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Purpose: To investigate the effects of 3 training volumes in the bench-press exercise performed with interrepetition rest periods, matched for fatigue, on strength gains and neuromuscular adaptations. Methods: Forty-three resistance-trained men were randomized into 3 groups: low (LOW), moderate (MOD), and high (HIG) volume. The intensities increased from 70% to 85% of 1-repetition maximum (1RM) over the 8-week training period. Each session consisted of only 1 set with short interrepetition rest periods. LOW performed only 3 repetitions per session (8-wk total: 48 repetitions); MOD completed 15, 12, 10, and 8 repetitions per session with 70%, 75%, 80%, and 85% 1RM, respectively (8-wk total: 180); and HIG performed 24, 21, 18, and 15 repetitions per session with 70%, 75%, 80%, and 85% 1RM, respectively (8-wk total: 312). Progressive loading and fatigue tests were conducted in the bench-press exercise before and after the training period. Electromyography (EMG) signals from the triceps brachii were registered during these tests. Results: HIG and MOD showed higher velocity loss than LOW (16% vs 12%). No significant group × time interaction was observed for any variable. All groups improved significantly in all strength-related variables, except for maximal unloaded velocity, where only MOD obtained significant gains. Only LOW and MOD induced significant improvements in EMG. MOD obtained the greatest effect sizes in almost all strength variables. Conclusions: No significant differences were found in the performance gains obtained by each group despite the wide differences in the total volume accumulated by each group. [ABSTRACT FROM AUTHOR]

Rationale: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. Methods: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. Measurements and Main Results: Among 2,255 participants with 6,978 plasma samples, pyrazinamide displayed sevenfold exposure variability (151-1,053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in therapeutic windows of 231-355 mg · h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1,000 mg would have permitted an additional 13.1% (n = 96) of participants allocated to the control and 9.2% (n = 70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared with the current weight-banded dosing. Conclusions: Flat dosing of pyrazinamide at 1,000 mg/d would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registered with www.clinicaltrials.gov (NCT02410772).

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Pharmacoepidemiologic studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a nonlinear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose–response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose–response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naive women with a vaginal delivery enrolled in Tennessee's Medicaid program (United States, 2007-2014). [ABSTRACT FROM AUTHOR]

The current study estimated effects of intervention dose (attendance) of a cognitive behavioral prevention (CBP) program on depression-free days (DFDs) in adolescent offspring of parents with a history of depression. As part of secondary analyses of a multisite randomized controlled trial, we analyzed the complete intention-to-treat sample of 316 at-risk adolescents ages 13 to 17 years. Youth were randomly assigned to the CBP program plus usual care (n  = 159) or to usual care alone (n  = 157). The CBP program involved 8 weekly acute sessions and 6 monthly continuation sessions. Results showed that higher CBP program dose predicted more DFDs, with a key threshold of approximately 75% of a full dose in analyses employing instrumental variable methodology to control multiple channels of bias. Specifically, attending at more than 75% of acute phase sessions led to 45.3 more DFDs over the 9-month period after randomization, which accounted for over 12% of the total follow-up days. Instrument sets were informed by study variables and external data, including weather and travel burden. In contrast, conventional analysis methods failed to find a significant dose-outcome relation. Application of the instrumental variable approach, which better controls the influence of confounding, demonstrated that higher CBP program dose resulted in more DFDs. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

Objective: Cancer survivors often face significant health-related quality of life (HRQoL) challenges. Although exercise has been proven to improve HRQoL in cancer survivors, the optimal dose and intensity of exercise for this population has not been fully determined. Adherence to exercise may vary based on exercise intensity, affecting results. This study explored the dose-response relationship of different exercise types and intensities to better understand their impact on HRQoL in cancer survivors. Methods: We searched five databases—PubMed, Embase, the Cochrane Library, Web of Science, and Scopus—from their inception until 1 December 2023. Data analysis was performed using R software with the MBNMA and RJAGS packages. Due to combining data from different scales, effect sizes were reported as standardized mean differences (SMD) with 95% credible intervals (95% CrI). The risk of bias was assessed independently by three reviewers using the RoB2 tool. Results: A total of 48 studies involving 3050 cancer survivors. Across all exercise types, the most beneficial exercise dose was identified to be 850 metabolic equivalents of task (METs)-min/week (SMD: 0.753, 95%Crl: 0.463 to 1.096), with diminishing returns observed beyond 1,100 METs-min/week. Among the various types of exercises, mixed training (MT) emerged as the optimal choice, demonstrating its efficacy at 970 METs-min/week (SMD: 0.883, 95% Crl: 0.455 to 1.345). Aerobic exercise (AE) at a dose of 430 METs-min/week (SMD: 0.681, 95% Crl: 0.206 to 1.099) and resistance training (RT) at 450 METs-min/week (SMD: 0.695, 95% Crl: 0.227 to 1.203) also showed significant benefits. Additionally, mind-body exercises, such as tai chi, qigong, or yoga, exhibited optimal effects at a dose of 390 METs-min/week (SMD: 0.672, 95% Crl: 0.259 to 1.087). Conclusion: Our study sheds light on the intricate relationship between exercise interventions and health-related quality of life in cancer survivors, as elucidated through a systematic review and Bayesian network meta-analysis. The identified optimal exercise dose of 850 METs-min/week resulted in a significant improvement in health-related quality of life, underscoring the importance of regular exercise in cancer survivorship. MT emerged as the most effective modality, closely followed by RT, AE, and MBE. Systematic review registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=493328 , identifier CRD42024493328. [ABSTRACT FROM AUTHOR]

