Dose-response Research Articles

Quantitative Assessment of Human Health Risks Associated with Heavy Metal and Bacterial Pollution in Groundwater from Mankweng in Limpopo Province, South Africa

Heavy metal and microbial pollution in groundwater raises health concerns due to its adverse effects. This study aimed to assess the health risks associated with heavy metal and bacterial pollution in groundwater in Mankweng. Heavy metals and Escherichia coli were detected using inductively coupled plasma mass spectrophotometry and a Colilert system, respectively. The heavy metal pollution index (HPI) and non-carcinogenic and carcinogenic risks were computed. The β-Poisson dose–response model was employed to predict the probability of E. coli infection. The metals’ concentrations were all within the permissible limits of the South African National Standard (SANS). However, Pb levels at sites E and G exceeded the World Health Organization (WHO) guideline (≤0.01 mg/L). HPI values were all less than 100, indicative of low contamination. The hazard quotient values were all less than 1, except for vanadium. The cumulative cancer risk ranged between 3.06 × 10−5 and 1.81 × 10−4 and between 3.55 × 10−5 and 2.20 × 10−4 for adults and children, respectively. E. coli was only detected at site L. The annual risk of E. coli infection exceeded the WHO risk limit of 10−4. The results underscore the need for the regular monitoring of groundwater.

An investigation to improve a nonlinear mixed-effects approach for EC50 estimation based on multi-donor dose–response data

ABSTRACT Dose–response relationships are important in assessing the efficacy and potency of compounds, which can usually be characterized by a 4-parameter logistic (4-PL) model estimating EC50, slope factor, lower asymptote, and upper asymptote. EC50, the concentration of a compound that induces a response halfway between the baseline and maximum, is a key quantity to evaluate compound potency. For multi-donor dose–response data, it is often of interest to estimate the overall EC50 (i.e. the average EC50 of the population of donors) and its 95% confidence interval (CI). A few multi-donor EC50 estimation methods have been proposed in the literature. Jiang and Kopp-Schneider (2014) systematically compared the meta-analysis approach and the nonlinear mixed-effects approach and concluded that the meta-analysis approach is simple and robust to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments, while the nonlinear mixed-effects approach has the issue of convergence failures probably due to overparameterization. In this article, we propose a modification of the nonlinear mixed-effects approach by using the stochastic approximation expectation-maximization (SAEM) algorithm to estimate model parameters and using multiple starting points to search for globally optimal values, which can substantially alleviate the issue of convergence failures even for small number of donors (e.g. n = 3), and achieve a smaller absolute median bias and better coverage probability of 95% confidence interval than the meta-analysis approach when the number of donors is not too small (e.g. n ≥ 7).

Non-fermented and fermented milk intake in relation to risk of ischemic heart disease and to circulating cardiometabolic proteins in swedish women and men: Two prospective longitudinal cohort studies with 100,775 participants

BackgroundThe effect of milk on the risk of ischemic heart disease (IHD) and acute myocardial infarction (MI) is unclear. We aimed to examine the association between non-fermented and fermented milk consumption on these endpoints and investigate the relationship between milk intake and cardiometabolic-related proteins in plasma.MethodsOur study is based on two Swedish prospective cohort studies that included 59,998 women and 40,777 men without IHD or cancer at baseline who provided repeated measures of diet and lifestyle factors and plasma proteomics data in two subcohorts. Through registry linkage, 17,896 cases with IHD were documented during up to 33 years of follow-up, including 10,714 with MI. We used time-updated multivariable Cox regression analysis to examine non-fermented or fermented milk intake with time to IHD or MI. Using high-throughput multiplex immunoassays, 276 cardiometabolic plasma proteins were measured in two subcohorts. We applied multivariable-adjusted regression models using a discovery-replication design to examine protein associations with increasing consumption of non-fermented or fermented milk.ResultsThe results for non-fermented milk differed by sex (p-value for interaction = 0.01). In women, we found a pattern of successively greater risk of IHD and MI at non-fermented milk intake levels higher than 1.5 glasses/day. Compared with an intake of 0.5 glass/day (100 mL/day), non-fermented milk intake of 2 glasses/day in women conferred a multivariable-adjusted hazard ratio (HR) of 1.05 (95% CI 1.01–1.08) for IHD, an intake of 3 glasses/day an HR of 1.12 (95% CI 1.06–1.19), and an intake of 4 glasses/day an HR of 1.21 (95% CI 1.10–1.32). Findings were similar for whole, medium-fat, and low-fat milk. We did not detect higher risks of IHD with increasing milk intakes in men. Fermented milk intake was unrelated to the risk of IHD or MI in either sex. Increasing non-fermented milk intake in women was robustly associated with a higher concentration of plasma ACE2 and a lower concentration of FGF21.ConclusionsWe show a positive association between high amounts of non-fermented milk intake and IHD in women but not men. We suggest metabolic pathways related to ACE2 and FGF21 potentially underlie the association.Graphical abstractOur analysis of two large cohort studies involving 100,775 participants and 17,896 clinically confirmed IHD events supports a dose–response positive association between non-fermented milk intake higher than 300 mL/day with higher rates of IHD (and acute MI specifically) in women, but not in men. The higher risk of IHD with high milk intake in women was evident, irrespective of the fat content of the milk. Fermented milk intake was unrelated to the risk of IHD in both women and men. Non-fermented milk intake was associated in different directions with circulating levels of ACE2 and FGF21 in women—two essential cardiometabolic proteins, also related to IHD in women in our study.

