Optimal dose and type of exercise to improve cognitive function in patients with mild cognitive impairment: a systematic review and network meta-analysis of RCTs.

Background: Mild cognitive impairment (MCI) represents a prodromal stage of dementia, characterized by cognitive decline exceeding that expected with normal aging. Exercise interventions have emerged as a promising approach to counter functional decline and enhance cognitive function in the elderly MCI population. However, the optimal exercise modalities and dosage (dose-response relationship) are understudied. Objective: It aims to determine the most effective exercise modality for MCI patients by optimizing the dose-response relationship to ensure sufficient intensity to induce positive neurological adaptations. Methods: A systematic search of electronic databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception to April 15, 2024. Studies evaluating the efficacy of exercise interventions in MCI participants were included. Primary outcomes of interest are global cognition and executive function. Random-effects models will be utilized for both pairwise and network meta-analysis. Results: Following the application of specific inclusion and exclusion criteria, a total of 42 articles, encompassing 2832 participants, were chosen for inclusion in a network meta-analysis. The findings revealed that multi-component exercise demonstrated superior efficacy in mitigating the deterioration of global cognition, as evidenced by standard mean differences (SMDs) of 1.09 (95% CI: 0.68 to 1.51) compared to passive controls. Additionally, multi-component exercise exhibited a significant impact on executive function, with SMDs of 2.50 (95% CI: 0.88 to 4.12) when contrasted with passive controls. Our research has demonstrated that sessions lasting 30 minutes, occurring 3-4 times per week, with interventions lasting 12-24 weeks and an intensity of 60-85% of maximum heart rate, yield higher effect sizes in improving global cognition. However, sessions lasting 30-61 minutes, with interventions lasting 25 weeks or longer, show greater effectiveness in enhancing executive function. Conclusion: A network meta-analysis identified multi-component exercise as the most effective intervention for improving global cognitive and executive function in patients with mild cognitive impairment. Notably, moderate-intensity exercise performed at least three times weekly appears beneficial, with evidence suggesting shorter sessions and higher frequencies may optimize cognitive outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024534922.

Life table analysis and RNA-Seq reveal hormesis and transgenerational effects of deltamethrin on Aphis gossypii.

BACKGROUND: Deltamethrin, as a highly effective and broad-spectrum insecticide, has been widely used for agricultural pest control such as Aphis gossypii worldwide. Increasing evidence has shown that despite great economic benefits brought by it, deltamethrin has also non-negligible side effects. However, the potential risks and related molecular mechanisms remain largely unclear. RESULTS: Herein, the life table parameters and transcriptome sequencing analyses of the four successive aphid generations were performed to investigate the hormesis and transgenerational effects of deltamethrin on A. gossypii. The life table analysis showed that although the exposure of G0 aphid to 30% lethal concentration (LC30) deltamethrin significantly reduced the net reproduction rate (R0), intrinsic rate of increase (r), and fecundity of G0, but it significantly enhanced the R0 and fecundity of subsequent two generations (G1 and G2) of A. gossypii. Moreover, transcriptomic analyses showed that the signaling pathways related to posttranscriptional regulation (spliceosome), protein processing, longevity regulating, and cell proliferation (DNA replication, homologous recombination and non-homologous end-joining) were significantly up-regulated in G1 or G2 under LC30 deltamethrin treatment. Additionally, we also found that the deltamethrin-sulfoxaflor rotation of G0 and G1 still induced reproductive stimulation, but the reproductive stimulation induced by insecticides rotation treatment was significantly lower than that in the deltamethrin exposure alone. CONCLUSION: Our study demonstrates that sublethal concentrations of deltamethrin significantly enhanced the offspring fecundity of cotton aphid. In addition, our study also reveals the transcriptional response mechanism of hormesis-induced fecundity increase, providing valuable reference for optimizing the application of deltamethrin in integrated pest management. © 2024 Society of Chemical Industry.

Short Course Brachytherapy in Locally Advanced Cervical Cancer; Safety and Response Rate.

