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In São Paulo, Brazil, the first case of coronavirus disease 2019 (CoViD-19) was confirmed on 26 February, the first death due to CoViD-19 was registered on 16 March, and on 24 March, São Paulo implemented the isolation of persons in non-essential activities. A mathematical model was formulated based on non-linear ordinary differential equations considering young (60 years old or less) and elder (60 years old or more) subpopulations, aiming to describe the introduction and dissemination of the new coronavirus in São Paulo. This deterministic model used the data collected from São Paulo to estimate the model parameters, obtaining R0 = 6.8 for the basic reproduction number. The model also allowed to estimate that 50% of the population of São Paulo was in isolation, which permitted to describe the current epidemiological status. The goal of isolation implemented in São Paulo to control the rapid increase of the new coronavirus epidemic was partially succeeded, concluding that if isolation of at least 80% of the population had been implemented, the collapse in the health care system could be avoided. Nevertheless, the isolated persons must be released one day. Based on this model, we studied the potential epidemiological scenarios of release by varying the proportions of the release of young and elder persons. We also evaluated three different strategies of release: All isolated persons are released simultaneously, two and three releases divided in equal proportions. The better scenarios occurred when young persons are released, but maintaining elder persons isolated for a while. When compared with the epidemic without isolation, all strategies of release did not attain the goal of reducing substantially the number of hospitalisations due to severe CoViD-19. Hence, we concluded that the best decision must be postponing the beginning of the release.
A 2-year fertilization experiment was conducted to study the effect of different ratios of organic (pig) manure on wheat yield and nitrogen use efficiency (NUE). The four treatments were no nitrogen (N) (CK); 100% chemical fertilizer N (urea; T1); 70% chemical fertilizer N + 30% organic manure N (T2) and 50% chemical fertilizer N + 50% organic manure N (T3), with the same amount of applied nitrogen (120 kg/ha). The results showed the maximum grain yield (3049 kg/ha), crop nitrogen uptake (216 kg/ha), NUE (65.4%) and accumulated nitrate nitrogen (NO3−-N in 0–200 cm, 142 kg/ha) were observed in the T1 among all treatments in the first year. However, the largest grain yield (5074 kg/ha), crop nitrogen uptake (244 kg/ha) and NUE (82.5%) were under T2 treatment in the second year. Furthermore, T2 had the maximum NO3−-N content in 0–100 cm layer (116 kg/ha), especially 0–40 cm layer, and the lowest NO3−-N content in 100–200 cm (58.8 kg/ha). However, 50% organic manure N in T3 increased apparent nitrogen loss by 39.0% compared to that in T2. Therefore, 30% organic manure N application was more conducive for enhancing wheat yield and NUE and promoting environmental safety after 1-year fertilization time.
Methods that include the time-varying nature of healthcare-associated infections (HAIs) avoid biases when estimating increased risk of death and excess length of stay. We determined the excess mortality risk and length of stay associated with HAIs among inpatients in Singapore using a multistate model that accommodates the timing of key events.
Analysis of existing prospective cohort study data.
Seven public acute-care hospitals in Singapore.
Inpatients reviewed in a HAI point-prevalence survey (PPS) conducted between June 2015 and February 2016.
We modeled each patient’s admission over time using 4 states: susceptible with no HAI, infected, died, and discharged alive. We estimated the excess mortality risk and length of stay associated with HAIs, with adjustment for the baseline characteristics between the groups for mortality risk.
We included 4,428 patients, of whom 469 had ≥1 HAI. Using a multistate model, the expected excess length of stay due to any HAI was 1.68 days (95% confidence interval [CI], 1.15–2.21 days). Surgical site infections were associated with the longest excess length of stay of 4.68 days (95% CI, 2.60–6.76 days). After adjusting for baseline differences, HAIs were associated with increased hazards of in-hospital mortality (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.09–1.65) and decreased hazards in being discharged (aHR, 0.75; 95% CI, 0.67–0.84).
HAIs are associated with increased length of hospital stay and mortality in hospitalized patients. Avoiding nosocomial infections can improve patient outcomes and free valuable bed days.
Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-ﬂight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.
While genome-wide association analysis and related multi-omic strategies have in recent years dominated the field of complex disorders including mental health and addictions, in pharmacogenomics, drug metabolizing enzymes show Mendelian patterns of inheritance with correspondingly large effect sizes. Consistent with this, genes encoding these enzymes make up the majority of the genes for which the strength of the association with clinical effect of psychiatric medications is sufficient to recommend clinical utility (Bousman et al., 2018). Moreover, such enzymes are expressed in the brain (Aitchison et al., 2010; Kalow & Tyndale, 1992). We herein provide a comprehensive review of the relevance of drug metabolizing enzyme and transporter genes to mental health and addictions.
