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The accumulation of nutrients during diapause preparation is crucial because any lack of nutrition will reduce the likelihood of insects completing diapause, thereby decreasing their chances of survival and reproduction. The fall webworm, Hyphantria cunea, diapause as overwintering pupae and their diapause incidence and diapause intensity are regulated by the photoperiod. In this study, we test the hypothesis that photoperiod influences energy reserve accumulation during diapause preparation in fall webworm. We found that the body size and mass, lipid and carbohydrate content of pupae with a short photoperiod during the diapause induction phase were significantly greater than those of pupae with a relatively short photoperiod, and the efficiency of converting digested food and ingested food into body matter was greater in the short-photoperiod diapause-destined larvae than the relatively short-photoperiod diapause-destined larvae. We also observed higher lipase and amylase activities in short-photoperiod diapause-destined larvae relative to the counterparts. However, no obvious difference was found in protein and protease in the pupae with a short photoperiod during the diapause induction phase and short-photoperiod diapause-destined larvae compared with the counterparts. Therefore, we conclude that the energy reserve patterns of diapausing fall webworm pupae are plastic and that short-photoperiod diapause-destined larvae increase their energy reserves by improving their feeding efficiency and increase their lipid and carbohydrate stores by increasing the lipase and amylase activities in the midgut.
We investigated the effects of botulinum toxin on gait in Parkinson’s disease (PD) patients with foot dystonia. Six patients underwent onabotulinum toxin A injection and were assessed by Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), visual analog scale (VAS) of pain, Timed Up and Go (TUG), Berg Balance Test (BBT), and 3D gait analysis at baseline, 1 month, and 3 months. BFMDRS (p = 0.002), VAS (p = 0.024), TUG (p = 0.028), and BBT (p = 0.034) were improved. Foot pressures at Toe 1 (p = 0.028) and Midfoot (p = 0.018) were reduced, indicating botulinum toxin’s effects in alleviating the dystonia severity and pain and improving foot pressures during walking in PD.
Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.
In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.
Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = −0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.
Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.
To understand the characteristics and influencing factors related to cluster infections in Jiangsu Province, China, we investigated case reports to explore transmission dynamics and influencing factors of scales of cluster infection. The effectiveness of interventions was assessed by changes in the time-dependent reproductive number (Rt). From 25th January to 29th February, Jiangsu Province reported a total of 134 clusters involving 617 cases. Household clusters accounted for 79.85% of the total. The time interval from onset to report of index cases was 8 days, which was longer than that of secondary cases (4 days) (χ2 = 22.763, P < 0.001) and had a relationship with the number of secondary cases (the correlation coefficient (r) = 0.193, P = 0.040). The average interval from onset to report was different between family cluster cases (4 days) and community cluster cases (7 days) (χ2 = 28.072, P < 0.001). The average time interval from onset to isolation of patients with secondary infection (5 days) was longer than that of patients without secondary infection (3 days) (F = 9.761, P = 0.002). Asymptomatic patients and non-familial clusters had impacts on the size of the clusters. The average reduction in the Rt value in family clusters (26.00%, 0.26 ± 0.22) was lower than that in other clusters (37.00%, 0.37 ± 0.26) (F = 4.400, P = 0.039). Early detection of asymptomatic patients and early reports of non-family clusters can effectively weaken cluster infections.
It is essential to investigate the experiences behind why adolescents start and continue to self-harm in order to develop targeted treatment and prevent future self-harming behaviours.
The aims of this study are to understand the motivations for initiating and repeating nonfatal self-harm, the different methods used between first-time and repeated self-harm and the reasons that adolescents do not seek help from health services.
Adolescents with repeated nonfatal self-harm experiences were recruited to participate in individual, semi-structured qualitative interviews. The interviews were analysed with interpretative phenomenological analysis.
We found that nonfatal self-harm among adolescents occurred comparatively early and was often triggered by specific reasons. However, the subsequent nonfatal self-harm could be causeless, with repeated self-harm becoming a maladaptive coping strategy to handle daily pressure and negative emotions. The choice of tools used was related to the ease of accessibility, the life-threatening risk and the size of the scars. Adolescents often concealed their scars on purpose, which made early identification insufficient. Peer influence, such as online chat groups encouraging self-harm by discussing and sharing self-harm pictures, could also lead to increased self-harm. The results also included participants’ opinions on how to stop nonfatal self-harm and their dissatisfaction with the current healthcare services.
