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Studies have indicated that psychological stress impairs human fertility and that various stressors can induce apoptosis of testicular cells. However, the mechanisms by which psychological stress on males reduces semen quality and stressors induce apoptosis in testicular cells are largely unclear. Using a psychological (restraint) stress mouse model, we tested whether male psychological stress triggers apoptosis of spermatozoa and spermatogenic cells through activating tumour necrosis factor (TNF)-α signalling. Wild-type or TNF-α−/− male mice were restrained for 48 h before examination for apoptosis and expression of TNF-α and TNF receptor 1 (TNFR1) in spermatozoa, epididymis, seminiferous tubules and spermatogenic cells. The results showed that male restraint significantly decreased fertilization rate and mitochondrial membrane potential, while increasing levels of malondialdehyde, active caspase-3, TNF-α and TNFR1 in spermatozoa. Male restraint also increased apoptosis and expression of TNF-α and TNFR1 in caudae epididymides, seminiferous tubules and spermatogenic cells. Sperm quality was also significantly impaired when spermatozoa were recovered 35 days after male restraint. The restraint-induced damage to spermatozoa, epididymis and seminiferous tubules was significantly ameliorated in TNF-α−/− mice. Furthermore, incubation with soluble TNF-α significantly reduced sperm motility and fertilizing potential. Taken together, the results demonstrated that male psychological stress induces apoptosis in spermatozoa and spermatogenic cells through activating the TNF-α system and that the stress-induced apoptosis in spermatogenic cells can be translated into impaired quality in future spermatozoa.
Recent evidence suggests that synchronizing eating-fasting schedules with body's circadian rhythms or day-night cycles is important for metabolic health. Besides food quantity and quality, food timing may contribute to weight regulation. However, it is unclear if this factor during pregnancy can influence maternal weight retention after childbirth. Using data from a prospective cohort, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, we examined the associations of maternal circadian eating pattern and diet quality in pregnancy with substantial postpartum weight retention (PPWR) at 18 months. We assessed 687 pregnant women for their circadian eating pattern (night-eating, night-fasting and eating episodes) and diet quality (Healthy Eating Index) based on information derived from 24-h dietary recall at 26–28 weeks’ gestation. Night-eating was defined as > 50% of total energy intake during 1900–0659 h; night-fasting duration was determined based on the longest fasting interval between consumption of a calorie-containing food or beverage during 1900–0659 h; eating episodes were defined as events that provided ≥ 210 kJ with time intervals between eating episodes of ≥ 15 min; diet quality was ascertained using the Healthy Eating Index which measures adherence to the Singapore dietary guidelines for pregnant women. PPWR was calculated by subtracting the weight at the first antenatal clinic visit from weight at 18-month postpartum. Substantial PPWR was defined as weight retention of 5 kg or more. Adjusting for maternal age, ethnicity, education, parity, night shift, mood, body mass index and total energy intake, multivariable binary logistic regression analysis was performed to estimate odds ratio (OR) of substantial PPWR in relation to circadian eating pattern and diet quality. Of 687 women, 110 (16%) had substantial PPWR. After confounders adjustment, night-eating (OR 1.95; 95% confidence interval 1.05, 3.62) and lower diet quality (1.91; 1.17, 3.10) were independently associated with higher odds of substantial PPWR. No associations with substantial PPWR were observed for night-fasting duration and number of eating episodes. During pregnancy, women with higher caloric consumption at night and lower diet quality had a greater likelihood of substantial PPWR. These findings suggest that aligning eating time with day-night cycles and adherence to dietary guidelines during pregnancy may help to alleviate overweight and obesity risk in postpartum life. There is a possibility that these eating patterns persist beyond pregnancy and pose implications for long-term obesity development. Further investigation on this area is required.