This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = −0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.
Antibiotics are designed to affect gut microbiota and subsequently gut homeostasis. However, limited information exists about short- and long-term effects of early antibiotic intervention (EAI) on gut homeostasis (especially for the small intestine) of pigs following antibiotic withdrawal. We investigated the impact of EAI on specific bacterial communities, microbial metabolites and mucosal immune parameters in the small intestine of later-growth-stage pigs fed with diets differing in CP levels. Eighteen litters of piglets were fed creep feed with or without antibiotics from day 7 to day 42. At day 42, pigs within each group were offered a normal- or low-CP diet. Five pigs per group were slaughtered at days 77 and 120. At day 77, EAI increased Enterobacteriaceae counts in the jejunum and ileum and decreased Bifidobacterium counts in the jejunum and ileum (P < 0.05). Moreover, tryptamine, putrescine, secretory immunoglobulin (Ig) A and IgG concentrations in the ileum and interleukin-10 (IL-10) mRNA and protein levels in the jejunum and ileum were decreased in pigs with EAI (P < 0.05). At day 120, EAI only suppressed Clostridium cluster XIVa counts in the jejunum and ileum (P < 0.05). These results suggest that EAI has a short-term effect on specific bacterial communities, amino acid decarboxylation and mucosal immune parameters in the small intestine (particularly in the ileum). At days 77 and 120, feeding a low-CP diet affected Bifidobacterium, Clostridium cluster IV, Clostridium cluster XIVa and Enterobacteriaceae counts in the jejunum or ileum (P < 0.05). Moreover, feeding a low-CP diet increased the concentrations of Igs in the jejunum and decreased pro-inflammatory cytokines levels in the jejunum and ileum (P < 0.05). At day 120, feeding a low-CP diet increased short-chain fatty acid concentrations, reduced ammonia and spermidine concentrations and up-regulated genes related to barrier function in the jejunum and ileum (P < 0.05). These results suggest that feeding a low-CP diet changes specific bacterial communities and intestinal metabolite concentrations and modifies mucosal immune parameters. These findings contribute to our understanding on the duration of the impact of EAI on gut homeostasis and may provide basis data for nutritional modification in young pigs after antibiotic treatment.
During recent stratigraphical and micropaleontological investigations of the Gulupu section in Tüna, Yadong, of the Eocene Zhepure Formation, numerous holoplanktonic mollusks (pteropods) were recovered. Four species, assignable to two genera of pteropods (including Limacina yadongensis new species) were systematically described and illustrated, and a gastropod-bivalve biofacies was identified. This is the first report of Eocene (Ypresian) pteropods in southern Tibet; the same stratum also yields many other neritic faunas. The data presented in this study suggest that a semi-closed restricted gulf in the Tüna area existed and the occurrence of pteropods in Tüna may indicate transport from more open, deep water by oceanic currents during early Eocene. Based on the analysis of paleogeographical distribution of pteropods, it indicates that a Tethys seaway existed during the early Eocene (Ypresian).
Introduction: In a busy emergency department (ED), effective communication is integral to the provision of safe medical care. Physicians working in the ED interact with multiple team members including patients, allied healthcare professionals and other physicians, who all need to understand their verbal and written instructions. Our study's objective was to identify and describe communication problems occurring in the ED setting, and how these problems contributed to patient safety events and increased medico-legal risk for physicians. Methods: The Canadian Medical Protective Association (CMPA) is a not-for-profit, medico-legal organization which represented over 97,000 physicians at the time of this study. We conducted a retrospective descriptive analysis where we extracted five years (2013-2017) of CMPA data describing closed medico-legal cases occurring in the ED involving physicians (any specialty) who experienced complaints due to communication issues. We then applied an internal contributing factor framework to identify data themes. Data were summarized using descriptive statistics. Results: We identified 517 eligible cases involving 521 patients (some cases involved >1 patient). We found that 99.8% (520/521) of patients experienced some form of healthcare-related harm in the ED. Specifically, there was poor communication between: the physician and patient or patient's family (202/517, 39.1%); two or more physicians (79/517, 15.3%), and physicians and other healthcare providers (55/517, 10.6%). Inadequate documentation was observed in more than half of the cases (324/517, 62.7%) and poor team communication affected physicians’ decision making process (326/517, 63%) in areas such as deficient assessments, inadequate investigations, failure or delay to attend to the patient, and disposition decisions. Conclusion: Team communication issues are prevalent among physician medico-legal cases occurring in the ED. Efforts to strengthen communication skills may enhance patient safety and reduce medico-legal risk.
