Psychiatric assessment and therapy in an adolescent with ALG6-CDG: a six-month follow-up case report.

ALG6-congenital disorder of glycosylation (ALG6-CDG) is a complex of rare inherited disorders caused by mutations in the ALG6 gene, which encodes the α-1,3-glucosyltransferase enzyme required for N-glycosylation. ALG6-CDG affects multiple systems and exhibits clinical heterogeneity. Besides developmental delays and neurological signs and symptoms, behavioral and psychological symptoms are also an important group of clinical features of ALG6-CDG. Here, we present the case of a 17-year-old Chinese girl with ALG6-CDG who first visited the psychiatric department with apathy, language reduction, and substupor symptoms. The psychiatric assessments and treatment processes performed are described and discussed in this report. During diagnostic process, we found a novel mutation, c.849delT, in ALG6 by whole-exome sequencing. The patient's symptoms improved with escitalopram and risperidone treatment. However, above a certain dosage, she was sensitive to extrapyramidal side effects. This study accumulates clinical experience for diagnosing and treating ALG6-CDG and improves our understanding of this rare genetic disorder.

Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

Minimal change disease with papillary thyroid carcinoma: a report of two adult cases.

BACKGROUND: Minimal change disease (MCD), a pathological type of nephrotic syndrome (NS), can occur in patients with tumors. We report two adult cases of MCD associated with papillary thyroid carcinoma (PTC), known to be extremely rare in adults. CASE PRESENTATION: A 35-year-old female patient was simultaneously diagnosed with MCD and PTC. The MCD was effectively treated with thyroidectomy and prednisone.In addition, a 50-year-old male patient, who had been diagnosed with PTC three years prior, had MCD confirmed by renal biopsy. The patient achieved complete remission following treatment with tacrolimus and rituximab. CONCLUSIONS: The present case report describes and discusses the diagnostic and treatment processes employed in these two patients. Clinicians need to be aware of the renal effects of treating patients with solid tumors.

Tribochemically Controlled Atom Transfer Radical Polymerization Enabled by Contact Electrification.

Traditional mechanochemically controlled reversible-deactivation radical polymerization (RDRP) utilizes ultrasound or ball milling to regenerate activators, which induce side reactions because of the high-energy and high-frequency stimuli. Here, we propose a facile approach for tribochemically controlled atom transfer radical polymerization (tribo-ATRP) that relies on contact-electro-catalysis (CEC) between titanium oxide (TiO2 ) particles and CuBr2 /tris(2-pyridylmethylamine (TPMA), without any high-energy input. Under the friction induced by stirring, the TiO2 particles are electrified, continuously reducing CuBr2 /TPMA into CuBr/TPMA, thereby conversing alkyl halides into active radicals to start ATRP. In addition, the effect of friction on the reaction was elucidated by theoretical simulation. The results indicated that increasing the frequency could reduce the energy barrier for the electron transfer from TiO2 particles to CuBr2 /TPMA. In this study, the design of tribo-ATRP was successfully achieved, enabling CEC (ca. 10 Hz) access to a variety of polymers with predetermined molecular weights, low dispersity, and high chain-end fidelity.

Bidirectional relationship between nocturnal subjective sleep duration and cognitive performance in Chinese over 45 years old: a national representative longitudinal study.

INTRODUCTION: Previous studies have inconsistent associations between changes in sleep duration and cognitive function and have not separated interindividual effects from intraindividual effects. This study aimed to examine the bidirectional associations between subjective night sleep duration and cognitive function while differing intraindividual and interindividual effects. METHODS: A national representative sample was obtained from China Health and Retirement Longitudinal Study during 2011-2018. Night sleep duration and potential confounders were assessed and collected by questionnaires. Cognition was assessed in three categories (orientation, executive function, and memory), and z scores were used for global cognitive performance. The random intercept cross-lagged panel model was used to examine the temporal associations during 2011-2018. RESULTS: Across 9404 participants over 45, at interindividual level, moderate (ß= -0.014) and long sleepers (ß= -0.06) had positive association between sleep duration and cognitive decline after adjusted covariates, but short sleepers had negative associations between sleep duration and cognitive decline (ß = 0.87). At intraindividual level, prolonged sleep duration predicted better cognition for short (ß= -0.021 at wave2-3; ß= -0.04 at wave3-4) and moderate (ß= -0.017 at wave3-4) sleepers. CONCLUSION: For short sleepers, longer subjective nocturnal sleep duration predicted better cognitive performance; but moderate and long sleepers showed opposite results-short and moderate sleepers with prolonged subjective nocturnal sleep duration would have later cognitive decline. Our findings tentatively suggested that an increased subjective night sleep duration and subjective long sleep duration could be regarded as useful tools for identifying middle- and old adults at higher risks of progressing to cognitive decline.

