Association between fat-soluble vitamins and metabolic syndromes in US adults: a cross-section study from NHANES database.

BACKGROUND: Previous studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It's necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years. METHODS: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003-2006 and 2017-2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose-response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components. RESULTS: The presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose-response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels. CONCLUSION: Findings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds.

Dose-response relationship between body mass index and hypertension: A cross-sectional study from Eastern China.

Background: A high body mass index (BMI) increases the risk of hypertension. However, little is known about the dose-dependent association between BMI and hypertension. Therefore, this study investigated the prevalence of hypertension in 7568 subjects from the Jiangsu Province, Eastern China, and analyzed the dose-response relationship between BMI and hypertension risk. Methods: The eligible subjects completed a structured questionnaire and clinical biochemical indicators were measured according to standardized protocols. Multivariate logistic regression models were used to evaluate the association between BMI and hypertension. Restricted cubic spline (RCS) analysis was used to analyze the dose-response relationship between BMI and hypertension risk. Moreover, sensitivity analysis was performed to verify the robustness of our findings. Results: The prevalence of hypertension was 35.3 % in the total population. BMI was significantly associated with systolic and diastolic blood pressure. The fully-adjusted odds ratio (OR) with 95 % confidence interval (CI) for hypertension was 1.17 (1.15, 1.19) for every 1 kg/m2 increase in BMI. Furthermore, the OR (95 % CI) for hypertension in the highest BMI group (Obesity) was 4.14 (3.45, 4.96) after adjusting for covariates compared with the normal group. Multivariable adjusted RCS analysis showed a positive and linear dose-response relationship between BMI and hypertension risk both in male and female populations (all P for non-linearity > 0.05). Conclusion: Our study demonstrated a positive and linear dose-response relationship between BMI and the risk of hypertension. The results of this study provide evidence for BMI-related clinical interventions to reduce the risk of hypertension.

Association between PFAS exposure and thyroid health: A systematic review and meta-analysis for adolescents, pregnant women, adults and toxicological evidence.

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python.

Drug and biomarker tissue levels in a randomized presurgical trial on exemestane alternative schedules.

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a pre-surgical study of alternative exemestane schedules. Postmenopausal women candidate for breast surgery for estrogen receptor-positive breast cancer were randomized to exemestane 25 mg once daily (QD), 25 mg three times/week (TIW), or 25 mg per/week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in non-malignant tissue. Estradiol was nearly suppressed in all groups in the non-malignant tissue (QD vs TIW p = .364 and QD vs QW p = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in non-malignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy.

Effects of N-acetylcysteine on hepatocellular carcinoma in chronic hepatitis C.

Hepatitis C virus (HCV) infection significantly contributes to global hepatocellular carcinoma (HCC) incidence. N-Acetylcysteine (NAC), known for its antioxidant properties, is a potential therapeutic agent. However, evidence on its efficacy in reducing HCC risk among HCV patients is limited. A retrospective cohort analysis using Taiwan's National Health Insurance Research Database (2008-2018) included ≥18-year-old HCV patients. NAC usage (≥28 cumulative defined daily doses [cDDDs]) was assessed for its association with HCC risk using Cox regression models and propensity score matching. The study comprised 269,647 HCV patients, with detailed NAC dosage characterization and hazard ratios (HRs) for HCC risk. Post-matching, NAC usage emerged as the significant predictor of reduced HCC risk (adjusted HR: 0.39, 95% CI: 0.37-0.41, P<0.0001). Dose-response analysis showed reduced HCC risk with increasing cDDDs of NAC (P<0.0001). Higher daily NAC dosage (≥1 DDD) was associated with significantly lower HCC risk (adjusted HR: 0.33, 95% CI: 0.31-0.36, P<0.0001). The study provides compelling evidence for NAC's potential in reducing HCC risk among HCV patients. Insights into dose-dependent effects and optimal daily intensity thresholds offer valuable directions for future therapeutic strategies and clinical trials targeting HCC burden in HCV-infected individuals.

