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Significant differences in clinical manifestations between first-episode and recurrent major depression disorder (FE-MDD/R-MDD) have been demonstrated in previous studies, including the degree of suicide attempt. However, the potential brain mechanism underlying the effect of depressive episode frequency on suicidal ideation (SI) remains unclear. In this study, 102 patients with FE-MDD (SI/non-SI: N = 70/32) and 71 matched normal controls (NCs), as well as 75 patients with R-MDD (SI/non-SI: N = 37/38) and 49 matched NCs were screened from the Chinese REST-meta-MDD consortium. T1-weighted and resting-state fMRI images were used to calculate gray matter volume (GMV) and fractional amplitude of low-frequency fluctuations (fALFF), respectively. Group comparisons revealed that FE-MDD showed changes only in GMV, while R-MDD showed changes in both GMV and fALFF compared to NCs. SI-specific GMV decreases were observed in the right cerebellum, superior marginal gyrus, and left middle temporal gyrus in FE-MDD patients, while SI-specific fALFF decreases in bilateral superior frontal gyrus and increases in bilateral cerebellum and left parahippocampal gyrus were obserevd in R-MDD patients. Moreover, a negative correlation was found between GMV value in right cerebellum and HAMD score. These findings suggest that first-episode and recurrent MDD show different effects on brain structure and function in patients with SI, providing a potential explanation for the distinct clinical manifestations of MDD patients from a brain mechanisms perspective. • This study used multimodal MRI to examine effect of depressive episode on brain changes related to suicidal ideation (SI). • First-episode and recurrent depression predominantly affected SI-related brain structure and function, respectively. • Structural measurement in right cerebellum negatively correlated with depressive scores. • Different depressive episodes have distinct effects on brain structure, function and their association in patients with SI. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that many regions in the human brain include multidirectional fiber tracts, in which the diffusion of water molecules within image voxels does not follow a Gaussian distribution. Therefore, the conventional diffusion tensor imaging (DTI) that hypothesizes a single fiber orientation within a voxel is intrinsically incapable of revealing the complex microstructures of brain tissues. Diffusion spectrum imaging (DSI) employs a pulse sequence with different b-values along multiple gradient directions to sample the diffusion information of water molecules in the entire q-space and then quantitatively estimates the diffusion profile using a probability density function with a high angular resolution. Studies have suggested that DSI can reliably observe the multidirectional fibers within each voxel and allow fiber tracking along different directions, which can improve fiber reconstruction reflecting the true but complicated brain structures that were not observed in the previous DTI studies. Moreover, with increasing angular resolution, DSI is able to reveal new neuroimaging biomarkers used for disease diagnosis and the prediction of disorder progression. However, so far, this method has not been used widely in clinical studies, due to its overly long scanning time and difficult post-processing. Within this context, the current paper aims to conduct a comprehensive review of DSI research, including the fundamental principles, methodology, and application progress of DSI tractography. By summarizing the DSI studies in recent years, we propose potential solutions towards the existing problem in the methodology and applications of DSI technology as follows: (1) using compressed sensing to undersample data and to reconstruct the diffusion signal may be an efficient and promising method for reducing scanning time; (2) the probability density function includes more information than the orientation distribution function, and it should be extended in application studies; and (3) large-sample study is encouraged to confirm the reliability and reproducibility of findings in clinical diseases. These findings may help deepen the understanding of the DSI method and promote its development in clinical applications. [ABSTRACT FROM AUTHOR]