Both konjac glucomannan (KGM) and inulin oligosaccharide have been shown to improve bowel function, but their effects on the mucosal barrier function and immunity are not fully understood. The aim of the present study was to determine the effects of a low-level supplementation of dietary fibres on the colonic mucosal barrier function, antioxidant enzyme defence and immunity. C57BL/6J mice (6 weeks of age, eight per group) were randomly assigned to consume one of the following diets: control or control diet supplemented with 2 % (w/w) of KGM, inulin oligosaccharide (degree polymerisation = 8) or KGM+inulin (1 %, w/w each (K+I)). Fresh faeces were collected on days 19–21. Mice were killed on day 22 after fasting. Segments of colon tissues were processed for histological procedure and stained for acidic mucins and tight junction protein marker zona occludin-1 (ZO-1). The remaining tissues were processed to determine the gene expression of mucin 2, tight junction proteins, antioxidant enzymes and cytokines. The plasma cytokines were measured. Results indicated that KGM, inulin and K+I significantly increased the mucosal layer thickness, mucin density (granule number/crypt) and gene expression of Muc2 as compared with the control. All fibre treatments increased the gene expressions of ZO-1, occludin, glutathione peroxidase, glutathione S-transferase π, catalase and IL-10. In addition, all fibre treatments increased faecal butyrate and probiotics, and plasma IL-10 concentrations. In conclusion, supplementation of low-level, 2 % (w/w), of K+I was sufficient to enhance the mucosal barrier function and anti-inflammatory status.
To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD).
Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up.
At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen’s d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36−0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32−0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02−4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27−6.16, p=0.01).
Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.
Among 300 advanced cancer patients with potential urinary tract infection (UTI), 19 had symptomatic UTI. Among remaining patients (n = 281), 21% had asymptomatic bacteriuria or candiduria, and 14% received inappropriate therapy for 279 antimicrobial days. Bacteriuria or candiduria predicted antimicrobial therapy. At 10,000 to <100,000 CFU/mL, the incidence rate ratio [IRR] was 16.9 (95% confidence interval [CI], 6.0–47.2), and at ≥100,000 CFU/mL, the IRR was 27.9 (95% CI, 10.9–71.2).
The aim was to attach importance to the hazards of ventricular pre-excitation on left ventricular systolic function and size.
We analysed the clinical, electrophysiological, and echocardiographic characteristics of the 25 cases with abnormal ventricular wall motion, left ventricular systolic dysfunction, or dilation with co-existing right-sided overt accessary pathways before and after ablation or medication during March 2011 and June 2017. Moreover, we compared the therapy effect between patients with ventricular pre-excitation-induced dilated cardiomyopathy and idiopathic dilated cardiomyopathy without ventricular pre-excitation.
Abnormal ventricular wall motion was demonstrated using M-mode echocardiography in 23 cases. The basal segments of the interventricular septum became thin and moved similarly to an aneurysm with typical bulging during end-systole, which was observed in 16 cases. Dilated cardiomyopathy was diagnosed in 14 cases. A total of 23 patients underwent successful ablations and received medications, and the other two patients received only oral medications because of young age. The prognosis of pre-excitation-induced dilated cardiomyopathy is better than idiopathic dilated cardiomyopathy. All the cases with abnormal ventricular wall motion demonstrated recovery of normal left ventricular ejection fraction and decreased left ventricular end-diastolic diameter through ablation.
Ventricular pre-excitation caused by right-sided accessory pathways may result in abnormal ventricular wall motion, left ventricular systolic dysfunction, dilation, and even dilated cardiomyopathy. In some cases with dilated cardiomyopathy, ventricular pre-excitation may not be the cause of disease but a harmful factor which hampered the recovering of left ventricular systolic function. These conditions are indications for ablation with good prognosis.
This study was conducted to evaluate the cost-effectiveness of sunitinib versus interferon-alfa for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) in Singapore.
A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from a healthcare payer perspective over a 10-year time horizon. Survival curves from the pivotal trial of sunitinib versus interferon-alfa were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from local public healthcare institutions. The sunitinib dose in the model reflected local prescribing practices whereby a combination of 50 mg (28 percent) and 37.5 mg (72 percent) strengths are used.
The base-case analysis comparing sunitinib versus interferon-alfa resulted in an incremental cost effectiveness ratio (ICER) of SGD191,061 (USD139,757) per quality-adjusted life-year gained. Sensitivity analysis demonstrated that the ICER was most sensitive to variations in the utility value assumed for the progression-free health state and the price of sunitinib.
In the absence of any price reduction, sunitinib had an exceedingly high ICER and was not considered a cost-effective use of healthcare resources in Singapore's context for the first-line treatment of advanced RCC. The findings from our evaluation will be useful to inform local healthcare decision making and resource allocations for tyrosine kinase inhibitors when appraised alongside comparative clinical effectiveness data and payer affordability considerations.
Although many studies worldwide have focused on the relationship between vitamin D and insulin resistance, results remain controversial. Furthermore, concentrations of serum 25-hydroxyvitamin D (25(OH)D) in the Chinese population are unclear. We aimed to investigate vitamin D status and its correlation with insulin resistance among a Chinese adult population.