Association of norepinephrine with pressure ulcer development in critically ill patients with COVID-19-related acute respiratory distress syndrome: A dose-response analysis.

OBJECTIVES: To investigate the correlation between varying doses of norepinephrine (NE) and the incidence of pressure injuries (PIs) in COVID-19 patients in intensive care units (ICUs). DESIGN: A retrospective multicenter study was conducted on 1,078 COVID-19 patients admitted to ICUs with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. The research spanned from March 2020 to April 2021 across five university-affiliated hospitals in Iran. Univariate and multivariate binary logistic regression analyses, along with linear and non-linear dose-response assessments, were utilized to evaluate the relationship between NE dosages and the probability of PI development. FINDINGS: The multivariate analysis revealed a significant association between higher doses of NE administered over 24 h (OR: 1.832, 95 % CI: 1.218-2.754, P=0.004) and cumulative doses (OR: 1.408, 95 % CI: 1.204-1.975, P=0.048) with the occurrence of PIs. Moreover, patients receiving high NE doses had a nearly fourfold increased risk of developing PIs, regardless of PIs stage, compared to those on low or moderate doses (>15 µg/min vs. ≤ 15 µg/min; OR: 4.401, 95 % CI: 3.339-5.801, P=0.001). Although the linear dose-response analysis did not show a significant correlation between NE doses (µg/min) and PI development (P>0.05), the non-linear analysis indicated that NE doses ≤ 9 µg/min were associated with a reduced risk of PI development. CONCLUSION: Maintaining NE infusion within the range of 1-9 µg/min appears to be most effective in reducing the likelihood of PIs in ICU patients with COVID-19. Lower NE doses (≤9 µg/min) were associated with a lower risk of PI development, suggesting that factors beyond NE dosage or the use of other vasopressors may play a crucial role in PI formation in this patient cohort. IMPLICATIONS FOR CLINICAL PRACTICE: Rather than suggesting a specific threshold, clinicians should consider further studies to determine the optimal dose that balances microvascular perfusion and patient outcomes. It is crucial to comprehensively evaluate additional factors and selectively use vasopressors. Individualized care, including regular monitoring and personalized treatment plans, is essential for achieving the best outcomes in this patient population.

Testing for similarity of multivariate mixed outcomes using generalized joint regression models with application to efficacy-toxicity responses.

A common problem in clinical trials is to test whether the effect of an explanatory variable on a response of interest is similar between two groups, for example, patient or treatment groups. In this regard, similarity is defined as equivalence up to a pre-specified threshold that denotes an acceptable deviation between the two groups. This issue is typically tackled by assessing if the explanatory variable's effect on the response is similar. This assessment is based on, for example, confidence intervals of differences or a suitable distance between two parametric regression models. Typically, these approaches build on the assumption of a univariate continuous or binary outcome variable. However, multivariate outcomes, especially beyond the case of bivariate binary responses, remain underexplored. This paper introduces an approach based on a generalized joint regression framework exploiting the Gaussian copula. Compared to existing methods, our approach accommodates various outcome variable scales, such as continuous, binary, categorical, and ordinal, including mixed outcomes in multi-dimensional spaces. We demonstrate the validity of this approach through a simulation study and an efficacy-toxicity case study, hence highlighting its practical relevance.

Pharmacokinetics of trastuzumab and its efficacy and safety in HER2-positive cancer patients.

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.

Optimal methods of vitamin D supplementation to prevent acute respiratory infections: a systematic review, dose-response and pairwise meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10). CONCLUSION: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.

Vitamin D and Cognitive Performance in Older Adults: A Cross-Sectional and Mendelian Randomization Study.

