Can transcranial direct current stimulation combined with interactive computerized cognitive training boost cognition and gait performance in older adults with mild cognitive impairment? a randomized controlled trial.

BACKGROUND: Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI. METHOD: Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions. RESULTS: The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT. CONCLUSION: The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI. TRIAL REGISTRATION: This trial was registered at http://www. CLINICALTRIALS: in.th/ (TCTR 20,220,328,009).

Role of Dopamine Transporter in the Relationship Between Plasma Cortisol and Cognition.

OBJECTIVE: Cortisol is associated with cognition in both healthy individuals and patients with neuropsychiatric disorders. Regarding the effects of cortisol on the dopamine system and the association between dopamine transporter (DAT) and cognition, DAT might be a central target linking cortisol and cognition. This study explored the role of striatal DAT in the cortisol-cognition relationship. METHODS: We recruited 33 patients with carbon monoxide poisoning and 33 age- and sex-matched healthy controls. All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT was used to determine striatal DAT availability. Plasma cortisol, tumor necrosis factor α, and interleukin-10 levels were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with healthy controls, patients with carbon monoxide poisoning had lower cognitive performance, bilateral striatal DAT availability, and plasma tumor necrosis factor-α levels and higher cortisol and interleukin-10 levels. In all participants, plasma cortisol level and bilateral striatal DAT availability were negatively and positively related to cognition, respectively, including memory and executive function with ß from -0.361 (95% confidence interval [CI] = -0.633 to -0.090) to 0.588 (95% CI = 0.319 to 0.858). Moreover, bilateral striatal DAT mediated the cortisol-cognition relationship with indirect effects from -0.067 (95% CI = -0.179 to -0.001) to -0.135 (95% CI = -0.295 to -0.024). The cytokine levels did not influence the mediation effects. CONCLUSIONS: This is the first study to demonstrate that striatal DAT mediates the cortisol-cognition relationship. Future studies are needed to comprehensively evaluate the role of the dopamine system in cortisol-cognition associations and treatment implications.

Impact of Amyloid Pathology in Mild Cognitive Impairment Subjects: The Longitudinal Cognition and Surface Morphometry Data.

The amyloid framework forms the central medical theory related to Alzheimer disease (AD), and the in vivo demonstration of amyloid positivity is essential for diagnosing AD. On the basis of a longitudinal cohort design, the study investigated clinical progressive patterns by obtaining cognitive and structural measurements from a group of patients with amnestic mild cognitive impairment (MCI); the measurements were classified by the positivity (Aß+) or absence (Aß-) of the amyloid biomarker. We enrolled 185 patients (64 controls, 121 patients with MCI). The patients with MCI were classified into two groups on the basis of their [18F]flubetaben or [18F]florbetapir amyloid positron-emission tomography scan (Aß+ vs. Aß-, 67 vs. 54 patients) results. Data from annual cognitive measurements and three-dimensional T1 magnetic resonance imaging scans were used for between-group comparisons. To obtain longitudinal cognitive test scores, generalized estimating equations were applied. A linear mixed effects model was used to compare the time effect of cortical thickness degeneration. The cognitive decline trajectory of the Aß+ group was obvious, whereas the Aß- and control groups did not exhibit a noticeable decline over time. The group effects of cortical thickness indicated decreased entorhinal cortex in the Aß+ group and supramarginal gyrus in the Aß- group. The topology of neurodegeneration in the Aß- group was emphasized in posterior cortical regions. A comparison of the changes in the Aß+ and Aß- groups over time revealed a higher rate of cortical thickness decline in the Aß+ group than in the Aß- group in the default mode network. The Aß+ and Aß- groups experienced different APOE ε4 effects. For cortical-cognitive correlations, the regions associated with cognitive decline in the Aß+ group were mainly localized in the perisylvian and anterior cingulate regions. By contrast, the degenerative topography of Aß- MCI was scattered. The memory learning curves, cognitive decline patterns, and cortical degeneration topographies of the two MCI groups were revealed to be different, suggesting a difference in pathophysiology. Longitudinal analysis may help to differentiate between these two MCI groups if biomarker access is unavailable in clinical settings.

[Analysis of variation trend in health workforce equity allocation in China].

