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

BACKGROUND: This study investigates factors contributing Amaranthus albus control failure in processing tomato fields in northern Israel. The study region is characterized by a significant climate gradient from east to west, providing the opportunity to investigate the effect of critical elements of the agricultural environment, e.g., temperature. Eight populations were collected from commercial fields in this region. Post‐emergence herbicide efficacy of metribuzin, a photosystem II inhibitor, and rimsulfuron, an acetolactate synthase (ALS) inhibitor, was assessed through dose–response analyses at various growth stages. Temperature effects on control efficacy and resistance mechanisms were also explored. RESULTS: Standard metribuzin dose (X) was ineffective on A. albus plants with more than six true‐leaves, whereas 2X dose proved effective. Rimsulfuron at 16X dose was ineffective on plants with more than four true‐leaves. We report here the first case of target site resistance to ALS inhibitors in A. albus, due to point mutation in the ALS gene (Pro197 to Leu). Furthermore, our findings suggest potential involvement of CYT P450 enzymes in enhanced metabolizing of rimsulfuron. An overall decrease in dry weight was observed in response to both herbicides at 16/22 °C (P < 0.0001). Rimsulfuron was effective against only one population when applied at 28/34 °C. A possible fitness cost associated with target site‐resistant biotypes was observed under low temperature conditions, leading to effective control. CONCLUSION: This regional‐scale study highlights the challenges faced by growers, emphasizes the need for adapting management practices to the local climatic conditions and lays the groundwork for implementing location‐specific weed management strategies in commercial fields. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

A logarithmic sprayer was suggested about 70 years ago, but it has not yet been seriously used in research and development, and subsequent registration of plant protection products. Logarithmic sprayers have resorted to mere demonstration experiments to show end users and others how plant protection products work. Fitting dose–response curves in field experiments, however, generates much essential information, e.g., extraction of various effective field rate levels (e.g., ED20, ED50, and ED80). One of the reasons for it rarely being used in the registration of plant protection products is that the dose–response curve regression was hitherto difficult to fit; the registration requirement solely focuses on analyses of variance. Another alleged obstacle is that the logarithmic plots have systematically, not randomly distributed field rates. This paper goes through some of the problems of how to non‐randomly analyze field rates by taking autocorrelation into account to make the logarithmic sprayer palatable as registration documentation by assessing efficacy, selectivity, environmental side effects, general toxicity of plant protection products, and cost‐effectiveness. The development in precision agriculture, drone technology, and automation of data capture and subsequent analysis could make the logarithmic sprayer a cost‐effective alternative to numerous ANOVA experiments with very few fixed field rates to aid the precision spraying of pesticides and thus reduce unnecessary environmental side effects. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background and aims: Increasing levels of alcohol use are associated with a risk of developing an alcohol use disorder (AUD), which, in turn, is associated with considerable burden. Our aim was to estimate the risk relationships between alcohol consumption and AUD incidence and mortality. Method: A systematic literature search was conducted, using Medline, Embase, PsycINFO and Web of Science for case–control or cohort studies published between 1 January 2000 and 8 July 2022. These were required to report alcohol consumption, AUD incidence and/or AUD mortality (including 100% alcohol‐attributable deaths). The protocol was registered with PROSPERO (CRD42022343201). Dose–response and random‐effects meta‐analyses were used to determine the risk relationships between alcohol consumption and AUD incidence and mortality and mortality rates in AUD patients, respectively. Results: Of the 5904 reports identified, seven and three studies from high‐income countries and Brazil met the inclusion criteria for quantitative and qualitative syntheses, respectively. In addition, two primary US data sources were analyzed. Higher levels of alcohol consumption increased the risk of developing or dying from an AUD exponentially. At an average consumption of four standard drinks (assuming 10 g of pure alcohol/standard drink) per day, the risk of developing an AUD was increased sevenfold [relative risk (RR) = 7.14, 95% confidence interval (CI) = 5.13–9.93] and the risk of dying fourfold (RR = 3.94, 95% CI = 3.53–4.40) compared with current non‐drinkers. The mortality rate in AUD patients was 3.13 (95% CI = 1.07–9.13) per 1000 person‐years. Conclusions: There are exponential positive risk relationships between alcohol use and both alcohol use disorder incidence and mortality. Even at an average consumption of 20 g/day (about one large beer), the risk of developing an alcohol use disorder (AUD) is nearly threefold that of current non‐drinkers and the risk of dying from an AUD is approximately double that of current non‐drinkers. [ABSTRACT FROM AUTHOR]

Objective: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all‐cause mortality remains unclear. We conducted a systematic review and dose–response meta‐analysis to determine the effects of HRT on CRC mortality and all‐cause mortality. Methods: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two‐stage random‐effects dose–response meta‐analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality. Results: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I2 = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all‐cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I2 = 89.6%, p < 0.05). A linear dose–response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose–response analysis showed a nonsignificant decrease in the risk of all‐cause mortality for each additional year of HRT use. Conclusions: This study suggests that the use of HRT is inversely associated with all‐cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) is gaining interest as a tool to combat aquatic invasive species, including zebra mussels (Dreissena polymorpha). However, the effects of water chemistry on CO2 efficacy are not well described. We conducted five trials in which we exposed adult zebra mussels to a range of CO2 in water with adjusted total hardness and specific conductance. We compared dose–responses and found differences in lethal concentration to 50% of organisms (LC50) estimates ranging from 108.3 to 179.3 mg/L CO2 and lethal concentration to 90% of organisms (LC90) estimates ranging from 163.7 to 216.6 mg/L CO2. We modeled LC50 and LC90 estimates with measured water chemistry variables from the trials. We found sodium (Na+) concentration to have the strongest correlation to changes in the LC50 and specific conductance to have the strongest correlation to changes in the LC90. Our results identify water chemistry as an important factor in considering efficacious CO2 concentrations for zebra mussel control. Additional research into the physiological responses of zebra mussels exposed to CO2 may be warranted to further explain mode of action and reported selectivity. Further study could likely develop a robust and relevant model to refine CO2 applications for a wider range of water chemistries. Environ Toxicol Chem 2024;43:1312–1319. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Background: Accumulating studies indicate that maternal obesity is associated with the risk of cerebral palsy (CP); however, their conclusions have been inconsistent. Objectives: To quantitatively estimate the association between maternal body mass index (BMI) and CP in offspring. Data Sources: PubMed, Embase and Web of Science. Study Selection and Data Extraction: Articles published up to 18 September 2022 were searched that reported the correlation between maternal BMI and CP in children. Two reviewers independently extracted data and critically assessed articles. Synthesis: Pooled relative risks (RR) and 95% confidence intervals (CI) were estimated by the random‐effects model. Subgroup analysis and meta‐regression were performed to explore sources of heterogeneity. Results: In total, 11 articles (8,407,668 participants) were identified for inclusion in our meta‐analysis. For maternal underweight, no significant association was found with CP risk (RR 1.11, 95% CI 0.90, 1.38). The risk of CP was increased by 25% (RR 1.25, 95% CI 1.06, 1.47), 38% (RR 1.38, 95% CI 1.18, 1.61) and 127% (RR 2.27, 95% CI 1.82, 2.83) for maternal overweight, obesity and obesity grade 3, respectively. In addition, we observed a positive linear dose‐response relationship, with the pooled risk of cerebral palsy in offspring increasing by 3% with each unit increase in maternal BMI. Conclusion: This meta‐analysis indicates that the risk of CP in offspring grew with maternal overweight or obesity grades increasing, and was positively correlated with maternal BMI. [ABSTRACT FROM AUTHOR]