Serum 25(OH)D, fasting blood glucose, fasting insulin, glycated Hb (HbA1c) and other metabolic parameters were assessed. Neck circumference, waist circumference, hip circumference, weight and height were also measured. Lifestyle factors including smoking and drinking status were obtained. Diabetes mellitus was diagnosed by HbA1c according to the 2010 American Diabetes Association criteria.
Of 7200 residents included, 6597 individuals were ultimately analysed.
We enrolled 2813 males (mean age 52·7 (sd 13·5) years) and 3784 females (52·3 (sd 13·5) years); mean serum 25(OH)D concentration was 43·1 (sd 11·6) and 39·6 (sd 9·8) nmol/l, respectively. Additionally, 83·3 % of participants were 25(OH)D deficient. A significant difference in 25(OH)D was observed between males and females in winter and spring (P<0·001). Furthermore, 25(OH)D concentrations were inversely associated with the homeostasis model assessment of insulin resistance (HOMA-IR) in the overweight and pre-diabetic populations. After adjusting for several variables, 25(OH)D was significantly associated with HOMA-IR in winter. When 25(OH)D values were categorized into quartiles, HOMA-IR was significantly associated with decreasing 25(OH)D.
The majority of the Chinese population was vitamin D deficient and this deficiency was negatively associated with insulin resistance, particularly in the overweight and pre-diabetic populations. Moreover, these associations might be more evident in the winter.
The protection of civilians against natural and man-made disasters has increasingly become a governmental responsibility. Urbanization, industrialization and globalization have highlighted vulnerabilities to “natural disasters, industrial or transportation accidents, terror attacks, critical infrastructure failures, or a ‘near miss’ of one of these” (ANVIL n.d.). Befittingly, civil protection has become a salient security issue for the European Union as well as China. Yet, as will be argued below, this increased prominence has only led to a partial convergence in policy responses. Notable differences remain in the understanding of the nature of (the) security threats, the allocation of responsibilities and the general approach to civil protection.
In the EU, civil protection is progressively a transnational policy area, whereas in China it is largely still developing as a national policy area. At the same time, civil protection is a policy area where some convergence can be observed. China has developed a broader nontraditional understanding of civil protection and the role of the military has become less pronounced. China's capabilities in civil protection have also strengthened so it is better able and more willing to respond to external and transboundary crises. Agreement on the need to respond to specific crises – and mutual interest in effective responses – creates space for collaboration, which so far has been limited to mainly technical matters. Arguably, civil protection is an area where there are clear opportunities to build trust and to broaden the scope of collaboration.
Civil protection is commonly referred to as civil security, civil (air) defense and crisis management. These related concepts reveal subtle differences in the understanding of the nature of (in)security addressed in civil protection. The Chinese distinction between renfang (civil air defense) and minfang (civil defense) shows the origins of civil protection against air raids as well as a more recent broader understanding of civil protection. In Europe, civil protection developed under the shadow of the Cold War, but it has evolved strongly from the predominantly traditional security domain (for example, nuclear attacks) to the largely nontraditional one (for example, natural disasters such as earthquakes and flooding, but also industrial accidents). The EU has combined responsibilities for civil protection and humanitarian aid in one Directorate-General of the EU Commission (the Directorate-General for Civil Protection and Humanitarian Aid, DG ECHO), illustrating a broad nontraditional interpretation.
Recent studies have suggested an association between vitamin D and non-alcoholic fatty liver disease (NAFLD); however, some results are subject to debate. This study was carried out to evaluate the correlation between NAFLD and vitamin D in men and women in East China. The data were obtained from a cross-sectional study that focused on the health and metabolic status of adults in sixteen areas of East China. According to ultrasonic assessments, the patients were divided into normal and NAFLD groups. Demographic characteristics and biochemical measurements were obtained. Binary logistic regression analysis was used to explore the association. In total, 5066 subjects were enrolled, and 2193 (43·3 %) were diagnosed with NAFLD; 84·56 % of the subjects showed vitamin D deficiency. Subjects with high vitamin D levels had a lower prevalence of NAFLD, particularly male subjects. Within the highest quartile of vitamin D levels, the prevalence of NAFLD was 40·8 %, whereas the lowest quartile of vitamin D levels showed a prevalence of 62·2 %, which was unchanged in women across the vitamin D levels. Binary logistic analysis showed that decreased vitamin D levels were associated with an increased risk of NAFLD (OR 1·54; 95 % CI 1·26, 1·88). This study suggests that vitamin D levels are significantly associated with NAFLD and that vitamin D acts as an independent factor for NAFLD prevalence, particularly in males in East China. Vitamin D interventional treatment might be a new target for controlling NAFLD; elucidating the mechanism requires further research.