OBJECTIVE: Overall treatment time (OTT) is an important index for local control in patients with locally advanced| cervical cancer treated with definitive chemoradiation (External Beam Radiation Therapy (EBRT), Brachytherapy (BT) and concomittant chemotherapy). This study aimed to evaluate the efficiency and safety of reducing OTT by shortening the brachytherapy duration to one week in the intervention group copared to three weeks in the control group. METHOD: The study was a non-randomized open-label phase II clinical trial, carried out on 49 cervical cancer patients (26 in intervention grouop and 23 in control group) who received EBRT concomitant with Cisplatin, followed by brachytherap in order to deliver 60 Gy  equivalent total doses in 2-Gy fractions (EQD2) to Intermediate Risk-Clinical Tumor Volume (IR-CTV) and 85-90 Gy EQD2 to High Risk-Clinical Tumor Volume (HR-CTV). In the intervention group, all brachytherapy sessions were performed in 1 week, while for the control group, it was administrated in 3 consecutive weeks. The participants were followed (Minimum follow up time was 6 month and median follow up time was 10 month) to assess response and toxicity of the treatment. RESULTS: Overall, more than 95% of study participants had a complete response and more than 4.0% reported partial response, and no treatment failure was observed. The complete response in intervention and control groups was 96.1% and 95.6%, respectively (P value > 0.05). There was no difference in acute toxicity between the two groups. CONCLUSION: considering that short course brachytherapy was non inferior to conventional course from point of  Response Rate and Side Effects during follow up time; so this strategy can be  considered as an option for reducing the OTT which can at least cause decreasing the costs. Studies with larger sample size and phase 3 are recommended.

Optimizing the detection of N-nitrosamine mutagenicity in the Ames test.

Accurately determining the mutagenicity of small-molecule N-nitrosamine drug impurities and nitrosamine drug substance-related impurities (NDSRIs) is critical to identifying mutagenic and cancer hazards. In the current study we have evaluated several approaches for enhancing assay sensitivity for evaluating the mutagenicity of N-nitrosamines in the bacterial reverse mutagenicity (Ames) test. Preincubation assays were conducted using five activation conditions: no exogenous metabolic activation and metabolic activation mixes employing both 10% and 30% liver S9 from hamsters and rats pretreated with inducers of enzymatic activity. In addition, preincubations were conducted for both 60 minutes and 30 minutes. These test variables were evaluated by testing 12 small-molecule N-nitrosamines and 17 NDSRIs for mutagenicity in Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537, and Escherichia coli strain WP2 uvrA (pKM101). Eighteen of the 29 N-nitrosamine test substances tested positive under one or more of the testing conditions and all 18 positives could be detected by using tester strains TA1535 and WP2 uvrA (pKM101), preincubations of 30 minutes, and S9 mixes containing 30% hamster liver S9. In general, the conditions under which NDSRIs were mutagenic were similar to those found for small-molecule N-nitrosamines.

Dose Effect of Polyethylene Microplastics Derived from Commercial Resins on Soil Properties, Bacterial Communities, and Enzymatic Activity.

Soils are the largest reservoir of microplastics (MPs) on earth. Since MPs can remain in soils for a very long time, their effects are magnified. In this study, different concentrations of polyethylene (PE) MPs derived from commercial resins (0%, 1%, 7%, and 14%, represented as MP_0, MP_1, MP_7, and MP_14) were added to soils to assess the changes in the soils' chemical properties, enzyme activities, and bacterial communities during a 70-day incubation period. The results show that PE MP treatments with low concentrations differed from other treatments in terms of exchangeable Ca and Mg, whereas at high concentrations, the pH and availability of phosphate ions differed. Fluorescein diacetate (FDA), acid phosphatase (ACP), and N-acetyl-ß-d-glucosaminidase (NAG) enzyme activities exhibited a dose-related trend with the addition of the PE MPs; however, the average FDA and ACP activities were significantly affected only by MP_14. Changes in the microbial communities were observed at both the phylum and family levels with all PE MP treatments. It was revealed that even a low dosage of PE MPs in soils can affect the functional microbes, and a greater impact is observed on those that can survive in polluted environments with limited resources.

