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Supported by (1) medical research grants CMRPG3C0041/42 from Chang Gung Memorial Hospital and NRRPG2H0031 from Ministry of Science and Technology, Taiwan to Chemin Lin (2) NMRPG3G6031/32 from Ministry of Science and Technology, Taiwan to Shwu-Hua, Lee (3) the KKHo International Charitable Foundation to Tatia Lee.
Suicide rate tends to peak in old age, and major depression is the most salient risk factor for late-life suicide. However, few studies have focused on the neuroscientific facet of suicide in the context of late-life depression (LLD).
We recruited 114 participants of LLD (28 with history of suicide attempt and 86 without) and 47 elderly controls. They received MRI scanning and behavioral assessment. White matter hyperintensity (WMH) was quantified by an automated segmentation algorithm and graph theoretical analysis was applied to resting-state fMRI. We used ANCOVA to compare group difference in WMH loading and multivariate generalized linear model to compare global and local topological parameters in fMRI signals, controlling for demographics. Partial correlation was conducted between imaging parameters and behavioral data in group of suicide attempters.
We found significant higher WMH in suicide attempters than those of LLD without suicide attempts and elderly controls (F =7.091; p = 0.001). Suicide attempters also had increased betweenness centrality (BC) in right superior occipital gyrus (SOG) (Bonferroni corrected), right precuneus (False positive corrected) and right superior temporal gyrus (uncorrected) and decreased BC in left hippocampus (uncorrected). In suicide attempters, higher BC in right SOG correlated with higher WMH, higher depression severity, higher illness awareness and insight, and lower cognitive function (digit backward), while higher BC in right precuneus correlated with higher decrease awareness and insight and higher cognitive function (digit backward).
Resonating with the vascular hypothesis in LLD, higher WMH was found in those having history of suicide attempts. However, the re-organized brain topology changes are related with divergent cognitive function and convergent heightened disease insight.
Multiple neurotrophic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF) and insulin-like growth factor(IGF)-1, have been shown to play important roles in the pathophysiology of mood disorders. However, insufficient clinical data supporting the importance of these neurotrophic factors in mood disorders, especially manic episode, have made inconclusive to make a connection between these factors and the disorder.
This study intended to investigate possible peripheral biomarkers in serum of manic episode of bipolar disorder.
We aimed to investigate whether or not serum levels of VEGF, FGF-2, NGF and IGF-1 varied in manic state.
Serum levels of VEGF, FGF-2, NGF and IGF-1 were examined in 70 drug-naïve patients with manic episode of bipolar disorder (BM) as well as 50 healthy controls, using an ELISA method.
The mean serum levels of VEGF, FGF-2, NGF and IGF-1 were 168.13±225.61pg/ml, 279.09±378.62pg/ml, 61.38±171.67pg/ml and 162.01±72.00ng/ml in BM patients, and 140.80±143.71pg/ml, 275.46±235.29pg/ml, 36.34±15.14pg/ml and 138.90±80.11ng/ml in healthy controls, respectively. Serum levels of FGF-2, NGF and IGF-1 in patients were significantly higher than those in healthy controls (Z=−2.896, P=0.004; Z=− 2.050, P=0.040; Z=−2.188, P=0.029; respectively), although there was no statistical difference in the serum levels of VEGF between two groups (Z=-0.468, P=0.639). Moreover, serum levels of NGF in patients correlated with the duration of disorder (rs=−0.241, P=0.044).
The increase in serum levels of FGF-2, NGF and IGF-1 in manic state may reflect a neuroprotective role for these factors, and these factors may be considered biological markers for manic episode.
Prior data on long-term association between legume consumption and hypertension risk are sparse. We aimed to evaluate whether total legume and subtype intakes prospectively associate with hypertension incidence among 8758 participants (≥30 years) from the China Health and Nutrition Survey 2004–2011. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. Incident hypertension was identified by self-reports or blood pressure measurements. We applied multivariable Cox regressions to estimate hazard ratios (HR) with corresponding 95 % CI for hypertension across increasing categories of cumulatively averaged legume intakes. For 35 990 person-years (median 6·0 years apiece), we documented 944 hypertension cases. After covariate adjustment, higher total legume intakes were significantly associated with lower hypertension risks, with HR comparing extreme categories being 0·56 (95 % CI 0·43, 0·71; Ptrend < 0·001). Then we found that intakes of dried legumes (HR 0·53 (95 % CI 0·43, 0·65); Ptrend < 0·001) and fresh legumes (HR 0·67 (95 % CI 0·55, 0·81); Ptrend < 0·001) were both related to decreased hypertension hazards. However, further dried legume classification revealed that negative association with hypertension substantially held for soyabean (HR 0·51 (95 % CI 0·41, 0·62); Ptrend < 0·001) but not non-soyabean intakes. In stratified analyses, the association of interest remained similar within strata by sex, BMI, physical activity, smoking and drinking status; rather, significant heterogeneity showed across age strata (Pinteraction = 0·02). Total legume consumption among the over-65s was related to a more markedly reduced hypertension risk (HR 0·47 (95 % CI 0·30, 0·73); Ptrend < 0·001). Our findings suggest an inverse association of all kinds of legume (except non-soyabean) intakes with hypertension risks.