• AOS patients showed several state-specific connectivity decreases within the mirror neuron system (MNS) network. • The dFC between left middle temporal gyrus and left V5 negatively correlated with clinical assessments across AOS patients. • Social dysfunctions in AOS patients may be associated with the altered dFCs within the MNS and mentalizing networks. Previous studies based on an assumption of connectivity stationarity reported disconnections in mirror neuron system (MNS) and mentalizing networks of schizophrenic brains with social cognitive disruptions. However, recent studies demonstrated that functional brain connections are dynamic, and static connectivity metrics fail to capture time-varying properties of functional connections. The present study used a dynamic functional connectivity (dFC) method to test whether alterations of functional connectivity in the two networks are time-varying in adolescent-onset schizophrenia (AOS) patients. We collected resting-state fMRI data from 28 patients with AOS and 22 matched healthy controls. Static functional connectivity and dFC were used to explore the connectivity difference in the MNS and mentalizing networks between the two groups, respectively. Then a Pearson's correlation analysis between the connectivity showing intergroup differences and clinical scores was conducted in the AOS group. Compared with static functional connectivity analyses, dFC revealed state-specific connectivity decreases within the MNS network in the AOS group. Additionally, the dFC between the left middle temporal gyrus and left V5 was negatively correlated with the item2 of PANSS negative scores across all the AOS patients. Our findings suggest that social dysfunctions in AOS patients may be associated with the altered integrity and interaction of the MNS and mentalizing networks, and the functional impairments in the MNS are dynamic over time. [ABSTRACT FROM AUTHOR]

Abundant evidence has revealed that social observation could enhance people's norm-enforcement behaviors to norm violators. However, whether such enhancement is strategically reputation-based without changes on awareness of social norms or it is accompanied with strengthened perception of norm violations remains unclear. We aimed to test these two hypotheses using a modified Ultimatum Game (UG). Participants played the UG as responders in the fMRI scanner after being instructed the rules of the game and how the observers monitored their performances during the task. Behavioral results showed that unfair offers were perceived more unfair (decreased fairness ratings) and rejected more often under the condition with social observation than that without observation (the control condition). The changes in fairness ratings predicted the increase of rejection rates between two conditions, which provided more evidence for the latter hypothesis. Neural results demonstrated that right insula and anterior cingulate cortex associated with processing norm violations and/or negative emotions were more activated in response to unfair treatments under social observation relative to the control condition. Furthermore, bilateral anterior insula, anterior cingulate cortex, and right amygdala (an emotional processing structure) showed increased activations with the reduction of fairness ratings under social observation. Besides, compared to the control condition, rejecting unfair trials under social observation induced more left anterior insula activation. These findings indicated that the increase of norm-enforcement behaviors in the UG under social observation was more than a behavioral strategy for social desirability, but a result of enhanced sensitivity to fairness norm violations and unfairness-related negative feelings. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic effect of sequential detection of Adenosine deaminase (ADA) screening and T-SPOT assay on tuberculosis (TB) pleurisy in pleural effusion patients. Materials and methods: 248 pleural effusion patients (172 TB and 76 non-TB) were retrospectively analyzed in the study. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. T-SPOTT assays were performed in pleural fluids. The relationship between ADA, T-SPOT and the occurrence of TB pleurisy was evaluated using logistic regression analysis. Results: The level of pleural ADA and positive rate of T-SPOT were all higher in TB pleurisy group than non-TB pleurisy group (p <.001). The positive rate of T-SPOT detection reached 98.83% in the TB pleurisy group while only 40.7% in non-TB pleurisy group (p <.001). Additionally, 8 patients (4.65%) in the TB pleurisy group showed the level of pleurisy ADA exceeded 40 IU/L while only one patient (1.31%) in the non-TB pleurisy group. Conclusion: The sequential detection of ADA screening and T-SPOT assay was found to be an accurate and rapid method for identifying TB pleurisy from pleural effusion, which would promote effective treatment. [ABSTRACT FROM AUTHOR]

Chicken anemia virus (CAV) is a small, single-stranded DNA virus of Anelloviridae family. Its genome segments encode three proteins, VP1, VP2, and VP3. This study identified an interaction between VP2 and VP3 and mapped the interaction domains. Through the yeast two-hybrid (Y2H) system, VP2 was found to interact with VP3. The presence of the VP2–VP3 complex in CAV-infected chicken cells was confirmed by co-immunoprecipitation. Confocal microscopy showed that VP2 and VP3 were expressed in the cytoplasm in cotransfected Vero cells. In the Y2H system, the interaction domains were identified as being within the N-terminal aa 1–30 and C-terminal aa 17–60 for VP2 and the N-terminal aa 46–60 and C-terminal aa 1–7 for VP3. This study showed the interaction between VP2 and VP3 of CAV and identified multiple independent interactive domains within the two proteins. This provides novel information for investigating the biological functions of these proteins. [ABSTRACT FROM AUTHOR]