A Dose-Response Study on the Relationship between White Meat Intake and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Southern Italy: Results from the Nutrihep Study.

(1) Background: Metabolic dysfunction-associated liver disease (MASLD) is one of the most important causes of liver disease worldwide. Meat consumption is a growing trend and white meat has been shown to have beneficial effects on cardiometabolic risk factors. The aim of this study was to investigate the dose-response relationship between white meat intake and MASLD at survey level in a Southern Italy setting. (2) Methods: This cross-sectional study encompassed 1192 subjects (509 males, 42.7%) without missing data from the second wave of the NUTRIHEP cohort (2014-2016). Adjusted dose-response modeling was employed for statistical analysis; (3) Results: There were 587 subjects with MASLD (49.2%), i.e., 278 males (54.6%) and 309 females (45.2%). By increasing the intake, an unfavorable influence of white meat on MASLD was significantly revealed in females, whereas a protective effect of white meat was detectable in males. Male sex was shown to be involved in other associations in this study, such as influencing the preference for specific foods such as poultry and chicken skin. (4) Conclusions: Our data suggest that white meat does not have a clear-cut independent dose-response effect on MASLD, but sex may be a trigger moderator for age and BMI, with an increasing unfavorable effect of white meat in women, and a favorable effect in men.

Adverse Events During a 12-month Multi-Site and Dose-Response Aerobic Exercise Intervention.

Purpose: This study aimed to assess the incidence of adverse events (AE) in older adults participating in a year-long exercise intervention, investigating potential dose-response relationships between exercise intensity and AE frequency, and identifying demographic factors associated with AE risk. Methods: A total of 648 older adults were randomized into one of three exercise groups: low-intensity stretching and toning (S&T), 150 minutes of aerobic exercise per week (150Ex), or 225 minutes of aerobic exercise per week (225Ex). Adverse events were tracked during the intervention, with event rates calculated based on participant adherence and time in the study. Generalized linear models were employed to compare AE incidence across groups. Post hoc comparisons were used to calculate incidence rate ratios (IRRs) for AE between groups, adjusting for multiple comparisons. Results: Overall, 306 AE were reported, with 44% related to the intervention. No significant dose-response relationship was observed for all-cause AE between groups. However, intervention-related AE were more frequent in the aerobic exercise groups. Participants in the 150Ex group had a 77% higher rate of intervention-related AE compared to the S&T group, and the 225Ex group had an 88% higher rate. Higher adherence was associated with fewer all-cause AE, and greater comorbid burden was associated with more AE. Conclusions: While aerobic exercise increased the risk of intervention-related AE, the overall risk remained low. Higher adherence to the exercise regimen was associated with fewer AE. These findings suggest aerobic exercise is generally safe in older adults, with the benefits outweighing the risks.

Optimal exercise dose and type for improving schizophrenia symptoms in adults: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Exercise has shown promise in aiding patients with schizophrenia, potentially improving symptoms, quality of life, mood, and cognition. This review evaluates the effectiveness of different physical activities in this context, aiming to guide treatment and research towards the most beneficial exercise interventions for schizophrenia management. METHODS: This systematic review and network meta-analysis searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, Web of Science, and CNKI up to March 30, 2024. We utilized the "gemtc," "MBNMAdose," "metafor," and "ggplot2" packages for data analysis in R. Additionally, our results were reported as standardized mean differences with 95 % confidence intervals. To assess the risk of bias in the included studies, we used ROB2 and CINeMA tools. RESULTS: In the results section of our systematic review and network meta-analysis, we analyzed data from 47 studies involving 4031 participants. Our findings indicate that among the various exercise interventions examined for schizophrenia patients, yoga emerged as the most effective in improving Total symptoms, positive and negative symptoms. RT+AE (Resistance Training + Aerobic Exercise) showed the greatest improvement in general symptoms, whereas Tai Chi (TC) was the least effective. In terms of improvement of cognitive functions and depression, AE proved the most beneficial, while TC was found to be the least effective. EX+PT (Physical Exercise + Psychological Nursing) was identified as the most effective approach for improved quality of life, with TC again showing the least efficacy. The optimal total exercise dose to improve the patient's total symptoms was estimated to be 1200 METs-min/week. (SMD: -0.956, 95 %Crl: -1.376 to -0.536). CONCLUSIONS: Yoga, RT+AE, EX+PT, and Baduanjin have demonstrated enhanced efficacy in alleviating clinical symptoms, quality of life, depressive states, and cognitive functions in patients with schizophrenia. We identified optimal overall exercise doses and provided exercise guidance recommendations for healthcare professionals.