Perceived Housing Problems and Depressive Symptoms Among Middle-Aged and Older Americans

ABSTRACT Housing insecurity has been shown to be associated with worse mental health. However, previous studies mostly examined one aspect of housing insecurity (e.g., affordability), and few focused on older adults. This study examined the relationship between perceived housing problems and depressive symptoms among middle-aged and older Americans. Data from the Health and Retirement Study between 2006 and 2018 were used. A total of 7,119 respondents (aged 50+ at baseline in 2006) were followed up every 4 years. Respondents self-reported the status, severity, and duration of their housing problems. Depressive symptoms were assessed by the Center for Epidemiological Studies-Depression Scale. Mixed-effect models examined the association between perceived housing problems and depressive symptoms. Results show about 5%-7% of respondents had housing problems during every study visit and 5.73% of them experienced persistent housing problems over 12 years. Having housing problems was associated with a higher risk of depressive symptoms (incidence risk ratio = 1.29, 95% CI = 1.23, 1.36). A dose–response relationship was observed in the severity and duration of housing problems, with a greater increase of depressive symptoms risk among those experiencing more severe or prolonged housing problems. The dose–response pattern highlighted the importance of early intervention and persistent assistance to those experiencing housing problems.

Pharmacokinetic/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham.

Pegcetacoplan is a complement C3/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham-treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose-response and PK/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15 mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear-with-time over the 24-month maximal study duration. Disease-specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and >20 intermediate or large drusen groups (≥63 μm) at baseline. The dose-response model estimated 0.80-fold (95% CI: 0.75, 0.84) and 0.83-fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log-transformed vitreous pegcetacoplan concentration in the PK/PD model. PK/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.

Effect of microencapsulated/photoresistant extract of Azadirachta indica A. Juss seeds on Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctudae) and its persistence in semi-field

The development of bioinsecticides as an alternative to synthetic insecticides can benefit the economy of exporting and importing countries, family farming, production of high-quality commodities, food security, quality of life, and the natural environment. This study aimed to evaluate the effect of microencapsulated extracts of Azadirachta indica A. Juss on Spodoptera frugiperda J.E. Smith and their persistence in the plant under semi-field conditions. The fresh seeds of A. indica, collected in Brazil, were separated for the preparation of the microencapsulated dry extract (MDE) according to criteria registered in the patent. Lethal concentrations for S. frugiperda were determined using a dose response curve. The treatments were compared: MDE, control and positive control based on azadirachtin, evaluating mortality and growth inhibition. There was a significant difference in mortality between the treatments tested. The lethal concentrations LC50 and LC95, expressed in azadirachtin for the bioinsecticide, were 194.98 and 630.95 ppm, respectively. The growth inhibition of S. frugiperda was above 98 % in the treatments, except for the control. The MDE presented lethal times LT50 and LT90 lower than the other treatments (lethal time LT50 = 2.79 d; lethal time LT90 = 3.97 d). The MDE of A. indica seeds was effective in controlling S. frugiperda up to the fifth instar and is considered as slightly persistent to persistent depending on environmental conditions and irrigation, based on IOBC/WPRS parameters. The MDE has the potential to be a phytosanitary product approved for use in organic agriculture and with greater effectiveness in controlling S. frugiperda compared to similar pesticides.Abbreviations: BOD, Biochemical Oxygen Demand; CPA, commercial product based on azadirachtin; CLE, concentrated liquid extract; DAS, days after spraying; GI, growth inhibition; LC50, lethal concentration for 50% of the population; LC95, lethal concentration for 95% of the population; LT50, lethal time for 50% of the population; LT90, lethal time for 90% of the population; MDE, microencapsulated dry extract.

