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Diarrhea caused by pathogens such as enterotoxigenic E. coli (ETEC) is a serious threat to the health of young animals and human infants. Here, we investigated the protective effect of fructooligosaccharides (FOS) on the intestinal epithelium with ETEC-challenge in a weaned piglet model. Twenty-four weaned piglets were randomly divided into three groups: (1) non-ETEC-challenged control (CON), (2) ETEC-challenged control (ECON), and (3) ETEC challenge + 2.5 g/kg FOS (EFOS). On day 19, the CON pigs were orally infused with sterile culture, while the ECON and EFOS pigs were orally infused with active ETEC (2.5 × 109 colony-forming units). On day 21, pigs were slaughtered to collect venous blood and small intestine. Result showed that the pre-treatment of FOS improved the antioxidant capacity and the integrity of intestinal barrier in the ETEC-challenged pigs without affecting their growth performance. Specifically, comparing with ECON pigs, the level of GSH-Px (glutathione peroxidase) and CAT (catalase) in the plasma and intestinal mucosa of EFOS pigs was increased (P<0.05), and the intestinal barrier marked by ZO-1 and plasmatic DAO was also improved in EFOS pigs. A lower level (P<0.05) of inflammatory cytokines in the intestinal mucosa of EFOS pigs might be involved in the inhibition of TLR4/MYD88/NF-κB pathway. The apoptosis of jejunal cells in EFOS pigs was also lower than that in ECON pigs (P<0.05). Our findings provide convincing evidence of possible prebiotic and protective effect of FOS on the maintenance of intestinal epithelial function under the attack of pathogens.
Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.
We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.
MDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.
Late-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.
This paper investigates optimal capital taxation in an innovation-driven growth model. We examine how the optimal capital tax rate varies with externalities associated with R&D and innovation. Our results show that the optimal capital tax rate is higher when (i) the “stepping on toes effect” is smaller, (ii) the “standing on shoulders effect” is stronger, or (iii) the extent of creative destruction is smaller. The optimal capital tax rate is more likely to be positive when there is underinvestment in R&D. Moreover, the optimal capital tax rate and the monopolistic markup exhibit an inverted-U relationship. By calibrating our model to the US economy, we find that the optimal capital tax rate is positive, at a rate of around 6.6%. Finally, we consider a number of extensions and find that the result of a positive optimal capital tax is robust.
Understanding factors associated with post-discharge sleep quality among COVID-19 survivors is important for intervention development.
This study investigated sleep quality and its correlates among COVID-19 patients 6 months after their most recent hospital discharge.
Healthcare providers at hospitals located in five different Chinese cities contacted adult COVID-19 patients discharged between 1 February and 30 March 2020. A total of 199 eligible patients provided verbal informed consent and completed the interview. Using score on the single-item Sleep Quality Scale as the dependent variable, multiple linear regression models were fitted.
Among all participants, 10.1% reported terrible or poor sleep quality, and 26.6% reported fair sleep quality, 26.1% reported worse sleep quality when comparing their current status with the time before COVID-19, and 33.7% were bothered by a sleeping disorder in the past 2 weeks. After adjusting for significant background characteristics, factors associated with sleep quality included witnessing the suffering (adjusted B = −1.15, 95% CI = −1.70, −0.33) or death (adjusted B = −1.55, 95% CI = −2.62, −0.49) of other COVID-19 patients during hospital stay, depressive symptoms (adjusted B = −0.26, 95% CI = −0.31, −0.20), anxiety symptoms (adjusted B = −0.25, 95% CI = −0.33, −0.17), post-traumatic stress disorders (adjusted B = −0.16, 95% CI = −0.22, −0.10) and social support (adjusted B = 0.07, 95% CI = 0.04, 0.10).
COVID-19 survivors reported poor sleep quality. Interventions and support services to improve sleep quality should be provided to COVID-19 survivors during their hospital stay and after hospital discharge.
