Background:The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD).Methods:We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (>= 18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships.Results:The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages.Conclusions:Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit.Registration:No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?

BACKGROUND:Patients with severe mental disorders (SMD) face a heavy financial burden, and somatic comorbidity is one of the factors that cannot be ignored. The purpose of this study is to understand the current status of somatic comorbidity in patients and to explore the relationship between medical expenses and different somatic disease comorbidities. METHOD:The group obtained medical data of 4940 patients in 2019 through a follow-up survey. Descriptive statistics were used to analyze the distribution of patient co-morbidities, and CLAD was used to analyze the impact of various factors on patient expenses. RESULTS:The most common comorbidity was circulatory disorders (36.6%), followed by respiratory disorders (32.3%), digestive disorders (30.6%) and endocrine, nutritional or metabolic disorders (29.8%). As the types of somatic comorbidity increase, the expenses will also increase. In terms of comorbidity types, a total of 9 ICD-11 chapter group diseases will lead to increased expenses, while 5 chapter group diseases have no statistically significant impact on expenses. CONCLUSIONS:This study found that comorbidities are widespread in patients with SMD, and most of them lead to a significant increase in patients' medical expenses. Therefore, the treatment of patients with severe mental disorders should take into account the needs of the prevention, management and treatment of the comorbidity of the population, reduce the occurrence and development of patients' somatic comorbidity, and thus reduce the burden of patients' medical expenses.

Background:Diabetes peripheral neuropathy (DPN) is closely related to the occurrence and development of sarcopenia. However, the relevant early biological metabolites and their pathophysiological mechanism is unclear. Aim:To explore the underlying mechanisms of Diabetic Peripheral Neuropathy with Sarcopenia (DPNS) by integrating metabolomics and 16S rRNA sequencing. Methods:A total of 151 diabetic neuropathy patients were enrolled in the study. Untargeted metabolomics was performed using ultra-high-performance liquid. Chromatography-mass spectrometry, andgut microbiota was assessed through 16S rRNA sequencing. Differential metabolites and microbial taxa were identified, and theirassociations were explored using correlation analysis. Results:A total of 376 differential metabolites were identified. Compared with the DPN group, the contents of glycerophosphocholine(GPC), taurine, and succinic acid in the DPNS group were significantly decreased, while that of 2-amino-1-methyl-6-phenylimidazo(4, 5-b)pyridine(PhIP), Sphingosine were increased. Gutmicrobiota analysis revealed reduced diversity in DPNS, with decreased beneficial genera (Faecalibacterium, Bacteroides) and increased pathogenic taxa (Streptococcus). Additionally, KEGG enrichment analysis showed that the mammalian target of necroptosis, sphingolipid metabolism, the mTOR signaling pathway, ABC transporters, and bile secretion pathways are closely related to DPNS. Conclusion:We systematically explored the biomarkers and potential therapeutic targets in the patients with DPNS, which may provide new insights that may advance the treatment of sarcopenia.

Spinal cord tumors significantly contribute to neurological morbidity and mortality. Precise morphometric quantification, encompassing the size, location, and type of tumors, holds promise for enhancing monitoring protocols and optimizing treatment planning strategies. Such quantification requires segmenting and identifying intramedullary tumors into specific disease types. Nevertheless, the traditional manual segmentation of three-dimensional structures remains time-consuming and laborious, as it is susceptible to intra- and inter-rater variability. To overcome these shortcomings, this paper introduces a deep learning model specifically crafted for the segmentation and classification of spinal cord tumors. The model comprises a novel three-stage coarse-to-fine multi-class segmentation strategy, where the spinal cord regions are first identified, followed by a binary segmentation model and a multi-class segmentation model to distinguish different tumor types precisely. Extensive experiments show that our proposed method achieves superior performance on multi-class tumor segmentation.