Association between the serum albumin–creatinine ratio and 28-day intensive care unit mortality among patients with sepsis: a multicenter retrospective cohort study

IntroductionSepsis is a substantial global health challenge with a considerable disease burden. Despite advancements in sepsis research, the mortality rates associated with this condition remain high. The relationship between the serum albumin-to-creatinine ratio (sACR) and mortality in patients with sepsis remains unclear. Therefore, this study aimed to investigate the association between the sACR and 28-day mortality in intensive care unit (ICU) patients with sepsis.MethodsIn this retrospective cohort study, we used data sourced from the eICU Collaborative Research Database. The primary exposure variable was sACR, and the primary outcome measure was mortality within 28 days after ICU admission. Statistical analyses included univariate and multivariate logistic regression models, generalized additive models, and two-piecewise linear regression models, which were employed to explore non-linear relationships and threshold effects between sACR and mortality.ResultsThe study cohort comprised 9,690 ICU patients with sepsis, with a 28-day mortality rate of 9.99%. The results of the multivariate logistic regression model indicated that elevated sACR levels were significantly associated with a reduced risk of mortality (odds ratio = 0.78, 95% confidence interval: 0.71–0.87, p < 0.001), even after adjusting for potential confounding variables. Curve fitting revealed a non-linear relationship between sACR and 28-day mortality, with an inflection point of 4.79.DiscussionThis study demonstrated that sACR is an independent risk factor for 28-day mortality in ICU patients with sepsis, exhibiting a non-linear negative dose–response relationship and a threshold effect. These findings may serve as early warning indicators in high-risk populations.

Association of blood vitamin A with osteoarthritis: a nationally representative cross-sectional study

ObjectivesVitamin A plays an important role in health, especially regarding its impact on bone tissue. Vitamin A can lead to bone damage and deformity, thus becoming an important causative factor in osteoarthritis. In this study, we aimed to evaluate the association of serum vitamin A with osteoarthritis.MethodsWe included participants who self-reported whether they had OA in NHANES 2001–2006 and NHANES 2017–2018 to explore the association and dose–response relationship between vitamin A concentration and risk of osteoarthritis through weighted multivariate logistic models and restricted cubic splines. Sensitivity and stratification analyses were also used to assess the robustness of the results.ResultsA total of 18,034 participants were included in this study, and a linear association between serum vitamin A concentration and osteoarthritis risk was observed. The OR of osteoarthritis was 1.22 (95% CI: 0.98, 1.52), 1.40 (95% CI: 1.05,1.85), and 1.47 (95% CI: 1.14, 1.91) for participants in the second, third, and fourth quartiles, respectively, compared with the lowest vitamin A reference group. Similar results were obtained when sensitivity and stratification analyses were performed.ConclusionSerum vitamin A is positively associated with osteoarthritis risk. Within a certain range of vitamin A concentrations, vitamin A is a protective factor against osteoarthritis, beyond which it becomes a causative factor for osteoarthritis.

Association between blood heavy metals and diabetic kidney disease among type 2 diabetic patients: a cross-sectional study.

Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011-2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.

The association of serum albumin with 28 day mortality in critically ill patients undergoing dialysis: a secondary analysis based on the eICU collaborative research database