The value of nurse-led anthropometric and oropharyngeal measurements combined with STOP-Bang questionnaire in screening for obstructive sleep apnea in patients with acute coronary syndrome: a prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients. METHODS: From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses. RESULTS: Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients. CONCLUSIONS: The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017.

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OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS: There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.

Changes in Homogalacturonan Metabolism in Banana Peel during Fruit Development and Ripening.

Though numerous studies have focused on the cell wall disassembly of bananas during the ripening process, the modification of homogalacturonan (HG) during fruit development remains exclusive. To better understand the role of HGs in controlling banana fruit growth and ripening, RNA-Seq, qPCR, immunofluorescence labeling, and biochemical methods were employed to reveal their dynamic changes in banana peels during these processes. Most HG-modifying genes in banana peels showed a decline in expression during fruit development. Four polygalacturonase and three pectin acetylesterases showing higher expression levels at later developmental stages than earlier ones might be related to fruit expansion. Six out of the 10 top genes in the Core Enrichment Gene Set were HG degradation genes, and all were upregulated after softening, paralleled to the significant increase in HG degradation enzyme activities, decline in peel firmness, and the epitope levels of 2F4, CCRC-M38, JIM7, and LM18 antibodies. Most differentially expressed alpha-1,4-galacturonosyltransferases were upregulated by ethylene treatment, suggesting active HG biosynthesis during the fruit softening process. The epitope level of the CCRC-M38 antibody was positively correlated to the firmness of banana peel during fruit development and ripening. These results have provided new insights into the role of cell wall HGs in fruit development and ripening.

Association of C1q/TNF-Related Protein-9 (CTRP9) Level with Obstructive Sleep Apnea in Patients with Coronary Artery Disease.

BACKGROUND: Obstructive sleep apnea (OSA) is closely related to the incidence and progression of coronary artery disease (CAD), and the mechanisms linking OSA and CAD are multifactorial. C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that protects the heart against ischemic injury and ameliorates cardiac remodeling. We aimed to ascertain the clinical relevance of CTRP9 with OSA prevalence in patients with CAD. METHODS: From August 2016 to March 2019, consecutive eligible patients with CAD (n = 154; angina pectoris, n = 88; acute myocardial infarction [AMI], n = 66) underwent cardiorespiratory polygraphy. OSA was defined as an apnea-hypopnea index (AHI) ≥15 events·h-1. Plasma CTRP9 concentrations were measured by ELISA method. RESULTS: Moderate/severe OSA was present in 89 patients (57.8%). CTRP9 levels were significantly decreased in the moderate/severe OSA group than in the no/mild OSA group (4.7 [4.1-5.2] ng/mL vs. 4.9 [4.4-6.0] ng/mL, P = 0.003). The difference between groups was only observed in patients with AMI (3.0 [2.3-4.9] vs. 4.5 [3.2-7.9], P = 0.009). Correlation analysis showed that CTRP9 levels were negatively correlated with AHI (r = -0.238, P = 0.003) and oxygen desaturation index (r = -0.234, P = 0.004) and positively correlated with left ventricular ejection fraction (r = 0.251, P = 0.004) in all subjects. Multivariate analysis showed that male gender (OR 3.099, 95% CI 1.029-9.330, P = 0.044), BMI (OR 1.148, 95% CI 1.040-1.268, P = 0.006), and CTRP9 levels (OR 0.726, 95% CI 0.592-0.890, P = 0.002) were independently associated with the prevalence of moderate/severe OSA. CONCLUSIONS: Plasma CTRP9 levels were independently related to the prevalence of moderate/severe OSA in patients with CAD, suggesting that CTRP9 might play a role in the pathogenesis of CAD exacerbated by OSA.

The Tendency of Modified Electroconvulsive Therapy-Related Working Memory and Subjective Memory Deficits in Depression: A Prospective Follow-up Study.

