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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
The extent of the reduction of maize (Zea mays L.) kernel moisture content through drying is closely related to field temperature (or accumulated temperature; AT) following maturation. In 2017 and 2018, we selected eight maize hybrids that are widely planted in Northeastern China to construct kernel drying prediction models for each hybrid based on kernel drying dynamics. In the traditional harvest scenario using the optimal sowing date (OSD), maize kernels underwent drying from 4th September to 5th October, with variation coefficients of 1.0–1.9. However, with a latest sowing date (LSD), drying occurred from 14th September to 31st October, with variation coefficients of 1.3–3.0. In the changed harvest scenario, the drying time of maize sown on the OSD condition was from 12th September to 9th November with variation coefficients of 1.3–3.0, while maize sown on the LSD had drying dates of 26th September to 28th October with variation coefficients of 1.5–3.6. In the future harvest scenario, the Fengken 139 (FK139) and Jingnongke 728 (JNK728) hybrids finished drying on 20th October and 8th November, respectively, when sown on the OSD and had variation coefficients of 2.7–2.8. Therefore, the maize kernel drying time was gradually delayed and was associated with an increased demand for AT ⩾ 0°C late in the growing season. Furthermore, we observed variation among different growing seasons likely due to differences in weather patterns, and that sowing dates impact variations in drying times to a greater extent than harvest scenarios.
Online grocery shopping could improve access to healthy food, but it may not be equally accessible to all populations – especially those at higher risk for food insecurity. The current study aimed to compare the socio-demographic characteristics of families who ordered groceries online v. those who only shopped in-store.
Design:
We analysed enrollment survey and 44 weeks of individually linked grocery transaction data. We used univariate χ2 and t-tests and logistic regression to assess differences in socio-demographic characteristics between households that only shopped in-store and those that shopped online with curbside pickup (online only or online and in-store).
Setting:
Two Maine supermarkets.
Participants:
863 parents or caregivers of children under 18 years old enrolled in two fruit and vegetable incentive trials.
Results:
Participants had a total of 32 757 transactions. In univariate assessments, online shoppers had higher incomes (P < 0 0001), were less likely to participate in Special Supplemental Nutrition Program for Women, Infants, and Children or Supplemental Nutrition Assistance Program (SNAP; P < 0 0001) and were more likely to be female (P = 0·04). Most online shoppers were 30–39 years old, and few were 50 years or older (P = 0·003). After controlling for age, gender, race/ethnicity, number of children, number of adults, income and SNAP participation, female primary shoppers (OR = 2·75, P = 0·003), number of children (OR = 1·27, P = 0·04) and income (OR = 3·91 for 186–300 % federal poverty line (FPL) and OR = 6·92 for >300 % FPL, P < 0·0001) were significantly associated with likelihood of shopping online.
Conclusions:
In the current study of Maine families, low-income shoppers were significantly less likely to utilise online grocery ordering with curbside pickup. Future studies could focus on elucidating barriers and developing strategies to improve access.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
In order to maximize the utility of future studies of trilobite ontogeny, we propose a set of standard practices that relate to the collection, nomenclature, description, depiction, and interpretation of ontogenetic series inferred from articulated specimens belonging to individual species. In some cases, these suggestions may also apply to ontogenetic studies of other fossilized taxa.