The current study provides important implications both for early identification and interventions for adolescents who engage in repeated nonfatal self-harm, and for individualising treatment planning that benefits them. It is also worthwhile to further investigate how peer influence and social media may affect self-harm in adolescents.
The ab initio molecular dynamics (MD) simulations using an atom-centered density matrix propagation method are carried out in the first time to investigate the dissociative electron attachment (DEA) processes of adenine and its tautomer in the gas phase. Since the incoming electron are captured on the lowest π∗ anti-bond orbital, which is led to the different N–H bond, the C–H bond and the C–N bond are broken. The dominant anion observed in DEA dissociation process is the closed-shell dehydrogenated anion (Ade − H)−. The additional anions (Ade − NH2)− and (Ade − 2H)− are also obtained in ADMP simulation. The results are well consistent with the previous DEA experimental results. Thus, the ADMP method is used to gain a more intuitive and better understanding of the necessary dissociation process in the DEA experiment.
The outbreak of coronavirus disease-2019 (COVID-19) impacts public health dramatically around the world. The demographic characteristics, exposure history, dates of illness onset and dates of confirmed diagnosis were collected from the data of 24 family clusters from Beijing. The characteristics of the cases and the estimated key epidemiologic time-to-event distributions were described. The basic reproductive number (R0) was calculated. Among 89 confirmed COVID-19 patients from 24 family clusters, the median age was 38.0 years and 43.8% were male. The median of incubation period was 5.08 days (95% confidence interval (CI) 4.17–6.21). The median of serial interval was 6.00 days (95% CI 5.00–7.00). The basic reproductive number (R0) was 2.06 (95% CI 2.02–2.08). The median of onset-to-care-seeking days and the median of onset-to-hospital admission days were significantly reduced after 23 January 2020, which implied the enhanced public health awareness among families. With epidemic containment measures in place, the results can inform health authorities about possible extent of epidemic transmission within families. Furthermore, following initiation of interventions, public health measures are not only important for curbing the epidemic spread at the community level but also improve health seeking behaviour at the individual level.
Sugarcane brown rust, caused by Puccinia melanocephala, is one of the main diseases of sugarcane in China. The identification and discovery of new resistance genes have important theoretical and practical significance for preventing outbreaks of brown rust and ensuring the sustainable production of sugarcane. To screen for polymorphic simple-sequence repeat (SSR) molecular markers for localization of brown rust resistance genes, we used two populations that are suitable for genetic linkage map construction and mapping of new resistance genes to construct resistant and susceptible genetic pools. We then screened 449 pairs of primers to identify polymorphic SSR markers in the parental lines and the resistant/susceptible genetic pools. The results showed that 25 pairs of primers directed amplification of polymorphic DNA fragments between the parents of the cross combination ‘Yuetang 03-393’ × ‘ROC 24’, and 16 pairs of primers amplified polymorphic fragments between the parents of the cross combination ‘Liucheng 03-1137’ × ‘Dezhe 93-88’. Four pairs of primers (SMC236CG, SCESSR0928, SCESSR0636 and SCESSR2551) amplified polymorphic DNA fragments between the parental lines and the resistant/susceptible genetic pools in ‘Yuetang 03-393’ × ‘ROC 24’. The results of this study will establish a solid foundation for the mapping of new brown rust resistance genes, genetic linkage map construction and the development of closely-associated molecular markers in sugarcane.
To assess the prevalence of metabolic syndrome (MetS) in Chinese adults living in Ningbo and to examine the association between alcohol consumption, and MetS and its medical components.
A representative survey in Ningbo was conducted in 2015 covering socio-demography. A food frequent questionnaire together with additional questionnaires was used to collect information on alcohol consumption, diet, demography, lifestyle, and medical information. Multivariable logistic regression and generalized linear models were used to examine the association between alcohol consumption, and both MetS and its medical components, respectively.
Total 2853 adults ≥20 years (44% men) in this final analysis.
The prevalence of frequent alcohol drinkers and MetS were 29.9% and 28.0%, respectively. Significantly higher prevalence of MetS and mean values of medical components were found in the group of frequent alcohol drinkers with an exception for HDL-C, compared to less or non-alcohol drinkers. Frequent alcohol consumption was associated with higher odds of developing MetS and positively associated with medical components excepting waist circumference.
Frequent alcohol consumption contributed to higher prevalence of MetS, and unfavorable influence on MetS and its medical components among Chinese adults. A public health intervention on alcohol restriction is necessary for the prevention and control the ongoing epidemic MetS.
