded clinical study.

Objective: This randomized double-blinded clinical study is to investigate the clinical efficacy of per-paravertebral disk ozone injection combined with steroids in the treatment of patients with chronic discogenic low back pain (CDLBP). Methods: Group A (N = 60) received a per-paravertebral injection of a steroid mixture of 10 mL with pure oxygen 20 mL, while group B (N = 60) received a per-paravertebral injection of a steroid mixture of 10 mL combined with ozone 20 mL (30 µg/mL). Injections were administered once a week for 3 weeks, with a follow-up of 6 months. Clinical outcomes were assessed at week 1, month 3, and month 6 with the help of Visual Analog Scale (VAS) scores and Macnab efficacy evaluation. Results: The VAS score of both group A (1.65 vs. 6.87, p = 0.000) and group B (1.25 vs. 6.85, p = 0.000) at week 1 was significantly reduced compared to baseline. The effect was sustained at the 3- and 6-month follow-up periods (p < 0.05). Group B had significantly lower VAS scores at month 3 (1.53 vs. 3.82, p = 0.000) and month 6 (2.80 vs. 5.05, p = 0.000) compared to group A, respectively. Based on Macnab criteria, 95 and 96.7% of patients in groups A and B had good rates "excellent plus good" at week 1, respectively. Good rates were significantly higher in group B at month 3 (91.7 vs. 78.3%, p = 0.041) and month 6 (85.0 vs. 68.3%, p = 0.031) compared to group A, respectively. No serious adverse events were noted in both groups. Conclusion: Per-paravertebral injection of steroid and ozone combination resulted in better relief of CDLBP compared to pure oxygen plus steroid. Clinical Trial Registration: ChiCTR2100044434 https://www.chictr.org.cn/showproj.html?proj=121571.

Exploring the effect of Ulva prolifera decay on the immune tissue of Paralichthys olivaceus based on transcriptomics and histopathological analysis.

For 17 consecutive years, the outbreak of Ulva prolifera in the South Yellow Sea area of China has caused significant negative impacts on coastal ecological environment. However, its specific influence on fish immunity is rare. In this study, the juvenile Paralichthys olivaceus was exposed to fresh U. prolifera algae (FU) and decomposing algal effluent (DU). After short-term stress for 14 days, the histopathological and transcriptome analysis were performed to study the effect of U. prolifera decay on P. olivaceus. Histopathological analysis found that the liver, spleen and head kidneys of P. olivaceus were damaged after the short-term stress. The transcriptome results showed that the steroid biosynthesis signaling pathway and the PI3K-Akt signaling pathway were significantly enriched. Some immune related genes, including c1qc-like, dusp1, dusp16, HSP90 and metabolic related genes serotransferrin, were differentially expressed. These results highlighted the harmfulness of U. prolifera on marine fish, setting a solid foundation for further analyses.

Development of matrix-based reference materials for 17 beta-estradiol by the recommended reference method of ID-LC-MS/MS.

We developed and evaluated two-level, namely 2017011 and 2017012, serum-based reference materials (RMs) for 17 beta-estradiol (17 ß-E2) by the reference method of isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) from the remaining serum samples after routine clinical tests, to help improve clinical routine testing and provide the traceability of results. This paper describes the development process of these RMs. The National Metrology Institute of Japan (NMIJ) certified reference material (CRM) 6004-a was used as the primary RM for the measurement of 17 ß-E2. These serum-based RMs showed satisfactory homogeneity and stability. They also assessed the commutability between the reference method and the three routine clinical immunoassay systems. Besides, a collaborative study was carried out in five reference laboratories, all of which had been accredited by the China National Accreditation Service for Conformity Assessment (CNAS) in accordance with ISO/WD 15725-1. Statistical analysis of raw results and uncertainty assessment obtained certified values: 2017011 was 445.2 ± 39.0 pmol/L, and 2017012 was 761.9 ± 35.5 pmol/L.

Impact of microRNA polymorphisms on high-dose methotrexate-related hematological toxicities in pediatric acute lymphoblastic leukemia.