OBJECTIVE: To analyze the long-term trends of the changes in the equity of China's health workforce allocation to provide a reference for the more balanced and orderly development of China's health system. METHODS: The Gini coefficient was used to evaluate the degree of equity in the allocation of health workforce between regions, and the Gini coefficients for the allocation of doctors and nurses based on population and regional gross domestic product (GDP) distribution were calculated respectively. RESULTS: In 2019, the number of licensed (assistant) physicians per 1 000 population in China was 2.77, and the number of registered nurses per 1 000 population was 3.18. The Gini coefficient for the distribution of licensed (assistant) physicians by population was 0.141 in 2002, decreasing to 0.081 by 2014 and then remained stable. The Gini coefficient for the distribution of registered nurses by population was 0.164 in 2002 and decreased to 0.066 in 2018. The Gini coefficient for the distribution of licensed (assistant) physicians by GDP was 0.236 in 2002, decreased to 0.169 in 2013, then increased to 0.183 and remained stable. The Gini coefficient for the distribution of registered nurses by GDP was 0.206 in 2002, decreased to 0.150 in 2013, and then increased each year to 0.180 in 2019. The equity of the allocation of registered nurses by population was worse than the equity of the allocation of licensed (assistant) physicians in 2002, and in 2016, for the first time, exceeded that of licensed (assistant) physicians. CONCLUSION: Equity in the allocation of health workforce across China has improved, but the improvement in equity between regions has hit a bottleneck, with health workforce allocation in the western regions still relatively scarce. Although nursing workforce allocation equity caught up with licensed (assistant) physicians, the number of licensed (assistant) physicians is close to that of developed western countries, while there is a large gap in registered nurses. It is recommended that the relevant authorities make good long-term planning for health workforce, further increase the policy for the introduction of health workforce in the western region, and increase the supply of healthcare services in the western region with the help of digital transformation of healthcare and internet healthcare. At the same time, they should further increase investment in resources for higher nursing education and actively plan to cope with the ageing population.

High-Frequency External Muscle Stimulation Reduces Depressive Symptoms in Older Male Veterans: A Pilot Study.

OBJECTIVE: Late-life depression (LLD) is a severe public health problem. Given that pharmacological treatments for LLD are limited by their side effects, development of efficient and tolerable nonpharmacological treatment for LLD is urgently required. This study investigated whether high-frequency external muscle stimulation could reduce depressive symptoms in LLD. METHODS: Twenty-two older male veterans with major depression were recruited and randomized into a treatment (n = 9) or sham control group (n = 13). The groups received high-frequency external muscle stimulation or sham intervention 3 times per week for 12 weeks. Clinical symptoms and muscle strength were evaluated at baseline and every 2 weeks. RESULTS: The 2 groups were homogeneous in age, baseline clinical symptoms, and muscle strength. The treatment group showed significant improvement in depression and anxiety scores and muscle strength (all P < .01), whereas the control group showed no significant change after the 12-week follow-up. Compared to the control group, the treatment group showed significant improvements in depression (Geriatric Depression Scale, P = .009; Hamilton Depression Rating Scale, P = .007) and anxiety scores (HAMA, P = .008) and muscle strength (all P < .001). Changes in depression and anxiety levels were significantly correlated with changes in muscle strength after the study. In the treatment group, we observed a trend of correlation between the reduction in depression and muscle strength gains. CONCLUSION: High-frequency external muscle stimulation appears to be an effective treatment for older patients with LLD. Large studies with more tests and/or conducted in different populations are warranted to validate these preliminary findings.

Group Music Intervention Using Percussion Instruments to Reduce Anxiety Among Elderly Male Veterans with Alzheimer Disease.

BACKGROUND This study aimed to assess the impact of a group music intervention on anxiety and depression of elderly male veterans with dementia. MATERIAL AND METHODS In total, 50 elderly men with Alzheimer disease were randomly divided into intervention and control groups. Patients in the intervention group attended a 60-minute group music session that used percussion instruments with familiar music in the morning once a week for 12 weeks, whereas those in the control group received a rest and reading session at the same intervals and under the same conditions. The Hamilton Anxiety Rating Scale and Geriatric Depression Scale were used to assess anxiety and depression at baseline, week 6, and week 12. The Primary Measures of Music Audiation (PMMA) was used to assess musical aptitude at the baseline. RESULTS A significant reduction in the anxiety level following the 12-week music sessions was observed in the intervention group (P<.001), but there was no significant change in the control group. However, the change in depressive symptoms between the 2 groups was nonsignificant. In the intervention group, when stratifying patients based on music aptitude determined through PMMA assessment, patients with high PMMA scores had significantly reduced anxiety symptoms over time compared with those with low scores. CONCLUSIONS For elderly male veterans with dementia, participating in a group music intervention reduced anxiety symptoms. In patients with high musical aptitude, the treatment effects on anxiety reduction were satisfactory. Measures of music aptitude may provide valuable information regarding patients' response to music intervention.

