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Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD).
Methods
In this case–control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities.
Results
In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC.
Conclusions
The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.
COVID-19 has long-term impacts on public mental health, while few research studies incorporate multidimensional methods to thoroughly characterise the psychological profile of general population and little detailed guidance exists for mental health management during the pandemic. This research aims to capture long-term psychological profile of general population following COVID-19 by integrating trajectory modelling approaches, latent trajectory pattern identification and network analyses.
Methods
Longitudinal data were collected from a nationwide sample of 18 804 adults in 12 months after COVID-19 outbreak in China. Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Insomnia Severity Index were used to measure depression, anxiety and insomnia, respectively. The unconditional and conditional latent growth curve models were fitted to investigate trajectories and long-term predictors for psychological symptoms. We employed latent growth mixture model to identify the major psychological symptom trajectory patterns, and ran sparse Gaussian graphical models with graphical lasso to explore the evolution of psychopathological network.
Results
At 12 months after COVID-19 outbreak, psychological symptoms generally alleviated, and five psychological symptom trajectories with different demographics were identified: normal stable (63.4%), mild stable (15.3%), mild-increase to decrease (11.7%), mild-decrease to increase (4.0%) and moderate/severe stable (5.5%). The finding indicated that there were still about 5% individuals showing consistently severe distress and approximately 16% following fluctuating psychological trajectories, who should be continuously monitored. For individuals with persistently severe trajectories and those with fluctuating trajectories, central or bridge symptoms in the network were mainly ‘motor abnormality’ and ‘sad mood’, respectively. Compared with initial peak and late COVID-19 phase, aftermath of initial peak might be a psychologically vulnerable period with highest network connectivity. The central and bridge symptoms for aftermath of initial peak (‘appetite change’ and ‘trouble of relaxing’) were totally different from those at other pandemic phases (‘sad mood’).
Conclusions
This research identified the overall growing trend, long-term predictors, trajectory classes and evolutionary pattern of psychopathological network of psychological symptoms in 12 months after COVID-19 outbreak. It provides a multidimensional long-term psychological profile of the general population after COVID-19 outbreak, and accentuates the essentiality of continuous psychological monitoring, as well as population- and time-specific psychological management after COVID-19. We believe our findings can offer reference for long-term psychological management after pandemics.
The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019.
Design:
All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review.
Setting:
All data sourced from the GBD Study 2019.
Participants:
All age groups for both sexes.
Results:
The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe.
Conclusions:
The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.
Our study aimed to investigate the epidemiology of extrapulmonary tuberculosis (EPTB) and analyse the epidemiological characteristics of EPTB patients with or without pulmonary tuberculosis (PTB). EPTB cases admitted in our hospital from January 2015 to December 2020 were included. Uni- and multi-variable logistic regression analysis was carried out to identify risk factors and prognostic factors of concomitant EPTB and PTB or exclusively EPTB. A total of 3488 EPTB patients were reviewed, including 2086 patients with concurrent PTB and EPTB, and 1402 patients with exclusively EPTB. Logistic regression analysis showed that age >60 years (OR = 1.674, 95% CI = 1.438–1.949, P < 0.001) and female (OR = 1.325, 95% CI = 1.155–1.520, P < 0.001) were risk factors of exclusively EPTB, while co-morbidities (OR = 0.676, 95% CI = 0.492–0.929, P = 0.016) and severe symptoms (OR = 0.613, 95% CI = 0.405–0.929, P = 0.021) were risk factors for concurrence of EPTB and PTB. Age >60 years was an independent prognostic factor in EPTB patients with or without PTB (HR = 11.059, 95%CI = 5.097–23.999, P < 0.001; HR = 23.994, 95%CI = 3.093–186.151, P = 0.0020). Female gender was an independent prognostic factor in patients with concurrent PTB and EPTB (HR = 23.994, 95%CI = 3.093–186.151, P = 0.002). Our study disclosed the differential epidemiological characteristics of EPTB patients with or without PTB in China.