OBJECTIVE: The aim of the study was to explore the tendency of modified electroconvulsive therapy (MECT)-related working memory and subjective memory deficits in depressed patients. METHODS: Sixty patients with unipolar/bipolar depression were prepared and enrolled for MECT and 56 subjects were enrolled as healthy controls (HCs). Their demographics (sex, age, body mass index, years of schooling, etc) and clinical characteristics (dosage and number of MECT, etc) were compared. Depression severity, working memory, and subjective memory were measured using the Hamilton Depression Rating Scale 17 (HAMD17), a Digit Span Backwards (DSB), and self-reported assessments, respectively. Measurements were taken at baseline, within 24 hours after each MECT session, and in every month for a 6-month follow-up period. RESULTS: (a) The patients had poorer performance than the HCs on DSB and HAMD17 at baseline, and the DSB score and HAMD17 total scores were negatively correlated. However, after the second MECT session, the patients' HAMD17 score was significantly improved compared with that at the baseline (P < 0.05), whereas the DSB score showed no significant difference compared with the HCs (P > 0.05). (b) After the first MECT session, 62% of the patients reported subjective memory deficits, which were exacerbated over the subsequent sessions and relieved with antidepressant treatment during the follow-up period. (c) The risk factors for prolonged subjective memory deficits were overweight and the maximum MECT dosage/age (dosage/age = the percentage of output part of total dosage × 100/age, unit: 1/year) ≥ 1.5/year (odds ratio [OR] = 15.36 and 7.98). CONCLUSIONS: Depressed patients showed poorer working memory than the HCs. Such memory deficit may be aggravated by MECT, although it may improve with the relief of depression. Although subjective memory deficits can occur after the first MECT session and gradually recover after the treatment, they may last for 6 months or longer. Persistent deficits may be related to being overweight and having a high MECT dosage.

Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect.

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole-brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting-state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole-brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph-theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal-limbic-thalamic-cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole-brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD.

[Pathological mechanisms of chronic insomnia: Evidence from neuro-electrophysiology and neuroimaging research].

As a widely recognized public health problem as well as prevalent and challenging to modern society, chronic insomnia is involved in wide brain areas (such as prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, and thalamus) and emotion-cognition neuro-circuit. It is closely related to the conditioned hyperarousal and the increased information process and/or the impaired inhibitory ability to withdraw from awaking state. Thus, some specific abnormal mode may exist in the emotion-cognition circuit, which is associated with abnormal cognition load, such as repeated retrieval/intrusion of aversive memories during night. Studies through the combination of multiple techniques including psychology, electrophysiology and neuroimaging methods are needed to further enhance the understanding of chronic insomnia.

The beneficial effects of Rosuvastatin in inhibiting inflammation in sepsis.

Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes is still needed. Rosuvastatin, a typical ß-hydroxy ß-methylglutaryl-CoA reductase inhibitor licensed for reducing the levels of low-density lipoprotein cholesterol in patients with hyperlipidemia, has displayed anti-inflammatory capacity in different types of organs and tissues. However, its effects on the development of sepsis are less reported. Here, we found that the administration of Rosuvastatin reduced the mortality of sepsis mice and prevented body temperature loss. Additionally, it inhibited the production of inflammatory cytokines such as tumor necrosis factor (TNF-α), Interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and migration inhibitory factor (MIF) in peritoneal lavage supernatants of animals. The increased number of mononuclear cells in the peritoneum of sepsis mice was reduced by Rosuvastatin. Interestingly, it ameliorated lung inflammation and improved the hepatic and renal function in the sepsis animals. Further in vitro experiments show that Rosuvastatin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory cytokines in RAW 264.7 macrophages by preventing the activation of nuclear factor kappa-B (NF-κB). Our findings demonstrate that the administration of Rosuvastatin hampered organ dysfunction and mitigated inflammation in a relevant model of sepsis.

Multi-angle property analysis and stress-strain curve prediction of cementitious sand gravel based on triaxial test.

In order to further promote the application of cementitious sand gravel (CSG), the mechanical properties and variation rules of CSG material under triaxial test were studied. Considering the influence of fly ash content, water-binder ratio, sand rate and lateral confining pressure, 81 cylinder specimens were designed and made for conventional triaxial test, and the influence laws of stress-strain curve, failure pattern, elastic modulus, energy dissipation and damage evolution of specimens were analyzed. The results showed that the peak of stress-strain curve increased with the increase of confining pressure, and the peak stress, peak strain and energy dissipation all increased significantly, but the damage variable D decreased with the increase of confining pressure. Under triaxial compression, the specimen was basically sheared failure from the bonding surface, and the aggregate generally did not break. Sand rate had a significant effect on the peak stress of CSG, and decreased with the increase of sand rate. Under the conditions of the same cement content, fly ash content and confining pressure, the optimal water-binder ratio 1.2 existed when the sand rate was 0.2 and 0.3. After analyzing and processing the stress-strain curve of triaxial test, a Cuckoo Search-eXtreme Gradient Boosting (CS-XGBoost) curve prediction model was established, and the model was evaluated by evaluation indexes R2, RMSE and MAE. The average R2 of the XGBoost model based on initial parameters under 18 different output features was 0.8573, and the average R2 of the CS-XGBoost model was 0.9516, an increase of 10.10%. Moreover, the prediction curve was highly consistent with the test curve, indicating that the CS algorithm had significant advantages. The CS-XGBoost model could accurately predict the triaxial stress-strain curve of CSG.

Sequential mediation analysis of physical activity, healthy diet, BMI, and academic burnout in the Pakistani educational landscape.