[Economic burden and factors associated with Crohn's disease].

OBJECTIVE: To study the economic burden of Crohn's disease and its related factors, and to provide opinions for reducing personal burden and improving reimbursement policy. METHODS: Using a cross-sectional method, a self-created questionnaire based on the basic principles of health services research was used to survey Crohn's disease patients served by the Shanghai volunteer service foundation platform. Information collected included basic characteristics, therapy, and medical costs related to Crohn's disease in the past 12 months. Descriptive statistics were used to analyse the composition of inpatient and outpatient costs of Crohn's disease for treatment of the disease in the past year. Further, a logarithm-linear model was constructed to analyse the factors associated with the financial burden of Crohn's disease. RESULTS: In the study, 820 questionnaires were distributed and 799 questionnaires were returned, of which 797 were valid. There were 528 (66.25%) males and 269 (33.75%) females. The mean age of the patients was (34.02±11.49) years, with a concentration between 18-39 years (510 cases, 63.99%) and a mean disease duration of (5.58±5.13) years. 10.7% of the patients did not receive continuous treatment, and the average annual treatment cost for the patients with continuous treatment was 54 246 Yuan, of which 30 279 Yuan (55.8%) was paid by the individuals and 23 966 Yuan (44.2%) was paid by the insurance. The personal financial burden was close to the national per capita disposable income in 2020, which was 32 189 Yuan (94.1%), exceeding the annual cost for type 2 diabetes in China in 2016, 8 245 Yuan. In terms of the distribution of outpatient and inpatient services, the average annual cost of inpatient services was 31 092 Yuan, of which 14 673 Yuan (48.5%) was paid out of pocket by the individuals and 16 418 Yuan (51.5%) was paid by the insurance; the average annual cost of outpatient services was 23 154 Yuan, of which 15 606 Yuan (65.1%) was paid out of po-cket by the individuals and 7 548 Yuan (34.9%) was paid by the insurance. The personal burden of outpatient care was higher than of inpatient care. The regression results of the logarithm-linear model showed that the total annual treatment cost was related to the duration of illness (ß=0.03, P < 0.01), having complications (ß=-0.68, P < 0.01), receiving surgical treatment (ß=0.52, P < 0.01), using immunosuppressive drugs (ß=0.51, P < 0.01), annual outpatient visits (ß=0.02, P < 0.05), and number of hospitalizations per year (ß=0.08, P < 0.01). CONCLUSION: The annual financial burden for patients with Crohn's disease is heavy and rises significantly with the duration of illness, exceeding that of chronic diseases such as diabetes. The personal financial burden is close to the national per capita disposable income, and the medical security department should develop policies to reduce the financial burden. The inclusion of Crohn's disease as a special outpatient disease is a possible measure that could be considered in response to the fact that the outpatient personal financial burden is heavier than the inpatient's.

Level of circulating concentrations of progesterone during ovulatory follicle development affects timing of pregnancy loss in lactating dairy cows.