Short‐term monocular deprivation (MD) shifts sensory eye balance in favour of the previously deprived eye. The effect of MD on eye balance is significant but brief in adult humans. Recently, researchers and clinicians have attempted to implement MD in clinical settings for adults with impaired binocular vision. Although the effect of MD has been studied in detail in single‐session protocols, what is not known is whether the effect of MD on eye balance deteriorates after repeated periods of MD (termed 'perceptual deterioration'). An answer to this question is relevant for two reasons. Firstly, the effect of MD (i.e., dose‐response) should not decrease with repeated use if MD is to be used therapeutically (e.g., daily for weeks). Second, it bears upon the question of whether the neural basis of the effects of MD and contrast adaptation, a closely related phenomenon, is the same. The sensory change from contrast adaptation depends on recent experience. If the observer has recently experienced the same adaptation multiple times for consecutive days, then the adaptation effect will be smaller because contrast adaptation exhibits perceptual deterioration, so it is of interest to know if the effects of MD follow suit. This study measured the effect of 2‐h MD for seven consecutive days on binocular balance of 15 normally sighted adults. We found that the shift in eye balance from MD stayed consistent, showing no signs of deterioration after subjects experienced multiple periods of MD. This finding shows no loss of effectiveness of repeated daily doses of MD if used therapeutically to rebalance binocular vision in otherwise normal individuals. Furthermore, ocular dominance plasticity, which is the basis of the effects of short‐term MD, does not seem to share the property of 'perceptual deterioration' with contrast adaptation, suggesting different neural bases for these two related phenomena. [ABSTRACT FROM AUTHOR]

Non‐native annual grasses have invaded western rangelands in the United States, and novel approaches are needed to supplement existing management strategies. The aim of this study was to investigate biofumigation, the use of Brassicaceae products to suppress weeds, as a control for two non‐native annual grasses (cheatgrass, Bromus tectorum and ventenata, Ventenata dubia) and its effects on two dominant native perennial grasses (bluebunch wheatgrass, Pseudoroegneria spicata and Idaho fescue, Festuca idahoensis). We tested the effect of the biofumigant Brassica juncea (brown mustard), applied as seed meal and mulch, on germination metrics of the four grass species in Petri dishes. Germination metrics included emergence and viability, time to cotyledon and radicle emergence and their lengths at 14 days after sowing. Impacts on emergence and viability were assessed using a binomial mixed effects model, while time to cotyledon and radicle emergence and lengths were assessed using linear mixed effects models. Seed meal reduced emergence and viability at lower application rates for V. dubia and F. idahoensis than the other two species. Mulch did not consistently reduce emergence or viability. P. spicata was the least inhibited by the biofumigants. When using seed meal, radicle emergence and length were inhibited in B. tectorum, V. dubia and F. idahoensis and cotyledon emergence and length were inhibited for all. The mulch did not impact these metrics consistently and may not be a viable management tool. The use of seed meal biofumigant to suppress undesired annual grasses in rangelands seems promising, but response is species‐specific. [ABSTRACT FROM AUTHOR]

Background: Most studies of the effects of prenatal alcohol exposure (PAE) on cognitive function have assumed that the dose-response curve is linear. However, data from a few animal and human studies suggest that there may be an inflection point in the dose-response curve above which PAE effects are markedly stronger and that there may be differences associated with pattern of exposure, assessed in terms of alcohol dose per drinking occasion and drinking frequency. Methods: We performed second-order confirmatory factor analysis on data obtained at school age, adolescence, and early adulthood from 2227 participants in six US longitudinal cohorts to derive a composite measure of cognitive function. Regression models were constructed to examine effects of PAE on cognitive function, adjusted for propensity scores. Analyses based on a single predictor (absolute alcohol (AA)/day) were compared with analyses based on two predictors (dose/occasion and drinking frequency), using (1) linear models and (2) nonparametric general additive models (GAM) that allow for both linear and nonlinear effects. Results: The single-predictor GAM model showed virtually no nonlinearity in the effect of AA/day on cognitive function. However, the two-predictor GAM model revealed differential effects of maternal drinking pattern. Among offspring of infrequent drinkers, PAE effects on cognitive function were markedly stronger in those whose mothers drank more than ~3 drinks/occasion, and the effect of dose/occasion was strongest among the very frequent drinkers. Frequency of drinking did not appear to alter the PAE effect on cognitive function among participants born to mothers who limited their drinking to ~1 drink/occasion or less. Conclusions: These findings suggest that linear models based on total AA/day are appropriate for assessing whether PAE affects a given cognitive outcome. However, examination of alcohol dose/occasion and drinking frequency is needed to fully characterize the impact of different levels of alcohol intake on cognitive impairment. [ABSTRACT FROM AUTHOR]

BACKGROUND: The environmental and economic costs of conventional insecticides have stirred an interest in alternative management tactics, including the use of nanotechnologies. Selenium nanoparticles (SeNPs) have many applications in agriculture but may not be compatible with biological control; however, low concentrations of SeNPs may benefit natural enemies via hormesis. This study investigates the concentration‐dependent effects of SeNPs (0–1000 mg L−1) on Anisopteromalus calandrae (Howard) (Hymenoptera: Pteromalidae), a generalist parasitoid of stored product pests. RESULTS: The LC50 of SeNPs was 1540 mg L−1 for female parasitoids and 1164 mg L−1 for males. SeNPs had a significant hormetic effect; average lifespan increased by 10% at a concentration of 4.03 mg L−1 for females and by 35% at 13.83 mg L−1 for males. In a bioassay including hosts [the azuki bean beetle, Callosobruchus chinensis (L.) (Coleoptera: Chrysomelidae: Bruchinae)], a low concentration of SeNPs (25 mg L−1) enhanced the performance of female parasitoids; lifespan increased by 23% and the number of offspring increased by 88%. However, the number of emerging hosts did not significantly decrease; in the absence of parasitism, SeNPs actually improved host emergence by 17%. CONCLUSION: Because higher concentrations of SeNPs reduced parasitoid lifespan, whereas low concentrations enhanced not only parasitoid performance but also host emergence, practitioners should exercise caution when considering SeNPs for use in integrated pest management. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aims: A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods: This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The solution combustion synthesis method is employed to prepare Magnesium, Zinc, Aluminate doped with dysprosium (Dy3+) using the general formula Mg(1‐x‐y) Zn(y)Al2O4:xDy (x = 0.05 and y = 0.3 mol%). From X‐ray diffraction studies, the crystal structure belongs to a cubic close‐packed spinel structure with space group Fd3ˉm and an average crystallite size is 26.18 nm. In the Fourier transform infrared spectra, the peaks at 683.69 cm−1, 503.12 cm−1 correspond to the AlO6 groups. The peak temperature (Tm) from the Thermoluminescent glow curve is recorded at 235°C, 237°C, and 235°C, at irradiation doses of 600 Gy, 800 Gy, and 1000 Gy, respectively. The kinetic parameters are evaluated from the thermoluminescent glow curve by calculating the activation energy (E), order of kinetics (b), and frequency factor (s−1). Nanophosphor Mg0.65Zn0.3Al2O4:0.05Dy shows sub linear dose relationship at doses 600–675 Gy and 925–1000 Gy. Further, at doses between 675 and 925 Gy, it shows a super linear relationship. The optimum activation energy (E) of 0.77–0.82 eV and negligible fading make it suitable for high radiation thermoluminescent dosimetry. [ABSTRACT FROM AUTHOR]