BackgroundThe relationship between serum albumin and prognosis in critically ill patients has been studied, however, there is a paucity of exploration into non-linear relationships, particularly in critically ill patients undergoing dialysis. This study intends to investigate the association between serum albumin (ALB) and 28 day mortality in critically ill patients undergoing dialysis.MethodsWe conducted a multi-center retrospective cohort study of patients undergoing dialysis by utilising data from the eICU Collaborative Research Database from 208 distinct ICUs across the United States between 2014 and 2015. The study focused on mortality within 28 days of ICU admission. We employed univariate analysis, multi-factor logistic regression, subgroup analysis, curve-fitting, and threshold effect analysis to examine the correlation between ALB levels and 28 day mortality.ResultsAmong the 2,315 patients with a median age of 63 years, 205 (8.86%) died within 28 days of ICU admission. When ALB level was < 2.7 g/dL, the mortality decreased with an adjusted odds ratio (OR) of 0.34 (95% CI 0.22–0.51, P < 0.0001) for every 1 increment in the ALB. However, no significant mortality changes were observed when ALB levels were at or above this threshold.ConclusionOur study identifies a nonlinear dose–response relationship between serum ALB levels and 28 day mortality in critically ill patients undergoing dialysis, with a specific turning point observed. This finding underscores a significant negative correlation between ALB levels and mortality risk, with lower ALB levels being associated with higher mortality risk in this particular population.

Glucose-albumin ratio (GAR) as a novel biomarker for predicting postoperative pneumonia (POP) in older adults with hip fractures

Postoperative pneumonia (POP) is a common complication after hip fracture surgery and is associated with increased mortality and other complications in elderly patients. This study aims to evaluate biomarkers, especially the glucose-albumin ratio (GAR), for predicting POP in elderly hip fracture patients. A total of 1279 elderly patients admitted to our hospital with hip fractures were included. We assessed 29 biomarkers and focused on GAR to determine its prognostic and predictive value for POP. Multivariable logistic regression and propensity score-matched analyses were conducted to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for POP, adjusting for potential confounders. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cut-off of GAR for predicting POP. Among the biomarkers and combinations assessed, GAR demonstrated superior predictive capability for POP in elderly hip fracture patients. ROC analyses showed moderate predictive accuracy of GAR for POP, with an area under the curve of 0.750. Using the optimal cut-off of 0.175, the high GAR group was significantly associated with increased odds of POP (adjusted OR 2.14, 95%, CI 1.50–3.05). These associations remained significant after propensity score matching and subgroup analyses. Dose–response relationships between GAR and POP were observed. In conclusion, GAR may be a promising biomarker to predict POP risk in elderly hip fracture patients. Further studies are warranted to validate its clinical utility. However, this study has certain limitations, including its retrospective design, potential for selection bias due to the exclusion criteria, and the single-center nature of the study, which should be addressed in future prospective, multicenter studies.

Association of dietary anthocyanidins intake with all-cause mortality and cardiovascular diseases mortality in USA adults: a prospective cohort study

Anthocyanins, as a type of polyphenolic compound, have been discovered to offer multiple health benefits to humans, including anti-aging and anti-inflammatory properties. This prospective cohort study aims to examine the relationship of dietary intake of anthocyanin with all-cause mortality and cardiovascular diseases mortality in the US. The aim of this research was to explore the possible correlation between anthocyanin consumption and the mortality rate from all causes as well as from cardiovascular disease. Based on the Public Access NHANES-linked National Death Index files up to December 31, 2019, we identified mortality status and heart disease-specific causes of death. A multivariate Cox regression analysis was employed to evaluate the effects of anthocyanin intake on mortality outcomes, generating hazard ratios and 95% confidence intervals, adjusting for various demographic characteristics, lifestyle factors, and comorbid conditions. Additionally, we utilized Kaplan-Meier survival curves, subgroup analyses. In different scenarios, dietary anthocyanin intake was assessed using restricted cubic spline models. A total of 11,959 participants completed the final cohort, averaging 47.12 years of age (SD ± 0.35). Following adjustments for multiple variables, an inverse relationship was identified between anthocyanin intake in the highest quartile and all causes mortality, yielding a hazard ratio (HR) of 0.68 (95% CI: 0.52–0.89). Similarly, elevated anthocyanin consumption was linked to a reduction in heart disease mortality, with HR of 0.61 (95% CI: 0.38–0.97). Additionally, dose–response curve revealed a consistent decrease in both all-cause and cardiovascular mortality with increasing anthocyanin intake. Further subgroup analyses revealed that elevated intake of anthocyanins was linked to decreased all-cause mortality in White individuals and males. Moreover, high anthocyanin intake was significantly correlated with reduced all-cause mortality irrespective of hypertension or hyperlipidemia status. Our research indicates that an appropriate dietary intake of anthocyanins is associated with a reduction in overall mortality rates. Furthermore, the findings reveal a substantial association between anthocyanin intake and decreased mortality from cardiovascular diseases, suggesting that anthocyanins may effectively lower the risk of cardiovascular-related deaths.