Previous studies have shown that the Dietary Approaches to Stop Hypertension (DASH) diet might contribute to managing risk factors of non-alcoholic fatty liver disease (NAFLD), but evidence is limited. We examined the association of DASH diet score (DASH-DS) with NAFLD, as well as the intermediary effects of serum retinol-binding protein-4 (RBP4), serum high-sensitivity C-reactive protein (hs-CRP), serum TAG, homeostasis model assessment of insulin resistance (HOMA-IR) and BMI.
We performed a cross-sectional analysis of a population-based cohort study. Dietary data and lifestyle factors were assessed by face-to-face interviews and the DASH-DS was then calculated. We assessed serum RBP4, hs-CRP and TAG and calculated HOMA-IR. The presence and degree of NAFLD were determined by abdominal sonography.
Guangzhou Nutrition and Health Study participants, aged 40–75 years at baseline (n 3051).
After adjusting for potential covariates, we found an inverse association between DASH-DS and the presence of NAFLD (Ptrend = 0·009). The OR (95 % CI) of NAFLD for quintiles 2–5 were 0·78 (0·62, 0·98), 0·74 (0·59, 0·94), 0·69 (0·55, 0·86) and 0·77 (0·61, 0·97), respectively. Path analyses indicated that a higher DASH-DS was associated with lower serum RBP4, hs-CRP, TAG, HOMA-IR and BMI, which were positively associated with the degree of NAFLD.
Adherence to the DASH diet was independently associated with a marked lower prevalence of NAFLD in Chinese adults, especially in women and those without abdominal obesity, and might be mediated by reducing RBP4, hs-CRP, TAG, HOMA-IR and BMI.
The relationship between serum Mg and blood cell counts in Chinese adult diabetes or central obesity was assessed by investigating 8163 subjects with China Health and Nutrition Survey (mean age 59⋅6 years, 54⋅9 % men). Participants were classified according to blood Mg (below 0⋅65 mmol/l, or 0⋅66–0⋅94 mmol/l or above 0⋅95 mmol/l), type 2 diabetes (yes/no) and central obesity (yes/no). Leucocytes, erythrocytes, platelets (PLT), Hb and glycated Hb (HbA1c) were determined using standardised methods and conditions. HbAc1, leucocytes and PLT were significantly higher among subjects with central obesity than without central obesity (P < 0⋅05). A significant increase for Hb, erythrocytes, PLT, but not leucocytes, across progressive Mg groups was observed in subjects without diabetes (P < 0⋅05). Hb, erythrocytes and HbAc1 were significantly higher among subjects with higher Mg than in subjects with lower Mg with diabetes (P < 0⋅05). Central obesity disturbed the positive association between PLT count and serum Mg. Type 2 diabetes caused metabolism disorder in serum Mg, blood sugar and blood cell count. Hb, erythrocytes and PLT, but not leucocytes, are positively correlated with serum Mg, but this association is somehow disturbed by type 2 diabetes or central obesity.
Colistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene, mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission of mcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA, mcr-1-positive Escherichia coli isolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.
The semilocal convergence of a third-order Newton-like method for solving nonlinear equations is considered. Under a weak condition (the so-called γ-condition) on the derivative of the nonlinear operator, we establish a new semilocal convergence theorem for the Newton-like method and also provide an error estimate. Some numerical examples show the applicability and efficiency of our result, in comparison to other semilocal convergence theorems.