Background: The combination of esketamine and propofol has become a common choice for total intravenous anesthesia in hysteroscopic procedures. However, the optimal effective dose has not yet been determined. The aim of this study was to determine the median effective dose (ED50) and 95% effective dose (ED95) of esketamine compounded with propofol for painless hysteroscopy. Methods: A total of 40 patients aged 20–60 years and scheduled for painless hysteroscopy under intravenous anesthesia were recruited, and a total of 31 patients were enrolled for the final analysis. Using the Dixon's up and down method, an initial dose of 0.5 mg/kg esketamine was administered intravenously before surgery, and after 1 min, it was followed by 2 mg/kg of propofol. If the hysteroscopy failed (a positive reaction) [defined as inadequate cervical dilatation, patient body movements interfering with surgical procedures during hysteroscopy placement, frowning, or Ramsay Sedation Scale (RSS) score <5 within 5 min], the subsequent patient's esketamine dosage was increased by 0.1 mg/kg. Conversely (a negative reaction), the dosage was decreased by 0.1 mg/kg. The test was not stopped until at least 7 crossovers occurred. The perioperative adverse events of each patient were recorded. The ED50 and ED95 with 95% confidence intervals (CIs) were estimated using probit regression. Results: The ED50 and ED95 with 95% (CIs) of esketamine in patients were 0.287 (0.220–0.342) mg/kg and 0.429 (0.365–0.705) mg/kg, respectively. No serious adverse events were observed in any patients. Conclusion: A dose of 0.429 mg/kg esketamine combined with propofol is recommended for painless hysteroscopy anesthesia, as it enhances anesthesia and postoperative analgesia efficacy without significant adverse reactions. However, potential risks associated with this dosage should be carefully considered in clinical practice. Clinical Trial Registration: https://www.chictr.org.cn/index.html, identifier ChiCTR2300075564. [ABSTRACT FROM AUTHOR]

Background: Cannabis use during pregnancy has been increasing and is associated with adverse neonatal outcomes, such as low birth weight (LBW) and preterm birth (PTB). It remains largely unknown whether the association between cannabis use in pregnancy and increased risk of adverse neonatal outcomes is impacted by the frequency of cannabis use and whether thresholds exist below which risk is not significantly increased. The objective of this systematic review is to assess whether the association between cannabis use during pregnancy and the risk of adverse neonatal outcomes is dependent on the frequency of use and whether risk thresholds exist. Methods: For this systematic review and dose–response meta-analysis, the Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science databases will be searched for relevant studies published in English from January 2010 onwards. Studies that include pregnant individuals with singleton pregnancies and evaluate the association between cannabis use in pregnancy and adverse neonatal outcomes using case–control, cohort, or cross-sectional designs will be considered for inclusion. Studies must include information on cannabis use frequency reported according to at least three of the pre-defined categories of no use, yearly (1–11 days per year), monthly (1–3 days per month), weekly (1–4 days per week), and daily/near daily use (5–7 days per week). At least one of the following neonatal outcomes must be reported, according to the frequency of cannabis use: LBW (< 1500 g), PTB (before 37 weeks gestation), neonatal intensive care unit (NICU) admission, and mortality. Studies will be included that report results as risk ratios (RR), odds ratios (OR), hazard ratios (HR), or that include the raw data to be able to calculate them. A two-stage dose–response meta-analysis will be conducted. The risk of bias of included studies will be assessed using the JBI tools for cohort, case–control, and cross-sectional studies. Certainty of the evidence will be reported according to the GRADE approach and the review will be reported according to PRISMA guidelines. Discussion: The frequency of cannabis is one factor that may influence the relationship between cannabis use in pregnancy and adverse neonatal outcomes. This review will quantify this relationship by determining whether risk thresholds exist. Systematic review registration: PROSPERO CRD42023479978. [ABSTRACT FROM AUTHOR]

Objective: We aim to evaluate the association of composite dietary antioxidant index (CDAI) and Benign Prostatic Hyperplasia (BPH) in a large population in the United States using a cross-sectional design. Methods: Data was retrieved from the National Health and Nutrition Examination Survey (NHANES) 2003–2008 and 2013–2020 datasets. Univariate and multivariate logistic regression were performed to explore the association between CDAI and BPH. The restricted cubic spline (RCS) model was also conducted to investigate the potential linear relationship. Sub-group analyses were also conducted. Results: Totally, this study included 13,419 participants with 1085 BPH patients among them. The higher continuous CDAI value was significantly related to higher BPH risk (OR = 1.05, 95%CI: 1.02, 1.08). Besides, individuals with the highest quartile (Q4) CDAI possessed 1.87 times risk of BPH than the lowest quartile (Q1, OR = 1.87, 95%CI: 1.41, 2.50). The RCS curve also showed a positive linear dose-response relationship between CDAI and BPH (cut-off = -0.64). The P for interaction in any subgroup was > 0.05, indicating that the main outcome was not affected by other covariates. The limitation of this study was the lack of data on the relationship between CDAI and the severity of BPH symptoms. Conclusions: This study reveals that an elevated CDAI may be associated with a linear higher risk of BPH. We do not recommend intentional or excessive antioxidant diet to prevent BPH based on the current results. [ABSTRACT FROM AUTHOR]

Tritrichomonas foetus, a sexually transmitted parasitic protozoan, causes abortion in cattle. Nitroimidazoles, such as metronidazole, treat bovine trichomonosis, but their use is precluded. Plant extracts might have antiparasitic effects. This study aimed to assess Cymbopogon nardus oil activity against T. foetus as an alternative to metronidazole. T. foetus trophozoites were incubated in culture medium containing serial dilutions of C. nardus oil. Cytotoxicity was assessed 24 hours later. C. nardus oil killed T. foetus cells. Half maximal effective concentration (EC50) was 0.4 µg/mL. These findings suggest that C. nardus oil could be exploited for discovery and compound isolation of plant-derived phytopharmaceuticals for bovine trichomoniasis and other protozoan diseases. [ABSTRACT FROM AUTHOR]

