OBJECTIVE: 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: 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 sub-analysis 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.

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.

BACKGROUND: 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.
OBJECTIVE: To determine whether perioperative blood transfusion increased the risk of SSI and to further explored whether there was a dose-response relationship.
METHODS: Retrospective nested case-control study.
METHODS: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between July 2011 and July 2021.
METHODS: In the current study, the primary outcome measure was SSI.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Many studies have demonstrated that long double-stranded RNAs (dsRNAs) targeting essential genes of white spot syndrome virus (WSSV) can induce a sequence-specific antiviral RNA interference (RNAi) response in shrimp, thereby offering protection against WSSV infection. However, further experimental data on the required dose of dsRNAs and the duration of protection from a single administration are necessary to establish RNAi-mediated methods as effective and practical antiviral measures. In this study, we evaluated the protective efficacy and the duration of protection provided by a single administration of various doses of long dsRNA targeting WSSV ribonucleotide reductase 2 (rr2) in white-leg shrimp Litopenaeus vannamei. The protective efficacy of long dsRNA targeting WSSV rr2 was not diminished by the reduction of the dose to 100 ng g-1 of body weight, suggesting that a relatively low dose can effectively induce an RNAi response in shrimp. Furthermore, shrimp were well-protected against WSSV challenges for up to 4 wk post-administration of the rr2-targeting long dsRNA, although the protective effect almost disappeared at 6 wk post-administration. These results suggest that long dsRNAs can provide protection against WSSV for at least 1 mo, and monthly administration of long dsRNAs could serve as a long-term protective strategy for shrimp against WSSV.

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.

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.

UNASSIGNED: Frailty is a significant public health issue facing aging societies and can be reduced by physical activity (PA), but the dose-response relationship between PA and frailty is not clear. This systematic review and dose-response meta-analysis aimed to assess the effect of PA on frailty in adults by aggregating data from observational studies.
UNASSIGNED: PubMed, Embase, Web of Science, Cochrane Library, Scopus, SAGE Reference Online, SinoMed, CINAHL and CNKI were retrieved for articles published before May 2024. After quality evaluation, data on PA and the risk of frailty were extracted. Stata/MP 17.0 was used for dose-response meta-analysis.
UNASSIGNED: A total of 15 articles were included, involving 34,754 participants, including 4250 subjects with frailty or pre-frailty. The consequence of the dose-response meta-analysis revealed that compared with those who were not active at all, a 22 % (95 % CI, 16 %-28 %) reduction in the risk of frailty in individuals with 11.25 MET h/week of cumulative activity and a 55 % (95 % CI, 44 %-63 %) reduction in the risk of frailty in those with 22.5 MET h/week of cumulative activity; for higher activity levels (36.75 MET h/week), the risk of frailty was reduced by 68 % (95 % CI, 58 %-76 %) and continued to be reduced as PA volum increased.
UNASSIGNED: There is a non-linear dose-response relationship between PA and frailty risk. Even small amounts of PA could reduce the risk of frailty. Meeting the minimum recommended PA target could reduce some risks, and doubling the recommended PA volumes could reduce most risks, which continue to increase as the volum of PA accumulates.

The fission yeast Schizosaccharomyces pombe is frequently used as a genetically manipulable model system, offering valuable understandings into cellular mechanisms. In the present study, a comprehensive step-by-step methodology for the research of the action mechanisms and detoxification by efflux pumps is showed. The protocol involves the thawing and culture of yeast cells in liquid medium under controlled conditions to ensure exponential growth. After that, a dose-response assessment is carried out by culturing wild-type cells in liquid medium, followed by exposure to increasing concentrations of the toxic substances. Optical density measurements are taken spectrophotometrically after exposure, and the process is repeated at least three times for quantitative analysis. Subsequently, defective mutants are selected to explore specific mechanisms of action or detoxification by efflux pumps, with cultures prepared and treated similarly to the wild type. Optical density measurements are again taken after exposure for quantitative analysis. This methodology ensures robust and reproducible results for the research toxic substances effects on S. pombe.-Schizosaccharomyces pombe is an adequate tool to evaluate contaminants toxicity.-Dose-responses curves are obtained on wild type to evaluate toxicity mechanisms.-This methodology ensures robust and reproducible results for the research toxic substances effects on S. pombe.

UNASSIGNED: To synthesize the knowledge about the association of total physical activity (TPA), leisure-time physical activity (LTPA), occupational physical activity (OPA) and lung cancer risk and explore the dose-response relationship between LTPA level and lung cancer.
UNASSIGNED: PubMed and Web of Science were searched up to 17 November 2021. The summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects or fixed-effects model. The dose-response analysis was conducted with restricted cubic splines.
UNASSIGNED: We identified 25 articles (42 cohort studies) that assessed the physical activity-lung cancer association, including 9,983,295 study participants and 85,988 incident cases of lung cancer. When comparing the highest to the lowest level of TPA and LTPA, lung cancer risk reduced 22% (RR, 0.78; 95% CI: 0.70, 0.86) and 12% (RR, 0.88; 95% CI: 0.83, 0.93), respectively. We found an approximately U-shaped association between LTPA and lung cancer (P non-linearity < 0.001), with the lowest risk at 15 metabolic equivalent of task hours per week (h/wk) of LTPA. Compared to participants with sitting occupations, lung cancer risk significantly increased among those being unemployed (RR, 1.33; 95% CI: 1.17, 1.51) or with standing occupations (RR, 1.37; 95% CI: 1.15, 1.63), but not among those with light or high OPA.
UNASSIGNED: Our meta-analysis supported a protective effect of TPA and LTPA, but not OPA, on lung cancer risk. The novel finding of a U-shaped association between LTPA and lung cancer risk warrants further investigation.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.