Background: Cognitive decline is a prevalent health problem in older adults, and effective treatments remain to be produced. Serum vitamin D, a commonly used biochemical marker, is widely recognized as an indicator of various diseases. Existing research has not fully elucidated the relationship between vitamin D and cognitive function. The aim of this study is to investigate the real relationship between vitamin D and cognitive function and to identify indicators that have a strong predictive effect on cognitive decline. Methods: At first, we used the dataset of the genome-wide association studies studying vitamin D and cognitive performance to conduct Mendelian randomization analysis. Subsequently, we employed linear regression and smooth curve fitting methods to assess the relationship using the National Health and Nutrition Examination Survey data. Finally, we investigated other predictive features of cognitive performance utilizing a machine learning model. Results: We found that a 1-unit increase in vitamin D is associated with a 6.51% reduction (P < .001) in the risk of cognitive decline. The correlation between vitamin D and cognitive performance is nonlinear, with the inflection point at 79.9 nmol/L (left: ß = 0.043, P < .001; right: ß = -0.007, P = .420). In machine learning, the top 5 predictors are vitamin D, weight, height, age, and body mass index. Conclusion: There is a causal relationship between vitamin D and cognitive performance. 79.9 nmol/L could be the optimal dose for vitamin D supplementation in the elderly. Further consideration of other factors in vitamin D interventions is necessary.

Effects of the intensity, duration and muscle mass factors of isometric exercise on acute local muscle hemodynamic responses and systematic blood pressure regulation.

Isometric exercise is a non-pharmacologic intervention to improve muscle hemodynamic responses and blood pressure in humans. However, the effects of intensity, duration, and muscle mass factors of isometric exercise on local muscle hemodynamic responses and systemic blood pressure regulation have not been studied. The purpose of this study was to assess whether various modes of isometric exercise could induce various levels of muscle hemodynamic responses that are related to the blood pressure changes. Near-infrared spectroscopy was used to assess muscle hemodynamic responses after 4 isometric exercise protocols in 20 healthy adults. One-way analysis of variance (ANOVA) with repeated measures was used to assess the effect of factors of isometric exercise on oxyhemoglobin, deoxy-hemoglobin, blood volume, and oxygenation. For oxygenation, the lowest mean was recorded for the unilateral isometric handgrip exercise at 30% of MVC for 2 min (-0.317 ± 0.379 µM) while the highest mean was observed for the isometric wall squat (1.496 ± 0.498 µM, P < 0.05). Additionally, both the bilateral isometric handgrip exercise at 30% MVC for 1 min (1.340 ± 0.711 µM, P < 0.05) and the unilateral isometric handgrip exercise at 20% MVC for 3 min (0.798 ± 0.324 µM, P < 0.05) are significantly higher than 30% of MVC for 2 min. Blood pressure showed an inverse trend with oxygenation changes of the forearm muscle. The study indicates that the duration and muscle mass of isometric exercise are more effective on oxygenation responses and systematic blood pressure regulation, and suggests that the local muscle oxygenation factor following isometric contractions may mediate systematic blood pressure regulation.

Oocyte maturation, blastocyst and embryonic development are mediated and enhanced via hormesis.

The present paper provides the first integrative assessment of the capacity of dietary, endogenous and other agents to induce hormetic dose responses in oocytes, their supportive cells such as granulosa cells, blastocyst formation and early stage embryo development with the goal of improving fertility and reproductive success. The analysis showed that numerous agents enhance oocyte maturation and blastocyst/embryonic development in an hormetic fashion. These findings indicate that numerous agents improve oocyte-related biological functioning under normal conditions as well as enhancing its capacity to prevent damage from numerous chemical toxins and related stressor agents, including heat and age-related processes in pre-post conditioning and concurrent exposures. The present assessment suggests that hormetic-based lifestyles and dietary interventions may offer the potential to enhance healthy reproductive performance with applications to animal husbandry and human biology. The present findings also significantly extend the generality of the hormesis dose response concept to multiple fundamental biological processes (i.e., oocyte maturation, fertilization and blastocyst/embryo development).

Dose-dependent dynamics of densovirus infection in two nymphalid butterfly species utilizing native or exotic host plants.