Role of physical activity and sedentary behavior in venous thromboembolism: a systematic review and dose-response meta-analysis.

Increasing studies have investigated the link between physical activity (PA) and sedentary behavior with venous thromboembolism (VTE) but the existing findings are not consistent and the independent relationship is uncertain. This meta-analysis aimed to comprehensively assess the shape of dose-response relationship between PA and sedentary behavior with VTE and further explore whether the relationship is independent after mutual adjustment. We systematically searched PubMed, Embase and Web of Science from inception to August 1, 2024. PA exposures were converted into MET-h/wk. Categorical meta-analyses and a cubic spline model were performed to evaluate the association between PA, sedentary behavior and VTE. Twenty-five articles including 31 studies were included. A curvilinear dose-response relationship between PA and VTE was observed, with steeper gradients even at lower PA levels. After adjustment for sedentary behavior, higher level of PA was independently associated with a reduced VTE risk (OR = 0.83, 95%CI:0.77-0.89). Based on population attributable fraction analyses, 2.37% (95%CI: 1.90-2.85%) of incident VTE could have been prevented if all adults had achieved half the PA minimum recommended level. A linear dose-response relationship between sedentary behavior and VTE risk was found, and there was a 2% higher risk of VTE (OR = 1.02, 95%CI: 1.00-1.03) for 1 h increment of sedentary behavior per day. After adjustment for PA, sedentary behavior was independently associated with an increased VTE risk (OR = 1.19, 95CI%:1.01-1.39). Our analyses demonstrated PA and sedentary time were indeed independently associated with the risk of VTE after mutually adjusting for sedentary time or PA, highlighting a unique perspective on their individual contributions. Further studies assessing the effects of different combinations of PA and sedentary time for assessing joint effects on VTE are needed.

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.

The Dynamics of Methylation Levels in GPX3 Promoter from Patients with Chronic Heart Failure and Their Association with Key Clinical Parameters.

OBJECT: This study investigated changes in methylation levels within the Glutathione peroxidase 3 (GPX3) promoter region among patients diagnosed with Chronic Heart Failure (CHF). Peripheral blood samples were collected from 20 CHF patients and 20 healthy individuals for analysis. METHODS: Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, methylation levels of 11 CpG sites within the GPX3 promoter region were quantified. RESULTS: Results showed a significant increase in methylation at the GPX3_FA10_CpG_24 site in CHF patients compared to the control group (P < 0.05). Furthermore, a nonlinear dose-response relationship was observed between methylation levels at this site and key clinical parameters including serum apolipoprotein A-1, D-dimer, Chlorine(Cl), Potassium(K), and Sodium(Na) (P < 0.05). CONCLUSIONS: These findings suggest that aberrant methylation of GPX3 promoter may impact disease progression by influencing physiological functions such as blood lipids, coagulation, and electrolytes. Further investigations are warranted to elucidate the role of GPX3 promoter methylation in CHF pathogenesis, potentially contributing valuable insights for its prevention, diagnosis, and treatment.

Hormetic dose response induced by sublethal-dose sulfoxaflor leads to reproductive stimulation of Aphis gossypii.