The objective of this experiment was to determine the effect of high versus low progesterone (P4) during the pre-dominance or dominance phase (or both) of ovulatory follicle development on follicular dynamics and fertility of lactating dairy cows. Progesterone (P4) was manipulated to reach high (H) or low (L) serum concentrations during the pre-dominance phase (d 0 to 4 of the wave) and dominance phase (d 5 to 7 of the wave) of a second follicular wave ovulatory follicle, creating 4 treatments: H/H, H/L, L/H, and L/L. Luteolysis was induced with PGF2α on d 7 of the wave and ovulation was induced with GnRH 56 h after PGF2α. Cows (n = 558) received artificial insemination (AI) 16 h following GnRH. Pregnancy was determined at 6 intervals during gestation and at calving to quantify pregnancy loss beginning at d 23 post-AI utilizing pregnancy-specific protein B (PSPB) in novel within-cow comparisons. Cows with single ovulations assigned to the L/L treatment had greater pre-ovulatory follicle diameter compared with cows assigned to the L/H or H/L treatments. Cows with single ovulations had greater pre-ovulatory follicle diameter compared with cows with double ovulations. Low P4 in H/L, L/H, and L/L increased double ovulation rate compared with H/H. Cows with double ovulations had greater pregnancies per AI (P/AI) on d 23 post-AI compared with cows with single ovulations but had greater losses if ovulations were unilateral. Cows with low P4 during the entire period of the ovulatory follicle development also had greater P/AI on d 23 post-AI compared with cows with high P4 during both phases. However, full-term P/AI was not different between treatments. This was a result of the greater incidence of pregnancy losses between d 35 and 56 of gestation for cows with unilateral double ovulations compared with bilateral double ovulations and single ovulatory cows. Cows with single ovulation and low circulating P4 during the dominance period of follicle development had increased pregnancy losses between d 35 and 56 of gestation compared with cows with single ovulations and high P4. The PSPB measurements on d 16 and 23 post-AI were highly accurate in the prediction of pregnancy at d 28. The PSPB differed on d 23 and 28 between cows that had versus cows that did not have pregnancy losses between d 28 and 35 of gestation. In summary, circulating concentrations of P4 during ovulatory follicle development affected numbers of follicles ovulated and timing of subsequent pregnancy losses.

[Application of 3D virtual reality technology with multi-modality fusion in resection of glioma located in central sulcus region].

Objective: To explore the clinical and teaching application value of virtual reality technology in preoperative planning and intraoperative guide of glioma located in central sulcus region. Method: Ten patients with glioma in the central sulcus region were proposed to surgical treatment. The neuro-imaging data, including CT, CTA, DSA, MRI, fMRI were input to 3dgo sczhry workstation for image fusion and 3D reconstruction. Spatial relationships between the lesions and the surrounding structures on the virtual reality image were obtained. These images were applied to the operative approach design, operation process simulation, intraoperative auxiliary decision and the training of specialist physician. Results: Intraoperative founding of 10 patients were highly consistent with preoperative simulation with virtual reality technology. Preoperative 3D reconstruction virtual reality images improved the feasibility of operation planning and operation accuracy. This technology had not only shown the advantages for neurological function protection and lesion resection during surgery, but also improved the training efficiency and effectiveness of dedicated physician by turning the abstract comprehension to virtual reality. Conclusion: Image fusion and 3D reconstruction based virtual reality technology in glioma resection is helpful for formulating the operation plan, improving the operation safety, increasing the total resection rate, and facilitating the teaching and training of the specialist physician.

Serum SOX11 promoter methylation is a novel biomarker for the diagnosis of Hepatitis B virus-related hepatocellular carcinoma.

Promoter methylation of tumor suppressor gene SOX11 has been reported to contribute to the diagnosis and prognosis of various cancerous diseases, including gastric cancer, hematopoietic malignancies and nasopharyngeal carcinoma. However, there is no data on the diagnostic potential of serum SOX11 promoter methylation in hepatocellular carcinoma (HCC). This study was therefore aimed to investigate the potential role of serum SOX11 promoter methylation as a noninvasive biomarker in the diagnosis of patients with hepatitis B virus (HBV) associated HCC. A total of 205 subjects were retrospectively included, which consisted of 111 HCC patients, 66 chronic hepatitis B (CHB) and 28 healthy controls (HCs). Methylation of SOX11 promoter was determined by methylation-specific polymerase chain reaction. The methylation frequency of serum SOX11 promoter in HCC patients (69.4%, 77/111) was significantly higher than that in CHB patients (13.6%, 9/66; χ2 = 51.467, P<0.001) and HCs (10.7%, 3/28; χ2 = 31.489, P<0.001). There was significant difference of serum SOX11 promoter methylation in HCC patients with vascular invasion (49/58) and those without vascular invasion (28/53; χ2 = 13.058, P<0.001). Furthermore, the sensitivity of 69% was identified for SOX11 methylation in discriminating HCC from CHB, which was significant higher than the sensitivity of 57% for serum alpha-fetoprotein (AFP) (P<0.05). Notably, SOX11 promoter methylation plus AFP showed a sensitivity of 85% in discriminating HCC from CHB. These results suggested that serum SOX11 promoter methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC.