Background: Singapore General Hospital (SGH) is the largest acute tertiary-care hospital in Singapore. Healthcare workers (HCWs) are at risk of acquiring COVID-19 in both the community and workplaces. SGH has a robust exposure management process including prompt contact tracing, immediate ring fencing, lock down of affected cubicles or single room isolation for patient contacts, and home isolation orders for staff contacts of COVID-19 cases during the containment phase of the pandemic. Contacts were also placed on enhanced surveillance with PCR testing on days 1 and 4 as well as daily antigen rapid tests (ARTs) for 10 days after exposure. Here, we describe the characteristic of HCWs with COVID-19 during the third wave of the COVID-19 pandemic. Methods: This retrospective observational study included all SGH HCWs who acquired COVID-19 during the third wave (ie, the 18-week period from September 1 to December 31, 2021) of the COVID-19 pandemic. Univariate analysis was used to compare characteristics of work-associated infection (WAI) and community-acquired infection (CAI) among HCWs. Results: Among a workforce of >10,000 at SGH, 335 HCWs acquired COVID-19 during study period. CAI (exposure to known clusters or household contact) accounted for 111 HCW infections (33.1%). Also, 48 HCWs (14.3%) had a WAI (ie, acquired at their work places where there was no patient contact). Among WAsI, only 5 HCWs had hospital-acquired infection (confirmed by phylogenetic analysis). The sources of exposure for the remaining 176 HCWs were unknown. Weekly incidence of COVID-19 among HCWs was comparable to the epidemiology curve of all cases in Singapore (Fig. 1 and 2). The mean age of HCWs with COVID-19 was 39.6 years, and most were women. At the time of positive SARS-CoV-2 PCR test, 223 HCWs were symptomatic, and 67 (20.0%) of them had comorbidities. Only 16 HCWs (4.8%) required hospitalization, and all recovered fully with no mortality (Table 1). Being female was associated with community COVID-19 acquisition (OR, 4.6, P Conclusions: During the thrid wave of the COVID-19 pandemic, a higher percentage of HCWs at SGH acquired the infection from the community than from the workplace. Safe management measures, such as universal masking, social distancing, and robust exposure management processes including prompt contact tracing and environmental disinfection, can reduce the risk of COVID-19 in the hospital work environment.
Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 δ (delta) variant. Genomic analysis facilitated timely cluster detection and uncovered additional linkages via HCWs moving between clinical areas and among HCWs sharing a common lunch area, enabling early intervention.
To describe OXA-48–like carbapenem-producing Enterobacteriaceae (CPE) outbreaks at Singapore General Hospital between 2018 and 2020 and to determine the risk associated with OXA-48 carriage in the 2020 outbreak.
Design:
Outbreak report and case–control study.
Setting:
Singapore General Hospital (SGH) is a tertiary-care academic medical center in Singapore with 1,750 beds.
Methods:
Active surveillance for CPE is conducted for selected high-risk patient cohorts through molecular testing on rectal swabs or stool samples. Patients with CPE are isolated or placed in cohorts under contact precautions. During outbreak investigations, rectal swabs are repeated for culture. For the 2020 outbreak, a retrospective case–control study was conducted in which controls were inpatients who tested negative for OXA-48 and were selected at a 1:3 case-to-control ratio.
Results:
Hospital wide, the median number of patients with healthcare-associated OXA-48 was 2 per month. In the 3-year period between 2018 and 2020, 3 OXA-48 outbreaks were investigated and managed, involving 4 patients with Klebsiella pneumoniae in 2018, 55 patients with K. pneumoniae or Escherichia coli in 2019, and 49 patients with multispecies Enterobacterales in 2020. During the 2020 outbreak, independent risk factors for OXA-48 carriage on multivariate analysis (49 patients and 147 controls) were diarrhea within the preceding 2 weeks (OR, 3.3; 95% CI, 1.1–10.7; P = .039), contact with an OXA-48–carrying patient (OR, 8.7; 95% CI, 1.9–39.3; P = .005), and exposure to carbapenems (OR, 17.2; 95% CI, 2.2–136; P = .007) or penicillin (OR, 16.6; 95% CI, 3.8–71.0; P < .001).