Aphis gossypii Glover is one of the most agriculturally important phloem-feeding economic pests, causing tremendous loss in crop yield annually. The hormesis is an important cause of A. gossypii resistance formation, population resurgence, and re-outbreak. However, whether the hormesises induced by different insecticides interact mutually remain largely unclear. In the study, four-generation A. gossypii experiment found that the 24-h sublethal-dose (LC20) sulfoxaflor treatment on G0 significantly increased the net reproductive rate (R0) and fecundity of G1 and G2 generation A. gossypii, but it did not significantly affect the fecundity of G3 and G4 individuals. Transcriptomic analyses revealed that the insecticide-induced significant up-regulation of pathways ribosome, energy metabolism, and the DNA replication and reparation might be responsible for the enhancement of fecundity in G1 and G2 A. gossypii. Notably, G0 exposure to LC20 sulfoxaflor followed by G1 exposure to LC30 deltamethrin resulted in a stronger reproductive stimulation than sulfoxaflor or deltamethrin exposure alone. Our findings provide valuable reference for optimizing sulfoxaflor application in integrated pest management strategies.

Neonatal high-dose riboflavin treatment channels energy expenditure towards sensorimotor and somatic development and reduces rodent growth and weight gain by modulating NRF-1 in the hypothalamus.

Metabolic adaptations early in life can drive energy expenditure towards brain and physical development, with less emphasis on body mass gain and somatic growth. Dietary or pharmacological manipulations can influence these processes, but to date, the effects provided by riboflavin have not been studied. The study aimed to evaluate the effects of neonatal treatment with different doses of riboflavin on sensorimotor and somatic development in rodents. Based on this, the following experimental groups were formed: Control (C, 0 mg/kg), Riboflavin 1 (R1, 1 mg/kg), Riboflavin 2 (R2, 10 mg/kg) and Riboflavin 3 (R3, 100 mg/kg). Treatment with 100 mg/kg riboflavin anticipated the reflex ontogeny of righting, cliff aversion, negative geotaxis, and free-fall righting. Intervention with 10 and 100 mg/kg of riboflavin anticipated the reflex maturation of vibrissae placement. Eye-opening, upper incisor eruption, and lower incisor eruption reached maturational age more quickly for animals treated with 100 mg/kg, while caudal growth and body weight gain were reduced from the second week of treatment, for groups R2 and R3. Pearson's correlation analysis indicated a positive association between the administration of high doses of riboflavin and murine growth in the first week of treatment. There was, however, a negative association between treatment with a high dose of riboflavin and growth in the second week of administration, coinciding with a reduction in body weight gain in the R3 group. Treatment with 100 mg/kg of riboflavin also reduced energy expenditure parameters in the open field and catwalk. Although high-dose treatment stimulates the physiological plasticity of the CNS and reduces weight gain, hepatic parameters were preserved, highlighting the participation of the liver in the supply of fatty acids for neural maturation. Furthermore, hypothalamic NRF-1 expression was increased in the R3 group inversely to the reduction in weight gain. Our results suggest that high-dose riboflavin stimulates sensorimotor and somatic development and reduces the energy invested in growth, body weight gain, and locomotor activity, possibly involving NRF-1 gene modulation in the hypothalamus.

In Vitro Prediction of Skin-Sensitizing Potency Using the GARDskin Dose-Response Assay: A Simple Regression Approach.

Toxicological assessments of skin sensitizers have progressed towards a higher reliance on non-animal methods. Current technological trends aim to extend the utility of non-animal methods to accurately characterize skin-sensitizing potency. The GARDskin Dose-Response assay has previously been described; it was shown that its main readout, cDV0 concentration, is associated with skin-sensitizing potency. The ability to predict potency from cDV0 in the form of NESILs derived from LLNAs or human NOELs was evaluated. The assessment of a dataset of 30 chemicals showed that the cDV0 values still correlated strongly and significantly with both LLNA EC3 and human NOEL values (ρ = 0.645-0.787 [p < 1 × 10-3]). A composite potency value that combined LLNA and human potency data was defined, which aided the performance of the proposed model for the prediction of NESILs. The potency model accurately predicted sensitizing potency, with cross-validation errors of 2.75 and 3.22 fold changes compared with NESILs from LLNAs and humans, respectively. In conclusion, the results suggest that the GARDskin Dose-Response assay may be used to derive an accurate quantitative continuous potency estimate of skin sensitizers.

Association between predicted level of water turnover deficit and all-cause and cause-specific mortalities among Japanese adults: The Japan Collaborative Cohort Study.