Different cerebrospinal fluid levels of Alzheimer-type biomarker Aß42 between general paresis and asymptomatic neurosyphilis.

BACKGROUND AND PURPOSE: Neurosyphilis is a neurological disease that involves infection of the central nervous system with Treponema pallidum. With increases in unsafe sexual behaviour, syphilis has re-emerged worldwide. To explore the amyloid and tau metabolism in neurosyphilis patients in different stages, the levels of Alzheimer-type biomarkers in general paresis (GP) and asymptomatic neurosyphilis (ANS) patients in comparison to patients with Alzheimer's disease (AD) and normal controls (NCs) were investigated. METHODS: ß-amyloid peptide 1-42 (Aß42) and Aß 1-40 (Aß40), tau hyperphosphorylated at threonine 181 (p-tau181) and total tau (t-tau) in cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay kits in 44 patients with GP, 10 patients with ANS, 45 patients with AD and 39 NCs. RESULTS: Alzheimer's disease patients had lower CSF Aß42 levels combined with higher CSF t-tau and p-tau181 levels than other groups (all P < 0.001). The CSF Aß42 levels decreased in GP compared to ANS and NCs (P < 0.001). CSF Aß40, t-tau and p-tau181 levels were not different between the GP, ANS or NC groups. CONCLUSIONS: Our research has demonstrated that GP, ANS and AD patients are characterized by distinct patterns of the CSF biomarkers Aß and tau. The distinct CSF Aß pattern in GP suggests the existence of abnormal Aß metabolism. Furthermore, different levels of CSF Aß will be helpful for the differentiation between different stages of neurosyphilis.

Exportin 4 gene expression and DNA promoter methylation status in chronic hepatitis B virus infection.

Exportin 4 (XPO4) is a novel identified candidate tumour-suppressor gene involved in the pathogenesis of hepatocellular carcinoma (HCC). This study was aimed to determine the clinical features of XPO4 mRNA expression and promoter methylation status in peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis B virus (HBV) infection. PBMCs were isolated from 44 HCC, 38 liver cirrhosis (LC), 34 chronic hepatitis B (CHB) patients and 17 healthy controls (HCs). The mRNA level and promoter methylation status of XPO4 were determined by quantitative real-time RT-PCR and methylation-specific PCR, respectively. XPO4 mRNA level of HCC patients was significantly lower compared with LC and CHB patients as well as HCs (all P < 0.01, respectively), and significant differences of the XPO4 mRNA level were found in LC and CHB group than in HCs (LC vs HCs, P < 0.01; CHB vs HCs, P < 0.05). Methylation rate of XPO4 promoter was significantly increased in patients with HCC than in patients with CHB and HCs (both P < 0.05). DNA methylation pattern was responsible for the suppression of XPO4 transcription in the progression of HBV infection (P = 0.000). Furthermore, AFP level was significantly higher in HCC patients with XPO4 methylation than in those without methylation ((8702 ± 15635) µm vs (1052 ± 5370) µm, P < 0.05). In conclusion, transcription of XPO4 gene was gradually decreased and methylation rate of XPO4 promoter was increased with the progression of HBV infection. Methylation status of XPO4 in PBMCs tended to be a noninvasive biomarker to predict HCC and the progression of HBV infection.

Cognitive impairment in schizophrenia is associated with prefrontal-striatal functional hypoconnectivity and striatal dopaminergic abnormalities.

BACKGROUND: A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments. AIMS: This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions. METHODS: Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT. RESULTS: Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function. CONCLUSIONS: This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.

Hippocampal subfields in remitted schizophrenia.

BACKGROUND: Current evidence of volume changes in hippocampal subdivisions in schizophrenia remains inconsistent, and few studies have investigated the relationship between regional hippocampal volumes and symptom remission. METHODS: In this cross-sectional study, we recruited 31 patients with schizophrenia and 31 healthy controls (HCs). Symptomatic remission in schizophrenia was determined according to Remission in Schizophrenia Working Group criteria. The volumes of hippocampal longitudinal subregions and transverse subfields were measured using manual and automatic techniques, respectively. Between-group regional hippocampal volume differences were analyzed using multivariate analysis of covariance followed by univariate analysis of covariance. RESULTS: Compared with the HCs, the patients with schizophrenia had smaller bilateral heads and tails along the longitudinal axis; they also had reduced volumes of the bilateral CA1, CA3, CA4, GC-ML-DG, molecular layer, tail, left subiculum, left HATA, and right parasubiculum along the transverse axis in the hippocampus (all corrected p < 0.05). Furthermore, compared with the HCs and patients with remitted schizophrenia, the patients with nonremitted schizophrenia had smaller bilateral hippocampal tail subfields (corrected p < 0.05). CONCLUSION: Our results indicated that the pathophysiology and symptomatic remission of schizophrenia are related to changes in the volumes of hippocampal subdivisions. These volume changes might be clinically relevant as biomarkers for schizophrenia identification and treatment.