Perioperative allogeneic transfusion was generally considered to be safe. However, there had been some literatures reporting a potential association between surgical site infections (SSI) and blood transfusion. To determine whether perioperative blood transfusion increased the risk of SSI and to further explored whether there was a dose-response relationship. Retrospective nested case-control study. We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between July 2011 and July 2021. In the current study, the primary outcome measure was SSI. All consecutive patients who underwent elective spinal surgery at our institution between July 2011 and July 2021 formed the retrospective cohort. Electronic patient record and radiographic data were reviewed retrospectively in our electronic database. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Then, we explored the nonlinear relationship between perioperative blood transfusion and SSI by a smoothed curve, with the adjustments for potential confounders. If a nonlinear relationship was observed, a two-piecewise regression model would be performed to calculate the threshold effect. The average time from surgery to diagnosis of SSI was 20.5 days. We matched 248 controls to 124 SSI cases. Of the 124 patients who developed SSI, 84 patients (67.7%) had deep SSI, 40 patients (32.3%) had superficial SSI. In the fully adjusted model, the risk of SSI increased by 27% for each additional unit of blood transfusion. It can be seen from the curve fitting plot that the risk of SSI has a greater increase after blood transfusion >3U. Subsequent piecewise regression identified an inflection point of 3U. We determined that 3U was a threshold volume of allogeneic blood transfusion that shifted the risk of SSI following spinal surgery, and there was a dose-response effect. [ABSTRACT FROM AUTHOR]

Background and Objectives: Current evidence on the associations of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) consumption with the risk of inflammatory bowel disease (IBD) is inconsistent. This study aimed to investigate the relationship between dietary EPA and DHA consumption with the incidence of IBD in a population of the United States, which potentially provides insights for global nutritional prevention and control strategies for IBD. Methods and Study Design: Data were sourced from the National Health and Nutrition Examination Survey for the years 2009-2010. EPA and DHA consumption was measured using twice 24-h dietary recall questionnaires. In the arthritis questionnaire, the incidence of IBD was inquired via a subanalysis for arthropathy. To assess the relationship between dietary EPA and DHA consumption with the incidence of IBD, binary logistic regression and limited cubic spline models were used. Results: A total of 4,242 individuals aged 20 years and older participated in this survey. IBD was diagnosed in 52 individuals, representing a prevalence of 1.23%. The 95% confidence interval for crude odds ratios (ORs) of IBD in quartiles 2 and 3 of dietary EPA consumption was 0.14 (0.04-0.55) (p<0.05) and 0.36 (0.18-0.73) (p<0.05) when compared to quartile 1, respectively. The 95% confidence interval for crude ORs of IBD in quartile 4 of dietary DHA consumption was 0.09(0.02-0.35) (p<0.05) when compared to quartile 1. Conclusions: For the National Health and Nutrition Examination Survey in 2009-2010, increased dietary EPA and DHA consumption may be related to a decreased risk of IBD in Americans aged 20 and above. [ABSTRACT FROM AUTHOR]

Although handgrip strength is associated with all-cause mortality in patients with chronic kidney disease (CKD), whether this relationship is dose-related is unknown. Therefore, we examined dose-response relationships between handgrip strength and all-cause mortality in CKD patients based on previous studies by meta-analysis. Data sources included three electronic databases (PubMed, Web of Science, and Embase) from inception through October 2023. The included cohort was a CKD population not limited to disease stage, and their handgrip strength was objectively measured. Two researchers independently screened studies, extracted data, and assessed the risk of bias. We utilized estimates of handgrip strength categories using robust-error meta-regression (REMR), pooled study-specific estimates, and established dose-response relationships. Outcomes of interest included only all-cause mortality. A total of 18 studies with 4810 participants (aged 47–71 years) were included. REMR modeling showed a U-shaped trend of association between handgrip strength and all-cause mortality in patients with CKD. Higher handgrip strength values, from 10 kg to approximately 28 kg, were associated with lower mortality risk. After that, the risk of death increased slightly. A U-shaped association exists between handgrip strength and all-cause mortality risk in CKD patients. Future studies with quantitative measurements for each CKD stage will help to determine precise relative risk estimates between handgrip strength and mortality risk in patients with different stages of CKD. [ABSTRACT FROM AUTHOR]

Background: Running can improve health status from a biopsychosocial perspective. However, isolation strategies, like the COVID-19 pandemic-induced lockdown, produce deleterious effects on both health status and sport performance. The aim of our study was to investigate recreational runners' sporting habits, subjective vitality (SV), and well-being after the COVID-19 pandemic-induced lockdown. Methods: After data filtration, 5542 recreational runners (74.5% men and 25.5% women, >18 years) were selected for further analyses. The participants answered preliminary questions regarding sporting habits and completed the validated Spanish version of the Subjective Vitality as a Dynamic Reflection of Well-Being questionnaire for assessing their SV after lockdown. Results: Subjective vitality scores did not differ between men and women, nor between age groups (p = 0.41 and p = 0.11, respectively). Subjective vitality was greater with weekly training frequency up to 5 days/week, where this enhancement plateaued, while average training session duration was positively related to SV, stabilizing at 91–120 min/session (p < 0.001 for both). Conclusions: There is a dose–response relationship between both weekly training frequency and training session duration, and mental health benefits in recreational runners. Further longitudinal studies are needed in order to determine the optimal dose–response relationship for simultaneously enhancing mental health outcomes and running performance in recreational runners, especially regarding weekly training frequency, training session duration, and exercise intensity. [ABSTRACT FROM AUTHOR]