Conclusions:
Multispecies OXA-48 outbreaks in our institution are likely related to a favorable ecological condition and selective pressure exerted by antimicrobial use. The integration of molecular surveillance epidemiology of the healthcare environment is important in understanding the risk of healthcare–associated infection to patients.
Prolonged parturition duration has been widely demonstrated to be a risk factor for incidence of stillbirth. This study evaluated the supply of dietary fibre on the parturition duration, gut microbiota and metabolome using sows as a model. A total of 40 Yorkshire sows were randomly given diet containing normal level of dietary fibre (NDF, 17·5 % dietary fibre) or high level of dietary fibre (HDF, 33·5 % dietary fibre). Faecal microbiota profiled with 16S rRNA amplicon sequencing, SCFA and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results showed that HDF diet significantly improved the parturition process as presented by the shorter parturition duration. HDF diet increased the abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFA levels in the faeces and plasma of sows at parturition were elevated in HDF group. The abundances of fifteen and twelve metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in energy metabolism and bacterial metabolism. Correlation analysis also showed associations between specific bacteria taxa and metabolites. Collectively, our study indicates that the improvement of parturition duration by high fibre intake in late gestation is associated with gut microbiota, production of SCFA and other metabolites, potentially serving for energy metabolism.
Ultraprocessed foods provide the majority of energy content in the American diet, yet little is known regarding consumption trends over time. We determined trends in diet processing level and diet quality from 1991 to 2008 within the prospective Framingham Offspring Cohort. Dietary intakes were collected by FFQ quadrennially 1991–2008 (total of four examinations). The analytical sample included 2893 adults with valid dietary data for ≥3 examinations (baseline mean age = 54 years). Based on the NOVA framework, we classified foods as: unprocessed/minimally processed foods; processed culinary ingredients (salt/sugar/fats/oils); and processed foods and ultraprocessed foods. We evaluated diet quality using the Dietary Guidelines for Americans Adherence Index (DGAI) 2010. Trends in consumption of foods within each processing level (servings/d) and diet quality over the four examinations were evaluated using mixed effects models with subject-specific random intercepts. Analyses were stratified by sex, BMI (<25 kg/m2, 25–29·9 kg/m2, ≥30 kg/m2) and smoking status. Over 17 years of follow-up, ultraprocessed food consumption decreased from 7·5 to 6·0 servings/d and minimally processed food consumption decreased from 11·9 to 11·3 servings/d (Ptrend < 0·001). Changes in intakes of processed foods, culinary ingredients and culinary preparations were minimal. Trends were similar by sex, BMI and smoking status. DGAI-2010 score increased from 60·1 to 61·5, P < 0·001. The current study uniquely describes trends in diet processing level in an ageing US population, highlighting the longstanding presence of ultraprocessed foods in the American diet. Given the poor nutritional quality of ultraprocessed foods, public health efforts should be designed to limit their consumption.
The dependence of fishbone cycle on energetic particle intensity has been investigated in EAST low-magnetic-shear plasmas. It is observed that the fishbone mode growth rate, saturation amplitude as well as fishbone cycle frequency clearly increase with increasing neutral beam injection (NBI) power. Moreover, enhanced electron density and temperature perturbations as well as energetic particle loss were observed with greater injected NBI power. Simulation results using M3D-K code show that as the NBI power increases, the resonant frequency and the energy of the resonant particles become higher, and the saturation amplitude of the mode also changes, due to the non-perturbative energetic particle contribution. The relationship between the calculated energetic particle pressure ratio and fishbone cycle frequency is obtained as ${f_{\textrm{FC}}} = 2.2{(1000{\beta _{\textrm{ep,calc}}} - 0.1)^{5.9 \pm 0.5}}$. Results consistent with the experimental observations have been achieved based on a predator–prey model.