Both vitamin K and probiotics can promote the bone health of poultry and mammals. The present study was conducted to investigate the interactive effects between vitamin K3 (VK3) and Bacillus subtilis PB6 on the growth performance and tibia quality of broiler chickens with sex separate rearing. In a 3 × 2 × 2 factorial arrangement, 720 one-day-old broiler chicks (Arbor Acres) were assigned to 12 groups with three levels of dietary VK3 (0, 0.5 and 4.0 mg/kg), with or without probiotic supplementation (500 g/t) and with sex separation (male and female). Each group included 3 replicates with 20 birds per replicate. During day 1 to 21, 0.5 and 4.0 mg/kg of VK3 increased average daily gain (ADG) of all birds and average daily feed intake of male birds (P < 0.05). During day 22 to 42, probiotic supplementation increased the ADG of birds (P < 0.05). Probiotic addition increased the weight, length, diameter and strength of tibia in all birds, and 0.5 and 4.0 mg/kg of VK3 increased the tibial breaking strength of male birds at day 21 (P < 0.05). Vitamin K3 and probiotic synergistically increased tibial breaking strength at day 42 and ash content at day 21 (P < 0.05). Three factors exhibited interactive effects on the chemical composition of tibia at day 42, and female birds fed 4 mg/kg of VK3 and probiotic had the highest contents of ash, calcium and phosphorus (P < 0.05). Bacillus subtilis PB6 increased the serum phosphorus level of male birds at day 21 and serum calcium level of female ones at day 42 (P < 0.05). At day 21, in the probiotic-supplemented birds, serum osteocalcin (OCN) and bone-specific alkaline phosphatase (BALP) were increased by 0 and 4.0 mg/kg of VK3, respectively (P < 0.05). Probiotic increased serum OCN and cooperated with VK3 to increase the serum BALP at day 42 (P < 0.05). Vitamin K3 and probiotic synergistically down-regulated the mRNA expression of Runt-related transcription factor 2 and OCN at day 21 (P < 0.05). Vitamin K3 down-regulated the alkaline phosphatase (liver/bone/kidney) expression in male birds at day 21 and 42, but probiotic up-regulated the expression of these genes at day 42 (P < 0.05). In conclusion, VK3 and B. subtilis PB6 promoted the growth performance of broilers during starter and grower phases, respectively. They synergistically improved the physical and chemical traits of tibias, especially in grower phase, by modulating calcium and phosphorus metabolism as well as osteogenic gene expression.
Chinese men who have sex with men (MSM) are at high risk for depression, anxiety and suicide. The estimated prevalence of these problems is essential to guide public health policy, but published results vary. This meta-analysis aimed to estimate the prevalence of depressive symptoms, anxiety symptoms and suicide among Chinese MSM.
Methods
Systematic searches of EMBASE, MEDLINE, PsycINFO, PubMed, CNKI and Wanfang databases with languages restricted to Chinese and English for studies published before 10 September 2019 on the prevalence of depressive symptoms, anxiety symptoms, suicidal ideation, suicide plans and suicide attempts among Chinese MSM. Studies that were published in the peer-reviewed journals and used validated instruments to assess depression and anxiety were included. The characteristics of studies and the prevalence of depression and anxiety symptoms, suicidal ideation, suicide plans and suicide attempts were independently extracted by authors. Random-effects modelling was used to estimate the pooled rates. Subgroup analysis and univariate meta-regression were conducted to explore potential sources of heterogeneity. This study followed the PRISMA and MOOSE.
Results
Sixty-seven studies were included. Fifty-two studies reported the prevalence of depressive symptoms, with a combined sample of 37 376 people, of whom 12 887 [43.2%; 95% confidence interval (CI), 38.9–47.5] reported depressive symptoms. Twenty-seven studies reported the prevalence of anxiety symptoms, with a combined sample of 10 531 people, of whom 3187 (32.2%; 95% CI, 28.3–36.6) reported anxiety symptoms. Twenty-three studies reported the prevalence of suicidal ideation, with a combined sample of 15 034 people, of whom 3416 (21.2%; 95% CI, 18.3–24.5) had suicidal ideation. Nine studies reported the prevalence of suicide plans, with a combined sample of 5271 people, of whom 401 (6.2%; 95% CI, 3.9–8.6) had suicide plans. Finally, 19 studies reported the prevalence of suicide attempts, with a combined sample of 27 936 people, of whom 1829 (7.3%; 95% CI, 5.6–9.0) had attempted suicide.
Conclusions
The mental health of Chinese MSM is poor compared with the general population. Efforts are warranted to develop interventions to prevent and alleviate mental health problems among this vulnerable population.
This study assessed the relationships between different perpetrator-victim roles in intimate partner violence (IPV), emotion regulation (ER) and mental health problems among men who have sex with men (MSM) in China.
Methods
From April to June 2019, 1233 participants were approached via gay-friendly non-governmental organisations in 15 cities across mainland China.