Accurate prognostication is important for patients and their families to prepare for the end of life. Objective Prognostic Score (OPS) is an easy-to-use tool that does not require the clinicians’ prediction of survival (CPS), whereas Palliative Prognostic Score (PaP) needs CPS. Thus, inexperienced clinicians may hesitate to use PaP. We aimed to evaluate the accuracy of OPS compared with PaP in inpatients in palliative care units (PCUs) in three East Asian countries.
This study was a secondary analysis of a cross-cultural, multicenter cohort study. We enrolled inpatients with far-advanced cancer in PCUs in Japan, Korea, and Taiwan from 2017 to 2018. We calculated the area under the receiver operating characteristics (AUROC) curve to compare the accuracy of OPS and PaP.
A total of 1,628 inpatients in 33 PCUs in Japan and Korea were analyzed. OPS and PaP were calculated in 71.7% of the Japanese patients and 80.0% of the Korean patients. In Taiwan, PaP was calculated for 81.6% of the patients. The AUROC for 3-week survival was 0.74 for OPS in Japan, 0.68 for OPS in Korea, 0.80 for PaP in Japan, and 0.73 for PaP in Korea. The AUROC for 30-day survival was 0.70 for OPS in Japan, 0.71 for OPS in Korea, 0.79 for PaP in Japan, and 0.74 for PaP in Korea.
Significance of results
Both OPS and PaP showed good performance in Japan and Korea. Compared with PaP, OPS could be more useful for inexperienced physicians who hesitate to estimate CPS.
Condensation inside marine containers occurs during voyages owing to weather changes. In this study, we define the condensation probability along one of the major routes for container ships between Asia and Europe. First, the inside and outside air conditions were measured on land in Japan, and a correlation analysis was conducted to derive their relationship. Second, onboard measurements were conducted for 20,000 twenty-foot equivalent unit (TEU) ships to determine the variation in outside air conditions. Complicated patterns of weather change were observed with changes in latitude, sea area, and season. Third, condensation probability was estimated based on a multi-regression analysis with land and onboard measured data. The maximum condensation probability in westbound or eastbound voyages in winter was found to be approximately 50%. The condensation probability estimation method established in this study can contribute to the quantification of cargo damage risks for the planning of marine container transportation voyages.
Dysregulated proinflammatory cytokines have been shown to be associated with suicidal behavior. Cognitive deficits in working memory and inhibitory control have been demonstrated in depressed patients and people with suicidal ideation (SI). However, the association between proinflammatory cytokines, SI, and cognitive deficits in patients with major depressive disorder (MDD) remains unclear.
A total of 77 patients with MDD and age-/sex-matched 60 healthy individuals were recruited. MDD patients were divided into two groups: with SI (n = 36) and no SI (n = 41). SI was defined by a score of ≥2 in item 3 of the 17-item Hamilton Rating Scale for Depression. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1, and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task.
Patients with SI had higher levels of CRP than those without SI and controls (P = .007). CRP was positively associated with SI (β = 0.21, P = .037), independent of cognitive function and depressive symptoms. Furthermore, SI was associated with cognitive deficits in working memory and inhibitory control after adjusting for confounding factors (P < .05).
Our findings suggest that higher levels of serum CRP and deficits in working memory and inhibitory control may be associated with higher SI among patients with MDD.
This paper examines the effect of a tariff on long-run growth and welfare in a two-country innovation-led growth model. We show that although raising the home country’s tariff reduces the growth and GDP of the foreign country, it will backfire by depressing R&D and growth of the home country. The Nash equilibrium tariffs can be positive, and they are larger when the government expenditure is more beneficial to private production and/or when the productivity of innovation is higher. The presence of positive Nash equilibrium tariffs provides a theoretical explanation for why countries have incentives to implement a tariff policy regardless of its negative effect on growth. Finally, the Nash equilibrium tariffs are higher than the globally optimal tariffs, that is, the levels that maximize the joint welfare of both countries.