Tamarixia radiata (Waterston) (Hymenoptera: Eulophidae) is the key parasitoid of the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), in several citrus‐producing regions of the world. Chemical control is common to suppress ACP. Insecticides from globally used classes of insecticides for controlling ACP were tested on its primary parasitoid, T. radiata. Evaluations included dose–response of dimethoate, fenpropathrin, and imidacloprid in a topical application and lethal and sublethal effects from residues of imidacloprid, fenpropathrin, horticultural mineral oil (HMO), pyrethrin, and spirotetramat at 1, 3, and 7 days after application (DAA) of sprays on citrus trees in the orchard. The parasitism potential of the females that survived insecticide exposure was evaluated on untreated nymphs of ACP developing on citrus shoots and untreated parasitoid females were evaluated on nymphs treated with insecticides. In the topical application, imidacloprid was 8× more toxic to T. radiata than dimethoate and fenpropathrin. The lethal effect of the residues from imidacloprid and fenpropathrin sprays was more detrimental than other insecticides. Parasitoid mortality from 1‐ to 3‐day‐old residues averaged 90–96% for imidacloprid, 83–94% for fenpropathrin, 38–77% for pyrethrin, 43–44% for HMO, and 17–33% for spirotetramat. Parasitism by females that survived insecticide exposure was reduced by 71–88% from fenpropathrin, 28–59% from pyrethrin, 31–55% from imidacloprid, 44–4% from spirotetramat, and 39–11% from HMO compared to untreated females. The lethal and sublethal effects of all insecticides on T. radiata were significantly reduced at 7 DAA, suggesting a lower impact on its establishment and performance if releases are made after a week from spray application. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify and describe trajectories of change in distress among highly challenging patients who had received long and intensive psychoanalytic psychotherapy. Methods: The longitudinal version of the K‐means algorithm was applied to the outcome measures data of 74 patients treated in four public mental health centers. The patients were measured five times at 6‐month intervals for three outcome measures. Results: For the OQ45 and Symptom Checklist‐90, one trajectory was marked by a lower initial distress level. In this trajectory, the improvement occurred in the first half of the measurements, with a plateau thereafter. A second trajectory was characterized by higher initial severity and an improvement, mainly in the second part of the measurements. For the Beck Depression Inventory, one trajectory was marked by lower initial distress. In this group, the improvement occurred throughout the entire period. The remaining patients were characterized by higher initial distress and a decreased level of distress in the last part of treatment. They began to improve only during the third year of therapy. Conclusion: The response to treatment is not uniform in long‐term treatment for highly challenging patients. A significant number of patients require a longer period of therapy to ignite improvement. [ABSTRACT FROM AUTHOR]

Background: Cimex lectularius L. (bed bug) (Hemiptera: Cimicidae) is a serious indoor pest worldwide, and this nuisance needs to be controlled using different methods in integrated pest management (IPM). Beauveria bassiana (Bals.‐Criv.) Vuill. (Hypocreales: Cordycipitaceae) kills bed bugs, and insect pathogenic fungi may be utilized to control bed bugs in IPM. To increase knowledge of this methodology, forced exposure experiments were conducted with different formulations, doses, and substrates, using bed bugs in variable physiological states. Results: Both oil‐ and water‐formulated fungal products showed significant improvement when conidial concentrations were raised in five steps from 0.02 to 2.0%. At low concentrations (0.02% in water) effects from substrate and application strategy were observed. Application on soft substrates (cotton and polyester) yielded significantly higher bed bug mortality rates than on harder substrates (paper, wood, and linoleum) with a final mortality of 35–63% against 8–10%. Multiple applications over time also improved B. bassiana's ability to kill bed bugs, and at low concentrations only a triple application on cotton showed 100% final mortality. Bed bug age and reproductive status significantly affected survival. Older and reproducing individuals showed higher mortality compared to newly emerged adults. Differences in feeding status also yielded differences in mortality timing, but only minor differences in final mortality rates. Egg production and hatching success were significantly reduced by some treatments. Conclusion: B. bassiana appears to be an asset in the fight against bed bugs. Substrate, dosage, application strategy, and bed bug physiology are important factors to consider for optimal efficacy and safe indoor control with insect pathogenic fungi. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Photobiomodulation therapy (PBMt) combined or not with oral hypoglycemic medication has not been investigated in type 2 diabetes (T2DM) patients. All 10 T2DM patients were assessed randomly at 6 different occasions (3 with and 3 without regular oral hypoglycemic medication). Capillary glycemia was assessed after overnight fast (pre‐prandial), 1 h postprandially (standardized meal, 338 kcal), and 30 min, 3 h, 6 h, 12 h post‐PBMt (830 nm; 25 arrays of LEDs, 80 mW/array). Three doses (0 J—sham, 100 J, 240 J per site) were applied bilaterally on quadriceps femoris muscles, hamstrings, triceps surae, ventral upper arm and forearm; and randomly combined or not with oral hypoglicemic medication, totaling six different therapies applied for all 10 TDM2 patients (PBMt sham, PBMt 100 J, PBMt 240 J, PBMt sham + medication, PBMt 100 J + medication, PBMt 240 J + medication). Cardiac autonomic control was assessed by heart rate variability (HRV) indices. Without medication, there was reduction in glycemia after all PBMt doses, with 100 J as the best dose that persisted until 12 h and presented lower area under the curve (AUC). With medication, glycemia decreased similarly among doses. No differences between 100 J and sham + medication, but AUC was significantly lower after 100 J, suggesting better glycemic control. Low frequency component of HRV increased after sham + medication and 100 J, suggesting higher sympathetic activation. PBMt showed time– and dose–response effect to reduce glycemia in T2DM patients. Effects on HRV were consistent with glycemic control. [ABSTRACT FROM AUTHOR]

Background: To investigate the risk of endophthalmitis after cataract surgery in patients with diabetes mellitus (DM) and evaluate the dose–response relationship. Methods: This retrospective cohort study enrolled patients who underwent bilateral cataract surgeries from 2000 to 2017 in Taiwan National Health Insurance Research Database. The endophthalmitis rates within 3 months after cataract surgery were compared between DM and non‐DM cohorts using a generalised estimating equation. The diabetes complications severity index (DSCI) score was adopted to assess the dose–response effect on the endophthalmitis rate. Results: A total of 883 398 patients (1 766 796 eyes) were included. Patients with DM had an increased risk of endophthalmitis after cataract surgery than patients without DM (0.261% vs. 0.242%, adjusted odds ratio = 1.09, 95% confidence interval = 1.03–1.16). The higher endophthalmitis rate in the DM group than in the non‐DM group remains after excluding those with prior vitrectomy or intravitreal injection (IVI), and took IVI between the cataract surgery and endophthalmitis (p = 0.0156, 0.0048, and 0.0139). There was a significant dose–response relationship on the likelihood of endophthalmitis in DM patients when DCSI score >10. The endophthalmitis rate is highest among DM complications in patients with metabolic disorders (0.342%). Conclusion: DM was a risk factor for endophthalmitis after cataract surgery after adjusting for age, sex, common systemic disorders, and excluding those with prior vitrectomy or IVI and having IVI between cataract surgery and endophthalmitis. A dose–response relationship was noted in DM patients with a DCSI score >10. [ABSTRACT FROM AUTHOR]

Recent studies have shown an inconsistent association between dietary niacin and cognitive function. And this remains unclear in the American outpatient population. The aim of this study was to assess whether there is an association between dietary niacin and cognitive performance in an older American population aged ≥60 years. A total of 2523 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were enrolled. Cognitive function was assessed by the CERAD Word Learning (CERAD‐WL) test, the CERAD Delayed Recall (CERAD‐DR) test, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Cognitive impairment that meets one of the four scoring conditions listed above is defined as low cognitive function. Dietary niacin intake was obtained from 2 days of a 24‐h recall questionnaire. Based on the quartiles of dietary niacin intake, they were divided into four groups: Q1 (<15.51 mg), Q2 (15.51–20.68 mg), Q3 (20.69–26.90 mg), and Q4 (>26.91 mg). The stability of the results was assessed using multifactorial logistic regression, restricted cubic spline (RCS) models, and sensitivity stratified analysis. More than half of the participants had cognitive impairment (52.52%). In the fully adjusted model, niacin was associated with a significantly reduced risk of cognitive impairment in Q3 and Q4 compared with the Q1 group (OR: 0.610, 95% CI: 0.403, 0.921, p =.022; OR: 0.592, 95% CI: 0.367, 0.954, p =.034). Meanwhile, niacin was negatively associated with poor cognition as assessed by the CERAD‐WL test, CERAD test, AFT, and DSST. An L‐shaped dose–response relationship between dietary niacin and cognitive function was observed in all participants (nonlinear p <.001). There were also interactions that existed in populations with different carbohydrate intakes and cholesterol intakes (p for interaction =.031, p for interaction =.005). These findings provide new evidence for the potential role of dietary niacin intake on cognitive function in the elderly. [ABSTRACT FROM AUTHOR]