Results
Of the total, 578 eligible participants completed an anonymous online survey. All participants provided informed consent and information about their violent perpetrator-victim role and mental health status. The results revealed a high prevalence of IPV in this study sample, with 32.7% of participants reporting IPV victimisation and 32.5% of participants reporting IPV perpetration during their lifetime. A total of 81 (14.0%) participants were suicidal, 309 (53.5%) participants reported poor general mental health and 208 (36.0%) had significant depressive symptoms. Adjusted logistic regression models revealed that both physical victimisation (adjusted odds ratio [ORa] = 3.22, 95% confidence interval [CI] = 1.11–9.32) and sexual victimisation (ORa = 2.90, 95% CI = 1.39–6.05) had positive associations with suicidality, and unidirectional and bidirectional psychological perpetration were associated with poor general mental health and significant depressive symptoms. Although high cognitive reappraisal showed a negative association with poor general mental health (ORa = 0.89,95% CI = 0.86–0.92), the correlation with victims of IPV was weaker than it was with non-victims.
Conclusions
This study revealed that different perpetrator-victim roles in different IPV situations should be considered comprehensively in research, prevention and intervention. ER is not enough to buffer the effects of IPV on the mental health of MSM victims.
It is well documented that intergenerational ties play important roles in adults’ well-being. However, most studies focus on the impact of individuals’ own perceptions of their ties without considering whether family members’ assessments of these ties affect well-being. We address this question using data from 296 adult children nested within 95 later-life families in which all offspring were interviewed. Applying a mixed-method within-family approach, we explored whether the effect of perceived maternal favoritism on depressive symptoms was increased when siblings shared ego’s perceptions. Multilevel regression analyses revealed that ego’s own perceptions predicted depressive symptoms, but only among daughters. Siblings’ perceptions that egos were most close to mothers did not affect the well-being of daughters or sons. Qualitative analyses suggested that differential effects of perceived favoritism by gender reflected differences in the meaning sons and daughters associated with being favored children. Favored daughters were more likely than favored sons to report that they were emotional caregivers to their mothers; this pattern was especially strong when siblings reinforced egos’ perceptions of being “best suited” for this role. These findings emphasize the salience of egos’ own perceptions, relative to those of family network members, in shaping role embracement and psychological well-being, especially among women.
Muscle fiber characteristics comprise a set of complex traits that influence the meat quality and lean meat production of livestock. However, the genetic and biological mechanisms regulating muscle fiber characteristics are largely unknown in pigs. Based on a genome-wide association study (GWAS) performed on 421 Large White × Min pig F2 individuals presenting well-characterized phenotypes, this work aimed to detect genome variations and candidate genes for five muscle fiber characteristics: percentage of type I fibers (FIB1P), percentage of type IIA fibers (FIB2AP), percentage of type IIB fibers (FIB2BP), diameter of muscle fibers (DIAMF) and number of muscle fibers per unit area (NUMMF). The GWAS used the Illumina Porcine SNP60K genotypic data, which were analyzed by a mixed model. Seven and 10 single nucleotide polymorphisms (SNPs) were significantly associated with DIAMF and NUMMF, respectively (P < 1.10E-06); no SNP was significantly associated with FIB1P, FIB2AP or FIB2B. For DIAMF, the significant SNPs on chromosome 4 were located in the previously reported quantitative trait loci (QTL) interval. Because the significant SNPs on chromosome 6 were not mapped in the previously reported QTL interval, a putative novel QTL was suggested for this locus. None of the previously reported QTL intervals on chromosomes 6 and 14 harbored significant SNPs for NUMMF; thus, new potential QTLs on these two chromosomes are suggested in the present work. The most significant SNPs associated with DIAMF (ALGA0025682) and NUMMF (MARC0046984) explained 12.02% and 11.59% of the phenotypic variation of these traits, respectively. In addition, both SNPs were validated as associated with DIAMF and NUMMF in Beijing Black pigs (P < 0.01). Some candidate genes or non-coding RNAs, such as solute carrier family 44 member 5 and miR-124a-1 for DIAMF, and coiled-coil serine rich protein 2 for NUMMF, were identified based on their close location to the significant SNPs. This study revealed some genome-wide association variants for muscle fiber characteristics, and it provides valuable information to discover the genetic mechanisms controlling these traits in pigs.
To examine the relationship between the therapeutic effect of intratympanic methylprednisolone perfusion and histone acetylation in refractory sudden sensorineural hearing loss.
Methods
Thirty-four refractory sudden sensorineural hearing loss patients were enrolled and treated with intratympanic methylprednisolone perfusion. Pure tone average, acetylated histone H3, acetylated histone H4 and histone deacetylase 2 (HDAC2) were measured in peripheral blood mononuclear cells before and after intratympanic methylprednisolone perfusion. Sixteen healthy volunteers were recruited to obtain normal reference values.