To provide a systematic and quantitative summary of dietary factors and rheumatoid arthritis (RA) risk. A systematic review and meta-analysis included prospective cohort studies from 2000 to 2024 reporting relative risks (RRs) with 95% confidence intervals (CIs) for RA incidence relating to 32 different dietary exposures. Linear and non-linear dose–response analyses were conducted. Thirty studies were included, involving 2,986,747 participants with 9,677 RA cases. Linear dose–response analysis suggested that each 2-unit per week increase in total alcohol intake was linked to 4% risk reduction (RR (95%-CI), heterogeneity (I2), NutriGrade score: 0.96 (0.94, 0.98), 58%, moderate certainty), and beer consumption was associated with a 10% reduction per 2 units/week increase (0.90 (0.84, 0.97), 0%, very low certainty). Each 2-unit/week increase in total alcohol intake was associated with a 3% decrease in seropositive RA risk (0.97 (0.96, 0.99), 28%, moderate certainty). Increased intakes of fruit (per 80 g/day) and cereals (per 30 g/day) were associated with 5% (0.95 (0.92, 0.99), 57%, moderate certainty) and 3% (0.97 (0.96, 0.99), 20%, moderate certainty) reduced risk, respectively. Conversely, tea consumption showed a 4% increased risk per additional cup/day (1.04 (1.02, 1.05), 0%, moderate certainty). Non-linear associations were observed for total coffee, vegetables, oily fish, and vitamin D supplementation. Data on dietary patterns and specific micronutrients were limited. The findings suggest that moderate alcohol consumption and a higher intake of fruits, oily fish, and cereals are associated with a reduced risk of RA, while tea and coffee may be linked to an increased risk. Optimising dietary intake of certain food components may reduce RA risk, despite moderate-quality evidence. [ABSTRACT FROM AUTHOR]

The impact of vitamin D supplementation on depressive symptoms remains uncertain. This study aimed to investigate the dose-dependent effects of vitamin D supplementation on depressive and anxiety symptoms in adults. We systematically searched PubMed, Scopus, and Web of Science up to December 2022 to identify randomized controlled trials evaluating the effects of vitamin D 3 supplementation on depression and anxiety symptoms in adults. Using a random-effects model, we calculated the standardized mean difference (SMD) for each 1000 IU/day vitamin D 3 supplementation. The GRADE tool assessed the certainty of evidence. Our analysis included 31 trials with 24189 participants. Each 1000 IU/day vitamin D 3 supplementation slightly reduced depressive symptoms in individuals with and without depression (SMD: −0.32, 95% CI −0.43 to −0.22; GEADE = moderate). The effect was more pronounced in those with depressive symptoms (SMD: −0.57, 95% CI −0.69 to −0.44; n = 15). The greatest reduction occurred at 8000 IU/day (SMD: −2.04, 95% CI −3.77 to −0.31). Trials with follow-up ⩽8 weeks (SMD: −0.45, 95% CI −0.70 to −0.20; n = 8) and 8 to ⩽24 weeks (SMD: −0.47, 95% CI −0.70 to −0.24; n = 15) showed stronger effects compared to those lasting 24 to ⩽52 weeks (SMD: −0.13, 95% CI −0.28 to 0.02; n = 5) or longer than 52 weeks (SMD: 0.14, 95% CI −0.16 to 0.44; n = 3) (p group difference <0.001). Vitamin D 3 supplementation had no significant effects on anxiety symptoms. In summary, this study suggests that vitamin D 3 supplementation may effectively reduce depressive symptoms in short term. Further high-quality trials are warranted for a conclusive assessment of its impact on anxiety. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used widely in industrial and commercial applications. Concerns exist about their potential link to cancer risk as possible endocrine-disrupting chemicals. We conducted a meta-analysis to evaluate the dose-response relationship between PFAS, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS) exposure and risk of breast, prostate, colorectal, and ovarian cancers. We systematically searched major databases through May 2022 and identified 13 observational studies for inclusion. Using random-effects models, we calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) comparing the highest versus lowest PFAS exposure categories. Additionally, we analyzed the dose-response correlation between PFAS and cancer risk in a subset of studies. The study revealed no substantial correlation between exposure to PFASs and the incidence of breast cancer (BC) (ORPFOS = 1.15, 95% CI = 0.91–1.46, ORPFOA = 1.01, 95% CI = 0.68–1.50, ORPFNA = 0.88, 95% CI = 0.64–1.21, ORPFHxS = 1.22, 95% CI = 0.40–3.77, and ORPFDA = 1.29, 95% CI = 0.41–4.10), ovarian cancer (ORPFOA = 1.43, 95% CI = 0.84–2.42), prostate cancer (ORPFOA = 1.05, 95% CI = 0.88–1.26), and colorectal cancer (ORPFOA = 0.77, 95% CI = 0.53–1.12) in the highest versus lowest exposure analysis. However, dose-response analysis showed that for every 1 ng/ml increase in PFNA and 2 ng/ml increase in PFOA, the relative risk for BC decreased significantly (RR 0.67, 95% CI 0.45–0.99 and RR 0.94, 95% CI 0.89–0.98, respectively). Non-linear dose-response analysis found no significant changes in BC risk with increasing PFAS levels. In conclusion, while the highest versus lowest analysis does not support associations between PFAS exposure and the risk of these cancers, linear dose-response analysis suggests potential inverse relationships between PFNA/PFOA levels and BC risk. Further research is warranted on these potential protective effects. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann–Whitney and Kruskall–Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p < 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06–68.48); followed by BPQ, 77.06 nM (IC95%: 70.16–86.01); ID + ELQ316, 197 nM (IC95%:129.0–311.2); ID, 635.1 nM (IC95%: 280.9–2119); and ELQ316, 654.9 nM (IC95%: 362.3–1411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis. [ABSTRACT FROM AUTHOR]