The studies of differences in life history and suitability of both water temperatures and trophic levels among rotifer sibling species improve our understanding of speciation, sibling species coexistence and possible niche differentiation over space and time, and consequences for the functioning of ecosystems induced by climate change and eutrophication. We collected Brachionus calyciflorus from Lake Baixiang and Lake Kongque, two tropical shallow lakes, in Xishuangbanna city, Yunnan, China, clonally cultured them in laboratory, and found that the B. calyciflorus complex contains two sibling species named sibling species BNA13 and BNB3 by phylogenetic analysis, and investigated the life-table parameters of the two sibling species BNA13 and BNB3 at four temperatures (16, 20, 24 and 28°C) and four algal densities (0.5, 1.0, 2.0 and 4.0×106 cells.mL−1). The results showed that the responses to increasing temperature and algal density for each of the life-table parameters differed with rotifer sibling species. Sibling species, temperature, algal density and their interactions almost all significantly affected the durations of juvenile period, embryonic development, reproductive period, post-reproductive period, mean lifespan, net reproductive rate, generation time and intrinsic rate of population growth. Sibling species significantly affected the age-specific survivorship. Temperature, algal density and their interaction and the interaction of sibling species and temperature significantly affected the age-specific fecundity. Regardless of the effects of temperature and algal density, the durations of juvenile period, embryonic development, reproductive period, post-reproductive period and mean lifespan, age-specific survivorship, net reproductive rate and generation time of the B. calyciflorus sibling species BNA13 were greater than those of BNB3, but the intrinsic rate of population growth of BNA13 was lower than those of BNB3. This suggests that the two B. calyciflorus sibling species adopted variable life history strategies, low population growth and high survivorship for sibling species BNA13, and high population growth and low survivorship for sibling species BNB3. Both the intrinsic rates of population growth of BNA13 and BNB3 were the highest at 28°C and 4.0×106 cells.mL−1 algal density, indicating that some adaptations of the B. calyciflorus sibling species BNA13 and BNB3 in tropical shallow lakes to water temperatures and trophic levels were similar, and they have the potential for coexistence in single waterbody of higher temperature and higher trophic level.
To examine changes in food consumption during pregnancy and the postpartum period in women of major Asian ethnic groups.
Using interviewer-administered questionnaires, we assessed changes in food consumption during pregnancy (26–28 weeks’ gestation) and the postpartum period (3 weeks after delivery) as compared with the usual pre-pregnancy diet.
Pregnant women (n 1027) of Chinese, Malay and Indian ethnicity (mean age 30·4 (sd 5·2) years) who participated in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study.
During pregnancy, participants tended to increase their consumption of milk, fruit and vegetables and decrease their consumption of tea, coffee, soft drinks and seafood (all P < 0·001). Most participants reported adherence to traditional restrictions (‘confinement’) during the early postpartum period (Chinese: 94·8 %, Malay: 91·6 %, Indian: 79·6 %). During the postpartum period, participants tended to increase their consumption of fish and milk-based drinks and decrease their consumption of noodles, seafood, and chocolates and sweets (all P < 0·001). Ethnic differences in food consumption were pronounced during the postpartum period. For example, most Chinese participants (87·2 %) increased their ginger consumption during the postpartum period as compared with smaller percentages of Malays (31·8 %) and Indians (40·8 %; P for ethnic difference <0·001). Similar ethnic differences were observed for cooking wine/alcohol, herbs and spices, and herbal tea consumption.
Marked changes in food consumption that reflect both modern dietary recommendations and the persistence of traditional beliefs were observed in Singaporean women during pregnancy and the postpartum period. Traditional beliefs should be considered in interventions to improve dietary intakes during these periods.
Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid.