Objective: To study the relationship of Nε-(carboxymethyl)-lysine level (CML)
with microstructure changes of white matter (WM), and cognitive impairment
in patients with type 2 diabetes mellitus (T2DM) and to discuss the
potential mechanism underlying T2DM-associated cognitive impairment. Methods: The study was performed in T2DM patients (n=22) with disease course
≥5 years and age ranging from 65 to 75 years old. A control group consisted
of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of
several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML
levels were measured by enzyme-linked immunosorbent assay, and cognitive
function was assessed by Mini-Mental State Examination and Montreal
cognitive assessment (MoCA). Results: The total Mini-Mental State Examination score in the patient group
(25.72±3.13) was significantly lower than the control group (28.16±2.45)
(p<0.05). In addition, the total MoCA score in the patient group
(22.15±3.56) was significantly lower than the control group 25.63±4.12)
(p<0.01). In the patient group, FA values were significantly decreased in
the corpus callosum, cingulate fasciculus, inferior fronto-occipital
fasciculus, parietal WM, hippocampus, and temporal lobes relative to
corresponding regions of healthy controls (p<0.05). Plasma CML level was
negatively correlated with average FA values in the global brain (r=−0.58,
p<0.01) and MoCA scores (r=−0.47, p<0.05). Conclusions: In T2DM, WM microstructure changes occur in older patients, and
elevations in CML may play a role in the development of cognitive
We determined the prevalence and seasonality of infections by Fasciola of goats and bovine species (cattle and water buffalo) in Hubei and Anhui provinces of China. Faecal samples were collected at 2- to 3-month intervals from 200 goats in Hubei province and from 152 bovine species in Anhui province. All faecal samples were examined for the presence of parasites. We determined the nucleotide sequences of the first and second internal transcribed spacers (ITS-1 and ITS-2) of the nuclear ribosomal DNA (rDNA) of 39 Fasciola worms from Anhui province. The prevalence of Fasciola infection in goats ranged between 3.5 and 37.0%, with mean eggs per gram (EPG) ranging between 29.0 and 166.0. Prevalence and EPG exhibited downward trends over time with significant differences. The prevalence of Fasciola infection in cattle ranged between 13.3 and 46.2% (mean EPG, 36.4–100.0), and that of water buffalo ranged between 10.3 and 35.4% (mean EPG, 25.0–89.6), with a higher prevalence of infection and EPG from June to October compared with December to March. Analysis of ITS-1 and ITS-2 sequences revealed that F. hepatica and F. gigantica were present in all bovine species of Anhui province and that F. gigantica mainly infected water buffalo. This is the first demonstration of Fasciola infection in Hubei province and detection of F. hepatica and F. gigantica in Anhui province. The present study of Hubei province shows that mass treatment of livestock with closantel sodium injections in April and August/September controlled Fasciola infection effectively.
The distribution of the Critically Endangered tree Manglietia longipedunculata, of which there are only 11 known wild individuals, is restricted to the Nankunshan Nature Reserve in South China. The species is threatened with extinction because of its small number of individuals and the impediments to its reproduction (a combination of protogyny, a short period of stigma receptivity, and a lack of efficient pollinators). To reduce the risk of extinction we conducted two conservation translocation trials: one to augment the sole extant population, and the other 202 km north of the current range. The latter trial was a conservation introduction in which the goals were to increase the population and to buffer against the effects of climate change. We used emerged and grafted seedlings as translocation materials. We compared the survival, growth, and eco-physiological properties of emerged and grafted seedlings at the two sites. The survival rate and growth were higher for grafted seedlings than for emerged seedlings at both sites. Eco-physiological data indicated that grafted seedlings at both sites were as efficient or more so in light and water usage than wild individuals, whereas emerged seedlings were less efficient. Grafted seedlings attained the flowering stage sooner than emerged seedlings. Our study suggests that grafting can facilitate the augmentation and establishment of new populations of M. longipedunculata and perhaps of new populations of other threatened species facing reproductive difficulties and climate change.
Tributyltin, an organotin, is ubiquitous in estuaries and freshwater systems. Previous reports suggest that tributyltin is an endocrine disruptor in many wildlife species and it inhibits aromatase in mammalian placental and granulosa-like tumor cell lines. However, no evidence showing the effects of tributyltin on oocytes or preimplantation embryonic developmental competence exists. Therefore, we investigated the role of tributyltin chloride (TBTCl) in the development of female oocytes and preimplantation embryos. Briefly, female ICR mice were gavaged with 0 (vehicle), 4, and 8 mg/kg of TBTCl each day for 18 days. The fluorescence intensity analysis showed that the 5-methylcytosine level decreased after TBTCl treatment, indicating that the general DNA methylation level decreased in the treated oocytes. Our results demonstrate that TBTCl treatment results in decreased mRNA levels of imprinted genes H19, Igf2r, and Peg3 during oocyte growth. The TBTCl-treated oocytes showed a significant increase in reactive oxygen species levels in germinal vesicle oocytes. In TBTCl-treated oocytes, there was no difference in GPx and Sod1 expression, but a decreased mRNA level of Cat occurred when compared with control. Moreover, the blastocysts with TBTCl exposure displayed higher apoptotic signals. These results suggest that TBTCl induces developmental defects in oocytes and preimplantation embryos.