Bis(triethoxysilyl)ethane (BTESE)-derived organosilica membranes prepared using sol-gel processing, were used in vapor permeation (VP) to dehydrate aqueous acetic acid (AcOH) solutions. It was discovered that BTESEderived membranes had outstanding stability and great permselectivity. BTESE-derived organosilica membranes showed a H2O/AcOH separation factor of 3000-5800 and a H2O/AcOH permeance ratio of 3000-5800 with the permeate flux of 12-28 kg m2 h-1 for H2O/AcOH mixtures (AcOH: 50 wt%) under 120 degrees C and 100 kPaA. The superior durability of organosilica membranes was confirmed by long-term stability tests conducted in aqueous AcOH mixtures, which indicates that BTESE membranes maintained almost the stable flux and separation factors. A comparison with gas permeation properties indicates that the molecular sieving effect dominates the separation mechanism.

Spinal cord tumors significantly contribute to neurological morbidity and mortality. Precise morphometric quantification, encompassing the size, location, and type of such tumors, holds promise for optimizing treatment planning strategies. Although recent methods have demonstrated excellent performance in medical image segmentation, they primarily focus on discerning shapes with relatively large morphology such as brain tumors, ignoring the challenging problem of identifying spinal cord tumors which tend to have tiny sizes, diverse locations, and shapes. To tackle this hard problem of multiclass spinal cord tumor segmentation, we propose a new method, called BATseg, to learn a tumor surface distance field by applying our new multiclass boundary-aware loss function. To verify the effectiveness of our approach, we also introduce the first and large-scale spinal cord tumor dataset. It comprises gadolinium-enhanced T1-weighted 3D MRI scans from 653 patients and contains the four most common spinal cord tumor types: astrocytomas, ependymomas, hemangioblastomas, and spinal meningiomas. Extensive experiments on our dataset and another public kidney tumor segmentation dataset show that our proposed method achieves superior performance for multiclass tumor segmentation.

ABSTRACTBackgroundTremor‐dominant (TD) and nontremor‐dominant (NTD) Parkinson's disease (PD) showed different responses to rehabilitation. However, the neural mechanism behind this remains unclear.MethodsThis cohort study explores changes in motor function, brain activation, and functional connectivity following 2 weeks of rehabilitation in TD‐PD and NTD‐PD patients, respectively. A total of 11 TD‐PD patients, 24 NTD‐PD patients, and 21 age‐matched healthy controls (HCs) were included. At baseline, all participants underwent functional magnetic resonance imaging (fMRI) while performing the foot tapping task. Motor symptoms, gait, balance, and task‐based fMRI were then evaluated in patients before and after rehabilitation.ResultsCompared to HCs, TD‐PD patients showed increased activity in the left inferior frontal gyrus and the right insula, and NTD‐PD patients showed increased activations in the left postcentral gyrus and decreased within‐cerebellar connectivity at baseline. Rehabilitation improved motor function in PD patients regardless of motor subtype. TD‐PD patients showed increased recruitments of the sensorimotor cortex and the bilateral thalamus after rehabilitation, and NTD‐PD patients showed increased cerebellar activation and within‐cerebellar connectivity that was associated with better motor performance.ConclusionsThis study demonstrated that rehabilitation‐induced brain functional reorganization varied by motor subtypes in PD, which may have important implications for making individualized rehabilitation programs.Trial RegistrationClinicalTrials.gov identifier: ChiCTR1900020771

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1–6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K–Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

The present study aimed to explore the potential neural correlates during feedback evaluation during decision-making under risk and ambiguity in MCI. Nineteen individuals with MCI and twenty age-matched HCs were enrolled. Decision-making performance under risk and ambiguity was examined with the modified game of dice task (GDT) and an Iowa gambling task (IGT). Using task-related EEG data, reward positivity (RewP) and feedback P3 (fb-P3) were used to characterize participants’ motivation and allocation of cognitive resources. Also, response time and event-related oscillation (ERO) were used to evaluate information processing speed, and the potent of post-feedback information integration and behavioral modulation. MCI patients had lower RewP (p = 0.022) and fb-P3 (p = 0.045) amplitudes in the GDT than HCs. Moreover, the amount and valence of feedback modulated the RewP (p = 0.008; p = 0.017) and fb-P3 (p < 0.001; p < 0.001). In the IGT, in addition to the significantly reduced fb-P3 observed in MCI patients (p = 0.010), the amount and valence of feedback modulated the RewP (p = 0.002; p = 0.020). Furthermore, MCI patients took longer to make decisions (t = 2.15, p = 0.041). The ERO analysis revealed that delta power was reduced in MCI (GDT: p = 0.045; p = 0.011). The findings suggest that, during feedback evaluation when making risky and ambiguous decisions, motivation, allocation of cognitive resources, information processing and neuronal excitability were attenuated in MCI. It implies that neural activity related to decision making was compromised in MCI.

