UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

Plants must cope with ever-changing temperature conditions in their environment. In many plant species, suboptimal high and low temperatures can induce adaptive mechanisms that allow optimal performance. Thermomorphogenesis is the acclimation to high ambient temperature, whereas cold acclimation refers to the acquisition of cold tolerance following a period of low temperatures. The molecular mechanisms underlying thermomorphogenesis and cold acclimation are increasingly well understood but neither signalling components that have an apparent role in acclimation to both cold and warmth, nor factors determining dose-responsiveness, are currently well defined. This can be explained in part by practical limitations, as applying temperature gradients requires the use of multiple growth conditions simultaneously, usually unavailable in research laboratories. Here we demonstrate that commercially available thermal gradient tables can be used to grow and assess plants over a defined and adjustable steep temperature gradient within one experiment. We describe technical and thermodynamic aspects and provide considerations for plant growth and treatment. We show that plants display the expected morphological, physiological, developmental and molecular responses that are typically associated with high temperature and cold acclimation. This includes temperature dose-response effects on seed germination, hypocotyl elongation, leaf development, hyponasty, rosette growth, temperature marker gene expression, stomatal conductance, chlorophyll content, ion leakage and hydrogen peroxide levels. In conclusion, thermal gradient table systems enable standardized and predictable environments to study plant responses to varying temperature regimes and can be swiftly implemented in research on temperature signalling and response.

BACKGROUND: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation.
OBJECTIVE: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with 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.
RESULTS: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 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 a therapeutic window 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 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing.
CONCLUSIONS: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www.
RESULTS: gov, ID: NCT02410772. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Pharmacoepidemiological 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 non-linear 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-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).

UNASSIGNED: Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method.
UNASSIGNED: A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 μg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis.
UNASSIGNED: The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) μg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups.
UNASSIGNED: The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) μg/kg/min for phenylephrine to prevent SIH.

UNASSIGNED: For cesarean delivery (CD), the 90% effective dosage (ED90) of oxytocin for a first bolus has been established. It is not yet known how much oxytocin to inject into obese women undergoing elective discectomy to keep their uterine tone (UT) appropriate. We hypothesized that patients who are overweight need a greater dose of oxytocin infusion; thus, we aimed to determine how the dose-response curve for oxytocin infusion changes following an initial 1 international unit (IU) bolus in obese women undergoing elective CD.
UNASSIGNED: One hundred parturients with a body mass index (BMI) greater than 30 kg/m2 were randomly assigned to receive an infusion rate of 14, 18, 22, or 26 IU/h of oxytocin. When the uterine palpation is as hard as touching the forehead or tip of the nose, it is considered sufficient UT according to the criteria used by obstetricians. The median effective dose (ED50) and ED90 values were determined using probit analysis.
UNASSIGNED: We found the ED50 and ED90 values for the infusion dose of oxytocin were around 11.0 IU/h and 19.1 IU/h, respectively. Each group had a different number of parturients who needed rescued oxytocin: 14 IU/h for six, 18 IU/h for three, one for 22 IU/h, and none for 26 IU/h. The correlation between the frequency of rescued oxytocin administration and the amount of oxytocin infusion needed to avoid uterine atony was statistically significant (p = 0.02).
UNASSIGNED: The present research showed that the most effective dosage of oxytocin infusion for obese parturients undergoing elective CD is 19.1 IU/h, following an initial loading dose of 1 IU. Patients with obesity should receive a greater dosage of prophylactic oxytocin, and further studies comparing patients with and without obesity (with higher BMI) are required.
UNASSIGNED: https://www.chictr.org.cn/showproj.html?proj=159951, identifier ChiCTR2200059582.

BACKGROUND: Pressure injuries (PIs) are one of the leading potentially preventable hospital-acquired complications associated with prolonged hospital length, poor quality of life and financial burden. The relationship between body mass index (BMI) and PIs occurrence is controversial.
OBJECTIVE: The aim of this study was to further examine relationships between BMI and PIs occurrence in hospitalized patients.
METHODS: A multi-center prospective study.
METHODS: 39 hospitals located in northwest China from April 2021 to July 2023.
METHODS: 175,960 hospitalized patients aged over 18 years were enrolled, and 170,800 patients were included in the final analysis.
METHODS: BMI and clinical characteristics were assessed at baseline. PIs assessment were performed by trained nurses, with data recorded for the presence, the location and stage of each PI. For staging PIs, the National Pressure Ulcer Advisory Panel（NPUAP） staging system were used. The multivariate logistic regressions analysis and restricted cubic splines (RCS) models were used to explore associations between BMI and PIs, adjusting for potential confounders.
RESULTS: Of 175,960 participants, 5160 were excluded from analyses. The multivariate logistic regression model identified a positive relationship between under-weight BMI and risk of PIs occurrence (OR = 1.60, 95% CI:1.18-2.17). We also found U shaped association between BMI and PIs occurrence (non-linear P < 0.001). BMI less than 23 kg/m2 significantly increased risk of PIs, and there was a tendency to increase risk of PIs at BMI higher than 30 kg/m2. We stratified participants by sex to further investigate their association and found the risk of PIs increases substantially in women at BMI below 17 kg/m2 and in men at BMI below 23 kg/m2.
CONCLUSIONS: The present study indicated that there was an approximate U shaped relationship between BMI and PIs occurrence, and this association was potentially different between men and women.