Background: This study examines the relationship between statin use and oral cancer squamous cell carcinoma (OCSCC) risk in a cohort of 47 942 betel nut chewers. Methods: The study used individual 1:1 matching and propensity score matching to compare statin users and nonusers. Results: The incidence rate of OCSCC was significantly lower in statin users compared to nonusers (17.12 vs. 26.75 per 10 000 person‐years), yielding an incidence rate ratio of 0.64. After adjusting for confounders, statin use was associated with a reduced risk of OCSCC (adjusted hazard ratio: 0.61; 95% confidence interval: 0.52–0.71). A dose–response relationship was observed, with a significant reduction in OCSCC incidence when the cumulative defined daily dose of statin use was equal to or greater than Q3. The risk of OCSCC was lower among users of both hydrophilic and lipophilic statins. Conclusion: This study provides evidence that statin use is associated with a reduced risk of OCSCC in betel nut chewers. [ABSTRACT FROM AUTHOR]

The phenolic content of olive oil has a role in cardiovascular protection. Some clinical trial studies demonstrated that phenolic compounds of olive oil have antioxidant activity which can protect macronutrients from oxidative damages. The aim of this study was to summarize the results of clinical trials which assessed the effects of high‐ versus low‐phenol olive oil on oxidative stress biomarkers levels. We searched Scopus, PubMed, Web of Science, Google Scholar, ProQuest, and Embase up to July 2021. Eight clinical trials which evaluated the effect of the phenolic content of olive oil on oxidized‐LDL (ox‐LDL), malondialdehyde (MDA), or ferric‐reducing ability of plasma (FRAP) were included the meta analysis. A significant decrease was observed in ox‐LDL level (WMD: −0.29 U/L; 95% CI: −0.51, −0.07) and MDA (WMD: −1.82 μmoL/L; 95% CI: −3.13, −0.50). However, after subgroup analysis for MDA, the result was not significant for not serious limitation (SMD: −0.05, 95% CI: −0.35 to 0.24), but significant for serious limitation (SMD: −3.64, 95% CI: −4.29 to −2.99). Also, no significant change was found in FRAP (WMD: 0.0 mmoL/L; 95% CI: −0.03, 0.04) level. Dose–response analysis indicated a significant linear relationship between the phenolic content of olive oil and ox‐LDL. The present study showed some beneficial effects of high‐phenol compared with low‐phenol olive oil on ox‐LDL and MDA levels. According to the meta‐regression analysis along with the increasing phenolic content of olive oil, a reduction in oxidative stress biomarkers was observed. [ABSTRACT FROM AUTHOR]

The gas leak in Chimaera near Çıralı, Antalya, has been active for thousands of years. It is also known to be the source of the first Olympic flame in the Hellenistic period. The sample taken from the Chimaere seepage annealed for thousands of years was determined to be calcite‐magnesian (Ca, Mg)O3. In this study, thermoluminescence (TL) properties of calcite‐magnesian annealed for thousands of years in the fire caused by methane gas were investigated for particle size, dose–response, heating rate, and fading experiments. It exhibits a clear TL glow curve with two distinct peaks positioned at 160 and 330°C, and its shape is not affected by variation in applied dose and reproduciility of experiment. There is a wide linear relationship between TL output and applied dose up to 614 Gy. Although the positions of the TL peaks are stable with the cycle of measurement, a poor reusability was observed in terms of the area under the TL glow curve and peak intensity. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to develop an approach to predict human dose– response relationship and first-in-human (FIH) dose for adeno-associated virus (AAV)-mediated haemophilia gene therapy. Methods: Preclinical dose–response relationships of 7 AAV vectors were normalized to a species-invariant scale using an exponent of 0.25, and the normalized dose– response relationship was then used for FIH dose prediction. The performance of this dose–response normalization approach for FIH dose prediction was compared to that of direct body weight-based dose (vg/kg) conversion and allometric scaling approaches. Results: A power regression analysis of normalized factor VIII (FVIII) or factor IX (FIX) showed a moderate-to-strong correlation between FVIII or FIX and vector dose across 3 species (R² ranged 0.59 to 0.89), indicating it was feasible to normalize dose–response in multiple species to a species-invariant scale. When the mean values of normalized FVIII or FIX at each dose level were used for regression, the R² values of the 7 vectors were improved to be >0.84. The FIH doses predicted by the 3 approaches were ranked as allometric scaling > dose–response normalization > direct vg/kg conversion for all vectors except for rAAV2-hAAT-FIX and scAAV2/8-LP1-hFIXco. Among the 7 vectors, dose–response normalization, direct vg/kg conversion and allometric scaling generated accurate FIH dose predictions for 2, 2 and 3 vectors, respectively. Conclusion: This study first demonstrated that it is feasible to normalize dose– response relationship of AAV-mediated haemophilia gene therapy in multiple species to a species-invariant scale. The normalized dose-response relationship from preclinical species was successfully extrapolated to patients for FIH dose prediction. [ABSTRACT FROM AUTHOR]

Genetic toxicology tests are used to categorize substances as genotoxic and potentially carcinogenic. In general, test results are designated as mutagenic, not mutagenic, or inconclusive and, depending on its potential use and applicable regulations, a mutagenic result can restrict or remove a substance from further development, or assign limits to its use. In these tests, mutation responses form a continuum without a clear delineation between an increase over the background, untreated, mutant frequency and a frequency that would define the test substance as a mutagen and a potential carcinogenic hazard. This situation is illustrated using the Salmonella mutagenicity (Ames) test which is the initial, and often only, test used to characterize substances as mutagenic or nonmutagenic. It has its widest use by industry and regulatory authorities to identify potential carcinogens among chemicals in development. The OECD Test Guideline No. 471 has been adopted by regulatory agencies internationally, and describes the minimum requirements for a negative response, but does not provide a specific approach for evaluating the test data. The most widely used criterion for making yes‐or‐no mutagenicity decisions is a 2‐ or 3‐fold increase over the background (solvent) mutant frequency. Other approaches rely on formal statistics and/or expert judgment. These approaches and recently proposed modifications are evaluated here. Recommendations are made that are in conformity with the OECD guideline and are based on biological relevance and the biology of the mutagenic response rather than on arbitrary decision points (e.g., ≥2‐fold increase or p ≤.05). [ABSTRACT FROM AUTHOR]

As human activities increase in intensity and extent, ecosystems face growing threats from multiple stressors. Successful management requires identifying measurable targets, which is challenging because of data limitations, nonlinear ecosystem responses, and potentially shifting targets under multiple stressors. To identify critical management values and determine whether these values shift in the presence of multiple stressors, we use eelgrass (Zostera marina) meadows as a model system. We reviewed 20 studies that measured the effects of light and temperature on eelgrass performance, providing 109 unique study–site–treatment combinations. We modeled the interactive effect of temperature and light on eelgrass population growth rate (i.e., lateral shoot production rates) using a hierarchical generalized additive model and predicted population growth rates across a range of light levels and temperatures. We found that two critical performance metrics of population growth, zero‐growth and maximum growth rates, shifted across a gradient of light and temperature, suggesting that fixed management targets linked to population growth rates might be unsuitable for managing meadows under multiple stressors. Our approach bridges the gap between data from laboratory and field studies and could be developed into an interactive management tool. [ABSTRACT FROM AUTHOR]

