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To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalized anxiety disorder (GAD).
170 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 (HAMD), the Severity Subscale of Clinical Global Impression Scale (CGI-S), Global Assessment Function (GAF), and the 12-item Short-Form Health Survey (SF-12). Assessments were conducted at baseline, 4-weeks, 8-weeks and 3-monthsfollow-up.
At 4-weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen 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-months 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 (OR=2.12, 95% 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 GCBT was effective in changing cognitive style.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
Suicide attempt is an important indicator of suicide and potential future mortality. However, the prevalence of suicide attempts has been inconsistent across studies. This meta-analysis aimed to examine the prevalence of suicide attempts in individuals with schizophrenia and associated correlates.
Relevant publications in Embase, PsycINFO, PubMed, Web of science and Cochrane were systematically searched. Data on the prevalence of suicide attempts in individuals with schizophrenia were pooled using a random-effects model.
Thirty-five studies with 16 747 individuals with schizophrenia were included. The pooled lifetime prevalence of suicide attempts was 26.8% (95% CI 22.1–31.9%; I2 = 97.0%), while the 1-year prevalence, 1-month prevalence and the prevalence of suicide attempts from illness onset were 3.0% (95% CI 2.3–3.7%; I2 = 95.6%), 2.7% (95% CI 2.1–3.4%; I2 = 78.5%) and 45.9% (95% CI 42.1–49.9%; I2 = 0), respectively. Earlier age of onset (Q = 4.38, p = 0.04), high-income countries (Q = 53.29, p < 0.001), North America and Europe and Central Asia (Q = 32.83, p < 0.001) were significantly associated with a higher prevalence of suicide attempts.
Suicide attempts are common in individuals with schizophrenia, especially those with an early age of onset and living in high-income countries and regions. Regular screening and effective preventive measures should be implemented as part of the clinical care.
The antibacterial hydrogels can be widely used in the biomedical area owing to their excellent properties. The main limitation of antibacterial hydrogels is their poor mechanical strength. In this study, the novel hydrogels were fabricated with a mixture of silk fibroin (SF), chitosan (CH), agarose (AG), and silver nanoparticles (SNPs) via facile reaction condition without inorganic substances. The mechanical property of these fabricated hydrogels can be modulated by the concentration of SF or AG. The rheological studies demonstrated enhanced elasticity of CH-doped hydrogels. Because of the presence of CH and Ag in hydrogels, the antimicrobial property against gram-positive and gram-negative bacteria was exhibited. Cytocompatibility test proved the very low toxic nature of the hydrogels. In addition, these composite hydrogels have a smaller porosity, higher swelling ratio, and good compatibility, indicating their great potential for biomedical application.
Magnetic iron oxide nanoparticles (MIONPs) are particularly attractive in biosensor, antibacterial activity, targeted drug delivery, cell separation, magnetic resonance imaging tumor magnetic hyperthermia, and so on because of their particular properties including superparamagnetic behavior, low toxicity, biocompatibility, etc. Although many methods had been developed to produce MIONPs, some challenges such as severe agglomeration, serious oxidation, and irregular size are still faced in the synthesis of MIONPs. Thus, various strategies had been developed for the surface modification of MIONPs to improve the characteristics of them and obtain multifunctional MIONPs, which will widen the applicational scopes of them. Therefore, the processes, mechanisms, advances, advantages, and disadvantages of six main approaches for the synthesis of MIONPs; surface modification of MIONPs with inorganic materials, organic molecules, and polymer molecules; applications of MIONPs or modified MIONPs; the technical challenges of synthesizing MIONPs; and their limitations in biomedical applications were described in this review to provide the theoretical and technological guidance for their future applications.
As the largest industrial and population centre in China, the Pearl River Delta is facing a growing threat of heavy metal pollution from local mining and power industries. This study investigates the distribution and potential health risks of copper (Cu), cadmium (Cd), lead (Pb) and zinc (Zn) in paddy soils and rice at four typical sites. The Nemerow synthetic pollution index (PN) of soils from Fogang, Dabao Mountain, Shaoguan and Lechang were 8.40, 9.10, 4.64 and 10.28, respectively, indicating serious pollution at all four sampling sites. The average concentrations of Cu, Cd, Pb and Zn in rice grains were 2.23, 10.98, 29.84 and 1.62 times their corresponding maximum allowable levels, indicating potential health risks to humans. Cd has greater bioavailability because of its high mobility from soil to roots, and its subsequent transfer to grains. Pb mainly accumulates in roots because of its lower translocation rate from roots to grains. The greatest health risk index for Cd and Pb for adults and children was at the Shaoguan site, probably due to pollution from atmospheric deposition. Cd and Pb had greater health risk indices than Cu and Zn at almost all sites, indicating a major health risk to local people.
Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD.
A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed.
In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27–34%], 1-year prevalence was 8% (95% CI 3–14%) and 1-month prevalence was 24% (95% CI 15–34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting.
This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.
Propofol is a intravenous anaesthetic most commonly used in ultrasound oocyte retrieval. We studied if the use of propofol had an effect on mouse oocyte maturation, pregnancy, childbirth and progeny and investigated the correlation between propofol side effects and reproductive performance in mice. There was no statistical difference in mating, pregnancy, childbirth, litter size, the number of stillbirths and survival between each group (P>0.05). Propofol also had no effect on polar body extrusion in oocyte maturation as well as on pronucleus formation and, subsequently, early embryo development (P>0.05). An increased concentration of propofol had no effect on this result, although propofol at more than 0.01 mg/ml reduced polar body extrusion. Different concentrations of propofol had no effect on oocyte culture in vitro, pronucleus formation and early embryo development.
Introduction: To investigate the effects of paroxetine (PAR) on motor and cognitive function recovery in patients with non-depressed ischemic stroke (nD-AIS).
Methods: One hundred sixty-seven patients hospitalized for non-depressed acute ischemic stroke were selected and divided into treatment (T) and control (C) groups using a random number table. All patients received conventional secondary ischemic stroke prevention and rehabilitation training; patients in Group T additionally received treatment with PAR (10 mg/day during week 1 and 20 mg/day thereafter) for 3 months. The follow-up observation lasted 6 months. The Fugl–Meyer motor scale (FMMS), Montreal cognitive assessment (MoCA), and Hamilton depression scale (HAMD) were used on D0, D15, D90, and D180 (T0, 1, 2, and 3, respectively; D180 = 90 days after treatment cessation) after study initiation, and scores were compared between the groups.
Results: The FMMS and MoCA scores differed significantly between Groups T and C at T2 and T3 (p < .05); by contrast, these scores did not differ significantly between the groups at T1 (p > .05). Furthermore, the HAMD scores differed significantly between the two groups at T3 (p < .05), but not at T1 and T2 (p > .05).
Conclusions: PAR treatment may improve motor and cognitive function recovery in patients with nD-AIS. Moreover, PAR may reduce the occurrence of depression after stroke.
Mastery of strengthening strategies to achieve high-capacity anodes for lithium-ion batteries can shed light on understanding the nature of diffusion-induced stress and offer an approach to use submicro-sized materials with an ultrahigh capacity for large-scale batteries. Here, we report solute strengthening in a series of silicon (Si)–germanium (Ge) alloys. When the larger solute atom (Ge) is added to the solvent atoms (Si), a compressive stress is generated in the vicinity of Ge atoms. This local stress field interacts with resident dislocations and subsequently impedes their motion to increase the yield stress in the alloys. The addition of Ge into Si substantially improves the capacity retention, particularly in Si0.50Ge0.50, aligning with literature reports that the Si/Ge alloy showed a maximum yield stress in Si0.50Ge0.50. In situ X-ray diffraction studies on the Si0.50Ge0.50 electrode show that the phase change undergoes three subsequent steps during the lithiation process: removal of surface oxide layer, formation of cluster-size Lix(Si,Ge), and formation of crystalline Li15(Si,Ge)4. Furthermore, the lithiation process starts from higher index facets, i.e., (220) and (311), then through the low index facet (111), suggesting the orientation-dependence of the lithiation process in the Si0.50Ge0.50 electrode.
We report a novel tip-type field emission (FE) emitter by synthesizing the few-layer graphene (FLG) flakes on tip of nichrome (8020) wire (ϕ≈80 μm) by microwave plasma enhanced chemical vapor deposition(PECVD). These resultant random arrays of free-standing FLG flakes are aligned vertically to the substrate surface in a high-density and stacked to each other to form several larger “flower-like” agglomerates in spherical shapes. The FE performance of the tip-type FLG flakes emitter shows a low threshold field of 0.55 V/μm, a large field enhancement factor of 9455 ± 46, a large field emission current density of 22.18 A/cm2 at 2.70 V/μm, and an excellent field emission stability at high emission current densities (6.93 A/cm2). It can be used in variety of applications that include cathode-ray tube monitors, X-ray sources, electron microscopes, and other vacuum electronic applications.