• Children and adolescents with high-functioning ASD showed increased gray matter volume and density in the precuneus and subcortical regions. • Different clinical symptoms of ASD were associated with gray matter structure in specific brain regions. • Structural abnormalities of gray matter were correlated with dysfunctions of ASD patients. The present study aimed to explore the brain structural mechanisms underlying clinical dysfunction in patients with ASD using magnetic resonance imaging (MRI). After screening T1 structural images from the Autism Brain Imaging Data Exchange (ABIDE) database, 111 children and adolescents with high-functioning ASD and 151 typically developing (TD) subjects matched were included in this study. We first compared the differences in gray matter volume (GMV) and gray matter density (GMD) between the two groups. Then, the relationships between GMV/GMD and clinical assessments in ASD patients were evaluated. We found that compared with the TD group, the ASD group showed increased GMV/GMD in the precuneus, thalamus, hippocampus and cingulate gyrus. Moreover, in the ASD group, social interaction was negatively correlated with GMD in the bilateral superior temporal gyrus and limbic system; communication was positively correlated with GMD in the right middle temporal gyrus, inferior frontal gyrus, and anterior cingulate gyrus; and repetitive behavior was positively correlated with GMD in the cerebellum and negatively correlated with GMV in the prefrontal cortex. In conclusion, the gray matter structure in children and adolescents with ASD was abnormal, and different clinical dysfunctions in ASD patients were related to structural abnormalities in specific regions. [ABSTRACT FROM AUTHOR]

Aims: To explore the inter-predictive role and causal relationship between family functioning, self-perceived burden and loneliness in people with type 2 diabetes. Methods: In this study, patients with type 2 diabetes admitted to two tertiary care hospitals in China were selected for an 8-month follow-up, and the patients' scores on the Family Functioning, Self-perceived Burden, and Loneliness scales were measured repeatedly at three time periods: during hospitalisation (T1), 1 month after discharge (T2), and 3 months after discharge (T3). Results: The results showed that family function at the T1 time point had a negative predictive effect on self-perceived burden at the T2 time point, β = − 0.43, P = 0.005. Loneliness at the T1 time point had a positive predictive effect on self-perceived burden at the T2 time point, β = 0.08, P = 0.021. Unlike the pathway at time point T1, family functioning at time point T2 negatively predicted loneliness at time point T3, β = − 0.32, P = 0.013. Loneliness at time point T2 positively predicted family functioning at time point T3, β = 0.025, P = 0.013. Loneliness at time point T2 negatively predicted self-perceived burden at time point T3 (P = 0.011). Conclusions: The results of the cross-lagged analysis show that there is a mutually predictive and moderating relationship between family functioning and loneliness in patients with type 2 diabetes. Loneliness can predict the level of self-perceived burden at the next time point. [ABSTRACT FROM AUTHOR]

