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Little is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia.
A three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12.
The MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement.
Our results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.
Engineered biomaterials provide unique functions to overcome the bottlenecks seen in biomedicine. Hence, a technique for rapid and routine tests of collagen is required, in which the test items commonly include molecular weight, crosslinking degree, purity, and sterilization induced structural change. Among them, the crosslinking degree mainly influences collagen properties. In this study, second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy are used in combination to explore the collagen structure at molecular and macromolecular scales. These measured parameters are applied for the classification and quantification among the different collagen scaffolds, which were verified by other conventional methods. It is demonstrated that the crosslinking status can be analyzed from SHG images and presented as the coherency of collagen organization that is correlated with the mechanical properties. Also, the comparative analyses of SHG signal and relative CARS signal of amide III band at 1,240 cm−1 to δCH2 band at 1,450 cm−1 of these samples provide information regarding the variation of the molecular structure during a crosslinking process, thus serving as nonlinear optical signatures to indicate a successful crosslinking.
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 present study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarisation and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to three groups: normal control fed with American Institute of Nutrition (AIN)-93G diet and two sepsis groups provided with either AIN-93G-based diet or identical components, except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with caecal ligation and puncture and were killed 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas IL-4-, and forkhead box p3 (Foxp3)-expressing CD4+ T cells percentages were up-regulated. Compared with the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells and reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker kidney injury molecule-1 (Kim-1) were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more balanced blood T helper cell polarisation, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects at risk of abdominal infection.
Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear.
Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram.
Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD.
TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.
Cellulitis is a common infection of the skin and soft tissue. Susceptibility to cellulitis is related to microorganism virulence, the host immunity status and environmental factors. This retrospective study from 2001 to 2013 investigated relationships between the monthly incidence rate of cellulitis and meteorological factors using data from the Taiwanese Health Insurance Dataset and the Taiwanese Central Weather Bureau. Meteorological data included temperature, hours of sunshine, relative humidity, total rainfall and total number of rainy days. In otal, 195 841 patients were diagnosed with cellulitis and the incidence rate was strongly correlated with temperature (γS = 0.84, P < 0.001), total sunshine hours (γS = 0.65, P < 0.001) and total rainfall (γS = 0.53, P < 0.001). The incidence rate of cellulitis increased by 3.47/100 000 cases for every 1° elevation in environmental temperature. Our results may assist clinicians in educating the public of the increased risk of cellulitis during warm seasons and possible predisposing environmental factors for infection.
Choices between options represented in a multidimensional space, in which each dimension signifies a distinct attribute describing the objects, are presumably guided by the principle of value maximization. However, the current study assumes that in a real-world setting, those who are able to imagine things that do not actually exist could modify the multidimensional space by self-generating an unoffered but fictional dimension. We define the utility (Uv) assigned by the decision makers to the options on the offered/given dimension as value (v[x]) and the utility (Uw) on the self-generated/fictional dimension as worth (w[xc]). Our series of experiments demonstrated that an option with a greater value established strictly on that given set of dimensions might not necessarily be chosen (which contradicted the principle of value maximization). Choosing an option with less value (i.e. giving away the bigger pear) behavior can be described and explained by the “worth-based choice” approach, as people behave to select the option with the highest worth rather than that with the highest value. We are optimistic that the resulting findings will facilitate our understanding of the beauty of such a “one step further” choice and assist us in understanding the following: the ability to further generate a fictional dimension and to assign a delayed utility (worth) to the options on the fictional dimension, and to make a worth-based choice, which could eventually be taken as the operational definition to measure the degree of “fiction-generating ability”, as proposed by Harari (2014).