Existing studies addressing alcohol consumption have not captured the multidimensionality of drinking patterns, including drinking frequency, binge drinking, beverage preference and changes in these measures across the adult life course. We examined longitudinal trends in drinking patterns and their association with diet over four decades in ageing US adults from the Framingham Offspring Study (n 4956; baseline mean age 36·2 years). Alcohol intake (drinks/week, drinking frequency, beverage-specific consumption, drinks/occasion) was assessed quadrennially from examinations 1 to 8. Participants were classified as binge drinkers, moderate drinkers or heavy drinkers (4+ and 5+ drinks/occasion; ≤1 and ≤2 drinks/d and >7 and >14 drinks/week for women and men, respectively). Dietary data were collected by a FFQ from examinations 5 to 8 (1991–2008). We evaluated trends in drinking patterns using linear mixed effect models and compared dietary intake across drinking patterns using heterogeneous variance models. Alcohol consumption decreased from 1971 to 2008 (3·7 v. 2·2 oz/week; P < 0·05). The proportion of moderate (66 v. 59·3 %), heavy (18·4 v. 10·5 %) and binge drinkers (40·0 v. 12·3 %) declined (P < 0·05). While average wine consumption increased (1·4 v. 2·2 drinks/week), beer (3·4 v. 1·5 drinks/week) and cocktail intake (2·8 v. 1·2 drinks/week) decreased. Non-binge drinkers consumed less sugary drinks and more whole grains than binge drinkers, and the latter consumed more total fat across all examinations (P < 0·05). There was a significant difference in consumption trends of total grains by drinking level (P < 0·05). In conclusion, alcohol drinking patterns are unstable throughout adulthood. Higher intakes were generally associated with poorer diets. These analyses support the nuanced characterisation of alcohol consumption in epidemiological studies.
We report a family cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involving five patients in a family cluster in Dazhou, China, including the epidemiological, clinical, laboratory and radiological findings. Three-generation transmission was observed. Through epidemiological investigation, we observed asymptomatic transmission to a cohabiting family member, as well as person-to-person transmission of SARS-CoV-2 outside Wuhan city. The asymptomatic transmission demonstrated here provides evidence that there could be a greater risk of Coronavirus Disease 2019 (COVID-19) spread. This cluster also demonstrated that COVID-19 is transmissible during the incubation period of an asymptomatic person. Early isolation and treatment, stressing prevention of cluster outbreaks, could help prevent further spread of the epidemic.
To investigate the effects of dietary fibre on follicular atresia in pigs fed a high-fat diet, we fed thirty-two prepubescent gilts a basal diet (CON) or a CON diet supplemented with 300 g/d dietary fibre (fibre), 240 g/d soya oil (SO) or both (fibre + SO). At the 19th day of the 4th oestrus cycle, gilts fed the SO diet showed 112 % more atretic follicles and greater expression of the apoptotic markers, Bax and caspase-3, and these effects were reversed by the fibre diet. The abundance of SCFA-producing microbes was decreased by the SO diet, but this effect was reversed by fibre treatment. Concentrations of serotonin and melatonin in the serum and follicular fluid were increased by the fibre diet. Overall, dietary fibre protected against high fat feeding-induced follicular atresia at least partly via gut microbiota-related serotonin–melatonin synthesis. These results provide insight into preventing negative effects on fertility in humans consuming a high-energy diet.