Insects are attacked by a diverse range of microbial pathogens in the wild. In herbivorous species, larval host plants frequently play a critical role in mediating susceptibility to infection. Characterizing such plant-mediated effects on herbivore-pathogen interactions can provide insight into patterns of infection across wild populations. In this study, we investigated the effects of host plant use by two North American butterflies, Euphydryas phaeton (Nymphalidae) and Anartia jatrophae (Nymphalidae), on entomopathogen infection across a range of three doses. Both of these herbivores recently incorporated the same exotic plant, Plantago lanceolata (Plantaginaceae), into their host range and are naturally infected by the same entomopathogen, Junonia coenia densovirus (Parvoviridae), in wild populations. We performed two factorial experiments in which E. phaeton and A. jatrophae were reared on either P. lanceolata or a native host plant [Chelone glabra (Plantaginaceae) for E. phaeton; Bacopa monnieri (Plantaginaceae) for A. jatrophae] and inoculated with either a low, medium, or high dose of the virus. In E. phaeton, the outcomes of infection were highly dose-dependent, with inoculation with higher viral doses resulting in faster time to death and greater mortality. However, neither survival nor postmortem viral burdens varied depending upon the host plant that was consumed. In contrast, host plant use had a strong effect on viral burdens in A. jatrophae, with consumption of the exotic plant appearing to enhance host resistance to infection. Together, these results illustrate the variable influences of host plant use on herbivore resistance to infection, highlighting the importance of investigating plant-herbivore relationships within a tritrophic framework.

A dose-response correlation between smoking and severity of acute pancreatitis: a propensity score-matched study.

Background: Acute pancreatitis, among the most prevalent gastrointestinal disorders, exhibits a continual rise in its incidence recent years. This study endeavor to explore the correlation between smoking exposure and the severity of acute pancreatitis (AP). Methods: Five hundred and eight patients diagnosed as acute pancreatitis (AP) were included in our data analysis. Patients were categorized based on their smoking pack-years into four groups: light, moderate, heavy, and non-smokers. Outcomes were classified as two: "mild acute pancreatitis (MAP)" and "moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP)". We conducted propensity score matching (PSM) to adjust confounding factors and multivariable logistic regression analysis to determine adjusted odds ratios and 95% confidence intervals. Additionally, a dose-dependent association analysis between smoking exposure and the incidence rate of "MSAP or SAP" was performed. Results: Smokers exhibited a higher risk of "MSAP or SAP" compared to non-smokers, both before (17.1 vs. 54.9%, p < 0.001) and after (9.4 vs. 24.7%, p < 0.001) PSM. With an area under the ROC curve of 0.708, smoking showed a moderate level of predictive ability. Furthermore, propensity score matching analysis showed that patients who smoked compared to non-smokers had significantly higher risks of "MSAP or SAP" for light smoking (OR 3.76, 95% CI 1.40-10.07, p = 0.008), moderate smoking (OR 4.94, 95% CI 2.23-10.92, p < 0.001), and heavy smoking (OR 8.08, 95% CI 3.39-19.25, p < 0.001). Conclusion: Smoking is an independent risk factor that can raise the severity of pancreatitis. Moreover, the severity of acute pancreatitis escalates in tandem with the accumulation of pack-years of smoking.

Optimal modalities and doses of mind-body exercise for depressive symptoms in adults: A systematic review of paired analyses, network analyses and dose-response meta-analyses.

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.

Determining the In Vitro Ligand-Target Interaction by Cellular Thermal Shift Assay and Isothermal Dose-Response Fingerprint Assay.

The cellular thermal shift assay (CETSA) and isothermal dose-response fingerprint assay (ITDRF CETSA) have been introduced as powerful tools for investigating target engagement by measuring ligand-triggered thermodynamic stabilization of cellular target proteins. Yet, these techniques have rarely been used to evaluate the thermal stability of RNA-binding proteins (RBPs) when exposed to ligands. Here, we present an adjusted approach using CETSA and ITDRFCETSA to determine the interaction between enasidenib and RBM45. Our assay is sensitive and time-efficient and can potentially be adapted for studying the interactions of RBM45 protein with other potential candidates. Key features • This protocol builds upon the method developed by Molina et al. and extends its application to new protein classes, such as RBPs.