The Golgi apparatus (GA), an organelle that processes, sorts, and transports proteins synthesized by the endoplasmic reticulum, is also involved in many cellular processes associated with cancer, such as angiogenesis, the innate immune response, and tumor invasion and migration. We aimed to construct a breast cancer (BC) prognosis prediction model based on GA-related genetic information to evaluate the prognosis of patients with BC more accurately than existing models and to stratify patients for clinical therapy. In this study, The Cancer Genome Atlas-breast invasive carcinoma was used as the training cohort, and the Molecular Taxonomy of Breast Cancer International Consortium cohort was used as the validation cohort. Using bioinformatics methods, we constructed a GA-related gene risk score (GRS). The GRS was used to divide BC patients into a high-GRS group and a low-GRS group, and functional analysis, survival analysis, mutation analysis, immune landscape analysis, and metabolic analysis were performed to compare the 2 groups. Finally, a nomogram was constructed for clinical application. The genes in the GRS model were mainly related to the glucose metabolism pathway, and the main mutations in the 2 groups of patients were mutations in TP53 and CHD1. The mutation rate in the high-GRS group was greater than that in the low-GRS group. The high GRS group had higher tumor immune activity glycolysis; the pentose phosphate pathway tended to be the dominant metabolic pathways in this group, while fatty acid oxidation and glutamine catabolism tended to be dominant in the low-GRS group. GA-related genes were used to construct a prediction model for BC patients and had high accuracy in predicting prognosis. The mutations associated with the GRS are mainly TP53 and CDH1. Interestingly, the GRS is correlated with glucose metabolism in terms of gene expression and functional enrichment. In summary, the role of GRS-related genes in glucose metabolism is worthy of further study.

This paper presents a detailed analysis of the development and evolution of community mental health policies in China, from their reestablishment in 1998 to the establishment and implementation of the "Mental Health Law of the People's Republic of China" in 2013.The development of these policies across a 15-year period is segmented into three distinct phases, each characterized by a thorough exposition and an encompassing view.The paper scrupulously reviews and elucidates the crucial occurrences in each phase, emphasizing the significant impact of the prevailing conditions on the progression of policy formation.The paper concludes by sharing insights acquired from the policy development process.Within this framework, community mental health policies entail a myriad of legislations, strategies, methodologies, protocols, regulations, and ordinances, instituted by national governance to enhance the proliferation of community-based mental health services.

In clinical practice, the underlying pathogenesis of Parkinson’s disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgery has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study, we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437); the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.

BACKGROUND AND OBJECTIVES:The use of over-the-counter laxatives is common in the general population. The microbiome-gut-brain axis hypothesis suggests that the use of laxatives could be associated with dementia. We aimed to examine the association between the regular use of laxatives and the incidence of dementia in UK Biobank participants.METHODS:This prospective cohort study was based on UK Biobank participants aged 40-69 years without a history of dementia. Regular use of laxatives was defined as self-reported use in most days of the week for the last 4 weeks at baseline (2006-2010). The outcomes were all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD), identified from linked hospital admissions or death registers (up to 2019). Sociodemographic characteristics, lifestyle factors, medical conditions, family history, and regular medication use were adjusted for in the multivariable Cox regression analyses.RESULTS:Among the 502,229 participants with a mean age of 56.5 (SD 8.1) years at baseline, 273,251 (54.4%) were female, and 18,235 (3.6%) reported regular use of laxatives. Over a mean follow-up of 9.8 years, 218 (1.3%) participants with regular use of laxatives and 1,969 (0.4%) with no regular use developed all-cause dementia. Multivariable analyses showed that regular use of laxatives was associated with increased risk of all-cause dementia (hazard ratio [HR] 1.51; 95% CI 1.30-1.75) and VD (HR 1.65; 95% CI 1.21-2.27), with no significant association observed for AD (HR 1.05; 95% CI 0.79-1.40). The risk of both all-cause dementia and VD increased with the number of regularly used laxative types (p trend 0.001 and 0.04, respectively). Among the participants who clearly reported that they were using just 1 type of laxative (n = 5,800), only those using osmotic laxatives showed a statistically significantly higher risk of all-cause dementia (HR 1.64; 95% CI 1.20-2.24) and VD (HR 1.97; 95% CI 1.04-3.75). These results remained robust in various subgroup and sensitivity analyses.DISCUSSION:Regular use of laxatives was associated with a higher risk of all-cause dementia, particularly in those who used multiple laxative types or osmotic laxative.