Objectives: It is well known that transporter and enzyme genes could be regulated by microRNA (miRNA) at the post-transcriptional level, and single-nucleotide polymorphisms (SNPs) in miRNA, which are involved in the miRNA production and structure, may impact the miRNA expression level and then influence drug transport and metabolism. In this study, we aim to evaluate the association between miRNA polymorphisms and high-dose methotrexate (HD-MTX) hematological toxicities in Chinese pediatric patients with acute lymphoblastic leukemia (ALL). Method: A total of 181 children with ALL were administered with 654 evaluable cycles of HD-MTX. Their hematological toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5. The association between 15 candidate SNPs of miRNA and hematological toxicities (leukopenia, anemia, and thrombocytopenia) was analyzed using Fisher's exact test. Further multiple backward logistic regression analysis was used to explore the independent risk factors for grade 3/4 hematological toxicities. Result: Rs2114358 G>A in pre-hsa-miR-1206 was related to HD-MTX-related grade 3/4 leukopenia after multiple logistic regression [GA + AA vs. GG: odds ratio (OR): 2.308, 95% CI: 1.219-4.372, P = 0.010], and rs56103835 T > C in pre-hsa-mir-323b was associated with HD-MTX-related grade 3/4 anemia (TT + TC vs. CC: OR: 0.360, 95% CI: 0.239-0.541, P = 0.000); none of the SNPs were significantly associated with grade 3/4 thrombocytopenia. Bioinformatics tools predicted that rs2114358 G>A and rs56103835 T>C would impact the secondary structure of pre-miR-1206 and pre-miR-323b, respectively, and then probably influence the expression level of mature miRNAs and their target genes. Conclusion: Rs2114358 G>A and rs56103835 T>C polymorphism may potentially influence HD-MTX-related hematological toxicities, which may serve as candidate clinical biomarkers to predict grade 3/4 hematological toxicities in pediatric patients with ALL.

Structure Reveals the Impact of Surface Charge Distribution on the Phase Separation and Aggregation of Slr0280.

Liquid-liquid phase separation (LLPS) plays a key role in the regulation of life activities. Here, we reported a protein from Synechocystis sp. PCC 6803 and annotated as Slr0280. To obtain a water-soluble protein, we deleted the N-terminus transmembrane domain and named it Slr0280Δ. Slr0280Δ with high concentration can undergo LLPS at a low temperature in vitro. It belongs to the phosphodiester glycosidase family of proteins and has a segment of a low-complexity sequence region (LCR), which is thought to regulate the LLPS. Our results show that electrostatic interactions impact the LLPS of Slr0280Δ. We also acquired the structure of Slr0280Δ, which has many grooves on the surface with a large distribution of positive and negative charges. This may be advantageous for the LLPS of Slr0280Δ through electrostatic interactions. Furthermore, the conserved amino acid (arginine at position 531) located on the LCR is important for maintaining the stability of Slr0280Δ as well as LLPS. Our research indicated that the LLPS of proteins can be transformed into aggregation by changing the surface charge distribution.

Characterization of the COVID-19 Vaccine Uptake in Patients With Chronic Diseases in a Large University-based Family Medicine Clinical Practice.

PURPOSE: To characterize COVID-19 vaccine uptake in patients with chronic conditions at the large university-based Family Medicine practice serving a population with low COVID-19 vaccine acceptance. METHODS: A rolling panel of patients attributed to the practice was submitted monthly to the Chesapeake Regional Health Information Exchange (CRISP) to monitor patients' vaccination status. Chronic conditions were identified using the CMS Chronic Disease Warehouse. An outreach strategy deploying Care Managers was developed and implemented. Associations between vaccination status and patients' characteristics were examined using a multivariable Cox's proportional hazard regression modeling. RESULTS: Among 8469 empaneled adult (18+) patients, 6404 (75.6%) received at least 1 dose of COVID-19 vaccine in December 2020 to March 2022. Patients were relatively young (83.4% <65 years old), predominantly female (72.3%), and non-Hispanic Black (83.0%). Among chronic conditions, hypertension had the highest prevalence (35.7%), followed by diabetes (17.0%). Associations between vaccine status and the presence of chronic conditions varied by age and race. Older patients (45+ years old) with diabetes and/or hypertension showed a statistically significant delay in receiving COVID-19 vaccine, while young Black adults (18-44 years old) with diabetes complicated by hypertension were more likely to be vaccinated compared to patients of the same age and race with no chronic conditions (Hazard ratio 1.45; 95% CI 1.19,1.77; P = .0003). CONCLUSIONS: The practice-specific COVID-19 vaccine CRISP dashboard helped to identify and address delays in receiving COVID-19 vaccine in the most vulnerable, underserved populations. Reasons for age and race-specific delays in patients with diabetes and hypertension should be explored further.

Correlation and predictive value of platelet biological indicators and recurrence of large-artery atherosclerosis type of ischemic stroke.

