Dose-effect Relationship Research Articles

Heat-induced kidney disease: Understanding the impact.

Research on Mesoamerican Nephropathy, chronic kidney disease of unknown cause and chronic kidney disease of nontraditional cause has been going on for more than 20 years. Thousands of manual workers, especially in agriculture, are affected. The disease has been reported in different countries and regions, not only from heat-stressed sugarcane cutters in Central America but also from other occupational groups with strenuous work in hot environments. The cause of this disease is still debated. A multitude of causative factors have been suggested, including agrochemicals, water quality, infections, and heavy metals. The evidence that heat stress is the major cause of kidney disease is convincing, whereas the support for alternative causes is weak. Associations between exposure and kidney damage are strong, consistent, and specific, occur after acute and chronic exposure, display dose-effect and dose-response relationships, are plausible, and coherent. Improving working conditions by providing hydration, rest, and shade to heat-stress-exposed workers is beneficial. Continued global warming will increase the number of people at risk for dangerous heat exposure and kidney disease.

Relationship between different levels of internet use and depressive tendencies in Chinese college students: the chain mediating effect based on physical activity and social adaptability

ObjectiveTo investigate the relationship between internet use, physical activity, social adaptability, and depressive tendencies of college students, and to reveal the “advantages” and “disadvantages” of internet use around the “dose-effect”.MethodThe Revised Chinese Internet Addiction Scale (CIAS-R), Physical Activity Rating Scale (PARS-3), Chinese College Student Social Adjustment Scale (CCSAS), and Self-rating Depression Scale (SDS) were used to conduct a random sampling survey among 3008 college students in China.Results(1) Internet use could directly and positively predict the depressive tendencies of college students. (2) Physical activity and social adaptability have a significant chain mediating effect between internet use and depressive tendencies. (3) There was a “U-shaped” dose-effect relationship between internet use and depression tendencies, indicating that normal internet use could directly and negatively predict depressive tendencies, and through the chain mediating effect of physical activity and social adaptability negatively predict depressive tendencies. In contrast, internet use dependence and addiction could directly predict depressive tendencies, and through the chain mediating effect of physical activity and social adaptability positively predict it.ConclusionTherefore, normal or moderate internet use has potential protective benefits on the physical and mental health of college students and can promote the positive development of physical activity and social adaptability to a certain extent, and prevent or reduce depressive tendencies, otherwise, it is not conducive to the healthy development of related behaviors and psychology.

Chemical Composition, Bioactivities, and Applications of Spirulina (Limnospira platensis) in Food, Feed, and Medicine.

Spirulina (Limnospira platensis) is a microalga recognised for its rich nutritional composition and diverse bioactive compounds, making it a valuable functional food, feed, and therapeutic agent. This review examines spirulina's chemical composition, including its high levels of protein, essential fatty acids, vitamins, minerals, and bioactive compounds, such as the phycocyanin pigment, polysaccharides, and carotenoids, in food, feed, and medicine. These compounds exhibit various biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiviral, anticancer, antidiabetic and lipid-lowering effects. Spirulina's potential to mitigate oxidative stress, enhance immune function, and inhibit tumour growth positions it as a promising candidate for preventing chronic diseases. Additionally, spirulina is gaining interest in the animal feed sector as a promotor of growth performance, improving immune responses and increasing resistance to diseases in livestock, poultry, and aquaculture. Despite its well-documented health benefits, future research is needed to optimize production/cultivation methods, improve its bioavailability, and validate its efficacy (dose-effect relationship) and safety through clinical trials and large-scale human trials. This review underscores the potential of spirulina to address global health and nutrition challenges, supporting its continued application in food, feed, and medicine.

Establishment and Application of a New Radiation Biodosimetric Method Based on the Quantitative RPA-SHERLOCK Amplification Technology.

Biodosimetry is a key diagnostic tool for radiation exposure, risk assessment and treatment planning of acute radiation sickness. To effectively respond to a large-scale radiological incident, there is a need for the development of biodosimetric methods with fast, portable, and convenient operating advantages. We employed the recombinase polymerase amplification specific high-sensitivity enzymatic reporter unlocking (RPA-SHERLOCK) technology to establish a method for fast radiation dose assessment by measuring the expression level of radiation-inducible genes. Moreover, we proposed for the first time the principle of quantitative detection of curve slopes based on this method. Using this new method, changes in mRNA expression were confirmed in a number of radiation-sensitive genes (XPC, CDKN1A, and ATM) in human lymphocytes after irradiation. The standard curve of the dose-effect relationship was established, which can be used to quickly determine the exposed dose of the irradiated samples. Compared with traditional detection methods such as RT-qPCR, this method was found to be more convenient, fast and easy to operate. With the same amount of template input as RT-qPCR, the detection time of this method can be shortened to less than 20 min. The detection instrument required by this method is also more portable than a qPCR system.