Optimal dosing of psychotherapeutic agents has implications for both symptom control and patient compliance. Trials of ziprasidone in bipolar mania and schizophrenia suggest a target dose of 120-160 mg/d and that rapid titration to this level provides maximum symptom improvement. In this report, data from 2 similarly designed fixed-dose placebo-controlled studies of ziprasidone (rapidly titrated to target doses of 40, 80, 120, or 160 mg/d) in patients with acute schizophrenia were pooled. 369 patients received ziprasidone and 171 patients received placebo. Efficacy was assessed using PANSS at Weeks 1 and 6 (LOCF endpoint) of treatment. Tolerability was assessed by discontinuations (all-cause and due to adverse events). There was a significant linear dose-response relationship between ziprasidone dose and PANSS total score (F = 12.32, P ≤ 0.001). All ziprasidone doses produced statistically significant improvement in PANSS total score; the largest effect size (0.52) was observed for the 160 mg/d group. At Week 6, least-squares mean PANSS total score decreases from baseline were 9.98, 9.54, 11.71, and 14.87 in 40, 80, 120, and 160 mg/d groups, respectively. The corresponding placebo decrease was 2.79. At Week 1, decreases from baseline were 6.18, 5.70, 7.80, and 8.96 in 40, 80, 120, and 160 mg/d groups, respectively. The corresponding placebo decrease was 0.84. Tolerability of ziprasidone 160 mg/d (all-cause/AE discontinuations at week 6: 22%/15% versus 35%/0% for placebo) was comparable with that of lower doses. Rapid titration of ziprasidone to 160 mg/d was associated with greater efficacy compared with lower doses and was well tolerated.
We compared cohorts of raters from different countries who received training on the PANSS. We attempted to determine if there was any consistent by-country impact on specific items, factors, or subscales. We also queried raters about their perceptions of the instrument they were asked to use vis-à-vis their local patient population.
The data set comes from standardized rater training events involving raters from four countries: India (n = 83), Russia (n = 59), the US (n = 63), and Romania (n = 76). Raters scored interviews of schizophrenic patients using the PANSS. Scores were compared and intra-class correlation coefficients (ICCs) and rater agreement with “gold standard” scores were evaluated. The results were viewed against raters’ responses to questions about how well the PANSS items correlated to the presentation of symptoms.
Raters from the US and Russia demonstrated a higher level of inter-rater consistency with ICCs of 0.883 and 0.835, respectively. For eight PANSS items, all raters demonstrated at least 80% agreement with the gold standard scores. For ten PANSS items, there was at least one country whose raters scored below 60% agreement. The PANSS items with the lower inter-rater reliability were the same items raters indicated as problematic in local settings.
The differences in rater performance indicate that standardized rater training is broadly effective but that there are some important differences in the way in which different groups conceptualize symptomatology and corresponding PANSS items. This suggests a need to tailor training to ensure reliability and validity in the use of this instrument.
The purpose of this study was to investigated the prevalence child depression in primary schools.
3685 students from Grade 3 to Grade 5 were selected from 7 primary schools of Pudong district in Shanghai by random and cluster sampling. The study design consisted of a screening stage in which the Center for Epidemiological Studies Depression Scale for Children(CES-DC) were used, and a clinical interview stage in which the K-SADS-present state version (K-SADS) and DSM-IV were used. The diagnoses of depressive disorder were made according the DSM-IV criteria.
The prevalence of children depression was 1.60% (95%CI = 1.19%∼2.00%). The prevalence rate of male(2.08%) was significant higher than that of female (1.09%)(X2=5.40, P = 0.02). The rate of depressive disorder increased with age from 0.57% (8 years old) to 2.47% (12 years old). The prevalence of depression was no significant difference between ages from 8 to 12 years old (X2 = 4.49, P = 0.34).
The prevalence rate of children depression in Shanghai is low. The prevalence of depression among boys is much higher than that of girls.It shows the prevalence of depression is no significant difference between ages from 8 to 12 years old.
Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.
Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.
Objectives and aims
The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.
The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.
PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).
PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR = 2.231, P = 0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR = 5.623, P = 0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
Atomic electron tomography (AET) has become a powerful tool for atomic-scale structural characterization in three and four dimensions. It provides the ability to correlate structures and properties of materials at the single-atom level. With recent advances in data acquisition methods, iterative three-dimensional (3D) reconstruction algorithms, and post-processing methods, AET can now determine 3D atomic coordinates and chemical species with sub-Angstrom precision, and reveal their atomic-scale time evolution during dynamical processes. Here, we review the recent experimental and algorithmic developments of AET and highlight several groundbreaking experiments, which include pinpointing the 3D atom positions and chemical order/disorder in technologically relevant materials and capturing how atoms rearrange during early nucleation at four-dimensional atomic resolution.
Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors.
DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined.
Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving.
These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.