The relative efficacy of various mind–body exercises in the treatment of depressive symptoms remains uncertain. We examined the optimal modalities (Tai Chi, qigong, yoga) and dose of mind–body exercise to improve depressive symptoms in adults. A systematic search of six electronic databases for randomized controlled trials on the relationship between exercise and depression was carried out, encompassing data from their inception up to November 2023. Pairwise analyses, network analyses and dose–response meta‐analyses using random‐effects models were performed to analyse the effect of exercise on depression. Forty studies were included. Results showed that Yoga [standardised mean difference (SMD) = −0.55; 95% confidence interval (CI): (−0.76, −0.35)] was the most effective form of exercise for improving depressive symptoms, followed by Qigong (SMD = −0.52; 95%CI: −0.92, −0.11) and Tai Chi exercise (SMD = −0.42; 95%CI: −0.71, −0.13). In addition, a non‐linear dose–response relationship was found between overall mind–body exercise dose and depression levels and a significant response was observed after 260 METs‐min. Our study examined the effectiveness of different types of mind–body exercise in improving depression and found that yoga may be the most effective adjunctive intervention. There was a non‐linear dose–response relationship between total exercise and depression levels. However, caution should be exercised in interpreting and applying these results. [ABSTRACT FROM AUTHOR]

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients. [ABSTRACT FROM AUTHOR]

This study conducted a rapid review to evaluate active air sampling and analytical methods for characterizing outdoor air microplastics in urban areas. We synthesized information from 35 peer-reviewed journal articles. Studies utilizing active sampling methods were able to provide detailed data on inhalation concentrations and doses. The analytical techniques reviewed were categorized into microscopy, Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), and mass spectrometry, including pyrolysis–gas chromatography (Py-GC). While conventional FTIR and Raman spectroscopy can identify microplastics in total suspended particles, advanced instruments such as µRaman and SEM are crucial for analyzing inhalable microplastics (e.g., particles smaller than 10 µm). Characterizing the shapes and colours of microplastics can provide qualitative estimates of their sources, with fibres and the colour black being the most predominant characteristics. Establishing dose–response relationships for health effects requires quantitative analyses; thus, combining techniques like µRaman with Py-GC is essential for comprehensive human risk assessments. Future studies should focus on identifying and quantifying inhalable microplastic compounds that are relevant to human health. [ABSTRACT FROM AUTHOR]

The International Nuclear Workers Study (INWORKS) contributes knowledge on the dose-response association between predominantly low dose, low dose rate occupational exposures to penetrating forms of ionizing radiation and cause-specific mortality. By extending follow-up of 309,932 radiation workers from France (1968–2014), the United Kingdom (1955–2012), and the United States (1944–2016) we increased support for analyses of temporal variation in radiation-cancer mortality associations. Here, we examine whether age at exposure, time since exposure, or attained age separately modify associations between radiation and mortality from all solid cancers, solid cancers excluding lung cancer, lung cancer, and lymphohematopoietic cancers. Multivariable Poisson regression was used to fit general relative rate models that describe modification of the linear excess relative rate per unit organ absorbed dose. Given indication of greater risk per unit dose for solid cancer mortality among workers hired in more recent calendar years, sensitivity analyses considering the impact of year of hire on results were performed. Findings were reasonably compatible with those from previous pooled and country-specific analyses within INWORKS showing temporal patterns of effect measure modification that varied among cancers, with evidence of persistent radiation-associated excess cancer risk decades after exposure, although statistically significant temporal modification of the radiation effect was not observed. Analyses stratified by hire period (< 1958, 1958+) showed temporal patterns that varied; however, these analyses did not suggest that this was due to differences in distribution of these effect measure modifiers by hire year. [ABSTRACT FROM AUTHOR]

Abstract To examine the dose–response relationship between specific types of exercise for improving walking velocity in Parkinson’s disease (PD). This systematic review and network meta-analysis included searches of PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 18th, 2024. Data analysis was performed using R software with the MBNMA and RJAGS packages. Outcome indicators were measured as mean standard deviation (SMD) along with 95% confidence intervals (95% CrI). The network’s risk of bias was independently evaluated by two reviewers employing the ROB2 tool. Our review encompassed 54 studies with 2,828 PD patients, examining the dose–response effects of different exercises on walking velocity. Aerobic Exercise (AE) demonstrated the greatest improvement at an optimal dose of 1,400 METs-min/week (SMD:1.215, 95% Crl: 0.113 to 2.306). Both Multicomponent Exercise (Mul) (SMD: 1.202, 95% Crl: 0.193 to 2.231) and Sensory Exercise (SE) (SMD: 0.649, 95% Crl: 0.139 to 1.183) showed optimal outcomes at a dose of 1,000 METs-min/week. Resistance Training (RT) was most effective at 750 METs-min/week (SMD:0.778, 95% Crl: 0.062 to 1.549), while Mind–Body Exercise (MBE) yielded significant improvements at a lower optimal dose of 500 METs-min/week (SMD: 0.580, 95% Crl: 0.218 to 1.137), offering valuable insights for exercise prescription in PD management. Various types of exercise showed specific optimal benefits at corresponding doses, among which AE was the most effective in improving the walking speed of PD patients at 1,400 Mets*min/week. Trial registration: PROSPERO (CRD42024506919).