Early identification of patients with bipolar disorder during their first depressive episode is beneficial to the outcome of the disorder and treatment, but traditionally this has been a great challenge to clinicians. Recently, brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the pathophysiology of bipolar disorder and major depressive disorder (MDD), but it is not clear whether BDNF levels can be used to predict bipolar disorder among patients in their first major depressive episode.
To explore whether BDNF levels can differentiate between MDD and bipolar disorder in the first depressive episode.
A total of 203 patients with a first major depressive episode as well as 167 healthy controls were recruited. After 3 years of bi-annual follow-up, 164 patients with a major depressive episode completed the study, and of these, 21 were identified as having bipolar disorder and 143 patients were diagnosed as having MDD. BDNF gene expression and plasma levels at baseline were compared among the bipolar disorder, MDD and healthy control groups. Logistic regression and decision tree methods were applied to determine the best model for predicting bipolar disorder at the first depressive episode.
At baseline, patients in the bipolar disorder and MDD groups showed lower BDNF mRNA levels (P<0.001 and P = 0.02 respectively) and plasma levels (P = 0.002 and P = 0.01 respectively) compared with healthy controls. Similarly, BDNF levels in the bipolar disorder group were lower than those in the MDD group. These results showed that the best model for predicting bipolar disorder during a first depressive episode was a combination of BDNF mRNA levels with plasma BDNF levels (receiver operating characteristics (ROC) = 0.80, logistic regression; ROC = 0.84, decision tree).
Our findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.
Mycotoxins, such as aflatoxin (AF), fumonisin B1, zearalenone (ZEA), and deoxynivalenol (DON), are commonly found in many food commodities. Mycotoxins have been shown to increase DNA methylation levels in a human intestinal cell line. We previously showed that the developmental competence of oocytes was affected in mice that had been fed a mycotoxin-containing diet. In this study, we explored possible mechanisms of low mouse oocyte developmental competence after mycotoxin treatment in an epigenetic modification perspective. Mycotoxin-contaminated maize (DON at 3,875 μg/kg, ZEA at 1,897 μg/kg, and AF at 806 μg/kg) was included in diets at three different doses (mass percentage: 0, 15, and 30%) and fed to mice for 4 weeks. The fluorescence intensity analysis showed that the general DNA methylation levels increased in oocytes from high dose mycotoxin-fed mice. Mouse oocyte histone methylation was also altered. H3K9me3 and H4K20me3 level increased in oocytes from mycotoxin-fed mice, whereas H3K27me3 and H4K20me2 level decreased in oocytes from mycotoxin-fed mice. Thus, our results indicate that naturally occurring mycotoxins have effects on epigenetic modifications in mouse oocytes, which may be one of the reasons for reduced oocyte developmental competence.
Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 107 colony-forming units (cfu)/d) and 3040 mg/l (with 109 cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.
Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people.
A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS.
In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus.
Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.
During mitosis nucleation-promoting factors (NPFs) bind to the Arp2/3 complex and activate actin assembly. JMY and WAVE2 are two critical members of the NPFs. Previous studies have demonstrated that NPFs promote multiple processes such as cell migration and cytokinesis. However, the role of NPFs in development of mammalian embryos is still unknown. Results of the present study show that the NPFs JMY and WAVE2 are critical for cytokinesis during development of mouse embryos. Both JMY and WAVE2 are expressed in mouse embryos. After injection of JMY or WAVE2 siRNA, all embryos failed to develop to the morula or blastocyst stages. Moreover, using fluorescence intensity analysis, we found that the expression of actin decreased, and multiple nuclei were observed within a single cell indicating that NPFs-induced actin reduction caused the failure of cell division. In addition, injection of JMY and WAVE2 siRNA also caused ARP2 degradation, indicating that involvement of NPFs in development of mouse embryos is mainly through regulation of ARP2/3-induced actin assembly. Taken together, these data suggested that WAVE2 and JMY are involved in development of mouse embryos, and their regulation may be through a NPFs-Arp2/3-actin pathway.
Pearlitic transformation in an ultrafine-grained (UFG) hypereutectoid steel was investigated. The steel was a plain carbon steel containing 1.0 wt% C and very few other elements. The UFG samples were prepared by thermomechanical treatment, and an average grain size of approximately 1 μm was achieved. The pearlitic transformation was conducted by heating the UFG samples at 1023 K for different times and then cooling in air. A new pearlitic transformation phenomenon was observed: traditional lamellar pearlite can be observed only when the grain size increases to a dimension larger than approximately 4 μm, which is a critical value. When grain size is smaller than this value, the pearlitic transformation occurs in the form of divorced eutectoid, and the microstructure is the ferrite matrix with granular cementite. This research indicates that grain size has a great influence on pearlitic transformation by shortening the diffusion distance and increasing the diffusion rate of carbon atoms in the UFG steel.