Effect of different durations of preoperative computerised cognitive training on postoperative delirium in older patients undergoing cardiac surgery: a study protocol for a prospective, randomised controlled trial

IntroductionPostoperative delirium (POD) is a common neurological complication after surgery among older patients, characterised by acute disturbances in consciousness, attention and cognition, usually occurring within 24–72 hours after surgery. POD...

Effect of Mexel®432 on DNA Damage in Haliotis Discus Hannai and Mesocentrotus Nudus

Mexel®432 is a surfactant-like substance that is a biosuppressant against marine fouling organisms. Therefore, to study the toxic effect of Mexel®432 on marine organisms, the wrinkled abalone and echinococcus was exposed to concentrations of 0.175 mg·L-1, 0.350 mg·L-1, 0.700 mg·L-1, 0.275 mg·L-1, 0.550 mg∙L−1, 1.100 mg·L-1 Mexel®432 solution, and single-cell gel electrophoresis (comet experiment) was used to detect different exposure times (0, 10, 20 d) DNA damage effect of digestive gland cells and echinococcus pallidae intestinal cells in wrinkled disc abalone, and tail DNA content, tail length, tail distance, and Olive tail distance were used as evaluation indexes. The results showed that different concentrations of Mexel®432 could cause DNA disintegration and tailing in digestive gland cells and intestinal cells in a short period of time (10 d), and with the increase of Mexel®432 concentration and the extension of exposure time, DNA deformation was obvious, the fragmentation increased, and the degree of damage was aggravated. When the concentration of Mexel®432 reaches 0.350 mg·L-1, it produces certain genotoxicity to the digestive gland cells of wrinkled abalone, and when the concentration of Mexel®432 reaches 1.1000 mg·L-1, it also has certain genotoxicity to the intestinal cells of Mesocentrotus nudus. The experimental results showed that Mexel®432 had a significant dose effect relationship on DNA damage in the cells of two biological tissues.

Prolonged use of chlormadinone acetate and risk of intracranial meningioma: A population-based cohort study.

Chlormadinone acetate (CMA) is a synthetic progestin for which cases of intracranial meningioma have been reported following prolonged exposure. An observational cohort study was conducted based on the French national health data system. Women aged 10-70 years and who started CMA between 2007 and 2017 were included. Participants were considered to be exposed if they had received a cumulative dose >360 mg of CMA during the first 6 months and very slightly exposed (control group) when they had received a cumulative dose ≤360 mg. The outcome was surgery or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma. In total, 828,499 women were included: 469,976 in the exposed group (mean age 39.1 years, SD 10.1) and 358,523 in the control group (38.3 years, SD 11.0). Surgery or radiotherapy for intracranial meningioma between 2007 and 2017 was recorded for 164 and 104 women in the exposed and control groups, respectively. The incidence of meningioma was 18.5 and 6.8 per 100,000 person-years for the exposed and control groups respectively (crude RR = 2.7, 95% confidence interval [CI] 2.1-3.5; age-adjusted RR = 3.1, 95% CI 2.4-4.0). Meningioma incidence reached almost 47 cases/100,000 person-years in the most exposed group (>8.64 g), giving an age-adjusted RR of 6.9, 95% CI 5.1-9.2, relative to the control group. A strong dose-effect relationship was observed between prolonged use of CMA and risk of meningiomas. As with other progestogens, meningiomas associated with CMA are more likely to be found at the base of the skull.

General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

BackgroundAntenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids.MethodsWe assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering.ResultsWe assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations.ConclusionsThere is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

SFRP1-Silencing GapmeR-Loaded Lipid-Polymer Hybrid Nanoparticles for Bone Regeneration in Osteoporosis: Effect of Dosing and Targeting Strategy.