Bile acids (BA) have emerged as signalling molecules regulating intestinal physiology. The importance of intestinal microbiota in production of secondary BA, for example, lithocholic acid (LCA) which impairs enterocyte proliferation and permeability, triggered us to determine the effects of oral probiotics on intestinal BA metabolism. Piglets were weaned at 28 d of age and allocated into control (CON, n 14) or probiotic (PRO, n 14) group fed 50 mg of Lactobacillus plantarum daily, and gut microbiota and BA profile were determined. To test the potential interaction of LCA with bacteria endotoxins in inducing damage of enterocytes, IPEC-J2 cells were treated with LCA, lipopolysaccharide (LPS) and LCA + LPS and expressions of genes related to inflammation, antioxidant capacity and nutrient transport were determined. Compared with the CON group, the PRO group showed lower total LCA level in the ileum and higher relative abundance of the Lactobacillus genus in faeces. In contrast, the relative abundances of Bacteroides, Clostridium_sensu_stricto_1, Parabacteroides and Ruminococcus_1, important bacteria genera in BA biotransformation, were all lower in the PRO than in the CON group. Moreover, PRO piglets had lower postprandial glucagon-like peptide-1 level, while higher glucose level than CON piglets. Co-administration of LPS and LCA led to down-regulated expression of glucose and peptide transporter genes in IPEC-J2 cells. Altogether, oral L. plantarum altered BA profile probably by modulating relative abundances of gut microbial genera that play key roles in BA metabolism and might consequently impact glucose homoeostasis. The detrimental effect of LCA on nutrient transport in enterocytes might be aggravated under LPS challenge.
We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (<818·9 μmol/l). Similar trends were found in males and females. Higher plasma Mg levels were associated with a decreased risk of new-onset hyperuricaemia in hypertensive adults.
To examine adherence to a Mediterranean-like diet at age 9–10 years in relation to onset of breast development (thelarche) and first menstruation (menarche).
Design:
We evaluated the associations of adherence to a Mediterranean-like diet (measured by an adapted Mediterranean-like Diet Score, range 0–9) with thelarche at baseline, age at thelarche and time to menarche. Data were collected at baseline during a clinic visit, complemented with a mailed questionnaire and three 24 hour telephone dietary recalls, followed by annual follow-up questionnaires. Multivariable Poisson regression, linear regression and Cox proportional hazards regression were used to evaluate timing of pubertal development in relation to diet adherence.
Setting:
New Jersey, USA.
Participants:
Girls aged 9 or 10 years at baseline (2006–2014, n 202).
Results:
High Mediterranean-like diet adherence (score 6–9) was associated with a lower prevalence of thelarche at baseline compared with low adherence (score 0–3; prevalence ratio = 0·65, 95 % CI 0·48, 0·90). This may have been driven by consumption of fish and non-fat/low-fat dairy. Our models also suggested a later age at thelarche with higher Mediterranean-like diet adherence. Girls with higher Mediterranean-like diet adherence had significantly longer time to menarche (hazard ratio = 0·45, 95 % CI 0·28, 0·71 for high v. low adherence). Further analysis suggested this may have been driven by vegetable and non-fat/low-fat dairy consumption.
Conclusions:
Consuming a Mediterranean-like diet may be associated with older age at thelarche and menarche. Further research is necessary to confirm our findings in other US paediatric populations and elucidate the mechanism through which Mediterranean-like diet may influence puberty timing.
We aimed to investigate the association between plasma retinol and incident cancer among Chinese hypertensive adults. We conducted a nested case–control study, including 231 patients with incident cancer and 231 matched controls during a median 4·5-year follow-up of the China Stroke Primary Prevention Trial. There was a significant, inverse association between retinol levels and digestive system cancer (per 10 μg/dl increases: OR 0·79; 95 % CI 0·69, 0·91). When compared with participants in the first quartile of retinol (< 52·3 μg/dl), a significantly lower cancer risk was found in participants in quartile 2–4 ( ≥ 52·3 μg/dl: OR 0·31; 95 % CI 0·13, 0·71). However, there was a U-shaped association between retinol levels and non-digestive system cancers where the risk of cancers decreased (although not significantly) with each increment of plasma retinol (per 10 μg/dl increases: OR 0·89; 95 % CI 0·60, 1·31) in participants with retinol < 68·2 μg/dl, and then increased significantly with retinol (per 10 μg/dl increase: OR 1·65; 95 % CI 1·12, 2·44) in participants with retinol ≥ 68·2 μg/dl. In conclusion, there was a significant inverse dose–response association between plasma retinol and the risk of digestive system cancers. However, a U-shaped association was observed between plasma retinol and the risk of non-digestive cancers (with a turning point approximately 68·2 μg/dl).