Large-artery atherosclerosis type of ischemic stroke happens when a blood clot forms in a major artery that carries blood to the brain. This causes a blockage and a decrease in blood flow to the brain tissue making up approximately 15-20% of all cases. This type of stroke is more prevalent in older adults and those with risk factors such as high blood pressure, high cholesterol, diabetes, smoking, and a family history of stroke. To investigate the correlation and predictive value of platelet-related biological indicators with recurrence of large-artery atherosclerosis type of ischemic stroke (LAA-IS)2. The patients were divided into a relapse group (R, n = 40) and non-relapse group (NR, n = 45). Platelet-related biological indicators were collected from both groups to analyze their correlation with neurological impairment score (NIHSS score). Risk factors were analyzed using binary logistic regression and a survival curve (ROC) was drawn to evaluate the predictive effect of clinical platelet-related biological indicators on LAA-IS recurrence. This study confirmed that PAg-ADP, PAg-COL, and FIB are closely related to the formation of LAA-IS due to carotid atherosclerosis, and the combined PAg-ADP, PAg-COL, and FIB index levels are the most promising for assessing the prognostic development of recurrence in patients with LAA-IS. Combined monitoring of platelet aggregation rate and FIB index is of important evaluation value in judging the recurrence prognosis of LAA-IS patients.

New insight into the irreversible membrane fouling in different pore-sized ultrafiltration ceramic membrane bioreactors (UCMBRs) for high-strength textile wastewater treatment.

Despite great achievements in ceramic membrane bioreactor applications, membrane fouling, which decreases the permeability and separation performance of bioreactors and is associated with increased operational costs and energy consumption, remains a problem. The aim of this study was to expand our understanding of the fouling behavior in the long-term performance of ultrafiltration ceramic membrane bioreactors (UCMBRs) for high-strength textile wastewater reclamation. Using real textile wastewater effluent, the effects of ultrafiltration (UF) membrane pore sizes, cleaning strategies, and foulant distribution were systematically evaluated over more than three months of continuous operation. The results showed that UCMBR system achieved chemical oxygen demand and total nitrogen removal efficiencies as high as 91-95% and 39-43%, respectively. The high PN concentration can easily increase the viscosity of mixed liquor samples, contributing to a fouling layer on the membrane surface. In addition, the fouling layer formed on the surface of small-pore-sized ceramic UF membranes was not completely reversible but was difficult to eliminate by simple physical cleaning. Soluble extracellular polymeric substances, especially proteins and low molecular weight neutrals, remained, resulting in irreversible fouling on the UF membrane. However, saturated CO2 backwash showed great potential for enhancing the system through efficient fouling control without using environmentally unfriendly cleaning chemicals. The cake-intermediate and complete-standard models were suitable for explaining the fouling mechanism in the large- and small-pore-sized UF membranes, respectively.

Correlates of self-reported and biomarker based adherence to daily oral HIV pre-exposure prophylaxis among a cohort of predominantly men who have sex with men in Nigeria.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) significantly reduces the risk of HIV acquisition. However, studies have demonstrated discordance between self-reported measures and biomedical benchmarks of PrEP adherence. We estimated the correlation between self-reported PrEP adherence and PrEP biomarkers and explored factors associated with adherence among men who have sex with men (MSM) in Nigeria. METHODS: TRUST-PrEP, an open-label, prospective study; conducted in Abuja between April 2018 and May 2019. MSM ≥ 18 years with substantial HIV risk were enrolled. Participants reported PrEP adherence in the last month using a 4-point scale from "poor" to "perfect" and serum samples for PrEP biomarkers were collected at months 3 and 9. Serum tenofovir concentration was measured by liquid chromatography-tandem mass spectrometry and considered protective for adherence if ≥ 4.2 ng/ml. Spearman's rank correlation was used to estimate correlation between self-reported adherence and measured tenofovir levels. Generalized estimating equations with a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between self-reported adherence and laboratory-measured adherence. RESULTS: A total of 219 MSM with median age 23 (interquartile range 20-27) years had at least one PrEP biomarker assay. Only 66/219 (30%) had at least one record of protective tenofovir concentration. Correlation between tenofovir and self-reported adherence at 3 and 9 months were 0.1 and 0.02 respectively. Furthermore, 17/219 (8%,) and 49/219 (22%) had serum tenofovir of 4.2-35.4 ng/mL and ≥ 35.5 ng/mL, corresponding to at least 4 and 7 days' PrEP use in a week, respectively. PrEP adherence was higher among participants introduced to PrEP in the clinics compared with communities (aOR: 8.35, 95%CI: [3.24, 21.5]) and those with same-sex practices family disclosure (aOR: 3.60 95% CI: [1.73, 7.51]). CONCLUSION: Self-reported PrEP adherence poorly correlated with biomarkers. Facilitating clinic-based PrEP introduction and disclosure of same-sex practices to family among MSM may improve PrEP adherence.