Association of serum 25-hydroxyvitamins D2 and D3 with hearing loss in US adults: analysis from National Health and Nutrition Examination Survey, 2015-2016.

Background: Hearing loss (HL) is increasingly recognized as a significant global public health issue, and research on its relationship with vitamin D levels has gained wider attention. However, the association between serum biomarkers 25-hydroxyvitamin D2 (25(OH)D2) and D3 (25(OH)D3) with different types of HL remains unclear. This study aimed to investigate the potential association of serum 25(OH)D2 and 25(OH)D3 with HL in US adults. Methods: A sample of 3,684 individuals aged 20-69 years from the 2015-2016 National Health and Nutrition Examination (NHANES) was analyzed in this study. HL was defined as a pure tone average > 25 dB in either ear at low frequencies (500, 1,000, 2000 Hz), speech frequencies (500, 1,000, 2000, 4,000 Hz), and high frequencies (3,000, 4,000, 6,000, 8,000 Hz). Logistic regression was employed to examine the association between serum 25(OH)D2 and 25(OH)D3 and HL. The study population was then stratified by age, gender, race, and education level to analyze potential differences between adults in different subgroups. Results: In the multivariate analysis, it was found that serum 25(OH)D2 was independently associated with low-frequency hearing loss (LFHL) (OR: 1.012 [95% CI, 1.005-1.020]) and speech-frequency hearing loss (SFHL) (OR: 1.011 [95% CI, 1.003-1.018]). Restrictive cubic spline analysis demonstrated a linear dose-response relationship between serum 25(OH)D2 levels and LFHL (p for linearity <0.001), as well as SFHL (p for linearity = 0.001). Conversely, an L-shaped association was observed between serum 25(OH)D3 levels and both LFHL (p for nonlinearity = 0.014) and SFHL (p for nonlinearity = 0.025), with threshold values identified at 35.3 and 36.5 nmol/L, respectively. Higher levels of serum 25(OH)D3 were associated with a lower probability of high-frequency hearing loss (HFHL) (OR: 0.994 [95% CI, 0.989-0.999]), with a threshold value identified at 53.9 nmol/L. Furthermore, a significant interaction between diabetes and serum 25(OH)D2 in LFHL was revealed through subgroup analysis (p = 0.041). In the non-diabetic population, serum 25(OH)D2 maintained its association with LFHL. Conclusion: Our findings suggested a positive association between serum 25(OH)D2 concentrations and both LFHL and SFHL in the studied cohort. Additionally, an L-shaped relationship was found between serum 25(OH)D3 and LFHL and SFHL, and higher levels of serum 25(OH)D3 were identified to be associated with a lower risk of HFHL.

Immediate and Transient Perturbances in EEG Within Seconds Following Controlled Soccer Head Impact.

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.

A Skin Testing Strategy for Non-IgE-Mediated Reactions Associated With Vancomycin.

BACKGROUND: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2, is the primary vancomycin-induced immediate drug reaction. Clinically, distinguishing the underlying drug-induced immediate drug reaction mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction. OBJECTIVE: To determine whether intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects. METHODS: This was a cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Data on demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose-response EC50, IDT-related local symptoms, and BAT results were compared between groups. RESULTS: A total of 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose-response mean EC50 was 328 µg/mL (95% CI, 296-367) in the VIR versus 1166 µg/mL (95% CI, 1029-1379) in the tolerant group (P < .0001). All VIR subjects reported IDT-related local pruritus compared with 60% of tolerant subjects (P = .0185). The %CD63+ basophils were consistently less than 2%, without significant differences between groups (P < .54). CONCLUSIONS: Variations in skin test methodologies could help identify other immediate drug reaction mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.