Background First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson’s disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson’s disease. Methods This randomised, double-blind clinical trial will enrol 50 Parkinson’s disease patients aged 45–70 years with Hoehn and Yahr scale scores of 1–3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson’s Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate. Discussion The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson’s disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson’s disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson’s disease. Trial registration Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022.

Background:Stress is an important risk factor to induce psychiatric disorders such as depression.Phloretin (PHL), a natural dihydrochalcone compound, has been shown to exhibit anti-inflammatory and anti-oxidative effects.However, the impact of PHL on the depression and the underlying mechanism remain unclear.Methods: The animal behavior tests were used to determine the protective of PHL on the chronic mild stress (CMS)-induced depression-like behaviors.The Magnetic Resonance Imaging (MRI), electron microscopy analysis, fiber photometry, electrophysiology, and Structure Illumination Microscopy (SIM) were used to investigate the protective of PHL on the structural and functional impairments induced by CMS exposure in the mPFC.The RNA sequencing, western blot, reporter gene assay, and chromatin immunoprecipitation were adopted to investigate the mechanisms.Results: We showed that PHL efficiently prevented the CMS-induced depressive-like behaviors.Moreover, PHL not only attenuated the decrease of synapse losses but also improved the dendritic spine density and neuronal activity in the mPFC after CMS exposure.Furthermore, PHL remarkably inhibited the CMS-induced microglial activation and phagocytic activity in the mPFC.In addition, we demonstrated that PHL decreased the CMS-induced synapse losses by inhibiting the deposition of complement C3 deposition onto synapses and subsequent microglia-mediated synaptic engulfment.Finally, we revealed that PHL inhibited the NF-κB-C3 axis to display neuroprotective effects. Conclusions:Our results indicate that PHL represses the NF-κB-C3 axis and subsequent microglia-mediated synaptic engulfment to protect against CMS-induced depression in the mPFC.

Effective rehabilitation in Parkinson's disease (PD) is related to brain reorganization with restoration of cortico-subcortical networks and compensation of frontoparietal networks; however, further neural rehabilitation evidence from a multidimensional perspective is needed. To investigate how multidisciplinary intensive rehabilitation treatment affects neurovascular coupling, 31 PD patients (20 female) before and after treatment and 30 healthy controls (17 female) underwent blood oxygenation level-dependent functional magnetic resonance imaging and arterial spin labeling scans. Cerebral blood flow (CBF) was used to measure perfusion, and fractional amplitude of low-frequency fluctuation (fALFF) was used to measure neural activity. The global CBF-fALFF correlation and regional CBF/fALFF ratio were calculated as neurovascular coupling. Dynamic causal modeling (DCM) was used to evaluate treatment-related alterations in the strength and directionality of information flow. Treatment reduced CBF-fALFF correlations. The altered CBF/fALFF exhibited increases in the left angular gyrus and the right inferior parietal gyrus and decreases in the bilateral thalamus and the right superior frontal gyrus. The CBF/fALFF alteration in right superior frontal gyrus showed correlations with motor improvement. Further, DCM indicated increases in connectivity from the superior frontal gyrus and decreases from the thalamus to the inferior parietal gyrus. The benefits of rehabilitation were reflected in the dual mechanism, with restoration of executive control occurring in the initial phase of motor learning and compensation of information integration occurring in the latter phase. These findings may yield multimodal insights into the role of rehabilitation in disease modification and identify the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD.SIGNIFICANCE STATEMENT Although rehabilitation has been proposed as a promising supplemental treatment for PD as it results in brain reorganization, restoring cortico-subcortical networks and eliciting compensatory activation of frontoparietal networks, further multimodal evidence of the neural mechanisms underlying rehabilitation is needed. We measured the ratio of perfusion and neural activity derived from arterial spin labeling and blood oxygenation level-dependent fMRI data and found that benefits of rehabilitation seem to be related to the dual mechanism, restoring executive control in the initial phase of motor learning and compensating for information integration in the latter phase. We also identified the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD patients.