This study is the first to report 50% and 95% effect-site concentrations (EC50 and EC95, respectively) of the new short-acting benzodiazepine, remimazolam, for the successful insertion of i-gels with co-administration of fentanyl. Thirty patients (38 ± 5 years old, male/female = 4/26) were randomly assigned into five groups to receive one of five different remimazolam doses (0.1, 0.15, 0.2, 0.25, and 0.3 mg/kg bolus followed by infusion of 1, 1.5, 2, 2.5, and 3 mg/kg/h, respectively, for 10 min), which were designed to maintain a constant effect-site concentration of remimazolam at the time of i-gel insertion. At 6 min after the start of remimazolam infusion, all patients received 2 µg/kg fentanyl. i-gel insertion was attempted at 10 min and the success or failure of insertion were assessed by the patient response. Probit analysis was used to estimate the EC50 and EC95 values of remimazolam with 95% confidence intervals (CIs). In the five remimazolam dose groups, two, two, four, five, and six of the six patients in each group had an i-gel successfully inserted. Two patients in the lowest remimazolam dose group were conscious at the time of i-gel insertion and were counted as failures. The EC50 and EC95 values of remimazolam were 0.88 (95% CI, 0.65-1.11) and 1.57 (95% CI, 1.09-2.05) µg/ml, respectively. An effect-site concentration of ≥ 1.57 µg/ml was needed to insert an i-gel using remimazolam anesthesia, even with 2 µg/kg fentanyl. Trial registration: The study was registered in Japan Registry of Clinical Trials on 19 April 2021, Code jRCTs041210009.

Background: Previous studies have explored the median effective concentration (EC50) of ropivacaine for labor epidural analgesia in parturients with obesity. However, the clinical relevance of the 90% effective concentration (EC90) remains unclear. This study aimed to determine and compare the dose-response curve of epidural ropivacaine for labor analgesia between parturients with and without obesity. Methods: Parturients were divided into two groups based on body mass index (BMI): group N, consisting of parturients with BMI <30 kg/m2, and group O, consisting of parturients with BMI >30 kg/m2. Within each group, the patients were randomized to receive one of five concentrations (0.0375%, 0.075%, 0.1125%, 0.15%, or 0.1875%) of epidural ropivacaine for labor analgesia. Analgesia was induced with a loading dose of 15 mL of the assigned concentration. Visual analogue scale (VAS) scores were recorded at baseline and 30 min post-dose to calculate the response (%) using the formula [(baseline VAS pain score-VAS pain score at 30 min)/baseline VAS pain score] ×100%. The EC50 and EC90 values were determined via nonlinear regression analysis. Results: The EC50 and EC90 values of ropivacaine were 0.061% (95% confidence interval [CI], 0.056%-0.066%) and 0.177% (95% CI, 0.152%-0.206%) in group N and 0.056% (95% CI, 0.051%-0.061%) and 0.161% (95% CI, 0.138%-0.187%) in group O, respectively. No significant differences were observed in the EC50 and EC90 values between the two groups (p-values = 0.121 and 0.351, respectively. Conclusion: In conclusion, within the parameters of this study, our findings suggest that obesity, characterized by a mean BMI value of 30.9, does not significantly influence the EC50 and EC90 values of epidural ropivacaine for labor analgesia. Further investigations are warranted to elucidate the dose-response relationship between ropivacaine and obesity with higher BMI values. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=190747, Identifier ChiCTR2300073273.

OBJECTIVE: Subjective cognitive decline represents a critical stage for preventing mild cognitive impairment and dementia, but the links between clinical progression in the subjective cognitive decline stage and various motor functions remain inconclusive. This cohort study aimed to elucidate the independent and joint associations between the clinical progression of subjective cognitive decline and motor functions.
METHODS: We enrolled 4880 community-dwelling elderly participants from a national cohort and used Cox proportional hazard regression model and restricted cubic spline models to explore the longitudinal associations between motor functions (gait, strength, balance, and endurance) and the clinical progression of subjective cognitive decline.
RESULTS: During 5-years follow-up, 1239 participants experienced clinical progression. After adjusting for demographics, vascular burden, body components, and polypharmacy, gait speed [hazard ratios (HRs)= 0.96, 95% confidence interval (CI) 0.94-0.99], chair stand test (HRs=1.02, 95%CI 1.01-1.03), and endurance limitation in jogging 1 kilometer (HRs=1.18, 95%CI 1.04-1.34) were significantly associated with clinical progression. Among all participants, individuals characterized by poor upper- and lower-body strength, as well as those with slow pace and reduced endurance, faced the highest risk of cognitive impairment.
CONCLUSIONS: This study emphasizes the potential of gait speed, muscle strength, and endurance as non-cognitive indicators of clinical progression in subjective cognitive decline. Understanding their combined effectiveness may reveal primary physiological mechanisms contributing to the dual decline of motor and cognition.