Can we explain machine learning-based prediction for rupture status assessments of intracranial aneurysms?

Although applying machine learning (ML) algorithms to rupture status assessment of intracranial aneurysms (IA) has yielded promising results, the opaqueness of some ML methods has limited their clinical translation. We presented the first explainability comparison of six commonly used ML algorithms: multivariate logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), multi-layer perceptron neural network (MLPNN), and Bayesian additive regression trees (BART). A total of 112 IAs with known rupture status were selected for this study. The ML-based classification used two anatomical features, nine hemodynamic parameters, and thirteen morphologic variables. We utilized permutation feature importance, local interpretable model-agnostic explanations (LIME), and SHapley Additive exPlanations (SHAP) algorithms to explain and analyze 6 Ml algorithms. All models performed comparably: LR area under the curve (AUC) was 0.71; SVM AUC was 0.76; RF AUC was 0.73; XGBoost AUC was 0.78; MLPNN AUC was 0.73; BART AUC was 0.73. Our interpretability analysis demonstrated consistent results across all the methods; i.e., the utility of the top 12 features was broadly consistent. Furthermore, contributions of 9 important features (aneurysm area, aneurysm location, aneurysm type, wall shear stress maximum during systole, ostium area, the size ratio between aneurysm width, (parent) vessel diameter, one standard deviation among time-averaged low shear area, and one standard deviation of temporally averaged low shear area less than 0.4 Pa) were nearly the same. This research suggested that ML classifiers can provide explainable predictions consistent with general domain knowledge concerning IA rupture. With the improved understanding of ML algorithms, clinicians' trust in ML algorithms will be enhanced, accelerating their clinical translation.

Treatment resistant depression in elderly.

Treatment refractory depression (TRD) in the elderly is a common psychiatric disorder with high comorbidity and mortality. Older adults with TRD often have complicated comorbidities and several predisposing risk factors, which may lead to neuropsychiatric dysfunction and poor response to treatment. Several hypotheses suggest the underlying mechanisms, including vascular, immunological, senescence, or abnormal protein deposition. Treatment strategies for TRD include optimization of current medication dose, augmentation, switching to an alternative agent or class, and combination of different antidepressant classes, as well as nonpharmacological adjuvant interventions such as biophysical stimulation and psychotherapy. In summary, treatment recommendations for TRD in the elderly favor a multimodal approach, combining pharmacological and nonpharmacological treatments.

Amygdala substructure volumes and serotonin transporter in first-episode, drug- naïve major depressive disorder: A pilot study.

INTRODUCTION: Amygdala and serotonergic system abnormalities have been documented in major depressive disorder (MDD). However, most studies have been conducted on recurrent MDD, and only a few have assessed their interaction. This study aimed to concurrently examine both the amygdala and serotonergic systems and their clinical relevance in first-episode, drug-naïve MDD. METHODS: This study included 27 patients with first-episode, drug-naïve MDD and 27 age- and gender-matched healthy controls (HCs). The amygdala substructure volumes were performed with Freesurfer from a 1.5 T magnetic resonance image. Serotonin transporter (SERT) availability was detected by single-photon emission computed tomography with 123I-ADAM. The Benjamini-Hochberg method was applied to adjust for multiple comparisons. RESULTS: No significant difference was found in the amygdala substructure volume and SERT availability between the two groups, respectively. Within MDD patients, the right medial, cortical nucleus, and centromedial volumes were positively associated with caudate SERT availability, respectively. Moreover, the right lateral nucleus volume in the amygdala was positively correlated with depression severity. However, these significances did not survive correction for multiple testing. CONCLUSIONS: There were no significant abnormalities in the amygdala substructure volumes and SERT availability in patients with first-episode, drug-naïve MDD. We did not observe an association between amygdala substructure volume and serotonergic dysregulation and their correlations with depression severity in patients with MDD. A larger sample size is warranted to elucidate the actual correlation.