Aims: To examined the relationship between fear of hypoglycemia and certain variables in people with type 2 diabetes mellitus (T2DM) based on the Capability, Opportunity, Motivation, and Behavior model, combined with the context unique to people with diabetes to provide a basis for developing targeted nursing interventions. Methods: In this cross-sectional study, 212 people with T2DM were recruited from February 2021 to July 2021. Data were collected using the Hypoglycaemia Fear Survey, Gold score, Patient Assessment of Chronic Illness Care (PACIC) scale and Diabetic Self-Management Attitudes Scale. Multiple linear regression analysis was performed to determine the predictors of fear of hypoglycemia using SPSS 26.0. Results: The mean fear of hypoglycemia score was 74.88 ± 18.28 (range: 37.00–132.00). In people with T2DM, the frequency of blood glucose monitoring, the frequency of hypoglycemia in the past half-year, degree of understanding of hypoglycemia, impaired awareness of hypoglycemia, PACIC, and self-management attitude of diabetes were the influencing factors of fear of hypoglycemia (adjusted R2 = 0.560, F[21,190] = 13.800, P < 0.001). These variables explained 56.0% of the variance in the fear of hypoglycemia. Conclusions: The level of fear of hypoglycemia in people with T2DM was relatively high. In addition to paying attention to the disease characteristics of people with T2DM, medical staff should also pay attention to patients' own perception and handling ability of disease and hypoglycemia, attitude toward self-management behavior and external environment support, all of which have a positive effect on improving the fear of hypoglycemia in people with T2DM, optimizing the self-management level and improving quality of life. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) induces gut barrier integrity impairment, which is crucial to the establishment of long-term infection in hosts. Cellular senescence is an imperative event that drives disease progression. Several studies have indicated that T. gondii induces oxidative stress and cell cycle blockade in the tissues of hosts, suggesting cellular senescence induced by the parasite. Here, we explored whether cell senescence is involved in T. gondii-mediated colonic barrier integrity damage in mice. C57BL/6J mice were infected with 10 cysts of T. gondii. Senolytic therapy (dasatinib and quercetin, DQ, a combination therapy for reducing senescent cells) was given by oral gavage 4 weeks post-infection. Alcian blue staining, immunofluorescence, western blot, quantitative PCR (qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate the thickness of the colonic mucus layer, the expression profiles of genes and proteins related to tight junction function and cellular senescence in the colonic tissues, and the levels of serum lipopolysaccharides (LPS), respectively. T. gondii-infected mice exhibited deteriorated secreted mucus, shortened length, decreased expression of zonula occludens-1 (ZO-1) and occludin in the colon, accompanied by elevated levels of serum LPS. Moreover, the infection upregulated cell senescence-related markers (p16INK4A, p21CIP1) while inhibiting Lamin B1 expression. In addition, the expression levels of senescence-associated secretory phenotypes (SASPs), including IL-1β, TNF-α, IL-6, MMP9 and CXCL10, were upregulated post-infection. Notably, reducing cell senescence with DQ administration, significantly ameliorated the colonic pathological alterations induced by T. gondii infection. This study uncovers for the first time that cellular senescence contributes to the colonic barrier integrity damage induced by chronic T. gondii infection. Importantly, we provide evidence that senolytic therapy exerts a therapeutic effect on the intestinal pathological lesions. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii (T. gondii) is a neuroinvasive parasite causing neuroinflammation, which in turn is associated with a higher risk for several psycho-behavioral disorders. There is an urgent need to identify drugs capable of improving cognitive deficits induced by T. gondii infection. β-Glucan, an active ingredient in mushrooms, could significantly enhance immunity. However, the effects of β-glucan against neuroinflammation and cognitive decline induced by T. gondii infection remain unknown. The present study aimed to investigate the neuroprotective effect of β-glucan on goal-directed behavior of mice chronically infected by T. gondii Wh6 strain. Methods: A mice model of chronic T. gondii Wh6 infection was established by infecting mice by oral gavage with 10 cysts of T. gondii Wh6. Intraperitoneal injection of β-glucan was manipulated 2 weeks before T. gondii infection. Performance of the infected mice on the Y-maze test and temporal order memory (TOM) test was used to assess the goal-directed behavior. Golgi-Cox staining, transmission electron microscopy, immunofluorescence, real-time PCR and western blot assays were used to detect prefrontal cortex-associated pathological change and neuroinflammation. Results: The administration of β-glucan significantly prevented T. gondii Wh6-induced goal-directed behavioral impairment as assessed behaviorally by the Y-maze test and TOM test. In the prefrontal cortex, β-glucan was able to counter T. gondii Wh6-induced degeneration of neurites, impairment of synaptic ultrastructure and decrease of pre- and postsynaptic protein levels. Also, β-glucan significantly prevented the hyperactivation of pro-inflammatory microglia and astrocytes, as well as the upregulation of proinflammatory cytokines caused by chronic T. gondii Wh6 infection. Conclusions: This study revealed that β-glucan prevents goal-directed behavioral impairment induced by chronic T. gondii infection in mice. These findings suggest that β-glucan may be an effective drug candidate to prevent T. gondii-associated psycho-behavioral disorders including goal-directed behavioral injury. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in disease sustainability. Therefore, downregulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC downregulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, and p-P38 in MAPK pathway and p-IκBα and NF-κB-p65 in NF-κB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after pre-treatment with TLR-2 agonist Pam3CSK4. In addition, PPC lost its anti-inflammatory effect and its suppressing capability on MAPK and NF-κB pathways in TLR-2−/− primary SFs after exposure to LPS. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2-mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA prevention. [ABSTRACT FROM AUTHOR]