Abstract Objective This study aimed to determine the therapeutic efficacy of tacrolimus (TAC) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on the renal response in systemic lupus erythematosus (SLE) patients. Methods A retrospective cohort study based on medical data was conducted among SLE patients who took at least one of the following medicines in 2010–2021: TAC, MMF and CYC. The odds ratio (OR) and 95% confidence interval (CI) were calculated, and the synergistic interaction was estimated using logistic regression models. Results Among 793 SLE patients, 27.9% patients (221 cases) achieved CR after at least 3 months. The TAC use was positively associated with CR with an adjusted OR (95% CI) of 2.82 (1.89, 4.22) overall and in subgroups of SLE patients with SLEDAI scores > 12, moderate or severe urinary protein and comorbidities. The dose-response effect on CR was also observed at TAC doses greater than 4 mg/d and more than 180 days, with adjusted ORs (95% CIs) of 5.65 (2.35, 13.55) and 3.60 (2.02, 6.41), respectively. Moreover, the combined effect of TAC with MMF or CYC was better than that of monotherapy, there was significant synergistic interactions with adjusted ORs (95% CIs) of 2.43 (1.20, 4.92) and 3.14 (1.49, 6.64), respectively, and similar results were observed for the combination of different doses of TAC with MMF or CYC. Conclusion TAC can effectively alleviate the condition of patients with SLE and may interact with MMF or CYC, which suggests that the combination therapy of TAC with MMF or CYC may produce greater benefits for patients with SLE. Trial registration This is a purely observational study that does not require registration.

Introduction: Epilepsy remains a challenge, with one-third of patients experiencing refractory seizures despite current anti-seizure medications. The nitrergic system, which involves nitric oxide (NO) and NO synthase (NOS) enzymes, plays a complex role in seizure pathophysiology. Pentoxifylline (PTPh), an FDA-approved phosphodiesterase inhibitor, has anticonvulsant effects; however, its relationship with the pathway is unclear. This study focused at how the nitrergic system could be involved in PTPh’s anticonvulsant effects. Methods: Seizures were induced in male mice by intravenous pentylenetetrazole (PTZ) infusion (absence-like seizures), intraperitoneal PTZ injection, and maximal electroshock (generalized tonic-clonic seizures). PTPh was administered at various doses, alone or in combination with the NO precursor L-arginine, as well as non-selective (L-NAME) and selective NOS inhibitors (nNOS inhibitor 7-NI and iNOS inhibitor aminoguanidine). Seizure thresholds, latencies, incidence, and mortality were assessed. Moreover, in the next paradigm, using maximal electroshock model, we evaluate possible protective effects of PTPh against generalized tonic-clonic seizures and subsequent mortality. Results: In the intravenous PTZ model, PTPh (≥150 mg/kg) increased the seizure threshold, potentiated by L-arginine but reduced by L-NAME and 7-nitroindazole. In the intraperitoneal PTZ model, 150 mg/kg PTPh decreased tonic seizure frequency, which was mitigated by aminoguanidine. However, PTPh failed to prolong clonic seizure latency. In the maximal electroshock test, 100 mg/kg PTPh protected against tonic seizure incidence (reduced by aminoguanidine). Although PTPh could not reduce mortality, its combination with L-NAME or 7-nitroindazole increased mortality compared with the vehicle-treated group. Conclusion: PTPh exerted anticonvulsant effects against absence-like and generalized tonic-clonic seizures, likely through modulation of the nitrergic system involving neuronal, endothelial, and inducible NOS isoform. These findings provide novel insights into the complex interplay between NO signaling and the anticonvulsant actions of PTPh, highlighting the potential therapeutic implications of targeting the NO pathway in epilepsy management.

Abstract Background Postoperative rehabilitation exercise is commonly prescribed after total hip arthroplasty (THA), but its efficacy compared to no or minimal rehabilitation exercise has been questioned. Preliminary efficacy would be indicated if a dose-response relationship exists between performed exercise dose and degree of postoperative recovery. The objective was to evaluate the preliminary efficacy of home-based rehabilitation using elastic band exercise on performance-based function after THA, based on the association between performed exercise dose and change in performance-based function (gait speed) from 3 (start of intervention) to 10 weeks (end of intervention) after surgery. Methods A prospective cohort study was conducted. Following primary THA, patients were prescribed home-based rehabilitation exercise using elastic bands. Performed exercise dose (repetitions/week) was objectively measured using attached sensor technology. Primary outcome was change in gait speed (40 m fast-paced walk test). Secondary outcomes included patient-reported hip disability. In the primary analysis, a linear regression model was used. Results Ninety-four patients (39 women) with a median age of 66.5 years performed a median of 339 exercise repetitions/week (1st-3rd quartile: 209–549). Across outcomes, participants significantly improved from 3 to 10-week follow-up. The association between performed exercise dose and change in mean gait speed was 0.01 m/s [95% CI: -0.01; 0.02] per 100 repetitions. Conclusions We found no indication of preliminary efficacy of home-based rehabilitation exercise using elastic bands, as no significant and clinically relevant associations between performed exercise dose and changes in outcomes were present. Trials comparing postoperative rehabilitation exercise with no exercise early after THA are warranted. Trial registration Pre-registered: ClinicalTrials.gov (Identifier: NCT03109821, 12/04/2017).

Objectives: To evaluate and rank the effectiveness of specific non-pharmacological treatments (NPTs) in improving the global cognitive function in individuals with Alzheimer's disease (AD) and to examine the dose-response relationship. Method: We conducted a systematic search in PubMed, MEDLINE, Embase, PsycINFO, CENTRAL, WOS, and CNKI from their inception to 15 February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Results: We included 68 studies involving 5053 participants in this meta-analysis. The treatments with the highest cumulative probabilities for improving global cognitive function were transcranial direct current stimulation (tDCS), followed by physical exercise (PE), and repetitive transcranial magnetic stimulation (rTMS). Additionally, cognitive stimulation (CS), cognitive training CT), multidisciplinary program (MD), and reminiscence treatment (RT) also significantly improve the global cognitive function of people with AD. A non-linear dose-response association was observed for tDCS, PE, rTMS, CS, and CT with global cognitive improvement. Notably, no minimal threshold was identified for the beneficial effects of PE on cognition. The estimated minimal doses for clinically relevant changes in cognition were 33 min per week for tDCS, 330 MET-min per week for PE, and 8000 pulses per week for rTMS. Conclusion: tDCS, PE, and rTMS are the better effective NPTs for enhancing global cognitive function in individuals with AD. Properly dosing these treatments can yield significant clinical benefits. Our findings support the clinical utility of low-dose exercise in improving cognition in people with AD. [ABSTRACT FROM AUTHOR]