Research has indicated a negative impact of physical activity on academic burnout among students, however, there is a paucity of evidence about the underlying mechanism of this association in Pakistani students. The present research seeks to investigate the relationship between physical activity and academic burnout by investigating the potential mediating effects of adherence to the Mediterranean diet (MD) and body mass index (BMI). A sample of 596 students using a cross-sectional survey design was gathered from two public universities (Riphah International University and Mohammed Ali Jinnah University) in Rawalpindi, Pakistan from June to July 2022. The study participants were asked to fill out the Physical Activity Rating Scale-3, the Learning Burnout Scale, and the Test of Adherence to MD questionnaires. The study employed descriptive, bivariate, and path analysis through regression utilizing the SPSS software version 27. The findings demonstrated a negative correlation between academic burnout and BMI, physical activity, and adherence to the MD. The relationship between physical activity and academic burnout was mediated by BMI. Physical activity and academic burnout were inversely correlated, with adherence to the MD and BMI interacting as sequential mediators. The outcomes of this research have expanded our knowledge of the association between physical activity and academic burnout and have suggested crucial and appropriate strategies for addressing student academic burnout.

Characterization of the novel broad-spectrum lytic phage Phage_Pae01 and its antibiofilm efficacy against Pseudomonas aeruginosa.

Introduction: Pseudomonas aeruginosa is present throughout nature and is a common opportunistic pathogen in the human body. Carbapenem antibiotics are typically utilized as a last resort in the clinical treatment of multidrug-resistant infections caused by P. aeruginosa. The increase in carbapenem-resistant P. aeruginosa poses an immense challenge for the treatment of these infections. Bacteriophages have the potential to be used as antimicrobial agents for treating antibiotic-resistant bacteria. Methods and Results: In this study, a new virulent P. aeruginosa phage, Phage_Pae01, was isolated from hospital sewage and shown to have broad-spectrum antibacterial activity against clinical P. aeruginosa isolates (83.6%). These clinical strains included multidrug-resistant P. aeruginosa and carbapenem-resistant P. aeruginosa. Transmission electron microscopy revealed that the phage possessed an icosahedral head of approximately 80 nm and a long tail about 110 m, indicating that it belongs to the Myoviridae family of the order Caudovirales. Biological characteristic analysis revealed that Phage_Pae01 could maintain stable activity in the temperature range of 4~ 60°C and pH range of 4 ~ 10. According to the in vitro lysis kinetics of the phage, Phage_Pae01 demonstrated strong antibacterial activity. The optimal multiplicity of infection was 0.01. The genome of Phage_Pae01 has a total length of 93,182 bp and contains 176 open reading frames (ORFs). The phage genome does not contain genes related to virulence or antibiotic resistance. In addition, Phage_Pae01 effectively prevented the formation of biofilms and eliminated established biofilms. When Phage_Pae01 was combined with gentamicin, it significantly disrupted established P. aeruginosa biofilms. Conclusion: We identified a novel P. aeruginosa phage and demonstrated its effective antimicrobial properties against P. aeruginosa in both the floating and biofilm states. These findings offer a promising approach for the treatment of drug-resistant bacterial infections in clinical settings.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study.

BACKGROUND: White matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear. METHODS: We used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females). RESULTS: We found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [-18 46-14]), left limbic lobe uncus (peak coordinates [-18 2-22]), and right cerebellum posterior lobe (peak coordinates [26-34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores. CONCLUSIONS: We found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.

Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

White matter integrity alterations in young healthy adults reporting childhood trauma: A diffusion tensor imaging study.

OBJECTIVE: To date, insufficient studies have focused on the relationship between childhood trauma and white matter integrity changes in healthy subjects. The aim of the present study was to explore the potential effects of childhood trauma on white matter microstructural changes by using voxel-based diffusion tensor imaging (DTI) to examine alterations in fractional anisotropy (FA) values in a group of young healthy adults. METHODS: A total of 21 healthy adults with a history of childhood trauma exposures and 21 age- and sex-matched individuals without childhood trauma were recruited in the present study. The Childhood Trauma Questionnaire was used to assess five aspects of childhood trauma exposures. DTI data were obtained on a Philips 3.0-Tesla scanner. Voxel-based analysis was conducted to compare white matter FA values between groups. RESULTS: Adults with self-reported childhood trauma experiences showed decreased white matter FA values in the genu and body of the corpus callosum and the left occipital fusiform gyrus (p < 0.001 uncorrected, voxel > 100). There was no significant difference in FA values between individuals with single and multiple childhood trauma exposures at the defined threshold. CONCLUSION: Our findings suggest that childhood trauma is associated with reduced microstructural integrity of the white matter in adulthood. These effects are still evident even in the absence of current psychiatric or medical symptoms, which may represent the vulnerability for developing mental disorders after childhood trauma experiences.