Estimating microbial dose–response is an important aspect of a food safety risk assessment. In recent years, there has been considerable interest to advance these models with potential incorporation of gene expression data. The aim of this study was to develop a novel machine learning model that considers the weights of expression of Salmonella genes that could be associated with illness, given exposure, in hosts. Here, an elastic net‐based weighted Poisson regression method was proposed to identify Salmonella enterica genes that could be significantly associated with the illness response, irrespective of serovar. The best‐fit elastic net model was obtained by 10‐fold cross‐validation. The best‐fit elastic net model identified 33 gene expression–dose interaction terms that added to the predictability of the model. Of these, nine genes associated with Salmonella metabolism and virulence were found to be significant by the best‐fit Poisson regression model (p < 0.05). This method could improve or redefine dose–response relationships for illness from relative proportions of significant genes from a microbial genetic dataset, which would help in refining endpoint and risk estimations. [ABSTRACT FROM AUTHOR]

Introduction: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. Methods: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose‐response relationship between late‐life physical activity and incident dementia among older adults. Results: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose‐response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)‐hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET‐hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET‐hours/week). Discussion: This cross‐national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET‐hours of energy per week may reduce dementia risk. [ABSTRACT FROM AUTHOR]

Quantitative relationships between carcinogenic potency and mutagenic potency have been previously examined using a benchmark dose (BMD)‐based approach. We extended those analyses by using human exposure data for 48 compounds to calculate carcinogenicity‐derived and genotoxicity‐derived margin of exposure values (MOEs) that can be used to prioritize substances for risk management. MOEs for 16 of the 48 compounds were below 10,000, and consequently highlighted for regulatory concern. Of these, 15 were highlighted using genotoxicity‐derived (micronucleus [MN] dose–response data) MOEs. A total of 13 compounds were highlighted using carcinogenicity‐derived MOEs; 12 compounds were overlapping. MOEs were also calculated using transgenic rodent (TGR) mutagenicity data. For 10 of the 12 compounds examined using TGR data, the results similarly revealed that mutagenicity‐derived MOEs yield regulatory decisions that correspond with those based on carcinogenicity‐derived MOEs. The effect of benchmark response (BMR) on MOE determination was also examined. Reinterpretation of the analyses using a BMR of 50% indicated that four out of 15 compounds prioritized using MN‐derived MOEs based on a default BMR of 5% would have been missed. The results indicate that regulatory decisions based on in vivo genotoxicity dose–response data would be consistent with those based on carcinogenicity dose–response data; in some cases, genotoxicity‐based decisions would be more conservative. Going forward, and in the absence of carcinogenicity data, in vivo genotoxicity assays (MN and TGR) can be used to effectively prioritize substances for regulatory action. Routine use of the MOE approach necessitates the availability of reliable human exposure estimates, and consensus regarding appropriate BMRs for genotoxicity endpoints. [ABSTRACT FROM AUTHOR]

BACKGROUND: Over the past 14 years, the invasive vinegar fly, spotted‐wing drosophila (Drosophila suzukii), has become one of the most damaging fruit pests in the United States. With regional economic losses estimated as high as $500 million for moderate infestations, D. suzukii control represents an often‐untenable cost to growers. Management relies heavily on chemical control, which may be applied up to nine times in one season. The widespread use of chemical controls has led to concerns about insecticide resistance, and resistant field populations have already been documented in California and Michigan. RESULTS: We cultured sub‐populations of three different Minnesota field populations of D. suzukii in the laboratory and exposed them to increasing concentrations of two commonly‐used insecticides, zeta‐cypermethrin (pyrethroid) and spinetoram (spinosyn). Over the exposure period, the sub‐populations experienced an 8‐ to 45‐fold increase in insecticide concentration. We saw significant increases in the median lethal concentration (LC50) values of one sub‐population exposed to zeta‐cypermethrin and one exposed to spinetoram. Across the spinetoram exposures, we also observed significant reductions in the top mortality values for three different sub‐populations. CONCLUSION: Our results suggest that field populations of D. suzukii can develop resistance to zeta‐cypermethrin and spinetoram in short periods of time under laboratory selection but that resistance to spinosyns occurs more readily than to pyrethroids. These results support other studies that have documented spinosyn resistance in field populations and in laboratory selections. Resistance evolution to spinosyns is a particularly important issue, as they represent one of few organic insecticide options for D. suzukii. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular medications are vital for the secondary prevention of coronary arterial disease (CAD). However, the effect of cardiovascular medication may depend on the optimal adherence of the patients. This meta‐analysis aims to determine the magnitude of adherence to vascular medications that influences the absolute and relative risks (RRs) of mortality in patients with CAD in real‐world settings. Methods: The Cochrane Library, PubMed, and EMBASE databases were searched through March 1, 2022. Prospective studies reporting association as RR and 95% confidence interval between cardiovascular medication adherence and any cardiovascular events and/or all‐cause mortality in patients with CAD were included. A one‐stage robust error meta‐regression method was used to summarize the dose‐specific relationships. Results: A total of 18 studies were included. There is a significant inverse linear association between cardiovascular medication adherence and cardiovascular events (pnonlinearity =.68) or mortality (pnonlinearity =.82). The exposure‐effect analysis showed that an improvement of 20% cardiovascular medication adherence was associated with 8% or 12% lower risk of any cardiovascular events or mortality, respectively. In subgroup analysis, the benefit was observed in adherence of stain (RR: 0.90, for cardiovascular events, RR: 0.85, for mortality), angiotensin‐converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB)(RR: 0.90, for mortality), and antiplatelet agent (RR: 0.89 for mortality) but not in beta‐blocker (RR: 0.90, p =.14, for cardiovascular events, RR: 0.97, p =.32 for mortality). Estimated absolute differences per 1 million individuals per year for mortality associated with 20% improvement were 175 cases for statin, 129 cases for antiplatelet, and 117 cases for ACEI/ARB. Conclusion: Evidence from the real word showed poor adherence to vascular medications contributes to a considerable proportion of all cardiovascular disease events and mortality in patients with CAD. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the dose‐response function in multidomain interventions for dementia prevention. Method: The Multidomain Alzheimer Preventive Trial is a 3‐year randomized controlled trial comprising cognitive training, physical activity, nutrition, and omega‐3 polyunsaturated fatty acids for at‐risk older adults. The dose delivered (number of sessions attended) was modeled against global cognition, memory, and fluency in 749 participants. Interaction effects were assessed for age, sex, education, dementia score (CAIDE), frailty score, and apolipoprotein E (APOE) ε4 status. Results: The dose‐response models were non‐linear functions indicating benefits up to about 12 to 14 training hours or 15 to 20 multidomain sessions followed by a plateau. Participants who benefited from a higher dose included women, younger participants, frail individuals, and those with lower education or lower risk of dementia. Discussion: The non‐linear function indicates that a higher dose is not necessarily better in multidomain interventions. The optimal dose was about half of the potentially available sessions. [ABSTRACT FROM AUTHOR]

Background: The typological approach of the employment quality (EQ) framework offers a comprehensive lens for assessing the heterogeneity of employment experiences while concurrently acknowledging associated health risk factors. EQ incorporates multiple employment characteristics-such as working hours, wages and benefits, and union representation, among others-where standard employment relationship (SER)-like (or high EQ) features are distinguished from nonstandard features (low EQ). Low EQ features are known to relate negatively to health outcomes. Addressing limitations from previous cross-sectional studies, we contribute to longitudinal research on the link between EQ and self-rated general health in the United States. Our objectives are: (1) to investigate the association between baseline EQ and poor self-rated general health 3 years later; and (2) to examine the relation between poor self-rated health and: (a) transitioning from low EQ to SER-like employment (the scarring hypothesis); (b) transitioning from SER-like employment to low EQ (the initial-impact hypothesis); and (c) consistent low EQ status (for example, the dose-response hypothesis)., Methods: Using the American Working Conditions Survey (AWCS), baseline and follow-up data on employees' self-rated health was collected (N = 1109). An EQ typology with five categories was created via latent class cluster analysis: SER-like, Instrumental, Precarious Unsustainable, Portfolio; and Precarious Intensive employment. Each EQ segment represents a unique combination of EQ features, with SER-like and Portfolio employment reflecting overall high EQ, while Instrumental, Precarious Unsustainable, and Precarious Intensive reflect varieties of low EQ constellations. We used lagged Poisson regression to link baseline EQ to follow-up self-rated health and Poisson regression to analyze multiple EQ paths between baseline and follow-up and their association with health., Results: Precarious Unsustainable and Instrumental employment at baseline associated significantly with poor self-rated general health at follow-up. Transitioning from SER-like employment to a low-EQ segment was linked to an increased risk of poor self-rated general health, confirming the initial-impact hypothesis. No evidence was found for the scarring hypothesis. Consistent Instrumental and Precarious Unsustainable employment were both associated with poorer health, underlining the importance of the dose-response effect., Conclusions: Enhancing EQ is crucial for public health, particularly in the context of limited welfare provisions in the United States. Policy and legislative measures to improve EQ can promote better health outcomes and reduce health disparities within the working population., (© 2024 Wiley Periodicals LLC.)