Rosmarinic acid is a polyphenol found in numerous fruits and vegetables, consumed in supplement form, and tested in numerous clinical trials for therapeutic applications due to its putative chemopreventive properties. Rosmarinic acid has been extensively studied at the cellular, whole animal, and molecular mechanism levels, presenting a complex array of multi-system biological effects. Rosmarinic acid-induced hormetic dose responses are widespread, occurring in numerous biological models and cell types for a broad range of endpoints. Consequently, this article provides the first assessment of rosmarinic acid-induced hormetic concentration/dose responses, their quantitative features, mechanistic foundations, extrapolative strengths/limitations, and their biomedical, clinical, and public health implications.

Background Stroke, as a major chronic non-communicable disease, seriously affects the health of the nation and imposes a heavy burden on patients, families and society. Alcohol consumption is common in China, and there is a close relationship between alcohol intake and stroke incidence, but the relationship between alcohol intake and stroke incidence is still controversial. Objective To investigate the relationship between alcohol intake and risk of stroke. Methods PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, Wanfang Data, and SinoMed were searched for prospective cohort studies on the relationship between alcohol intake and risk of stroke from inception to December 2023. Literature screening, data extraction, and literature quality evaluation were performed independently by 2 researchers. Stata/MP 17.0 was used for dose-response meta-analysis. Results A total of 16 papers with 548 595 study subjects were included. Meta-analysis results showed that alcohol intake was associated with the risk of stroke (RR=1.17, 95%CI=1.10-1.26, P40 g increased the risk of stroke by 35% (RR=1.35, 95%CI=1.23-1.49, P

Abstract The impact of vitamin B2 (riboflavin) intake on cognitive performance among older adults in the United States (US) remains inadequately understood. This study aimed to explore the association between vitamin B2 intake and cognitive performance among non-institutionalized elderly people in the US. Weighted logistic regression was used to evaluate the association between vitamin B2 intake and cognitive performance. Vitamin B2 intake was determined from the mean of two 24-hour dietary recall interviews. Three cognitive ability assessment tests, namely the Immediate Recall Test (IRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), were performed. Participants included all older adults over 60 who underwent cognitive scoring, with cut-offs defined based on the lowest quartile (25th percentile) for each test (the cut-offs for the three scores were 15.625, 12, and 33, respectively). Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 standard deviation (SD), recommended dietary allowance (RDA), and residual energy model analysis, were performed to solidify the solid association between vitamin B2 and cognitive performance. A total of 2893 individuals aged over 60 were included, with a mean age of 69 (7) years, and 46% were men. There was a significant association between vitamin B2 intake and all three cognitive scores (IRT, Odds Ratio = 0.77, 95% confidence interval: [0.65,0.92]; AFT, 0.75, [0.64,0.88]; DSST, 0.72, [0.59,0.88]). Moreover, vitamin B2 intake above the RDA reduced the risk of low cognitive performance (IRT, 0.66, [0.46,0.93]; AFT, 0.83, [0.62,1.11]; DSST, 0.65, [0.45,0.92]) compared to intake below the RDA. Dose-response curves indicated that higher vitamin B2 intake was negatively associated with the risk of low cognitive performance. Physical activity may modify the association between vitamin B2 and cognitive performance. Vitamin B2 intake was positively associated with cognitive performance among older adults. Adequate vitamin B2 intake could help protect cognitive function.

T-cell engagers (TCEs) represent a promising therapeutic strategy for various cancers and autoimmune disorders. These bispecific antibodies act as bridges, connecting T-cell receptors (TCRs) to target cells (either malignant or autoreactive) via interactions with specific tumour-associated antigens (TAAs) or autoantigens to form trimeric synapses, or trimers, that co-localise T-cells with target cells and stimulate their cytotoxic function. Bispecific TCEs are expected to exhibit a bell-shaped dose-response curve, with a defined optimal TCE exposure for maximizing trimer formation. The shape of the dose-response is determined by a non-trivial interplay of binding affinities, exposure and antigens expression levels. Furthermore, excessively low binding to the TCR may reduce efficacy, but mitigate risk of overstimulating cytokine secretion or induce effector cell exhaustion. These inevitable trade-off highlights the importance of quantitatively understanding the relationship between TCE concentration, target expression, binding affinities, and trimer formation. We utilized a mechanistic target engagement model to show that, if the TCE design parameters are close to the recommended ranges found in the literature, relative affinities for TCR, TAA and target expression levels have qualitatively different, but predictable, effects on the resulting dose-response curve: higher expression levels shift the curve upwards, higher antigen affinity shifts the curve to the left, and higher TCR affinity shifts the curve upwards and to the left. [ABSTRACT FROM AUTHOR]