Abnormalities of Hippocampal Subfield and Amygdalar Nuclei Volumes and Clinical Correlates in Behavioral Variant Frontotemporal Dementia with Obsessive-Compulsive Behavior-A Pilot Study.

(1) Background: The hippocampus (HP) and amygdala are essential structures in obsessive-compulsive behavior (OCB); however, the specific role of the HP in patients with behavioral variant frontotemporal dementia (bvFTD) and OCB remains unclear. (2) Objective: We investigated the alterations of hippocampal and amygdalar volumes in patients with bvFTD and OCB and assessed the correlations of clinical severity with hippocampal subfield and amygdalar nuclei volumes in bvFTD patients with OCB. (3) Materials and methods: Eight bvFTD patients with OCB were recruited and compared with eight age- and sex-matched healthy controls (HCs). Hippocampal subfield and amygdalar nuclei volumes were analyzed automatically using a 3T magnetic resonance image and FreeSurfer v7.1.1. All participants completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Neuropsychiatric Inventory (NPI), and Frontal Behavioral Inventory (FBI). (4) Results: We observed remarkable reductions in bilateral total hippocampal volumes. Compared with the HCs, reductions in the left hippocampal subfield volume over the cornu ammonis (CA)1 body, CA2/3 body, CA4 body, granule cell layer, and molecular layer of the dentate gyrus (GC-ML-DG) body, molecular layer of the HP body, and hippocampal tail were more obvious in patients with bvFTD and OCB. Right subfield volumes over the CA1 body and molecular layer of the HP body were more significantly reduced in bvFTD patients with OCB than in those in HCs. We observed no significant difference in amygdalar nuclei volume between the groups. Among patients with bvFTD and OCB, Y-BOCS score was negatively correlated with left CA2/3 body volume (τb = -0.729, p < 0.001); total NPI score was negatively correlated with left GC-ML-DG body (τb = -0.648, p = 0.001) and total bilateral hippocampal volumes (left, τb = -0.629, p = 0.002; right, τb = -0.455, p = 0.023); and FBI score was negatively correlated with the left molecular layer of the HP body (τb = -0.668, p = 0.001), CA4 body (τb = -0.610, p = 0.002), and hippocampal tail volumes (τb = -0.552, p < 0.006). Mediation analysis confirmed these subfield volumes as direct biomarkers for clinical severity, independent of medial and lateral orbitofrontal volumes. (5) Conclusions: Alterations in hippocampal subfield volumes appear to be crucial in the pathophysiology of OCB development in patients with bvFTD.

Interactions between dopamine transporter and N-methyl-d-aspartate receptor-related amino acids on cognitive impairments in schizophrenia.

BACKGROUND: Cognitive impairments, the main determinants of functional outcomes in schizophrenia, had limited treatment responses and need a better understanding of the mechanisms. Dysfunctions of the dopamine system and N-methyl-d-aspartate receptor (NMDAR), the primary pathophysiologies of schizophrenia, may impair cognition. This study explored the effects and interactions of striatal dopamine transporter (DAT) and plasma NMDAR-related amino acids on cognitive impairments in schizophrenia. METHODS: We recruited 36 schizophrenia patients and 36 age- and sex-matched healthy controls (HC). All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT and ultra-performance liquid chromatography were applied to determine DAT availability and plasma concentrations of eight amino acids, respectively. RESULTS: Compared with HC, schizophrenia patients had lower cognitive performance, higher methionine concentrations, decreased concentrations of glutamic acid, cysteine, aspartic acid, arginine, the ratio of glutamic acid to gamma-aminobutyric acid (Glu/GABA), and DAT availability in the left caudate nucleus (CN) and putamen. Regarding memory scores, Glu/GABA and the DAT availability in left CN and putamen exhibited positive relationships, while methionine concentrations showed negative associations in all participants. The DAT availability in left CN mediated the methionine-memory relationship. An exploratory backward stepwise regression analysis for the four biological markers associated with memory indicated that DAT availability in left CN and Glu/GABA remained in the final model. CONCLUSIONS: This study demonstrated the interactions of striatal DAT and NMDAR-related amino acids on cognitive impairments in schizophrenia. Future studies to comprehensively evaluate their complex interactions and treatment implications are warranted.