The most important issue for the clinical application of sarcopenic obesity (SO) is the lack of a consensus definition. The aim of the present study was to determine the best measurement for SO by estimating the association between various definitions and the risk of falls and metabolic syndrome (MS). We studied a community of 765 adults aged 65 years and older in 2015–2017. Sarcopenia obesity was measured by sarcopenia (defined by low muscle mass with either low handgrip strength or low gait speed or both) plus obesity (defined by waist circumference, body fat percentage and BMI). The MS was defined according to the National Cholesterol Education Program ATP III. Logistic regression models were constructed to examine the relationships between sarcopenia obesity and risk of fall and MS. In the analysis of the fall risk with SO defined by waist circumference, the participants with non-sarcopenia/non-obesity were treated as the reference group. The OR to fall in participants with SO was 10·16 (95 % CI 2·71, 38·13) after adjusting for confounding covariates. In the analysis of the risk of the MS between participants with individual components of sarcopenia coupled with obesity defined by waist circumference, the risk was statistically significant for low gait speed (OR: 7·19; 95 % CI 3·61, 14·30) and low grip strength (OR: 9·19; 95 % CI 5·00, 16·91). A combination of low grip strength and abdominal obesity for identifying SO may be a more precise and practical method for predicting target populations with unfavourable health risks, such as falls risk and MS.
We investigated the effects of botulinum toxin on gait in Parkinson’s disease (PD) patients with foot dystonia. Six patients underwent onabotulinum toxin A injection and were assessed by Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), visual analog scale (VAS) of pain, Timed Up and Go (TUG), Berg Balance Test (BBT), and 3D gait analysis at baseline, 1 month, and 3 months. BFMDRS (p = 0.002), VAS (p = 0.024), TUG (p = 0.028), and BBT (p = 0.034) were improved. Foot pressures at Toe 1 (p = 0.028) and Midfoot (p = 0.018) were reduced, indicating botulinum toxin’s effects in alleviating the dystonia severity and pain and improving foot pressures during walking in PD.
Cystic echinococcosis (CE) occurs in the intermediate host's liver, assuming a bladder-like structure surrounded by the host-derived collagen capsule mainly derived from activated hepatic stellate cells (HSCs). However, the effect of CE on liver natural killer (NK) cells and the potential of transforming growth factor-β (TGF-β) signalling inhibition on alleviating CE-related liver damage remain to be explored. Here, by using the CE-mouse model, we revealed that the inhibitory receptors on the surface of liver NK cells were up-regulated, whereas the activating receptors were down-regulated over time. TGF-β1 secretion was elevated in liver tissues and mainly derived from macrophages. A combination of TGF-β signalling inhibitors SB525334 and pirfenidone could reduce the expression of TGF-β1 signalling pathway-related proteins and collagen production. Based on the secretion of TGF-β1, only the pirfenidone group showed a depressing effect. Also, the combination of SB525334 and pirfenidone exhibited a higher potential in effectively alleviating the senescence of the hepatocytes and restoring liver function. Together, TGF-β1 may be a potential target for the treatment of CE-associated liver fibrosis.
To explore the effect of manno-oligosaccharide (MOS) on intestinal health in weaned pigs upon enterotoxigenic Escherichia coli K88 (ETEC) challenge, thirty-two male weaned pigs were randomly assigned into four groups. Pigs fed with a basal diet or basal diet containing MOS (0·6 g/kg) were orally infused with ETEC or culture medium. Results showed that MOS significantly elevated the digestibility of crude protein and gross energy in both ETEC-challenged and non-challenged pigs (P < 0·05). MOS also elevated serum concentrations of IgA and IgM (P < 0·05), but decreased serum concentrations of TNF-α, IL-1β and IL-6 (P < 0·05) in ETEC-challenged pigs. Interestingly, MOS increased villus height and the ratio of villus height:crypt depth in duodenum and ileum (P < 0·05). MOS also increased duodenal sucrase and ileal lactase activity in ETEC-challenged pigs (P < 0·05). MOS decreased the abundance of E. coli, but increased the abundance of Lactobacillus, Bifidobacterium and Bacillus in caecum (P < 0·05). Importantly, MOS not only elevated the expression levels of zonula occludens-1 (ZO-1), claudin-1 and GLUT-2 in duodenum (P < 0·05) but also elevated the expression levels of ZO-1, GLUT-2 and L-type amino acid transporter-1 in ileum (P < 0·05) upon ETEC challenge. These results suggested that MOS can alleviate inflammation and intestinal injury in weaned pigs upon ETEC challenge, which was associated with suppressed secretion of inflammatory cytokines and elevated serum Ig, as well as improved intestinal epithelium functions and microbiota.
Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).
This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.
The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.
These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.
The disease burden of infectious diarrhea cannot be underestimated. Its seasonal patterns indicate that weather patterns may play an important role and have an important effect on it. The objective of this study was to clarify the relationship between temperature and infectious diarrhea, and diarrhea-like illness.
Distributed lag non-linear model, which was based on the definition of a cross-basis, was used to examine the effect.
Viral diarrhea usually had high incidence in autumn-winter and spring with a peak at -6°C; Norovirus circulated throughout the year with an insignificant peak at 8°C, while related bacteria usually tested positive in summer and peaked at 22°C. The lag-response curve of the proportion of diarrhea-like cases in outpatient and emergency cases revealed that at -6°C, with the lag days increasing, the proportion increased. Similar phenomena were observed at the beginning of the curves of virus and bacterial positive rate, showing that the risk increased as the lag days increased, peaking on days 16 and 9, respectively. The shape of lag-response curve of norovirus positive rate was different from others, presenting m-type, with 2 peaks on day 3 and day 18.
Weather patterns should be taken into account when developing surveillance programs and formulating relevant public health intervention strategies.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
Few studies have assessed the characteristics of spousal psychopathologies among parents of schoolchildren with and without psychological disorders (PD) in China.
Parental symptoms were measured using the General Health Questionnaire (GHQ) in 275 mothers and 278 fathers of 298 schoolchildren with PDs diagnosed in a population survey and in 825 mothers and 834 fathers of 894 schoolchildren without PDs as a 1:3 matched comparison group. Spousal GHQ scores were compared. Childhood PD type, presence of childhood comorbidities, and multiple parental and family characteristics were examined as predictors for parental GHQ scores by multiple linear regression analyses.
The GHQ scores were significantly higher among mothers and fathers of children with any PD. Maternal GHQ scores were higher than paternal scores and significantly correlated with paternal GHQ scores in both groups. Spousal GHQ, personal PD history, and childhood PD comorbidity were significant independent predictors of both parents’ GHQ scores. There were also significant associations among parental chronic disease, low family income, and paternal and maternal GHQ score, as well as among low maternal education, less common disorder (LCD) prevalence in children and maternal GHQ score. The rate of GHQ score ≥3 for both parents was significantly higher in the study group than the control group (15.1 vs.7.0%).
Parents of children with any PD type demonstrate significantly elevated psychopathologies, and psychopathology tends to occur concomitantly and resemble that of the other spouse. Screening and treatment of parental psychiatric symptoms will benefit all family members.
Solid solution 0.94Na0.5Bi0.5TiO3–6BaTiO3 (NBT–6BT) is considered to be one kind of lead-free piezoelectric materials with excellent electrical properties due to the existence of morphotropic phase boundary (MPB). However, its relatively lower depolarization temperature is a long-standing bottleneck for the application of NBT-based piezoelectric ceramics. In this work, the influence of thermal quenching on depolarization temperature and electrical properties of rare-earth Ho-doped NBT–6BT lead-free ceramics was investigated. It was shown that the relative high piezoelectric performance, as well as an improvement of depolarization temperature (Td), can be realized by thermal quenching. The results showed that the quenching process induced high concentration of oxygen vacancy, giving rise to the change of octahedra mode and enhanced lattice distortion, which is benefit to the temperature stability of piezoelectric and ferroelectric properties. Furthermore, up-conversion photoluminescence (PL) of Ho-doped NBT–6BT could be effectively tuned by the introduction of oxygen vacancy, suggesting a promising potential in optical–electrical multifunctional devices.