Network approaches have revolutionized the study of ecological interactions. Social, movement and ecological networks have all been integral to studying infectious disease ecology. However, conventional (dyadic) network approaches are limited in their ability to capture higher‐order interactions. We present simplicial sets as a tool that addresses this limitation. First, we explain what simplicial sets are. Second, we explain why their use would be beneficial in different subject areas. Third, we detail where these areas are: social, transmission, movement/spatial and ecological networks and when using them would help most in each context. To demonstrate their application, we develop a novel approach to identify how pathogens persist within a host population. Fourth, we provide an overview of how to use simplicial sets, highlighting specific metrics, generative models and software. Finally, we synthesize key research questions simplicial sets will help us answer and draw attention to methodological developments that will facilitate this. [ABSTRACT FROM AUTHOR]

Probiotics have been used to alleviate disease transmission in aquaculture. However, there are limited studies on probiotic use in modulating tilapia lake virus (TiLV). We assessed commercially available probiotic supplements used in TiLV‐infected tilapia and performed mortality and cohabitation assays. We developed a mechanistic approach to predict dose–response interactions of probiotic effects on mortality and immune gene response. We used a susceptible–infected–mortality disease model to assess key epidemiological parameters such as transmission rate and basic reproduction number (R0) based on our viral load dynamic data. We found that the most marked benefits of probiotics are significantly associated with immune system enhancements (~30%) and reductions in disease transmission (~80%) and R0 (~70%) in tilapia populations, resulting in a higher tolerance of farming densities (~400 fold) in aquaculture. These findings provide early insights as to how probiotic use‐related factors may influence TiLV transmission and the immune responses in TiLV‐infected tilapia. Our study facilitates understanding the mode of action of probiotics in disease containment and predicting better probiotic dosages in diet and supplements to achieve the optimal culturing conditions. Overall, our analysis assures that further study of rationally designed and targeted probiotics, or mechanistic modelling is warranted on the basis of promising early data of this approach. [ABSTRACT FROM AUTHOR]

Multiple comparison procedures and modeling (MCPMod) has established itself as a method for dose‐finding under model uncertainty. A downside of MCPMod is that due to its frequentist nature in particular with respect to the multiple comparison part it is tough to incorporate historical information in a systematic fashion. A typical situation where such historical information is available is existing data for the placebo group from previous trials. There are multiple Bayesian concepts for integrating historical data in a systematic and even dynamic fashion like the meta‐analytic prior approach. In this article, we define Bayesian MCPMod (BMCPMod) that is build upon these two aspects. BMCPMod is able to mimic the results of the classical MCPMod for non‐informative priors. At the same time, it allows for the inclusion of historical data in a systematic fashion. After the definition of BMCPMod related characteristics for a Bayesian approach similar to the MCP‐testing part are derived. The BMCPMod is compared to classical MCPMod/non‐informative priors via simulations. Aspects of mixture priors, optimal contrast vectors, and impact of allocation ratios are discussed and an example for designing a BMPCMod trial is given. [ABSTRACT FROM AUTHOR]

BACKGROUND Eurasian spruce bark beetles (Ips typographus) use both attractant and anti‐attractant semiochemicals to find suitable mature host trees. Trans‐4‐thujanol is abundant in young, unsuitable spruce trees. Electrophysiological studies have demonstrated its high activity levels, but field data are lacking. RESULTS: Enantioselective GC–MS analysis showed that only (1R,4S)‐(+)‐trans‐4‐thujanol was present in Norway spruce bark volatiles. In a factorial design field‐trapping experiment, trans‐4‐thujanol alone was not attractive to Ips typographus. Traps baited with I. typographus' aggregation pheromone and trans‐4‐thujanol or the known anti‐attractant 1,8‐cineole caught fewer beetles than those baited with the aggregation pheromone alone. Catches for trans‐4‐thujanol and 1,8‐cineole were dose‐dependent. Intermediate doses of trans‐4‐thujanol and 1,8‐cineole had a similar effect. Surprisingly, in contrast to 1,8‐cineole and other known Ips anti‐attractants, which all inhibit males more strongly than females, the addition of trans‐4‐thujanol to the aggregation pheromone reduced the attraction of females more. CONCLUSION: The Norway spruce volatile (+)‐trans‐4‐thujanol is a novel I. typographus anti‐attractant with potency comparable to the known anti‐attractants 1,8‐cineole and verbenone, and is more effective for females than for males. Incorporating (+)‐trans‐4‐thujanol into anti‐attractant lures could improve protection of trees from mass attack by I. typographus. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the association between alcohol consumption and the risk of Alzheimer's disease (AD). Methods: PubMed and Web of Science databases were systematically searched as of 1 September 2019. Relative risk and 95% CI were used to evaluate the association between alcohol consumption and AD risk. Subgroup analyses based on the type of alcohol, ethnicity, study design and sex were carried out. An alcohol dose–response meta‐analysis was carried out. Results: A total of 13 studies were included in the quantitative synthesis, and six were used in the dose–response meta‐analysis. Compared with non‐drinkers, individuals who drank had a lower risk of AD (relative risk 0.68, 95% CI 0.53–0.87; I2 = 87.9%, P < 0.001). In subgroup analyses, drinking wine was found to reduce the occurrence of AD (relative risk 0.71, 95% CI 0.51–0.96). When stratified by ethnicity, sex and study design, no association was seen between AD risk and alcohol use. There was an overall non‐linear, but not significant, association between alcohol intake dose and AD risk. A significant non‐linear association was observed between excess AD risk and alcohol intake dose in men (overall P = 0.023; P for non‐linearity = 0.025) starting from 14.8 drinks per week. Women's alcohol intake dose <16.9 drinks per week showed a significant non‐linear association with decreased AD risk (overall P = 0.002; P for non‐linearity = 0.019). Conclusions: Drinking alcohol could reduce the risk of AD. Alcohol dose had a non‐linear, but non‐significant, relationship with the development of AD. The amount of alcohol consumption showed significant sex‐specific effects on AD. Geriatr Gerontol Int 2022; 22: 278–285. [ABSTRACT FROM AUTHOR]