Osteoporosis is a metabolic disorder characterized by the loss of bone mass and density. Nucleic acid-based therapies are among the most innovative approaches for osteoporosis management, although their effective delivery to bone tissue remains a challenge. In this work, SFRP1-silencing GampeR loaded-nanoparticles were prepared and functionalized with specific moieties to improve bone targeting and, consequently, therapeutic efficacy. SFRP1-silencing would promote osteoblastic differentiation by enhancing the WNT/β-catenin pathway and thus diminishing the progression of osteoporosis. A nucleic acid-based delivery system consisting of lipid-polymer hybrid nanoparticles (LPNPs) loading a GapmeR for SFRP1 silencing was developed and further functionalized with two bone-targeting moieties: a specific aptamer (Apt) for murine mesenchymal stem cells and an antiresorptive drug, namely alendronate (ALD). These systems were tested in vivo in osteoporotic mice at different dosage regimens to analyze dose dependence in bone-forming activity and potential toxicity. The quality of trabecular and cortical bone was assessed by both micro computed tomography (micro-CT) and histological and histomorphometric analyses. Early and late osteogenesis were quantified by immunohistochemistry. Results showed that functionalizing LPNPs loaded with an SFRP1-silencing GapmeR using both Apt and ALD improved bone quality and enhanced osteogenesis following a dose-effect relationship, as revealed by micro-CT, histological and immunohistochemical analyses. In contrast, non-functionalized LPNPs did not produce these effects. These findings highlight the relevance of proper targeting and dosage in nucleic acid-based therapeutics, proving to be crucial for exerting their therapeutic effect: a deficient targeting strategy and/or dosage may result in the therapeutic failure of an adequate gene therapy agent.

Auto-contouring of cardiac substructures for Stereotactic arrhythmia radioablation (STAR): A STOPSTORM.eu consortium study

Background/PurposeHigh doses to healthy cardiac substructures (CS) in stereotactic arrhythmia radioablation (STAR) raise concerns regarding potential treatment-induced cardio-toxicity. However, CS contours are not routinely created, hindering the understanding of the CS dose–effect relationships. To address this issue, the alignment of CS contouring was initiated within the STOPSTORM consortium. In this study, we developed and evaluated auto-contouring models trained to delineate CS and major vessels in ventricular tachycardia (VT) patients. MethodsEight centres provided standard treatment planning computed tomography (CT) and/or contrast-enhanced CT datasets of 55 VT patients, each including 16 CS. Auto-contouring models were trained to contour either large structures or small structures. Dice Similarity Coefficient (DSC), 95 % Hausdorff distance (HD95) and volume ratio (VR) were used to evaluate model performance versus inter-observer variation (IOV) on seven VT patient test cases. Significant differences were tested using the Mann-Whitney U test. ResultsThe performance on the four chambers and the major vessels (median DSC: 0.88; HD95: 5.8–19.4 mm; VR: 1.09) was similar to the IOV (median DSC: 0.89; HD95: 4.8–14.0 mm; VR: 1.20).For the valves, model performance (median DSC: 0.37; HD95: 11.6 mm; VR: 1.63) was similar to the IOV (median DSC: 0.41; HD95: 12.4 mm; VR: 3.42), but slightly worse for the coronary arteries (median DSC: 0.33 vs 0.42; HD95: 24.4 mm vs 16.9 mm; VR: 1.93 vs 3.30). The IOV for these small structures remains large despite using contouring guidelines. ConclusionCS auto-contouring models trained on VT patient data perform similarly to IOV. This allows for time-efficient evaluation of CS as possible organs-at-risk.

Efficacy and acceptability of lurasidone for bipolar depression: a systematic review and dose–response meta-analysis

QuestionThe optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose–response relationship for efficacy, acceptability, and metabolic/endocrine profiles.Study selection and analysisFive databases and grey literature published...

High sodium intake increases interstitial lung disease and pulmonary sarcoidosis based on the Global Burden of Disease study 1999–2019

This study investigated the relationships between dietary sodium intake and the incidence and prevalence of interstitial lung disease (ILD) and pulmonary sarcoidosis using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. This study assessed the strength of the abovementioned relationships via LASSO analysis and a generalized additive model with Poisson regression and determined the nonlinear and lagged effects via a distributed lag nonlinear model (DLNM). In the past three decades, global dietary sodium intake has decreased gradually. Two LASSO and generalized additive analyses both suggested that dietary sodium intake is obviously correlated with the incidence and prevalence of ILD and pulmonary sarcoidosis. The overall exposure‒response curve revealed a dose‒effect relationship between dietary sodium intake and the incidence and prevalence of ILD and pulmonary sarcoidosis. The maximum lag-specific RR of extremely high dietary sodium intake was 1.75 (95% CI: 1.61–1.91, lag 0 year) for incidence and 3.19 (95% CI: 2.24–4.53, lag 0 year) for prevalence relative to the reference. Our study suggests that dietary sodium intake is positively associated with the incidence and prevalence of ILD and pulmonary sarcoidosis. These findings may have important policy implications for dietary sodium intake-reduction strategies to decrease the burden of respiratory diseases and promote public health.