Chlorophyll films for radiation dosimetry: a feasibility study

Abstract Novel Chlorophyll-PVA composite films have been prepared and tested for the dosimetry of therapeutic radiation. The radiation response has been quantified using UV–vis spectroscopy. FTIR and XRD spectroscopies have been used to characterize the physical properties and irradiation response of the films. The films have shown response towards the therapeutic x-rays beams of 6 MV nominal energy in the tested dose range of 0.25 Gy to 32 Gy in discrete dose levels occurring in the geometric progression series of 2. The dosimeter has been found to exhibit sensitivity at a low dose of 0.25 Gy. The dose response curve of the dosimeter exhibits an exponential relationship of the absorbance and absorbed dose. A region of saturated absorbance has been observed beyond 4 Gy. The peak intensities of the FTIR spectra have been found to decrease with increasing doses as compared to the unirradiated samples, because of the changes in the bond polarities and molecular geometries. The XRD spectra indicates a change in the molecular orientation resulting in a decrease in peak intensity with increasing dose. This study indicates the feasibility of chl-PVA films in the dosimetry of therapeutic radiation. This film dosimeter can be processed locally with minimum resources and standardized against a known standard before clinical use. The chlorophyll molecules need careful handling owing to their sensitivity to light and temperature.

The association between vitamin intake and endometriosis: a cross-sectional study of the NHANES 1999–2006

BackgroundEndometriosis is a common cause of female reproductive problems, and vitamin intake may affect its incidence. Therefore, we further explored the association between multivitamin intake and endometriosis in a large population-based study.MethodsThis study included 3351 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2006. The dietary intake of eight vitamins was calculated as the average of two 24-h recall interviews, and information on endometriosis was obtained through questionnaires that included gynecological history. Multiple logistic regression analysis was used to explore the relationship between multivitamin intake and endometriosis. Smoothed curve fitting analysis was employed to assess the dose–response relationship between vitamins and endometriosis. Finally, subgroup analysis and interaction tests were conducted to determine the association of covariates between vitamins and endometriosis.ResultsIn this large-scale cross-sectional study, multiple logistic regression analysis showed that the intake of vitamins A, B1, B2, B6, C and folate was negatively associated with the occurrence of endometriosis. The odds ratios associated with a per-SD increase were 0.836 (95%CI: 0.702, 0.997), 0.817 (95%CI: 0.702, 0.951), 0.860 (95%CI: 0.746, 0.991), 0.784 (95%CI: 0.669, 0.919), 0.845 (95%CI: 0.718, 0.994), and 0.772 (95%CI: 0.660, 0.903), respectively. Smoothed curve fitting analysis revealed that the intake of vitamins A, B1, B2, B6, C, and folate was negatively associated with the risk of endometriosis (P < 0.05). Vitamin E showed a saturating effect, with an optimal cutoff point at 13.18. Below this cutoff, the intake of vitamin E was negatively correlated with the risk of endometriosis (OR = 0.947, 95% CI: 0.906, 0.989), whereas above the cutoff, there was no significant correlation between vitamin E intake and the risk of endometriosis (OR = 1.001, 95% CI: 0.997, 1.005).ConclusionsThe results of this study indicate a significant linear negative correlation between the intake of vitamins A, B1, B2, B6, C, and folate, and the risk of endometriosis, and reveal a threshold effect for vitamin E intake on the risk of endometriosis. These findings could inform clinical dietary interventions and may support the development of preventive strategies for endometriosis, potentially aiding in its reduction.

Inhibitory effects of N-trans-cinnamoyltyramine on growth of invasive weeds and weedy rice.