China's profoundly rapid modernization in the past two decades has resulted in dramatic changes in indoor environmental exposures. Among these changes, exposure to phthalates has attracted increasing attention. We aimed to characterize indoor phthalate exposure and to estimate the disease burden attributable to indoor phthalate pollution from 2000 to 2017 in China. We integrated the national exposure level of indoor phthalates from literature through systematic review and Monte Carlo simulation. Dose‐response relationships between phthalate exposure and health outcomes were obtained by systematic review and meta‐analysis. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we calculated the disability‐adjusted life years (DALYs) among the general Chinese population resulting from exposure to indoor phthalate pollution. We found that DnBP, DiBP, and DEHP were the most abundant phthalates in indoor environments of residences, offices, and schools with medians of national dust phase concentration from 74.5 µg/g to 96.3 µg/g, 39.6 µg/g to 162.5 µg/g, 634.2 µg/g to 1,394.7 µg/g, respectively. The national equivalent exposure for children to phthalates in settled dust was higher than that of adults except for DiBP and DnOP. Dose‐response relationships associated with DEP, DiBP, DnBP, BBzP, and DEHP exposures were established. Between 2000 and 2017, indoor phthalate exposure in China has led to 3.32 million DALYs per year, accounting for 0.90% of total DALYs across China. The annual DALY associated with indoor phthalate pollution in China was over 2000 people per million, which is about 2~3 times of the DALY loss due to secondhand smoke (SHS) in six European countries or the sum of the DALY loss caused by indoor radon and formaldehyde in American homes. Our study indicates a considerable socioeconomic impact of indoor phthalate exposure for a modernizing human society. This suggest the need for relevant national standard and actions to reduce indoor phthalate exposure. [ABSTRACT FROM AUTHOR]

Aims: To assess association between quetiapine treatment and risk of new‐onset hypothyroidism in schizophrenia patients. Methods: We conducted a retrospective cohort study in a tertiary hospital in China between January 2016 and December 2018. Schizophrenia patients with normal thyroid tests at admission were included. Hypothyroidism, which was defined as thyroid‐stimulating hormone >4.20 mU/L and free thyroxine <12.00 pmol/L, or on L‐thyroxine prescriptions, was the outcome measure, and quetiapine treatment between admission and subsequent thyroid test was the exposure measure of this study. Adjusted relative risks and 95% confidence intervals were used to assess the independent association of quetiapine treatment with risk of new‐onset hypothyroidism. The dose–response association was further analysed by 3 quetiapine doses: low (≤<=0.2 g/d), medium (0.2–0.6 g/d), and high (>0.6 g/d). Results: A total of 2022 eligible patients were included in the final analysis. Sixty patients (15.0%) in the quetiapine group developed hypothyroidism, while 56 patients (3.5%) in the nonquetiapine group developed hypothyroidism. Relative risk (95% confidence interval) of developing hypothyroidism for quetiapine use was 4.01 (2.86–5.64) after adjusting for several potential confounding factors. A strong dose–response association between quetiapine use and risk of developing hypothyroidism was observed: adjusted relative risks (95% confidence intervals) were 1.00 (0.25–2.59), 4.22 (2.80–6.25) and 5.62 (3.66–8.38), respectively, for low‐, medium‐ and high‐dose quetiapine, as compared with no quetiapine. Conclusion: Acute phase quetiapine treatment for schizophrenia patients was strongly associated with increased risk of developing new‐onset hypothyroidism, with a clear dose–response association. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low toxin doses that do not affect mean responses in plant populations can still change the growth of subpopulations. Studies covering vegetative stages ascribed fast‐growing plants higher thresholds for growth stimulation and inhibition, compared with the rest of the population. We hypothesized that such selective effects also play a role after reproduction; that is, the offspring of glyphosate‐treated tolerant, fast‐growing phenotypes is more tolerant than the offspring of untreated plants. An experimental, high‐density barley population was exposed to a range of glyphosate concentrations in the greenhouse, and reproduction and final growth were analyzed for selective effects. Therefore, F0, F1 treated and F1 non‐treated offspring were re‐exposed to glyphosate. RESULTS: Low doses of glyphosate inhibited the growth and reproduction of slow‐growing plants at concentrations that did not change the population mean. Concentrations that inhibited average‐sized plants hormetically increased the biomass and seed yield of fast‐growing plants. Compared with F0 and F1 non‐treated offspring, F1‐treated offspring from hormetically stimulated fast‐growing plants were more glyphosate tolerant. Hence, a pesticide can shape the reproductive pattern of a plant population and alter offspring tolerance at concentrations that have no effect on average yield. CONCLUSIONS: Toxin levels that do not change the population mean still alter the reproductive output of individuals. Sensitive phenotypes suffer, whereas the reproduction of tolerant phenotypes is boosted compared with toxin‐free conditions. Because glyphosate is one of the leading herbicides in the world, tolerant phenotypes may benefit from current agricultural practices. If these results apply to other toxicants, low toxin doses may increase the fitness of tolerant phenotypes in a way not previously anticipated. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aims: In heart failure with reduced ejection fraction (HFrEF), guidelines recommend up-titration of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptors blockers (ARBs) to the maximum tolerated dose. However, some studies suggest that women might need lower doses of ACEi/ARBs than men to achieve similar treatment benefit.Methods and Results: The HEAAL trial compared low vs. high dose of losartan. We reassessed the efficacy and safety of high- vs. low-dose in men vs. women using Cox models and machine learning algorithms. The mean age was 66 years and 30% of patients were women. Men appeared to have benefited more from high-dose than from low-dose losartan, whereas women appeared to have responded similarly to low and high doses [hazard ratio (95% confidence interval) comparing high- vs. low-dose losartan for the composite outcome of all-cause death or all-cause hospitalization: 0.89 (0.81-0.98) in men and 1.10 (0.95-1.28) in women; interaction P = 0.018]. Female sex clustered along with older age, ischaemic heart failure, New York Heart Association class III/IV, and estimated glomerular filtration rate <60 mL/min. Patients with these features had a poorer response to high-dose losartan. Subgroup analyses supported no benefit from high-dose losartan in patients with poorer kidney function and severe heart failure symptoms.Conclusions: Compared with men, women might need lower doses of losartan to achieve similar treatment benefit. However, beyond sex, other factors (e.g. kidney function, age, and symptoms) may influence the response to high-dose losartan, suggesting that sex-based subgroup findings may be biased by other confounders. [ABSTRACT FROM AUTHOR]

Background: The evidence for the association between metabolic score for insulin resistance (METS‐IR) and type 2 diabetes mellitus (T2DM) is limited. We aimed to explore the association of METS‐IR and its 6‐year change with risk of incident T2DM in a rural Chinese population. Methods: We analyzed data for 12 107 participants (mean age 50.48 years). A Cox proportional‐hazard model was used to estimate the association of METS‐IR with incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs); a logistic regression model was used to assess the association of 6‐year METS‐IR change with incident T2DM by using odds ratios (ORs) and 95% CIs. We used subgroup analyses of the association of METS‐IR and its 6‐year change with incident T2DM by sex, age, and baseline fasting plasma glucose (FPG) level as well as restricted cubic splines to describe the dose‐response association. Results: The association of METS‐IR and 6‐year METS‐IR change with incident T2DM was significant (per SD unit increase: HR = 1.80, 95% CI: 1.60‐2.02 for METS‐IR, OR = 1.42, 95% CI: 1.28‐1.57 and OR = 1.59, 95% CI: 1.44‐1.76 for relative and absolute METS‐IR change). The significant association remained on subgroup analyses by sex, age, and baseline FPG level. Dose‐response analysis demonstrated that the probability of incident T2DM was significantly increased with increasing METS‐IR and 6‐year METS‐IR change. Conclusions: Increased METS‐IR and 6‐year METS‐IR change were positively associated with risk of incident T2DM in a rural Chinese population. METS‐IR may be a vital indicator for identifying T2DM. [ABSTRACT FROM AUTHOR]