Cytochrome P450 monooxygenases (P450s) play significant roles in protecting organisms from abiotic stress damage. Here, we report the sequence and characterization of a P450s gene (AccCYP4AV1), isolated from Apis cerana cerana Fabricius. The open reading frame of AccCYP4AV1 is 1506 base pairs long and encodes a predicted protein of 501 amino acids and 57.84 kDa, with an isoelectric point of 8.67. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis indicated that AccCYP4AV1 is more highly expressed in the midgut than in other tissues. In addition, the highest expression occurs in newly emerged adult workers, followed by the first instar of the larval stage. In addition, the expression of the AccCYP4AV1 was upregulated by low temperature (4 °C), ultraviolet radiation, hydrogen peroxide, paraquat, and dichlorvos treatments. In contrast, AccCYP4AV1 transcription was downregulated by other abiotic stress conditions: exposure to increased temperature (44 °C), deltamethrin, cadmium chloride, and mercury (II) chloride. Moreover, when AccCYP4AV1 was knocked-down by RNA interference, the results suggested that multiple antioxidant genes (AccsHSP22.6, AccSOD2, AccTpx1, and AccTpx4) were downregulated and antioxidant genes AccGSTO1 and AccTrx1 were upregulated. The activity levels of peroxidase and catalase were upregulated in the AccCYP4AV1-knocked-down samples, compared with those in the control groups. These findings suggest that the AccCYP4AV1 protein might be involved in the defense against abiotic stress damage.
Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L−1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.
Identifying effective treatments is a critical issue for Alzheimer’s dementia (AD). The pathological amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Brain stimulation in dementia research, especially with relatively safe tDCS, has been taken seriously recently. In theory, tDCS affects long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Recently, an increasing number of studies have been conducted to evaluate the efficacy of tDCS in AD and concluded a positive therapeutic effect. Currently, there are no studies of tDCS for AD in Taiwan. In this study, we investigate the effects of tDCS in AD.
Using a double-blind, randomized and sham- controlled trial design, Sixteen AD aged 55-90 years (8 active, mean age 73.88 and 8 sham, mean age 74.75) were included in the study. AD diagnostics is according to DSM-5 criteria. The CDR ratings of AD participants ranged from 0.5 to 2. All subjects completed ten consecutive daily sessions in which they received either an active or a sham tDCS over the left dorsal lateral prefrontal cortex (anodal) and a cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 35 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI and WCST, before and after these treatment sessions on the first day and 4 weeks later. Chi- square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess the differences in participant demographic characteristics and to compare the differences among groups.
The active group showed significant improvement in total correct item, Conceptual level Responses (reflecting insight into the correct sorting principles), Categories Completed (reflecting overall success), and Trials to complete first categories (reflecting initial conceptual ability) of WCST 4 weeks later after the final stimulation. There were no statistically significant differences between before and after the 10-session course for the sham group.
tDCS stimulation improves cognitive operation and Conceptual Ability of AD.
A recently developed pneumonia caused by SARS-CoV-2 has quickly spread across the world. Unfortunately, a simplified risk score that could easily be used in primary care or general practice settings has not been developed. The objective of this study is to identify a simplified risk score that could easily be used to quickly triage severe COVID-19 patients. All severe and critical adult patients with laboratory-confirmed COVID-19 on the West campus of Union Hospital, Wuhan, China, from 28 January 2020 to 29 February 2020 were included in this study. Clinical data and laboratory results were obtained. CURB-65 pneumonia score was calculated. Univariate logistic regressions were applied to explore risk factors associated with in-hospital death. We used the receiver operating characteristic curve and multivariate COX-PH model to analyse risk factors for in-hospital death. A total of 74 patients (31 died, 43 survived) were finally included in the study. We observed that compared with survivors, non-survivors were older and illustrated higher respiratory rate, neutrophil-to-lymphocyte ratio, D-dimer and lactate dehydrogenase (LDH), but lower SpO2 as well as impaired liver function, especially synthesis function. CURB-65 showed good performance for predicting in-hospital death (area under curve 0.81, 95% confidence interval (CI) 0.71–0.91). CURB-65 ⩾ 2 may serve as a cut-off value for prediction of in-hospital death in severe patients with COVID-19 (sensitivity 68%, specificity 81%, F1 score 0.7). CURB-65 (hazard ratio (HR) 1.61; 95% CI 1.05–2.46), LDH (HR 1.003; 95% CI 1.001–1.004) and albumin (HR 0.9; 95% CI 0.81–1) were risk factors for in-hospital death in severe patients with COVID-19. Our study indicates CURB-65 may serve as a useful prognostic marker in COVID-19 patients, which could be used to quickly triage severe patients in primary care or general practice settings.