N-trans-cinnamoyltyramine (NTCT) has been identified from an allelopathic Vietnamese rice accession OM 5930. This study employed bioassays to analyze NTCT's effects on shoot and root growth of multiple test and weed species. NTCT demonstrated potent inhibitory effects on cress, lettuce, canola, palmer amaranth, timothy, barnyardgrass, red sprangletop, and weedy rice, with increasing concentrations leading to substantial reductions in growth in all species. Linear regression analysis of dose response curves revealed ED50 values for NTCT, providing critical insights into the concentration required for 50% growth inhibition in each species. They revealed high sensitivity of the test species cress and lettuce, intermediate sensitivities of barnyardgrass, red sprangletop, timothy, and amaranth, and comparatively lower sensitivity of two weedy rice accessions. The findings underscore NTCT's efficacy in suppressing the growth of a wide range of weeds, including both grasses and broadleaf species. As such, NTCT may hold promise as a tool for sustainable weed management, particularly in addressing herbicide-resistant weeds in diverse ecological settings.

Development of an assay to quantify tranexamic acid levels in plasma

Dysregulations during blood clot breakdown (fibrinolysis) during vascular trauma can lead to excessive blood loss. Tranexamic acid (TXA) is an inhibitor of fibrinolysis that works by blocking the interaction between plasminogen and fibrin degradation products (FDPs) – a key step in fibrinolysis. Despite the widespread usage, there are no tests available in a clinical setting to monitor TXA levels. We developed a fluorescence resonance energy transfer (FRET)-based assay to quantify TXA concentrations in plasma by using 1) fluorescently labeled plasminogen, and 2) FDPs labelled with a fluorescence quencher. Once plasminogen binds the FDPs, the fluorescent signal is quenched. TXA causes plasminogen to dissociate from the FDPs, thus increasing fluorescence signal in a dose-dependent manner. The dose response was sensitive between 1 and 100 μM (0.16 and 15.7 mg/L). The intraassay and interassay variabilities were determined to be 5.7% and 3.0%, respectively. Limit of detection was estimated to be 0.28 μM (0.044 mg/L). When tested for measuring known levels of TXA added to plasma samples, the ratio between measured and expected TXA concentration was 1.0151. Our study demonstrates a novel assay that can rapidly quantify TXA concentrations in plasma samples, thus demonstrating its potential as an in-hospital tool.

Undoped and Eu doped LaCa₄O(BO₃)₃ phosphors: Thermoluminescence characteristics with a focus on kinetic parameters, anomalous heating rate, and dose response

The thermoluminescence (TL) properties of LaCa₄O(BO₃)₃ (LACOB) phosphors, both undoped and doped with 0.5 % Eu³⁺, were synthesized using a microwave-assisted sol-gel method and analysed under beta irradiation doses ranging from 0.1 Gy to 700 Gy. The TL glow curves revealed prominent peaks at 100 °C and 285 °C for the Eu-doped sample. Activation energy values were calculated using the Hoogenstraaten and Booth-Bohun-Parfianovitch methods, yielding 1.52 eV and 1.48 eV for the undoped sample, and 2.07 eV and 2.01 eV for the Eu-doped sample, respectively. Eu³⁺ ions introduced deeper traps and enhanced the thermal stability of the material. Anomalous increases in TL intensity with rising heating rates were observed, deviating from typical thermal quenching behaviour; this phenomenon was explained using a semi-localized transition (SLT) model. The TL reusability measurements demonstrated a standard deviation of less than 5 %, indicating consistent and reliable performance across multiple cycles. The TL glow curve deconvolution identified six distinct peaks in the undoped sample, while the Eu-doped sample showed a more complex trap structure with eight peaks, indicating the introduction of additional or modified trapping sites by Eu doping. The figure of merit (FOM) values obtained from the deconvolution analysis were all below 2.5 %, indicating a good fit between the observed and fitted TL signals. These findings suggest that Eu³⁺-doped LACOB is a robust material for radiation dosimetry, with its enhanced sensitivity, stability, and versatility across various dosimetric applications.

Ultrasonic-assisted DES extraction optimization, characterization, antioxidant and in silico study of polysaccharides from Angelica dahurica Radix