The present study was undertaken to investigate the antiparasitic activity of extracellular products of Streptomyces albus. Bioactivity-guided isolation of chloroform extracts affording a compound showing potent activity. The structure of the compound was elucidated as salinomycin (SAL) by EI-MS, 1H NMR and 13C NMR. In vitro test showed that SAL has potent anti-parasitic efficacy against theronts of Ichthyophthirius multifiliis with 10 min, 1, 2, 3 and 4 h (effective concentration) EC50 (95% confidence intervals) of 2.12 (2.22–2.02), 1.93 (1.98–1.88), 1.42 (1.47–1.37), 1.35 (1.41–1.31) and 1.11 (1.21–1.01) mg L−1. In vitro antiparasitic assays revealed that SAL could be 100% effective against I. multifiliis encysted tomonts at a concentration of 8.0 mg L−1. In vivo test demonstrated that the number of I. multifiliis trophonts on Erythroculter ilishaeformis treated with SAL was markedly lower than that of control group at 10 days after exposed to theronts (P < 0.05). In the control group, 80% mortality was observed owing to heavy I. multifiliis infection at 10 days. On the other hand, only 30.0% mortality was recorded in the group treated with 8.0 mg L−1 SAL. The median lethal dose (LD50) of SAL for E. ilishaeformis was 32.9 mg L−1.
Isolation of multidrug-resistant gram-negative bacteria (MDR-GNB) from patients in the community has been increasingly observed. A prediction model for MDR-GNB colonization and infection risk stratification on hospital admission is needed to improve patient care.
A 2-stage, prospective study was performed with 995 and 998 emergency department patients enrolled, respectively. MDR-GNB colonization was defined as isolates resistant to 3 or more classes of antibiotics, identified in either the surveillance or early (≤48 hours) clinical cultures.
A score-assigned MDR-GNB colonization prediction model was developed and validated using clinical and microbiological data from 995 patients enrolled in the first stage of the study; 122 of these patients (12.3%) were MDR-GNB colonized. We identified 5 independent predictors: age>70 years (odds ratio [OR], 1.84 [95% confidence interval (CI), 1.06–3.17]; 1 point), assigned point value in the model), residence in a long-term-care facility (OR, 3.64 [95% CI, 1.57–8.43); 3 points), history of cerebrovascular accidents (OR, 2.23 [95% CI, 1.24–4.01]; 2 points), hospitalization within 1 month (OR, 2.63 [95% CI, 1.39–4.96]; 2 points), and recent antibiotic exposure (OR, 2.18 [95% CI, 1.16–4.11]; 2 points). The model displayed good discrimination in the derivation and validation sets (area under ROC curve, 0.75 and 0.80, respectively) with the best cutoffs of<4 and ≥4 points for low- and high-risk MDR-GNB colonization, respectively. When applied to 998 patients in the second stage of the study, the model successfully stratified the risk of MDR-GNB infection during hospitalization between low- and high-risk groups (probability, 0.02 vs 0.12, respectively; log-rank test, P<.001).
A model was developed to optimize both the decision to initiate antimicrobial therapy and the infection control interventions to mitigate threats from MDR-GNB.
It has been reported that up to 42% of the population aged over 60 are affected by mild cognitive impairment (MCI) worldwide. This study aims to investigate the prevalence and progression of MCI through a meta-analysis.
We searched Embase and PubMed for relevant literature. Stable disease rate (SR), reversion rate (RR), dementia rate (DR), and Alzheimer's disease rate (AR) were used to evaluate the progression of MCI. The prevalence and progression rates were both obtained by reported percentile and indirect data analysis. Additionally, we carried out sensitivity analysis of each index by excluding some studies due to influence analysis with the most publication bias.
Effect size (ES) was used to present adjusted overall prevalence (16%) and progression rates including SR (45%), RR (15%), DR (34%), and AR (28%) of MCI. Compared with clinic-based outcomes, MCI prevalence, SR, and RR are significantly higher in community, while DR and AR are lower. Despite significant heterogeneity found among the studies, no publication bias was observed.
Age and gender were observed to be associated with MCI, in which age was considered as an impact factor for DR. The strong heterogeneity may result from variations in study design and baselines. Standardized MCI criteria were suggested to systematically evaluate MCI in the future.