PO0242: The Dose-Effect Relationship for Vaginal Late Toxicity in Intracavitary Brachytherapy with Cylinder Applicator

PO0242: The Dose-Effect Relationship for Vaginal Late Toxicity in Intracavitary Brachytherapy with Cylinder Applicator

An optimized method for dose-effect prediction of traditional Chinese medicine based on 1D-ResCNN-PLS.

We introduce a one-dimensional (1D) residual convolutional neural network with Partial Least Squares (1D-ResCNN-PLS) to solve the covariance and nonlinearity problems in traditional Chinese medicine dose-effect relationship data. The model combines a 1D convolutional layer with a residual block to extract nonlinear features and employs PLS for prediction. Tested on the Ma Xing Shi Gan Decoction datasets, the model significantly outperformed conventional models, achieving high accuracies, sensitivities, specificities, and AUC values, with considerable reductions in mean square error. Our results confirm its effectiveness in nonlinear data processing and demonstrate potential for broader application across public datasets.

High-intensity interval training and moderate-intensity continuous training alleviate vascular dysfunction in spontaneously hypertensive rats through the inhibition of pyroptosis

Evidence-based guidelines suggest that High-Intensity Interval Training (HIIT) is more beneficial than aerobic exercise for patients with cardiovascular disease, but the differences in underlying pathophysiological mechanisms require further confirmation. The comparison between HIIT and Moderate-Intensity Continuous Training (MICT) in regulating vascular dysfunction in spontaneously hypertensive rats (SHR), along with their underlying mechanisms, has not been previously reported. The purpose of this study is to provide an experimental basis for exercise prescription therapy in hypertensive patients. In this study, six-week-old male SHR were randomly assigned to a HIIT group, MICT group, or sedentary group. Wistar Kyoto rats (WKY) of the same age were used as the control group. The weight, heart rate, and blood pressure of the rats were monitored weekly throughout twelve weeks of treadmill training. At the end of the protocol, serum and aortic vascular tissues were collected for further vascular function tests and molecular and biochemical analyses. The results show that MICT is more favorable for weight control than HIIT, while both forms of exercise offer equal protection against hypertension. However, MICT demonstrates a greater benefit in preserving vascular morphology, whereas HIIT is more effective in reducing oxidative stress. Both HIIT and MICT ameliorate vascular dysfunction in SHR by suppressing nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 3 (NLRP3)-induced pyroptosis. The superior effect of HIIT on vascular dysfunction may be related to the inhibition of oxidative stress injury through AMPKα-SIRT1 activation. This study provides insight into the dose-effect relationship of exercise for cardiovascular health and offers foundational evidence for the development of exercise prescription therapies.

Medial rectus re-advancement: more bang for your buck?

ABSTRACT Introduction: Although there are guidance tables in the literature on surgical dosage for primary medial rectus resection-lateral rectus recession surgery, there is a lack of consensus on the surgical gains in medial rectus re-advancement (MRR) for the management of consecutive exotropia. We compared the surgical outcomes of primary medial rectus resection-lateral recession (RR) surgery, to MRR in patients with consecutive exotropia. Methods: Retrospective, electronic note review of consecutive patients undergoing primary RR surgery for basic exotropia (RR group), convergence insufficiency-type exotropia, and divergence excess, and consecutive patients undergoing MRR with or without lateral rectus recession (MRR group) for consecutive exotropia in a teaching university hospital. Results: There were 84 patients in the RR group and 27 patients in the MRR group. The median age in the RR group was 25.50 years (range 4–79) and 45 years (18–87) in the MRR group (p = .002). Median follow-up was 7 months (3–43) in the RR group and 1 month (1–12) in the MRR group. Post-operatively, there was a median exotropia reduction of 27.00 prism diopters (PD) (range +5, –65; p < .0001) for near, and 27.00 PD (+10, –51; p < .0001) for distance in the RR group. In the MRR group, the median exotropia reduction was 34.50 PD (2, –67; p < .0001) for near and 33.00 PD (1, –67; p < .0001) for distance. There was a greater reduction in the exotropia in the MRR group compared to the RR group for distance (p = .047), but this did not meet statistical significance for near (p = 0.10). The median dose–effect relationship (PD/millimeter) was higher in the MRR group both for near deviation (2.90 vs 2.15, p = .0073) and for distance deviation (2.91 vs 2.15, =0.0041). Conclusion: Based on our study cohort, medial rectus re-advancement appears to have a greater dose-effect in reducing the distance angle of deviation for both near and distance compared to primary recess-resect surgery. Further prospective longitudinal studies would shed further light on the dose–effect relationship over time.