The fragile X mental retardation protein (FMRP), an RNA‐binding protein, regulates cocaine‐induced neuronal plasticity and is critical for the normal development of drug‐induced locomotor sensitization, as well as reward‐related learning in the conditioned place preference assay. However, it is unknown whether FMRP impacts behaviors that are used to more closely model substance use disorders. Utilizing a cocaine intravenous self‐administration (IVSA) assay in Fmr1 knockout (KO) and wild‐type (WT) littermate mice, we find that, despite normal acquisition and extinction learning, Fmr1 KO mice fail to make a normal upward shift in responding during dose–response testing. Later, when given access to the original acquisition dose under increasing fixed ratio (FR) schedules of reinforcement (FR1, FR3, and FR5), Fmr1 KO mice earn significantly fewer cocaine infusions than WT mice. Importantly, similar deficits are not present in operant conditioning using a palatable food reinforcer, indicating that our results do not represent broad learning or reward‐related deficits in Fmr1 KO mice. Additionally, we find an FMRP target, the activity‐regulated cytoskeleton‐associated protein (Arc), to be significantly reduced in synaptic cellular fractions prepared from the nucleus accumbens of Fmr1 KO, compared with WT, mice following operant tasks reinforced with cocaine but not food. Overall, our findings suggest that FMRP facilitates adjustments in drug self‐administration behavior that generally serve to preserve reinforcement level, and combined with our similar IVSA findings in Arc KO mice may implicate Arc, along with FMRP, in behavioral shifts that occur in drug taking when drug availability is altered. [ABSTRACT FROM AUTHOR]

Optically stimulated luminescence (OSL) is used for dating in archaeology and geology, and in dosimetry of ionizing radiation. Some crystalline wide band‐gap insulators may be used as OSL radiation detectors. Recently it was found that cerium‐doped potassium sulfate crystals have promising luminescence properties. This paper presents some OSL properties of K2SO4:Ce crystals that were prepared in the form of pellets. The crystals exhibited a strong luminescence signal, good measurement repeatability, and high sensitivity for ionizing radiation. Best results were obtained after annealing at 1000°C. Dose‐dependence characteristics were determined in the range 10 mGy to 11.2 Gy. OSL decay curves consisted of several components. Fast and slow OSL components of the phosphor had different properties. The slow component was quite stable and obeyed power law dependence. It decayed in the 55 days after irradiation. Its luminescence properties depended on sample preparation and the storage time after irradiation. [ABSTRACT FROM AUTHOR]

Within the challenging context of phase II dose-finding trials, longitudinal analyses may increase drug effect detection power compared to an end-of-treatment analysis. This work proposes cLRT-Mod, a pharmacometric adaptation of the MCP-Mod methodology, which allows the use of nonlinear mixed effect models to first detect a dose-response signal and then identify the doses for the confirmatory phase while accounting for model structure uncertainty. The method was evaluated through extensive clinical trial simulations of a hypothetical phase II dose-finding trial using different scenarios and comparing different methods such as MCP-Mod. The results show an increase in power using cLRT with longitudinal data compared to an EOT multiple contrast tests for scenarios with small sample size and weak drug effect while maintaining pre-specifiability of the models prior to data analysis and the nominal type I error. This work shows how model averaging provides better coverage probability of the drug effect in the prediction step, and avoids under-estimation of the size of the confidence interval. Finally, for illustration purpose cLRT-Mod was applied to the analysis of a real phase II dose-finding trial. [ABSTRACT FROM AUTHOR]

The objective of this study was to conduct QMRA (quantitative microbial risk assessment) of Clostridium perfringens through soy sauce consumption. Four hundred and ninety soy sauce samples from markets were analyzed to detect C. perfringens. Temperature and time were also measured during transportation and display of soy sauce. A primary model was developed by fitting the Weibull model to the C. perfringens cell counts in soy sauce at 7–35°C, and δ (the time needed to decrease 1 log CFU/ml) and ρ (curve shape) were calculated. The parameters were analyzed, using the Exponential model (secondary model) as a function of temperature. The consumption amount and percentage of soy sauce were surveyed, and a dose‐response model was searched. Using all collected data, a simulation model was prepared in the @RISK program to estimate the probability of C. perfringens foodborne illness by soy sauce consumption. C. perfringens were negative in 490 samples. Thus, the initial contamination level was estimated to be −2.9 log CFU/ml. The developed predictive models showed that C. perfringens cell counts decreased during transportation and display. The average consumption amounts, and the percentage of soy sauce were 7.81 ml and 81.2%, respectively. The simulation showed that the probability of C. perfringens foodborne illness by consumption of soy sauce was 1.7 × 10–16 per person per day. Therefore, the risk of C. perfringens by consumption of soy sauce is low in Korea. [ABSTRACT FROM AUTHOR]

National mortality statistics commonly provide disease‐specific absolute and relative frequencies of death by sex and age, but not by exposure status. However, it is often of interest to know how many of the diseased individuals, that is the cases, were exposed or not exposed to a specific risk factor. We present two methods to estimate the proportion and the number of exposed and nonexposed cases, both of which require an estimate of the exposure prevalence in the nondiseased population. Method I additionally requires an estimate of the relative effect of exposure, that is a relative risk function if the exposure has a continuous distribution, or a relative risk estimate for each category if the exposure is categorical. Method II additionally requires an estimate of the disease rate among the nonexposed. We provide theoretical justifications, discuss practical limitations, and provide an R script to calculate the probability for nonexposure among the diseased, and compare the approaches. Both methods are subsequently applied to the estimation of the number of never smokers among lung cancer deaths. The two suggested methods rely on the availability of specific data sources and might therefore be applicable in different research settings. Both methods yield unbiased estimates of the number of nonexposed cases, given that the respective underlying assumptions are fulfilled. [ABSTRACT FROM AUTHOR]

Due to global changes, fish are increasingly exposed to immune challenges associated with disease outbreaks in aquatic ecosystems. Adjustments in physiology and behavior are generally critical to maintaining homeostasis after an immune challenge, but there is limited knowledge on the specific thresholds and dynamics of responses across levels of biological organization in fish. In this study, we tested how different concentrations of an antigens mixture (phytohemagglutinin and lipopolysaccharide) affected innate immunity with potential consequences on oxidative stress, energy reserves, body condition, and behavior across time, using the common gudgeon (Gobio sp.) as model species. The immune challenge induced a transitory increase in lytic enzyme activity (i.e., lysozyme) and local immune response (i.e., skin swelling) 2 days after the antigen injection. The available energy stored in muscle was also reduced 4 days after injection, without inducing oxidative stress at the cellular level. Overall, the immune challenge induced limited costs at the molecular and cellular levels but had strong effects at the whole organism level, especially on behavior. Indeed, fish swimming activity and sociability were affected in a dose‐ and time‐dependent manner. These results suggest that immune challenges have dose‐dependent effects across levels of biological organization and that behavior is a key response trait to cope with pathogen‐induced immune costs in the wild, although fitness consequences remain to be tested. Highlights: The costs induced by immune challenge vary in fish in a dose‐ and time‐dependent manner.Medium and high doses of antigens mostly affected immune and behavioral traits with limited effects on fish condition, likely due to energy reallocation. [ABSTRACT FROM AUTHOR]

What is known and Objective: Non‐clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ‐associated reduction in viral load from small studies in COVID‐19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed. Methods: Published studies and rapidly emerging data were reviewed to gather evidence on safety and efficacy of CQ and HCQ in patients with COVID‐19 infection or as prophylaxis. The focus is on clinically relevant efficacy endpoints and their adverse effects on QT interval. Results and Discussion: At the doses used, the two agents, given alone or with azithromycin (AZM), are not effective in COVID‐19 infection. The choice of (typically subtherapeutic) dosing regimens, influenced partly by "QT‐phobia," varied widely and seems anecdotal without any pharmacologically reliable supporting clinical evidence. A substantial proportion of patients receiving CQ/HCQ/AZM regimen developed QTc interval prolongation, many with absolute QTc interval exceeding the potential proarrhythmic threshold, but very few developed proarrhythmia. What is new and Conclusion: The strategy to repurpose CQ/HCQ to combat COVID‐19 infection is overshadowed by concerns about their QT liability, resulting in choice of potentially subtherapeutic doses. Although the risk of QT‐related proarrhythmia is real, it is low and manageable by careful monitoring. Recent discontinuation of HCQ from at least four large studies effectively marks the end of efforts at repurposing of CQ or HCQ for COVID‐19 infection. This episode leaves behind important questions on dose selection and risk/benefit balance in repurposing drugs generally. [ABSTRACT FROM AUTHOR]