In this paper, we introduce a lower extremity exoskeleton CUHK-EXO that is developed to help paraplegic patients, who have lost the motor and sensory functions of their lower limbs to perform basic daily life motions. Since the sit-to-stand and stand-to-sit (STS) motion is the first step for paraplegic patients toward walking, analysis of the exoskeleton's applicability to the STS motion assistance is performed. First, the human-exoskeleton system (HES) is modeled as a five-link model during the STS motion, and the center of pressure (COP) on the ground and center of gravity of the whole system are calculated. Then, a description of the CUHK-EXO hardware design is presented, including the mechatronics design and actuator selection. The COP position is an important factor indicating system balance and wearer's comfort. Based on the COP position, a trajectory online modification algorithm (TOMA) is proposed for CUHK-EXO to counteract disturbances, stabilize system balance, and improve the wearer's comfort in the STS motion. The results of STS motion tests conducted with a paraplegic patient demonstrate that CUHK-EXO can provide a normal reference pattern and proper assistive torque to support the patient's STS motion. In addition, a pilot study is conducted with a healthy subject to verify the effectiveness of the proposed TOMA under external disturbances before future clinical trials. The testing results verify that CUHK-EXO can counteract disturbances, and help the wearer perform the STS motion safely and comfortably.
Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin.
Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy.
Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function.
Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.
This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99–21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling. Finally, on the basis of the specific growth rate, against the enteritis morbidity and IgM contents, the optimum threonine requirements were estimated to be 14·53 g threonine/kg diet (4·48 g threonine/100 g protein), 15.05 g threonine/kg diet (4·64 g threonine/100 g protein) and 15·17 g threonine/kg diet (4·68 g threonine/100 g protein), respectively.
The present study investigated the effects of dietary vitamin A on immune function in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). Fish were fed graded levels of dietary vitamin A for 10 weeks, and then a challenge test using an injection of Aeromonas hydrophila was conducted for 14 d. The results showed that, compared with the optimum vitamin A level, vitamin A deficiency significantly decreased fish growth performance, increased enteritis morbidity, decreased intestinal innate humoral immune response and aggravated intestinal inflammation. However, liver-expressed antimicrobial peptide 2A/B mRNA in the DI and IL-6, IL-17D, IL-10, transforming growth factor (TGF)-β1 and TGF-β2 mRNA in the PI were not affected by vitamin A levels. Meanwhile, vitamin A deficiency disturbed inflammatory cytokines in the PI, MI and DI, which might be partly linked to p38 mitogen-activated protein kinase (p38MAPK) signalling and NF-κB canonical signalling pathway (IκB kinase β (IKKβ), IKKγ, inhibitor of κBα, NF-κB p65 and c-Rel) rather than NF-κB non-canonical signalling pathway (NF-κB p52 and IKKα). However, the signalling molecules NF-κB p65 and p38MAPK did not participate in regulating cytokines in the PI. These results suggested that vitamin A deficiency decreased fish growth and impaired intestinal immune function, and that different immune responses in the PI, MI and DI were mediated partly by NF-κB canonical signalling and p38MAPK signalling pathways. On the basis of percentage of weight gain, to protect fish against enteritis morbidity and acid phosphatase activity, the optimum dietary vitamin A levels were estimated to be 0·664, 0·707 and 0·722 mg /kg, respectively.
Crack propagation behaviors in a precracked single crystal Ag under mode I loading at different temperatures are studied by molecular dynamics simulation. The simulation results show that the crack propagation behaviors are sensitive to external temperature. At 0 K, the crack propagates in a brittle manner. Crack tip blunting and void generation are first observed followed by void growth and linkage with the main crack, which lead to the propagation of the main crack and brittle failure immediately without any microstructure evolution. As the temperature gets higher, more void nucleations and dislocation emissions occur in the crack propagation process. The deformation of the single crystal Ag can be considered as plastic deformation due to dislocation emissions. The crack propagation dynamics characterizing the microstructure evolution of atoms around the crack tip is also shown. Finally, it is shown that the stress of the single crystal Ag changes with the crack length synchronously.
Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2–4 (v. 1) were 0·66 (95 % CI 0·48, 0·91), 0·52 (95 % CI 0·37, 0·74) and 0·34 (95 % CI 0·23, 0·50) (Ptrend<0·001) for folate and 0·72 (95 % CI 0·52, 1·00), 0·55 (95 % CI 0·39, 0·78) and 0·44 (95 % CI 0·30, 0·63) (Ptrend<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (Pinteraction=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population.
This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, μ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell–cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.
The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.