Assessment of industrial noise nuisance - guidelines for calculating the HA index - results of surveys on the population covered by strategic noise maps in Poland

The work contains the results of research conducted in the field based on the ISO 15666 standard. The aim was to assess the annoyance of industrial noise around sources mapped as part of strategic noise maps made in Poland. The research area included five selected industrial areas, among all those mapped in Poland. 431 people were surveyed. The analysis included residents of five noise ranges: 50 - 55, 55 - 60, 60 - 65, 65 - 70 dB, described by the LDWN index. The result of the research was the determination of the dose-effect relationship for the HA (High Annoyance) index and the method of its calculation for the sample analysis area.

Ozone: complicated effects in central nervous system diseases.

Oxidative stress is closely related to various diseases. Ozone can produce redox reactions through its unique response. As a source of the oxidative stress response, the strong oxidizing nature of ozone can cause severe damage to the body. On the other hand, low ozone concentrations can activate various mechanisms to combat oxidative stress and achieve therapeutic effects. Some animal experiments and clinical studies have revealed the potential medical value of ozone, indicating that ozone is not just a toxic gas. By reviewing the mechanism of ozone and its therapeutic value in treating central nervous system diseases (especially ischemic stroke and Alzheimer's disease) and the toxic effects of ozone, we find that ozone inhalation and a lack of antioxidants or excessive exposure lead to harmful impacts. However, with adequate antioxidants, ozone can transmit oxidative stress signals, reduce inflammation, reduce amyloid β peptide levels, and improve tissue oxygenation. Similar mechanisms to those of possible new drugs for treating ischemic stroke and Alzheimer's disease indicate the potential of ozone. Nevertheless, limited research has restricted the application of ozone. More studies are needed to reveal the exact dose-effect relationship and healing effect of ozone.

Quantitative assessment of corneal biomechanical changes in vivo after photorefractive intrastromal corneal cross-linking using optical coherence elastography.

Photorefractive intrastromal corneal cross-linking (PiXL) treatment corrects myopia by enhancing localized central corneal biomechanics. However, the dose-effect relationship between the changes in corneal biomechanics and alterations in corneal curvature resulting from this treatment remain unclear. We therefore developed an acoustic radiation force optical coherence elastography (ARF-OCE) technique to investigate the dose-effect relationship in PiXL. ARF-OCE measurements and corneal topography were performed 3 days before and 1 week after PiXL treatment. Depth-resolved Young's modulus images of the in vivo corneas were obtained based on the phase velocity of the Lamb wave. PiXL treatments with five ultraviolet-A (UVA) energy doses (5.4, 15, 25, 35, and 45 J/cm2) were administered to rabbit corneas in vivo (n=15). The percentage change in Young's modulus (ΔE%) of the cornea increased from 0.26 to 1.71 as the UVA energy dose increased from group I (5.4 J/cm2) to group V (45 J/cm2). Meanwhile, the change in the mean keratometry (ΔKm ) of the cornea increased from 0.40 to 2.10 diopters (D) as the UVA energy dose increased from group I to group IV (35 J/cm2). Furthermore, a statistically significant positive correlation was observed between ΔE% and ΔKm in groups I to IV. With increasing UVA energy dose, the corneal Young's modulus significantly increased. Given the observed correlation, ΔE% holds promise as a new quantitative biomechanical parameter for determining the dose-effect relationship in PiXL treatment. It should be emphasized that there may be an inflection point of ΔE%, at which corneal keratometry ceases to flatten and begins to increase. The ARF-OCE system has demonstrated its efficacy in quantitatively assessing changes in corneal biomechanics in vivo following PiXL treatment. This technique has great potential in facilitating the quantitative determination of the dose-effect relationship in PiXL treatment.

EP.03F.05 A Dose-Effect Relationship of a Novel Bronchoscopy Guided Endobronchial Radiofrequency Ablation for Peripheral Lung Tumors

EP.03F.05 A Dose-Effect Relationship of a Novel Bronchoscopy Guided Endobronchial Radiofrequency Ablation for Peripheral Lung Tumors