The different effects of ethanol on insulin sensitivity may be due to complex reasons. Here, we focus on the various daily ethanol consumption frequencies in rats fed a high-fat (HF) diet and explore the possible mechanism mediated by adiponectin and AMP-activated protein kinase (AMPK). A total of thirty-six male Wistar rats were fed a HF diet and were randomly divided into three groups: those that received tap water (C); those that received ethanol via a gastric tube twice per d (E1); those that received free access to ethanol for drinking (E2). The total daily ethanol dosage in groups E1 and E2 were the same (5 g/kg per d). At the end of 18 weeks, insulin sensitivity was evaluated. Adiponectin AMPK and GLUT4 levels were determined. We found that the different administration frequencies led to markedly different plasma ethanol concentrations and there were intimate relationships between plasma ethanol concentration and insulin sensitivity. Insulin resistance was markedly improved in group E1, whereas only a slight improvement was observed in group E2. Accordingly, adiponectin, phosphorylated AMPK and GLUT4 levels were significantly increased in group E1. Based on these findings, we propose that ethanol concentration might be the major influencing factor mediating the effect of ethanol on insulin sensitivity. At a total daily dosage of 5 g/kg per d, twice daily administration of ethanol was more beneficial than continuous drinking. The protective effect of ethanol might be mediated by increased adiponectin levels, which subsequently improve the activation of AMPKα and GLUT4 expression in adipose tissue.
Detecting corrosion by electrical field can be modeled by a Cauchy problem of Laplace equation in annulus domain under the assumption that the thickness of the pipe is relatively small compared with the radius of the pipe. The interior surface of the pipe is inaccessible and the nondestructive detection is solely based on measurements from the outer layer. The Cauchy problem for an elliptic equation is a typical ill-posed problem whose solution does not depend continuously on the boundary data. In this work, we assume that the measurements are available on the whole outer boundary on an annulus domain. By imposing reasonable assumptions, the theoretical goal here is to derive the stabilities of the Cauchy solutions and an energy regularization method. Relationship between the proposed energy regularization method and the Tikhonov regularization with Morozov principle is also given. A novel numerical algorithm is proposed and numerical examples are given.
Konjac glucomannan (KGM) has been shown to increase human colon microbial ecology and reduce faecal toxicity in mice. The main goal of the present study was to assess the effects of a KGM supplement into a low-fibre diet on precancerous markers of colon cancer in a double-blind, placebo- and diet-controlled study. Adult volunteers consumed defined diets supplemented with konjac (4·5 g/d) or placebo (maize starch) for 4 weeks. Stools collected before and at the end of the supplementation were analysed for β-glucosidase, β-galactosidase and β-glucuronidase activities, microflora and bile acids. Faecal water was co-incubated with Caco-2 cells, a model of human colonocytes, to determine the cytotoxicity and DNA-damaging effect as assessed by the comet assay. The results indicated that the KGM supplement significantly decreased faecal β-glucuronidase activity by 25·6 (se 7·8) % and faecal secondary bile acid level by 42·4 (se 11·8) %. In contrast, consuming the defined diet supplemented with placebo for 4 weeks did not improve these determinants. The KGM-supplemented diet, but not the placebo diet, significantly increased the survival rate (%) of Caco-2 cells co-incubated with faecal water for 1 and 3 h, respectively. In addition, KGM significantly reduced the DNA damage induced by the faecal water alone or in combination with H2O2. The faecal bifidobacteria and lactobacilli levels increased only with the KGM-supplemented diet. Therefore, we conclude that supplementation of KGM into a low-fibre diet improved the faecal microbial ecology and metabolites, which may contribute to the reduced toxicity of faecal water and precancerous risk factors of human colon cancer.
To identify neuropsychological and psychosocial factors predictive of amnestic Mild Cognitive Impairment (aMCI) among a group of 94 nondemented older adults, we employed a novel nonlinear multivariate classification statistical method called Optimal Data Analysis (ODA) in a dataset collected annually for 3 years. Performance on measures of memory and visuomotor processing speed or symptoms of depression in year 1 predicted aMCI status by year 2. Performance on a measure of learning at year 1 predicted aMCI status at year 3. No other measures significantly predicted incidence of aMCI at years 2 and 3. Results support the utility of multiple neuropsychological and psychosocial measures in the diagnosis of aMCI, and the present model may serve as a testable hypothesis for prospective investigations of the development of aMCI. (JINS, 2010, 16, 721–729.)
It was well beyond my expectations when I heard from Professor Ames that our meta-analysis paper (Han et al., 2000) was among the top-cited papers in International Psychogeriatrics. As an expression of my gratitude to the editor for the invitation and to the audience of this paper, I would like to offer this informal discussion on the background of the paper and extend a few ideas that were not conveyed fully at the time, due either to insufficient knowledge or unavailability of relevant data or methodologies.