A suite of Jurassic–Cretaceous migmatites was newly identified in the Liaodong Peninsula of the eastern North China Craton (NCC). Anatexis is commonly associated with crustal thickening. However, the newly identified migmatites were formed during strong lithospheric thinning accompanied by voluminous magmatism and intense deformation. Field investigations show that the migmatites are spatially associated with low-angle detachment faults. Numerous leucosomes occur either as isolated lenses or thin layers (dykes), parallel to or cross-cutting the foliation. Peritectic minerals such as titanite and sillimanite are distributed mainly along the boundaries of reactant minerals or are accumulated along the foliation. Most zircons show distinct core–rim structures, and the rims have low Th/U ratios (0.01–0.24). Zircon U–Pb dating results indicate that the protoliths of the migmatites were either the Late Triassic (224–221 Ma) diorites or metasedimentary rocks deposited sometime after c. 1857 Ma. The zircon overgrowth rims record crystallization ages of 173–161 Ma and 125 Ma, which represent the formation time of leucosomes. These ages are consistent with those reported magmatic events in the Liaodong Peninsula and surrounding areas. The leucosomes indicate a strong anatectic event during the Jurassic–Cretaceous period. Partial melting occurred through the breakdown of muscovite and biotite with the presence of water-rich fluid under a thermal anomaly regime. The possible mechanism that caused the 173–161 Ma and 125 Ma anatectic events was intimately related to the regional crustal extension during the lithospheric thinning of the NCC. Meanwhile, the newly generated melts further weakened the rigidity of the crust and enhanced the extension.
Accumulating studies have found structural and functional abnormalities of the striatum in bipolar disorder (BD) and major depressive disorder (MDD). However, changes in intrinsic brain functional connectivity dynamics of striato-cortical circuitry have not been investigated in BD and MDD. This study aimed to investigate the shared and specific patterns of dynamic functional connectivity (dFC) variability of striato-cortical circuitry in BD and MDD.
Brain resting-state functional magnetic resonance imaging data were acquired from 128 patients with unmedicated BD II (current episode depressed), 140 patients with unmedicated MDD, and 132 healthy controls (HCs). Six pairs of striatum seed regions were selected: the ventral striatum inferior (VSi) and the ventral striatum superior (VSs), the dorsal-caudal putamen (DCP), the dorsal-rostral putamen (DRP), and the dorsal caudate and the ventral-rostral putamen (VRP). The sliding-window analysis was used to evaluate dFC for each seed.
Both BD II and MDD exhibited increased dFC variability between the left DRP and the left supplementary motor area, and between the right VRP and the right inferior parietal lobule. The BD II had specific increased dFC variability between the right DCP and the left precentral gyrus compared with MDD and HCs. The MDD had increased dFC variability between the left VSi and the left medial prefrontal cortex compared with BD II and HCs.
The patients with BD and MDD shared common dFC alteration in the dorsal striatal-sensorimotor and ventral striatal-cognitive circuitries. The patients with MDD had specific dFC alteration in the ventral striatal-affective circuitry.
More than 80% of coronavirus disease 2019 (COVID-19) cases are mild or moderate. In this study, a risk model was developed for predicting rehabilitation duration (the time from hospital admission to discharge) of the mild-moderate COVID-19 cases and was used to conduct refined risk management for different risk populations.
A total of 90 consecutive patients with mild-moderate COVID-19 were enrolled. Large-scale datasets were extracted from clinical practices. Through the multivariable linear regression analysis, the model was based on significant risk factors and was developed for predicting the rehabilitation duration of mild-moderate cases of COVID-19. To assess the local epidemic situation, risk management was conducted by weighing the risk of populations at different risk.
Ten risk factors from 44 high-dimensional clinical datasets were significantly correlated to rehabilitation duration (P < 0.05). Among these factors, 5 risk predictors were incorporated into a risk model. Individual rehabilitation durations were effectively calculated. Weighing the local epidemic situation, threshold probability was classified for low risk, intermediate risk, and high risk. Using this classification, risk management was based on a treatment flowchart tailored for clinical decision-making.
