Aflatoxins and fumonisins (FB) are mycotoxins contaminating a large fraction of the world's food, including maize, cereals, groundnuts and tree nuts. The toxins frequently co-occur in maize. Where ...these commodities are dietary staples, for example, in parts of Africa, Asia and Latin America, the contamination translates to high-level chronic exposure. This is particularly true in subsistence farming communities where regulations to control exposure are either non-existent or practically unenforceable. Aflatoxins are hepatocarcinogenic in humans, particularly in conjunction with chronic hepatitis B virus infection, and cause aflatoxicosis in episodic poisoning outbreaks. In animals, these toxins also impair growth and are immunosuppressive; the latter effects are of increasing interest in human populations. FB have been reported to induce liver and kidney tumours in rodents and are classified as Group 2B ‘possibly carcinogenic to humans’, with ecological studies implying a possible link to increased oesophageal cancer. Recent studies also suggest that the FB may cause neural tube defects in some maize-consuming populations. There is a plausible mechanism for this effect via a disruption of ceramide synthase and sphingolipid biosynthesis. Notwithstanding the need for a better evidence-base on mycotoxins and human health, supported by better biomarkers of exposure and effect in epidemiological studies, the existing data are sufficient to prioritize exposure reduction in vulnerable populations. For both toxins, there are a number of practical primary and secondary prevention strategies which could be beneficial if the political will and financial investment can be applied to what remains a largely and rather shamefully ignored global health issue.
Summary
This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic ...acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not.
Introduction
Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery.
Methods
This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account.
Results
In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio HR 1.97 (95% CI, 1.09–3.56;
P
-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11–0.70;
P
-value = 0.007).
Conclusions
Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.
A consequent tendency toward high-performance quantum information processing is to develop the fully integrated photonic chip. Here, we report the on-chip generation and manipulation of entangled ...photons based on reconfigurable lithium-niobate waveguide circuits. By introducing a periodically poled structure into the waveguide circuits, two individual photon-pair sources with a controllable electro-optic phase shift are produced within a Hong-Ou-Mandel interferometer, resulting in a deterministically separated identical photon pair. The state is characterized by 92.9±0.9% visibility Hong-Ou-Mandel interference. The photon flux reaches ∼1.4×10(7) pairs nm-1 mW-1. The whole chip is designed to contain nine similar units to produce identical photon pairs spanning the telecom C and L band by the flexible engineering of nonlinearity. Our work presents a scenario for on-chip engineering of different photon sources and paves the way to fully integrated quantum technologies.
Abstract Warfarin has been the mainstay oral anticoagulant (OAC) medication prescribed for stroke prevention in atrial fibrillation (AF) patients. However, warfarin therapy is challenging because of ...marked interindividual variability in dose and response, requiring frequent monitoring and dose titration. These limitations have prompted the clinical development of new OACs (NOACs) that directly target the coagulation cascade with rapid onset/offset of action, lower risk for drug-drug interactions, and more predictable response. Recently, NOACs dabigatran (direct thrombin inhibitor), and rivaroxaban and apixaban (factor Xa FXa inhibitors) have gained regulatory approval as alternative therapies to warfarin. Though the anticoagulation efficacy of these NOACs has been characterized, differences in their pharmacokinetic and pharmacodynamic profiles have become a significant consideration in terms of drug selection and dosing. In this review, we outline key pharmacokinetic and pharmacodynamic features of each compound and provide guidance on selection and dosing of the 3 NOACs relative to warfarin when considering OAC therapy for AF patients. Importantly, we show that by better understanding the effect of clinical variables such as age, renal function, dosing interval, and drug metabolism (CYP3A4) and transport (P-glycoprotein), we might be able to better predict the risk for sub- and supratherapeutic anticoagulation response and individualize OAC selection and dosing.
Background
Gestational diabetes mellitus (GDM) is an increasingly prevalent disorder, associated with low blood vitamin D level.
Objectives
To evaluate the relationship between vitamin D and GDM.
...Search strategy
EMBASE, MEDLINE, Cochrane Library and China Biology Medicine disc were searched up to May 2017. The references of previous studies were screened.
Selection criteria
Observational studies on the relationship between vitamin D and GDM free from Hawthorne effect and randomised controlled trials of vitamin D supplementation during pregnancy for preventing or treating GDM were included.
Data collection and analysis
Data and information of included articles were extracted by duplicate using piloted tables. Newcastle–Ottawa Scale and Cochrane Handbook were used for quality assessment. Random‐effects models were used for meta‐analyses. Heterogeneity tests, sensitivity analysis and analysis of publication bias were conducted.
Main results
Eighty‐seven observational studies and 25 randomised controlled trials involving 55 859 and 2445 women, respectively, were included. Low blood vitamin D level during pregnancy was associated with a higher risk of GDM (OR 1.850, 95% CI 1.471–2.328). Blood vitamin D level for women with GDM were lower than in the control women. Blood vitamin D level was associated with fasting plasma glucose (FPG) and homeostasis model of assessment for insulin resistance index (HOMA‐IR) (r = −0.100 and r = −0.351), whereas the correlation between blood vitamin D level and fasting insulin (FINS) might be concealed by publication bias. Vitamin D intervention during pregnancy could change the blood levels of vitamin D, FINS, FPG, HOMA‐IR, glutathione, C‐reactive protein and lipid.
Conclusions
Low blood vitamin D level could increase the risk of GDM, and vitamin D supplementation during pregnancy could ameliorate the condition of GDM.
Tweetable
Low blood vitamin D increases gestational diabetes mellitus (GDM) risk. Vitamin D supplementation ameliorates GDM condition.