In this study, polysaccharides from Angelica dahurica Radix (ADR) were extracted by using ultrasonic-assisted deep eutectic solvent (DES) extraction method. The DES consist of choline chloride (HBA, hydrogen bonding acceptor) and 1, 4-butanediol (HBD, hydrogen bonding donor) with the molar ratio of 1:3 was proved as the best system for polysaccharides extraction. A Box-Behnken design with three factors and three levels was utilized to optimize ultrasonic power, extraction time and temperature for increased polysaccharides yield. The optimal extraction parameters were determined as follows: DES water content of 20 %, liquid–solid ratio of 10:1 mL/g, ultrasonic time of 21 min, temperature at 60 °C, and ultrasonic power of 435 W. These conditions yielded an extraction rate nearly matching the theoretical predicted value of the response surface model, surpassing the traditional hot water extraction method by 1.33 times and requiring less time. The antioxidant polysaccharides was assessed using DPPH,ABTS and Hydroxyl methods, which indicated that ADRP extracted by ultrasound assisted DES had excellent antioxidant capacity and showed a dose–response relationship with drug concentration. Structural analysis identified ADR polysaccharides as a heteropolysaccharide rich in sugar aldonic acids—namely, fucose, rhamnose, arabinose, galactose and glucose—with molar ratios of 0.47:1.99:17.61:64.76:15.17. The polysaccharides’ number-average molecular weight was determined to be 97.422 kDa, with a weight-average molecular weight of 245.678 kDa. Network pharmacology and molecular docking analysis suggest that the monosaccharides Rha and Ara could potentially interact with the proteins GSR and GSTA1, respectively, indicating that ADRP had good antioxidant potential and could be applied in multiple fields with promising development prospects in the future.

Dose response of leisure time physical activity and biological aging in type 2 diabetes: a cross sectional study

To investigate the relationship between Leisure time physical activity (LTPA) patterns and PhenoAgeAccel in patients with Type 2 diabetes (T2D), emphasizing the role of regular LTPA in mitigating biological aging. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, including 4,134 adults with T2D. Multivariable linear regression models and restricted cubic spline (RCS) methods were employed to assess the relationship between LTPA and Phenotypic age acceleration (PhenoAgeAccel), with segmented likelihood ratio tests to detect nonlinear thresholds. Stratified regression and interaction tests were conducted for robust analysis. Compared to individuals with no LTPA patterns, those with regular LTPA patterns had significantly lower PhenoAgeAccel scores (β = -1.164, 95% CI: -1.651 to -0.677, P < 0.0001), while the “Weekend Warrior” and “Inactive-LTPA” patterns showed no significant effects. A nonlinear threshold effect was identified; below 594.57 min of weekly LTPA, there was a significant negative correlation (β = -0.002, 95% CI: -0.003 to -0.001, P = 0.000), with gender-specific effects present. Regular LTPA significantly reduces phenotypic age acceleration in T2D patients, with a nonlinear threshold effect indicating that moderate physical activity is most beneficial. These findings highlight the necessity of personalized physical activity recommendations and provide evidence for public health strategies to promote healthy aging in T2D patients.

Prolonged L-NAME exposure changes the vasodilator factor from NO to H2O2 in human arterioles in response to A23187

The Ca2+ ionophore A23187 induces endothelium-dependent and non-receptor-mediated vasodilation in human adipose arterioles (HAAs). The purpose of this study was to determine the mechanism of A23187-induced dilation in HAAs from patients with and without coronary artery disease (CAD). HAAs were freshly isolated from adipose tissues obtained from non-CAD (n = 25) and CAD (n = 14) patients, and vascular reactivity was studied by videomicroscopy. No difference in baseline dose response to A23187 was observed between non-CAD and CAD subjects. However, acute (30 min) incubation with N(omega)-nitro-l-arginine methyl ester (L-NAME), NO synthase inhibitor strongly reduced A23187-induced dilation in non-CAD arterioles, while catalase, an H2O2 scavenger, largely abolished dilation in CAD. Surprising, prolonged (90 min) incubation with L-NAME restored A23187 response in non-CAD subjects, which was subsequently inhibited by catalase. The action of prolonged L-NAME exposure was not reversible after washing with Krebs while the effect of acute L-NAME exposure was largely reversible. To further determine the role of mitochondria-derived ROS in A23187-induced dilation, arterioles were treated with rotenone, an inhibitor of complex I of the electron transport chain. Rotenone abolished A23187 response in CAD patients and in non-CAD arterioles after prolonged L-NAME, but not in non-CAD controls. These data indicate that NO contributes to A23187-induced dilation in HAAs from non-CAD patients and H2O2 contributes to the dilation in CAD patients. Prolonged L-NAME exposure induces a NO-H2O2 switch in the mechanism of dilation in non-CAD subjects. Moreover, the effect of prolonged L-NAME exposure is not readily reversible, while the action of acute L-NAME exposure is reversible.