Abstract Background Naturally occurring antibodies (NAbs) are germline-encoded immunoglobulins that can bind to and clear out self-neo-epitopes as well as apoptotic and necrotic cells. However, NAbs pathological relevance in Alzheimer’s disease (AD) is not well-understood. Methods Twenty-eight candidate proteins encoded by AD-associated genes were selected for this study based on a number of selection criteria, including preferential expression in the brain and B-lymphocyte cells. The levels of NAbs in plasma were analyzed according to their epitopes in age- and gender-matched cognitively normal subjects (CN, n = 56), subjects with mild cognitive impairment (MCI, n = 16) and subjects with AD (n = 56). We aimed to study the levels of their NAbs in plasma and their associations with cognitive decline in individuals with AD. Results Of the 28 antigens tested, 17 showed decreased NAbs in individuals with AD; in particular, NAb-TREM2 had an area under the ROC curve of 0.806, with the highest sensitivity (0.370) at 95% specificity among all 28 tests. Further protein–protein interaction networks and functional enrichment analysis suggested that target genes were enriched in AD-related pathological processes classified under “Alzheimer’s disease”, “neurodegenerative disease” and “amyloidosis”. The “Alzheimer’s disease” and “neurodegenerative disease” clusters, which converged on the initial “recognition” step of microglial phagocytosis, showed the best diagnostic performance for AD. Conclusions This study suggests a decline in the function of the adaptive immune system in AD, and the levels of circulating NAbs are likely to serve as biomarkers for surveilling the progression of AD.

Background Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown. Methods Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group. Results We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a 'cortico-subcortical-cortical' network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls. Conclusions Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Aging population grows faster and has great demand for mental healthcare in the Western Pacific Region. Within the continuum of holistic care framework, mental healthcare for older adults is conceptualized to promote people's mental wellbeing, the "positive" states of mental health. As social determinants accounts much for mental health outcomes, addressing these factors may benefit older adults mental wellbeing in natural settings. Social prescribing, emerged as an innovative approach linking medical and social care, has been observed to potentially benefit mental wellbeing of older adults. However, it remained uncertain how to successfully implement social prescribing schemes in realistic world, such as community. In this viewpoint, we discuss three key elements, i.e., stakeholders, contextual factors, and outcome measures, that might facilitate identification of appropriate implementation strategies. Besides, we argue that implementation research needs to be strengthened and supported, aiming to accumulate evidence for scaling up social prescribing schemes to promote older adults mental wellbeing in the population level. We also provide directions for future implementation research on social prescribing for mental healthcare among older adults in the Western Pacific Region.

Objective: The study aimed to examine the effect of social prescribing on improving cognitive performance among community-dwelling older adults, and to explore the potential association between social support and the change of cognitive performance. Method: One hundred and eighteen older adults from Changtang community participated in the study and were followed up for three months. Cognitive function was assessed with Hong Kong Brief Cognitive test (HKBC) at baseline and 3-month follow-up. Pre- and post-social prescribing difference in cognitive performance was examined with paired t-test. Multivariate regression analysis was used to explore the potential factors of social support associated with the change of cognitive function. Results: Compared with baseline measurement (25.4±4.1), the total score of HKBC improved significantly after three-month social prescribing (26.5±3.6; t= -3.300， P =0.001). Multivariate regression analysis showed that baseline level of social support utilization was associated with the change of cognitive performance. The lower the utilization of social support at baseline, the more the change of cognitive performance due to social prescribing (β= -0.25, 95%CI = - 0.88 ~ -0.05). Conclusion: Social prescribing may have a beneficial effect on cognitive function for community older adults. The utilization of social support may be one of the factors associated with its effect on cognitive performance.