Tweetable
Low blood vitamin D increases gestational diabetes mellitus (GDM) risk. Vitamin D supplementation ameliorates GDM condition.
As life expectancy continues to increase, clinicians are challenged by age-related renal impairment that involves podocyte senescence and glomerulosclerosis. There is now compelling evidence that ...lithium has a potent antiaging activity that ameliorates brain aging and increases longevity in Drosophila and Caenorhabditis elegans. As the major molecular target of lithium action and a multitasking protein kinase recently implicated in a variety of renal diseases, glycogen synthase kinase 3β (GSK3β) is overexpressed and hyperactive with age in glomerular podocytes, correlating with functional and histological signs of kidney aging. Moreover, podocyte-specific ablation of GSK3β substantially attenuated podocyte senescence and glomerular aging in mice. Mechanistically, key mediators of senescence signaling, such as p16INK4A and p53, contain high numbers of GSK3β consensus motifs, physically interact with GSK3β, and act as its putative substrates. In addition, therapeutic targeting of GSK3β by microdose lithium later in life reduced senescence signaling and delayed kidney aging in mice. Furthermore, in psychiatric patients, lithium carbonate therapy inhibited GSK3β activity and mitigated senescence signaling in urinary exfoliated podocytes and was associated with preservation of kidney function. Thus, GSK3β appears to play a key role in podocyte senescence by modulating senescence signaling and may be an actionable senostatic target to delay kidney aging.
Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of ...voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.
A systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.
A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.
By excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal-limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.
It has been hypothesised that intense metabolism of nectar‐inhabiting yeasts (NIY) may change nectar chemistry, including volatile profile, which may affect pollinator foraging behaviours and ...consequently plant fitness. However, empirical evidence for the plant–microbe–pollinator interactions remains little known.
To test this hypothesis, we use a bumblebee‐pollinated vine Clematis akebioides endemic to southwest China as an experimental model plant. To quantify the incidence and density of Metschnikowia reukaufii, a cosmopolitan NIY in floral nectar, a combination of yeast cultivation and microscopic cell‐counting method was used. To examine the effects of NIY on plant–pollinator interactions, we used real flowers filled with artificial nectar with or without yeast cells. Then the volatile metabolites produced in the yeast‐inoculated nectar were analysed with coupled gas chromatography and mass spectrometry (GC‐MS).
On average 79.3% of the C. akebioides flowers harboured M. reukaufii, and cell density of NIY was high to 7.4 × 104 cells mm−3. In the field population, the presence of NIY in flowers of C. akebioides increased bumblebee (Bombus friseanus) pollinator visitation rate and consequently seed set per flower. A variety of fatty acid derivatives produced by M. reukaufii may be responsible for the above beneficial interactions.
The volatiles produced by the metabolism of M. reukaufii may serve as an honest signal to attract bumblebee pollinators and indirectly promote the female reproductive fitness of C. akebioides, forming a potentially tripartite plant–microbe–pollinator mutualism.
This paper reviews and analyses the importance of maize as staple food in Eastern and Southern Africa (E&SA) and contributes in understanding the nexus between maize nutritional composition and ...prevalence of micronutrient deficiencies (MNDs) in these regions. MNDs remain a major public health concern particularly for women and children, with calcium, iodine, iron, selenium, zinc, folate and vitamin A deficiencies being the most common. Estimates of their prevalence are among the highest in E&SA: iron-deficient anemia affected 26 to 31% of women of reproductive age, and deficiencies up to 53%, 36%, 66%, 75% and 62% for vitamin A, iodine, zinc, calcium and selenium, respectively, were measured in populations of these regions. Besides, these two regions show the highest worldwide maize per capita consumption (g/person/day) as main staple, with 157 in Eastern Africa and 267 in Southern Africa, including up to 444 in Lesotho. The analysis of food composition tables from these regions showed that 100 g of maize foods consumed by these populations could to some extent, contribute in satisfying dietary reference intakes (DRIs) of children and women in energy, proteins, carbohydrates, magnesium, zinc, vitamins B1 and B6. However, it provides very low supply of fats, calcium, sodium, selenium, vitamins C, A and E. The high occurrence of MNDs and considerable nutritional potential of maize consumed in E&SA can be explained by loss of nutrients due to processing practices, low food diversification and reduced nutrients bioavailability. Success cases of the main strategies to tackle the issue of MNDs in these regions by improving maize nutritional quality are discussed in this paper. Maize fortification was shown to improve nutrition and health outcomes of population. Increasing dietary diversity by complementing maize with other foods has improved nutrition through integration of micronutrient-rich foods in the diet. Mostly, biofortification has successfully contributed in reducing vitamin A and zinc deficiencies in rural communities more than nutrient supplementation, fortification and dietary diversity.
Deformation twins are three-dimensional domains, traditionally viewed as ellipsoids because of their two-dimensional lenticular sections. In this work, we performed statistical analysis of twin ...shapes viewing along three orthogonal directions: the 'dark side' (DS) view along the twin shear direction (η
), the twinning plane normal (TPN) view (k
) and the 'bright side' (BS) view along the direction λ(=k
× η
). Our electron back-scatter diffraction results show that twins in the DS and BS views normally exhibit a lenticular shape, whereas they show an irregular shape in the TPN view. Moreover, the findings in the TPN view revealed that twins grow faster along λ the lateral direction than along η
the forward propagation direction at the initial stages of twin growth. These twin sections are irregular, indicating that growth is locally controlled and the overall shape is not perfectly ellipsoidal. We explain these findings using atomistic models, and ascribe them to differences in the mobility of the edge and screw components of the twinning dislocations.
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