Background: It is well known that the thalamus is not a unitary and homogeneous entity but a complex and highly connected archeocortical structure. Although many neuroimaging studies have reported alterations in the thalamus in major depressive disorder (MDD), the structural alterations in thalamic subfields remain unclear. This study aimed to investigate changes in gray matter volume (GMV) in thalamic subfields in MDD patients.Methods: The present study included structural images of 848 MDD patients and 794 age-matched normal controls (NC) from 17 study sites of the REST-meta-MDD consortium. We performed voxel-based morphometric analyses to calculate the GMV in the entire thalamus and its subfields using three different automated anatomical labeling atlases and subsequently compared the differences between first-episode drug-naïve major depressive disorder (FEDN), recurrent major depressive disorder (RMDD), and NC groups. We also evaluated the relationships between thalamic GMV and clinical symptoms in MDD patients.Results: Compared to NC, the FEDN patients showed increased GMV in thalamic subfields but not in the entire thalamus, while RMDD patients showed no significant alterations in GMV in the entire thalamus and its subfields. Moreover, the mean GMV in the right anterior thalamus and left anteroventral thalamus in RMDD patients were mildly positively correlated with the Hamilton Anxiety Rating Scale scores.Limitations: The main limitations are a single-modal analysis based on T1-weighted MR images and a cross-sectional design.Conclusions: Our findings suggest that FEDN and RMDD patients show heterogeneous alterations across thalamic subfields, which may help us understand the pathophysiological mechanisms of MDD. [ABSTRACT FROM AUTHOR]

Background: Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear.Research Question: Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations?Study Design and Methods: This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost.Results: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027).Interpretation: Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group.Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02147015; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

The recovery of motor functions is accompanied by brain reorganization, and identifying the inter-hemispheric interaction post stroke will conduce to more targeted treatments. However, the alterations of bi-hemispheric coordination pattern between homologous areas in the whole brain for chronic stroke patients were still unclear. The present study focuses on the functional connectivity (FC) of mirror regions of the whole brain to investigate the inter-hemispheric interaction using a new fMRI method named voxel-mirrored homotopic connectivity (VMHC). Thirty left subcortical chronic stroke patients with pure motor deficits and 37 well-matched healthy controls (HCs) underwent resting-state fMRI scans. We employed a VMHC analysis to determine the brain areas showed significant differences between groups in FC between homologous regions, and we explored the relationships between the mean VMHC of each survived area and clinical tests within patient group using Pearson correlation. In addition, the brain areas showed significant correlations between the mean VMHC and clinical tests were defined as the seed regions for whole brain FC analysis. Relative to HCs, patients group displayed lower VMHC in the precentral gyrus, postcentral gyrus, inferior frontal gyrus, middle temporal gyrus, calcarine gyrus, thalamus, cerebellum anterior lobe, and cerebellum posterior lobe (CPL). Moreover, the VMHC of CPL was positively correlated with the Fugl–Meyer Score of hand (FMA-H), while a negative correlation between illness duration and the VMHC of this region was also detected. Furthermore, we found that when compared with HCs, the right CPL exhibited reduced FC with the left precentral gyrus, inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, thalamus and hippocampus. Our results suggest that the functional coordination across hemispheres is impaired in chronic stroke patients, and increased VMHC of the CPL is significantly associated with higher FMA-H scores. These findings may be helpful in understanding the mechanism of hand deficit after stroke, and the CPL may serve as a target region for hand rehabilitation following stroke. [ABSTRACT FROM AUTHOR]