The proposed novel model is a useful tool for individualized risk management of mild-moderate COVID-19 cases, and it may readily facilitate dynamic clinical decision-making for different risk populations.
The aim of this study was to determine the most cost-effective strategy for the prevention and control of multidrug-resistant organisms (MDROs) in intensive care units (ICUs) in areas with limited health resources. The study was conducted in 12 ICUs of four hospitals. The total cost for the prevention of MDROs and the secondary attack rate (SAR) of MDROs for each strategy were collected retrospectively from 2046 subjects from January to December 2017. The average cost-effectiveness ratio (CER), incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were calculated. Hand hygiene (HH) had the lowest total cost (2149.6 RMB) and SAR of MDROs (8.8%) while single-room isolation showed the highest cost (33 700.2 RMB) and contact isolation had the highest SAR of MDROs (31.8%). The average cost per unit infection prevention was 24 427.8 RMB, with the HH strategy followed by the environment disinfection strategy (CER = 21 314.67). HH had the highest iterative cost effect under willingness to pay less than 2000 RMB. Due to the low cost for repeatability and obvious effectiveness, we conclude that HH is the optimal strategy for MDROs infections in ICUs in developing countries. The cost-effectiveness of the four prevention strategies provides some reference for developing countries but multiple strategies remain to be examined.
In late December 2019, patients of atypical pneumonia due to an unidentified microbial agent were reported in Wuhan, Hubei Province, China. Subsequently, a novel coronavirus was identified as the causative pathogen which was named SARS-CoV-2. As of 12 February 2020, more than 44 000 cases of SARS-CoV-2 infection have been confirmed in China and continue to expand. Provinces, municipalities and autonomous regions of China have launched first-level response to major public health emergencies one after another from 23 January 2020, which means restricting movement of people among provinces, municipalities and autonomous regions. The aim of this study was to explore the correlation between the migration scale index and the number of confirmed coronavirus disease 2019 (COVID-19) cases and to depict the effect of restricting population movement. In this study, Excel 2010 was used to demonstrate the temporal distribution at the day level and SPSS 23.0 was used to analyse the correlation between the migration scale index and the number of confirmed COVID-19 cases. We found that since 23 January 2020, Wuhan migration scale index has dropped significantly and since 26 January 2020, Hubei province migration scale index has dropped significantly. New confirmed COVID-19 cases per day in China except for Wuhan gradually increased since 24 January 2020, and showed a downward trend from 6 February 2020. New confirmed COVID-19 cases per day in China except for Hubei province gradually increased since 24 January 2020, and maintained at a high level from 24 January 2020 to 4 February 2020, then showed a downward trend. Wuhan migration scale index from 9 January to 22 January, 10 January to 23 January and 11 January to 24 January was correlated with the number of new confirmed COVID-19 cases per day in China except for Wuhan from 22 January to 4 February. Hubei province migration scale index from 10 January to 23 January and 11 January to 24 January was correlated with the number of new confirmed COVID-19 cases per day in China except for Hubei province from 22 January to 4 February. Our findings suggested that people who left Wuhan from 9 January to 22 January, and those who left Hubei province from 10 January to 24 January, led to the outbreak in the rest of China. The ‘Wuhan lockdown’ and the launching of the first-level response to this major public health emergency may have had a good effect on controlling the COVID-19 epidemic. Although new COVID-19 cases continued to be confirmed in China outside Wuhan and Hubei provinces, in our opinion, these are second-generation cases.
For the guarantee of the long-distance transport of the bunches of China Initiative Accelerator Driven System (CIADS), a new scheme is proposed that extra magnetic field is used in the accelerator-target coupling section before the windowless target to minimize the self-modulation (SM) mechanism. Particle-in-cell simulations are carried out to study the influence of the solenoidal magnetic field on the self-modulation mechanism when long proton bunches move in the background plasmas. The long proton bunches used in the simulations are similar to these in the linear accelerator of CIADS. It is found that the presence of the solenoidal magnetic field will significantly inhibit the self-modulation process. For the strong magnetic field, the longitudinal separation and transverse focusing of the long bunches disappear. We attribute these phenomena to the reason that the strong solenoidal magnetic field restricts the transverse movement of plasma electrons. Thus, there are not enough electrons around the bunch to compensate the space charge effect. Moreover, without transverse current, the longitudinal pinched effect disappears, and the long bunch can not be separated into small pulses anymore.
The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.