BACKGROUND: Although water is essential for maintaining health and life, the association between water turnover as an indicator of daily water requirement and water deficit and mortality is unclear. OBJECTIVE: We aimed to investigate this association in Japanese adults. METHODS: A total of 63,488 (36,739 females and 26,749 males) Japanese aged 40-79 years in the Japan Collaborative Cohort Study in 1988-1990 were followed up their mortality through 2009. Water turnover was calculated considering lifestyle and environmental factors using an equation previously developed by the International Doubly Labeled Water Database Group. Participants were classified into sex-specific quintiles based on their water turnover. Water deficit levels were calculated from water turnover and dietary water consumption, which were estimated using a validated questionnaire. RESULTS: The average daily water turnovers were 2,950 mL and 3,466 mL in females and males, respectively. During 19.4 years of median follow-up (1,039,914 person-years), 12,551 deaths were recorded. After adjusting for lifestyle and medical history, the bottom quintile was associated with higher hazard ratios (HRs) of mortality from all causes (females: HR, 1.26; 95% confidence interval, 1.12, 1.41; males: HR, 1.18; 95% CI, 1.07, 1.29) and cardiovascular disease (CVD). In spline analyses, the water turnover range with the lowest HR for all-cause mortality was 3,000-3,300 mL/day in females and the water turnover at which the HR for all-cause mortality plateaued was approximately 3,500-3,700 mL/day in males. Water deficiency levels were associated with all-cause and CVD mortality in both sexes. CONCLUSION: This study showed an L-shaped association between water turnover and deficit and all-cause and CVD mortalities (especially coronary heart disease and ischemic stroke) in adults. These findings may be useful for setting the target values of water requirement, and differences between dietary requirements and actual intake may bridge the knowledge gap in water-mortality associations.

The relationship between arterial partial pressure of oxygen and pressure injuries in intensive care unit patients: A multi-center cross-sectional study.

BACKGROUND: Pressure injuries significantly impact patients in intensive care units and the healthcare system. Hypoxia, a major contributor to pressure injury development, can be promptly identified by monitoring arterial partial pressure of oxygen. However, the dose-response relationship between arterial partial pressure of oxygen and pressure injuries remains unclear. OBJECTIVES: To determine how mean arterial partial pressure of oxygen within 24 h before the appearance of a pressure injury influences pressure injury outcomes in ICU patients, elucidating the dose-response relationship, and underscoring the importance of including arterial oxygen pressure in routine pressure injury risk assessments. METHODS: We conducted this multi-center cross-sectional study in Gansu province of China from April 2021 to July 2023. The incidence and influencing factors of pressure injuries were collected. Logistic and restricted cubic spline regression analyses were used to assess the association between pressure injuries and arterial partial pressure of oxygen. Subgroup analyses stratified by age and sex were conducted to explore potential correlations. RESULTS: Among 6078 participants, the incidence of pressure injury was 2.34 %. After adjusting for all confounding factors, patients with low arterial partial pressure of oxygen were more likely to develop pressure injury than those with normal levels (OR 1.753, 95 %CI 1.142 âˆ¼ 2.693). The dose-response relationship shows a significant non-linear dose-response correlation between arterial partial pressure of oxygen and pressure injury risk (P = 0.011). Layered analysis shows that the impact is more pronounced in older individuals and males. CONCLUSIONS: As arterial partial pressure of oxygen decreases, the occurrence of pressure injuries gradually increases. Incorporating arterial partial pressure of oxygen into daily pressure injury risk assessments is crucial. IMPLICATIONS FOR CLINICAL PRACTICE: Our study results will offer targeted insights for the prevention and management of pressure injuries.

Effects of aerobic exercise on executive function of healthy middle-aged and older adults: A systematic review and meta-analysis.

