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The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration.
A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012–2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1–364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve.
The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60–0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury.
Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.
Fruit intake may influence gestational diabetes mellitus (GDM) risk. However, prospective evidence remains controversial and limited. The current study aimed to investigate whether total fruit and specific fruit intake influence GDM risk.
A prospective cohort study was conducted. Dietary information was collected by a 3-d 24-h dietary recall. All participants underwent a standard 75-g oral glucose tolerance test at 24–28 gestational weeks. Log-binomial models were used to estimate the association between fruit intake and GDM risk, and the results are presented as relative risks (RR) and 95 % CI.
Totally, 1453 healthy pregnant women in 2017.
Total fruit intake was not associated with lower GDM risk (RR of 1·03 (95 % CI 0·83, 1·27) (Ptrend = 0·789)). The RR of GDM risk was 0·73 for the highest anthocyanin-rich fruit intake quartile compared with the lowest quartile (95 % CI 0·56, 0·93; Ptrend = 0·015). A higher grape intake had a linear inverse association with GDM risk (Q4 v. Q1: RR = 0·65; 95 % CI 0·43, 0·98; Ptrend = 0·044), and after further adjustment for anthocyanin intake, the inverse association tended to be non-linear (Q4 v. Q1: RR = 0·65; 95 % CI 0·44, 0·98; Ptrend = 0·079). However, we did not find an association between glycaemic index-grouped fruit, glycaemic load-grouped fruit or other fruit subtype intake and GDM risk.
In conclusion, specific fruit intake (particularly anthocyanin-rich fruit and grapes) but not total fruit intake was inversely associated with GDM risk.
Redroot pigweed (Amaranthus retroflexus L.) is a dominant weed in soybean [Glycine max (L.) Merr.] fields in Heilongjiang Province, China. High selective pressure caused by the extensive application of the protoporphyrinogen oxidase (PPO)-inhibiting herbicide fomesafen has caused A. retroflexus to evolve resistance to this herbicide. Two susceptible and two resistant populations (S1, S2, R1, and R2) were selected in this study to illustrate the target-site resistance mechanism in resistant A. retroflexus. Whole-plant bioassays indicated that R1 and R2 had evolved high-level resistance to fomesafen, with resistance factors of 27.0 to 27.9. Sequence alignment of the PPO gene showed an Arg-128-Gly substitution in PPX2. The basal expression differences of PPX1 and PPX2 between the S1 and R1 plants were essentially nonsignificant, whereas the basal expression of PPX2 in R2 plants was slightly lower than in S1 plants. Compared with the PPX1 gene, the PPX2 gene maintained higher expression in the resistant plants after treatment with fomesafen. An enzyme-linked immunosorbent assay showed a similar basal PPO content between the susceptible and resistant plants without treatment. After fomesafen treatment, the PPO content decreased sharply in the susceptible plants compared with the resistant plants. Furthermore, after 24 h of treatment, the resistant plants showed increased PPO content, whereas the susceptible plants had died. The PPO2 mutation resulted in high extractable PPO activity and low sensitivity to fomesafen along with changes in PPO enzyme kinetics. Although the mutant PPO2 exhibited increased Km values in the resistant plants, the Vmax values in these plants were also increased. Changes in the properties of the PPO enzyme due to an Arg-128-Gly substitution in PPX2, including changes in enzyme sensitivity and enzyme kinetics, are the target-site mechanism of resistance in A. retroflexus.
Mode distortion induced by stimulated Raman scattering (SRS) has become a new obstacle for the further development of high-power fiber lasers with high beam quality. Here, an approach for effective suppression of the SRS-induced mode distortion in high-power fiber amplifiers has been demonstrated experimentally by adjusting the seed power (output power of seed source) and forward feedback coefficient of the rear port in the seed source. It is shown that the threshold power of the SRS-induced mode distortion can be increased significantly by reducing the seed power or the forward feedback coefficient. Moreover, it has also been found that the threshold power is extremely sensitive to the forward feedback power value from the rear port. The influence of the seed power on the threshold power can be attributed to the fact that the seed power plays an important role in the effective length of the gain fiber in the amplifier. The influence of the forward feedback coefficient on the threshold power can be attributed to the enhanced SRS configuration because the end surface of the rear port together with the fiber in the amplifier constitutes a half-opening cavity. This suppression approach will be very helpful to further develop the high-power fiber amplifiers with high beam quality.
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.
Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.
Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.
This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).
FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.
The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.
Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.
Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines—including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)—were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.
Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.
Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.
The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.
In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period.
Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo.
Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.