Results
Pure tone average in sudden sensorineural hearing loss patients improved from 84.14 ± 13.54 dB to 73.56 ± 18.45 dB after intratympanic methylprednisolone perfusion. Up-regulations in HDAC2 protein level, and down-regulations in histone H3 and H4 acetylation were observed in the intratympanic methylprednisolone perfusion sensitive group (pure tone average gain of 15 dB or more), while no significant changes were observed in the intratympanic methylprednisolone perfusion insensitive group (pure tone average gain of less than 15 dB).
Conclusion
Intratympanic methylprednisolone perfusion can improve hearing in a considerable number of refractory sudden sensorineural hearing loss patients. The therapeutic effect is closely related to reduced histone acetylation.
Although parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.
The euarthropod Luohuilinella deletres sp. nov. is described from rare material from the Chengjiang biota, Cambrian Series 2, Stage 3, of Yunnan Province, China. Phylogenetic analysis recovers a xandarellid affinity for L. deletres, representing only the fifth described species of this clade. L. deletres possesses a head shield that is about one-fifth of the total body length and a trunk with 30 tergites, the reduced anterior-most tergite and terminal three tergites lacking pleural elongations. Anteriorly situated notches in the head shield are associated with stalked eyes, in contrast to the more posterior, enclosed eye slits present in Xandarella. Posterior to the antennae there are at least 11 pairs of biramous appendages preserved, including three pairs in the head. The morphology of the midline gut of L. deletres, in which lateral, unbranched diverticula are wider towards the front of the body, is a characteristic also found in various trilobites. The dorsoventrally flattened exoskeleton suggests a benthic or nektobenthic mode of life for L. deletres, as for other trilobitomorphs, and it likely used its well-developed anteriorly positioned eyes for searching out food, either to scavenge or to find prey.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
Good canopy structure is essential for optimal maize (Zea mays L.) production. However, creating appropriate maize canopy structure can be difficult, because the characteristics of individual plants are altered by changes in plant age, density and interactions with neighbouring plants. The objective of the current study was to find a reliable method for building good maize canopy structure by analysing changes in canopy structure, light distribution and grain yield (GY). A modern maize cultivar (ZhengDan958) was planted at 12 densities ranging from 1.5 to 18 plants/m2 at two field locations in Xinjiang, China. At the silking stage (R1), plant and ear height increased with plant density as well as leaf area index (LAI), whereas leaf area per plant decreased logarithmically. The fraction of light intercepted by the plant (F) increased with increasing plant density, but the light extinction coefficient (K) decreased linearly from 0.61 to 0.39. Taking the optimum value of F (95%) as an example, and using measured values of K for each plant density at R1 and the equation from Beer's law, the corresponding (theoretical) LAI for each plant density was calculated and optimum plant density (9.72 plants/m2) obtained by calculating the difference between theoretical LAIs and actual observations. Further analysis showed that plant density ranging from 10.64 to 11.55 plants/m2 yielded a stable GY range. Therefore, taking into account the persistence time for maximum LAI, the plant density required to obtain an ideal GY maize canopy structure should be increased by 10–18% from 9.72 plants/m2.
Obesity and insulin resistance play important roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Mg intake is linked to a reduced risk of metabolic syndrome and insulin resistance; people with NAFLD or alcoholic liver disease are at high risk of Mg deficiency. The present study aimed to investigate whether Mg and Ca intakes were associated with risk of fatty liver disease and prediabetes by alcohol drinking status.
Design
We analysed the association between Ca or Mg intake and fatty liver disease, prediabetes or both prediabetes and fatty liver disease in cross-sectional analyses.
Setting
Third National Health and Nutrition Examination Survey (NHANES III) follow-up cohort of US adults.
Subjects
Nationally representative sample of US adults in NHANES (n 13 489).
Results
After adjusting for potential confounders, Mg intake was associated with approximately 30 % reduced odds of fatty liver disease and prediabetes, comparing the highest intake quartile v. the lowest. Mg intake may only be related to reduced odds of fatty liver disease and prediabetes in those whose Ca intake is less than 1200 mg/d. Mg intake may also only be associated with reduced odds of fatty liver disease among alcohol drinkers.
Conclusions
The study suggests that high intake of Mg may be associated with reduced risks of fatty liver disease and prediabetes. Further large studies, particularly prospective cohort studies, are warranted to confirm the findings.