BACKGROUND: The deterioration of executive function is a hallmark of cognitive aging. Reports indicate that signs of decline in executive function begin to emerge as early as middle age. Aerobic exercise improves executive function in healthy middle-aged and older adults, but the optimal exercise prescription variables are still unclear. OBJECTIVE: To investigate the effects of aerobic exercise on executive function of healthy middle-aged and older adults and explore the dose-response relationship and moderators. METHODS: We conducted comprehensive searches of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, PsycINFO, and SPORTDiscus for English literature, and CNKI, WanFang, and VIP for Chinese literature, covering the period from inception until April 25, 2024. Randomized controlled trials examining the effect of aerobic exercise on executive function in healthy middle-aged and older adults aged 45 or older were included. The Cochrane Collaboration's RoB2 tool was used to assess the methodological quality of the included studies. And subgroup analyses and meta-regressions were conducted to elucidate the impact of aerobic exercise on executive function. RESULTS: Forty-two eligible randomized controlled trials, involving a total of 2881 participants, met the inclusion criteria for the systematic review and meta-analysis. The pooled results showed that aerobic exercise had positive effects on improving cognitive flexibility (Hedge's g = 0.343, p < 0.001), working memory (Hedge's g = 0.392, p < 0.001), and inhibitory control (Hedge's g = 0.229, p < 0.001) in healthy middle-aged and older adults. However, it did not demonstrate an improvement in planning (Hedge's g = 0.094, p = 0.440). The dose-response relationships between different exercise parameters and subdomains of executive functions revealed that the largest effects on cognitive flexibility were observed after 13-24 weeks of progression-intensity mind-body exercise, 46-60 min per session, and 5-7 days per week. Regarding working memory, the largest effects were observed after 13-24 weeks of progression-intensity general aerobic exercise, 20-45 min per session, and 5-7 days per week. For inhibitory control, the greatest effects were noted after 13-24 weeks of low-intensity general aerobic exercise, 20-45 min per session, and 3-4 days per week. CONCLUSION: Aerobic exercise can significantly improve cognitive flexibility, working memory, and inhibitory control in healthy middle-aged and older adults. The effect of aerobic exercise on different aspects of executive function is influenced by specific exercise parameters, suggesting that personalized aerobic exercise programs may be more effective for enhancing executive function of healthy middle-aged and older adults.

Effects of chia (Salvia hispanica. L) on anthropometric measures and other cardiometabolic risk factors: A systematic review and dose-response meta-analysis.

BACKGROUND: Findings of available randomized controlled trials (RCTs) on the effects of chia are inconsistent. Although previous meta-analyses summarized available findings in this regard, some limitations may distort their findings. Moreover, none of these meta-analyses examined the dose-response association of chia on cardiometabolic risk factors (CMRFs). Therefore, the present study aimed to evaluate the effect of chia consumption on CMRFs. METHODS: Relevant RCTs were included by searching the ISI Web of Science, PubMed, and Scopus databases up to June 2, 2023. Mean differences (MD) and 95 % confidence intervals (CI) were pooled using random-effects model. RESULTS: Ten publications were included in this systematic review and the meta-analysis. The results showed a significant reduction in systolic blood pressure (SBP) (MD = -7.87 mmHg; 95 % CI: - 12.92 to - 2.82; I2 = 71.3 %, P heterogeneity = 0.004), diastolic blood pressure (MD = -6.33 mmHg; 95 %CI: - 7.33 to - 5.34, I2 = 0 %, P heterogeneity = 0.42) and high-density lipoprotein cholesterol (HDL-c) (MD = -4.09 mg/dl; 95 %CI: - 6.76 to - 1.43, I2 = 12.4 %, P heterogeneity = 0.33). However, the effects of chia on the other risk factors were not significant. Based on the dose-response analysis, a 10-g/d increase in chia consumption significantly reduced SBP (MD = -2.20 mmHg; 95 %CI: - 3.75 to - 0.66, I2 = 78.9 %, P heterogeneity < 0.001) and HDL-c (MD = -1.10 mg/dl; 95 %CI: - 1.72 to - 0.49, I2 = 0 %, P heterogeneity = 0.52). CONCLUSION: Chia consumption might have a beneficial effect on lowering blood pressure. Chia consumption can also lead to a slight reduction in HDL-c levels. As the quality of the included studies was mostly low, the findings should be interpreted with caution. Well-designed trials with larger sample sizes and longer duration of follow-up are needed to provide additional insight into the dose-dependent effects of chia consumption.