Choline and betaine are essential nutrients involved in one-carbon metabolism and have been hypothesised to affect breast cancer risk. Functional polymorphisms in genes encoding choline-related one-carbon metabolism enzymes, including phosphatidylethanolamine N-methyltransferase (PEMT), choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT), have important roles in choline metabolism and may thus interact with dietary choline and betaine intake to modify breast cancer risk. This study aimed to investigate the interactive effect of polymorphisms in PEMT, BHMT and CHDH genes with choline/betaine intake on breast cancer risk among Chinese women. This hospital-based case–control study consecutively recruited 570 cases with histologically confirmed breast cancer and 576 age-matched (5-year interval) controls. Choline and betaine intakes were assessed by a validated FFQ, and genotyping was conducted for PEMT rs7946, CHDH rs9001 and BHMT rs3733890. OR and 95 % CI were estimated using unconditional logistic regression. Compared with the highest quartile of choline intake, the lowest intake quartile showed a significant increased risk of breast cancer. The SNP PEMT rs7946, CHDH rs9001 and BHMT rs3733890 had no overall association with breast cancer, but a significant risk reduction was observed among postmenopausal women with AA genotype of BHMT rs3733890 (OR 0·49; 95 % CI 0·25, 0·98). Significant interactions were observed between choline intake and SNP PEMT rs7946 (Pinteraction=0·029) and BHMT rs3733890 (Pinteraction=0·006) in relation to breast cancer risk. Our results suggest that SNP PEMT rs7946 and BHMT rs3733890 may interact with choline intake on breast cancer risk.
The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta-analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised-controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR)=1·04; 95 % CI 0·90, 1·19; I2=39 %; P=0·58), hospital length of stay (HR=1·04; 95 % CI 0·83, 1·33; I2=57 %; P=0·74), treatment failure (relative risk (RR)=0·95; 95 % CI 0·79, 1·14; I2=20 %; P=0·58) or change of antibiotics (RR=1·07; 95 % CI 0·79, 1·45; I2=44 %; P=0·67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798.
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.
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.
The role of oxidative stress in skeletal health is unclear. The present study investigated whether a high dietary intake of antioxidant nutrients (vitamins C and E, β-carotene, animal-derived vitamin A, retinol equivalents, Zn and Se) is associated with a reduced risk of hip fracture in elderly Chinese. This 1:1 matched case–control study involved 726 elderly Chinese with hip fracture and 726 control subjects, recruited between June 2009 and May 2013. Face-to-face interviews were conducted to determine habitual dietary intakes of the above-mentioned seven nutrients based on a seventy-nine-item FFQ and information on various covariates, and an antioxidant score was calculated. After adjustment for potential covariates, dose-dependent inverse associations were observed between the dietary intake of vitamin C, vitamin E, β-carotene, and Se and antioxidant score and the risk of hip fracture (P for trend ≤ 0·005). The OR of hip fracture for the highest (v. lowest) quartile of intake were 0·39 (95 % CI 0·28, 0·56) for vitamin C, 0·23 (95 % CI 0·16, 0·33) for vitamin E, 0·51 (95 % CI 0·36, 0·73) for β-carotene, 0·43 (95 % CI 0·26, 0·70) for Se and 0·24 (95 % CI 0·17, 0·36) for the antioxidant score. A moderate-to-high dietary intake of retinol equivalents in quartiles 2–4 (v. 1) was found to be associated with a lower risk of hip fracture (OR range: 0·51–0·63, P< 0·05). No significant association was observed between dietary Zn or animal-derived vitamin A intake and hip fracture risk (P for trend >0·20). In conclusion, a higher dietary intake of vitamins C and E, β-carotene, and Se and a moderate-to-high dietary intake of retinol equivalents are associated with a lower risk of hip fracture in elderly Chinese.
Cancer is a serious public health problem worldwide, and its relationship
with affective disorders is not clear.
To investigate alcohol- and tobacco-related cancer risk among patients
with affective disorders in a large Taiwanese cohort.
Records of newly admitted patients with affective disorders from January
1997 through December 2002 were retrieved from the Psychiatric Inpatient
Medical Claims database in Taiwan. Cancers were stratified by site and
grouped into tobacco- or alcohol-related cancers. Standardised incidence
ratios (SIRs) were calculated to compare the risk of cancer between those
with affective disorders and the general population.
Some 10 207 patients with bipolar disorder and 9826 with major depression
were included. The risk of cancer was higher in patients with major
depression (SIR = 2.01, 95% CI 1.85–2.19) than in those with bipolar
disorder (SIR 1.39, 95% CI 1.26–1.53). The elevated cancer risk among
individuals ever admitted to hospital for affective disorders was more
pronounced in tobacco- and/or alcohol-related cancers.
Elevated cancer risk was found in patients who had received in-patient
care for affective disorders. They require holistic approaches to
lifestyle behaviours and associated cancer risks.