Cytomegalovirus (CMV) enters latency after primary infection and can reactivate periodically with virus excreted in body fluids which can be called shedding. CMV shedding during the early stage of pregnancy is associated with adverse pregnancy outcome. The shedding pattern in healthy seropositive women who plan to have babies has not been well characterised. Vaginal swabs, urine and blood were collected from 1262 CMV IgG-positive women who intended to have babies and tested for CMV DNA by fluorogenic quantitative PCR method. Serum IgM was also detected. The association between sociodemographic characteristics and CMV shedding prevalence was analysed. Among 1262 seropositive women, 12.8% (161/1262) were detected CMV DNA positive in at least one body fluid. CMV DNA was more frequently detected in vaginal secretion (10.5%) than in urine (3.2%) and blood (0.6%) also with higher viral loads (P < 0.00). CMV shedding was more likely detected in IgM-positive women than IgM-negative women (29.5% (13/44) vs. 12.2% (148/1218); OR 3.03, 95% CI 1.55–5.93; P = 0.001). CMV shedding in vaginal secretion was highly correlated with shedding in urine, the immune state of IgM, the adverse pregnant history and younger age. CMV shedding was more commonly detected in vaginal secretion than in urine or blood with higher viral loads among healthy seropositive women of reproductive age. Further studies are needed to figure out whether the shedding is occasional or continuous and whether it is associated with adverse pregnancy outcomes.
Terrorist attacks can occur anywhere. As the threat of terrorism develops, the China-Eurasia Expo held in Ürümqi, China is attracting fewer potential visitors. A nationwide survey of 2034 residents from 31 provinces and municipalities in China was conducted to examine the relation between the distance to respondents’ city of residence from Ürümqi and their levels of concern for safety and security concerning the Expo. The two were found to be positively related: the closer the respondents lived to Ürümqi, the less concerned they were with the safety and security of the Expo. This is consistent with the “psychological typhoon eye” effect, which states that people living closer to the center of an unfortunate event (whether natural or man-made hazards) are less concerned with the event’s negative consequences. This effect appears to hold for terrorism. There are implications of this finding for international counter-terrorism practice, tourism, and research.
To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women.
A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range.
Pregnant women (n 1910) in 2017.
After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8–1·2, 0·8–1·2 and 0·35–0·70 kg for underweight, normal-weight and overweight/obese women, respectively.
Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.
The topological structure of a parallel manipulator (PM) determines its intrinsic topological properties (TPs). The TPs further determine essential kinematic and dynamic properties of the mechanism. TPs can be expressed through topological characteristics indexes (TCI). Therefore, defining a set of TCIs is an important issue to evaluate the TPs of PMs. This article addresses the evaluation of topological properties (ETP) of PMs based on TCI. A general and effective ETP method for PMs is proposed. Firstly, 12 TCIs are proposed, including 8 quantitative TCIs, that is, position and orientation characteristics sets (POC), dimension of the POC set, degrees of freedom (DOF), number of independent displacement equations, types and number of an Assur kinematic chain (AKC), coupling degrees of the AKCs, degrees of redundancy and the number of overs; as well as 4 qualitative TCIs, that is, selection of actuated joints, identification of inactive joints, DOF type and Input–Output motion decoupling. Secondly, the ETP method is illustrated by evaluating some well-known PMs including the Delta, Tricept, Exechon, Z3, H4 and the Gough–Stewart platform manipulators, as well as 28 other typical PMs. Via the ETP analysis of these mechanisms also some valuable design knowledge is derived and guidelines for the design of PMs are established. Finally, a 5-DOF decoupled hybrid spraying robot is developed by applying the design knowledge and the design guidelines derived from the ETP analysis.
The dipeptide dl-methionyl-dl-methionine (Met-Met) has extremely low water solubility and better absorption than other methionine sources (such as dl-methionine and l-methionine) available in the market. Therefore, six diets (D1, D2, D3, D4, D5 and D6) containing 0, 0·07, 0·15, 0·21, 0·28 and 0·38 % Met-Met were formulated to investigate the effects of Met-Met in juvenile Nile tilapia, Oreochromis niloticus (17 g initial body weight). The results indicated that percentage weight gain and specific growth rate of fish fed with D2 and D3 diets were higher than those fed with D1, D4–D6 diets. The levels of total essential amino acid in whole body of fish fed with D3 and D4 diets were significantly higher than those fed the D1 diet. Superoxide dismutase activity and malondialdehyde content have no significant difference in fish fed the diet with or without Met-Met supplementation. Majority of reads derived from the fish intestine belonged to members of Fusobacteria, followed by Bacteroidetes and Proteobacteria. Diversity of intestinal microbiota and total antioxidant capacity in fish fed with D3 diet was significantly higher than that of other groups. Based on the growth results, the authors conclude that the optimal level of Met is 0·61 % Met with the addition of 0·15 % Met-Met for grower-phase O. niloticus.
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.