Findings on the association of dietary intake and tissue biomarkers of linoleic acid (LA) with the risk of prostate cancer are conflicting. Also, no meta-analysis summarized available findings in this regard. Therefore, the current systematic review and dose-response meta-analysis were done to summarize the findings of prospective cohort studies that assessed dietary intake and tissue biomarkers of LA in relation to prostate cancer risk in adults. We conducted a systematic search using online databases, including PubMed, Scopus, and ISI Web of Science, to identify eligible articles published up to January 2023. We included prospective cohort studies that examined the associations of dietary intake and tissue biomarkers of LA with the risk of prostate cancer (total, advanced, and fatal prostate cancer). Summary relative risks (RR) and 95% confidence intervals (CI) were calculated for the highest versus lowest intakes/tissue levels of LA using a fixed-effects model. Also, linear and non-linear dose-response analyses were conducted. In total, 15 prospective cohort studies were included. These studies recruited a total sample size of 511,622 participants with an age range of ≥18 years. During the follow-up periods ranging from 5 to 21 years, 39,993 cases of prostate cancer, 5,929 cases of advanced prostate cancer, and 1,661 cases of fatal prostate cancer were detected. In the meta-analysis, we found that higher tissue levels of LA were associated with a reduced risk of prostate cancer (RR: 0.86, 95% CI: 0.77–0.96) so that in the dose-response analysis, each 5% increase in levels of LA was associated with a 14% lower risk of prostate cancer. Such a significant association was not seen for advanced prostate cancer (RR: 0.86, 95% CI: 0.65–1.13). Also, we found no significant association between dietary intake of LA and risk of total (RR:1.00, 95% CI: 0.97–1.04), advanced (RR: 0.98, 95% CI: 0.90–1.07), and fatal prostate cancer (RR: 0.97, 95% CI: 0.83–1.13). Our findings support the protective association between tissue levels of LA and the risk of prostate cancer in men. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this article is to review interventions that have been shown to improve cognitive abilities in older adults, including aerobic training, resistance training, yoga, tai chi, dual tasking, and meditation. The purpose of this article is to identify findings that can lead to recommendations regarding optimal dosages of the above interventions. Methods: This literature review relied heavily on metaanalyses that combined data from randomized controlled studies in orderto identify interventions that reliably produce meaningful improvements in cognition. In addition, the meta-analyses were used to find dosage recommendations that appeared when similar studies were analyzed. Conclusions: There is ample evidence that various physical exercise and cognitive stimulation interventions can lead to meaningful improvements in cognition. The results often vary as a function of the participants' cognitive abilities and presence of cognitive impairment or dementia. In many cases, it is possible to begin making recommendations in terms of the length of sessions and the length of interventions for various populations. [ABSTRACT FROM AUTHOR]

Athletes in contact and collision sports can sustain frequent subconcussive head impacts. Although most impacts exhibit low kinematics around or below 10 g of head linear acceleration, there is growing concern regarding the cumulative effects of repetitive sports head impacts. Even mild impacts can lead to brain deformations as shown through neuroimaging and finite element modeling, and thus may result in mild and transient effects on the brain, prompting further investigations of the biomechanical dose—brain response relationship. Here we report findings from a novel laboratory study with continuous monitoring of brain activity through electroencephalography (EEG) during controlled soccer head impacts. Eight healthy participants performed simulated soccer headers at 2 mild levels (6 g, 4 rad/s and 10 g, 8 rad/s) and three directions (frontal, oblique left, oblique right). Participants were instrumented with an inertial measurement unit (IMU) bite bar and EEG electrodes for synchronized head kinematics and brain activity measurements throughout the experiment. After an impact, EEG exhibited statistically significant elevation of relative and absolute delta power that recovered within two seconds from the impact moment. These changes were statistically significantly higher for 10 g impacts compared with 6 g impacts in some topographical regions, and oblique impacts resulted in contralateral delta power increases. Post-session resting state measurements did not indicate any cumulative effects. Our findings suggest that even mild soccer head impacts could lead to immediate, transient neurophysiological changes. This study paves the way for further dose-response studies to investigate the cumulative effects of mild sports head impacts, with implications for long-term athlete brain health. [ABSTRACT FROM AUTHOR]

Introduction: Gout is a common type of inflammatory arthritis. Vitamin C is a potent antioxidant that neutralizes reactive oxygen species. However, the association between dietary vitamin C levels and gout remains unclear. This study evaluated the relationship between dietary vitamin C intake and gout. Methods: Cross-sectional data from individuals aged > 20 years who participated in the National Health and Nutrition Examination Survey between 2013 and 2018 were collected. Details on gout, dietary vitamin C intake, and several other essential variables were recorded. Results: There were 12589 participants, 5% (652/12589) of whom experienced gout. Compared with individuals with lower vitamin C consumption in the Q1 group (=19.9 mg/day), the adjusted odds ratio(OR)values for dietary vitamin C intake and gout in the Q2 group (19.9-49.7 mg/day), Q3 group (49.7-110.375 mg/day), and Q4 group (=110.375 mg/day) were 0.87 (95% confidence interval (CI): 0.69-1.1, P = 0.237), 0.81 (95% CI: 0.64-1.02, P = 0.076), and 0.77 (95% CI: 0.6-0.99, P= 0.042), respectively. Accordingly, the association between dietary vitamin C intake and gout exhibited an L-shaped curve (nonlinear, P = 0.245) in a restricted cubic spline. Subgroup analysis revealed significant interactions between vitamin C levels and gout according to sex (P < 0.05). When we used data on dietary vitamin C from the second survey, we observed a similar inverse association between vitamin C intake and gout. The vitamin C was also negatively associated with hyperuricemia (OR, 0.94; 95% CI, 0.9-0.98, P=0.005). Compared with Q1, the adjusted OR values for dietary vitamin C and hyperuricemia in Q2, Q3, and Q4 were 0.77 (95% CI: 0.69-0.86, P = 0.65), 0.81 (95% CI: 0.72-0.91, P = 0.014), and 0.72 (95% CI: 0.64-0.81, P < 0.001), respectively. No association was observed between vitamin C supplementation and gout. Conclusion: The population-based data indicate that dietary vitamin C intake is inversely associated with gout. These findings support the potential role of vitamin C in preventing gout. [ABSTRACT FROM AUTHOR]