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Mental disorders (MDs) are highly prevalent and potentially debilitating complex disorders which causes remain elusive. Looking into deeper aspects of etiology or pathophysiology underlying these diseases would be highly beneficial, as the scarce knowledge in mechanistic and molecular pathways certainly represents an important limitation. Association between MDs and inflammation/neuroinflammation has been widely discussed and accepted by many, as high levels of pro-inflammatory cytokines were reported in patients with several MDs, such as schizophrenia (SCZ), bipolar disorder (BD) and major depression disorder (MDD), among others. Correlation of pro-inflammatory markers with symptoms intensity was also reported. However, the mechanisms underlying the inflammatory dysfunctions observed in MDs are not fully understood yet. In this context, microglial dysfunction has recently emerged as a possible pivotal player, as during the neuroinflammatory response, microglia can be over-activated, and excessive production of pro-inflammatory cytokines, which can modify the kynurenine and glutamate signaling, is reported. Moreover, microglial activation also results in increased astrocyte activity and consequent glutamate release, which are both toxic to the Central Nervous System (CNS). Also, as a result of increased microglial activation in MDs, products of the kynurenine pathway were shown to be changed, influencing then the dopaminergic, serotonergic, and glutamatergic signaling pathways. Therefore, in the present review, we aim to discuss how neuroinflammation impacts on glutamate and kynurenine signaling pathways, and how they can consequently influence the monoaminergic signaling. The consequent association with MDs main symptoms is also discussed. As such, this work aims to contribute to the field by providing insights into these alternative pathways and by shedding light on potential targets that could improve the strategies for pharmacological intervention and/or treatment protocols to combat the main pharmacologically unmatched symptoms of MDs, as the SCZ.

The present study demonstrates, using human protein microarrays and plasma and cerebrospinal fluid samples obtained pre-surgically and simultaneously from 46 hip fracture repair patients, that CSF exhibits an extraordinarily complex IgG autoantibody profile composed of thousands of autoantibodies. We show that the pattern of expression levels of individual autoantibodies in CSF closely mimics that in the blood, regardless of age, gender or the presence or absence of disease, indicative of a blood-based origin for CSF autoantibodies. In addition, using five longitudinal serum samples obtained from one healthy individual over a span of nine years, we found that blood autoantibody profiles are remarkably stable over a long period of time, and that autoantibody profiles in both blood and CSF show features that are common among different individuals as well as individual-specific. Lastly, we demonstrate that an elevated CSF/plasma autoantibody ratio is more common in elderly hip fracture repair patients that experienced post-operative delirium than in non-delirium subjects, thus highlighting the crucial role that blood-brain and/or blood-CSF barrier compromise may play in the development of post-operative delirium.

UNASSIGNED: Finding a non-invasive and repeatable tool has been recommended to make an accurate diagnosis of Alzheimer\'s disease (AD) and Parkinson\'s disease (PD).
UNASSIGNED: 70 volunteers participated in three groups: 24 with mild dementia of AD, 24 in the first and second stages of PD, and 22 healthy controls. After valuing the scores of cognitive tests, the salivary levels of phosphorylated tau (p-tau), total alpha-synuclein (α-syn), and beta-amyloid 1-42 (Aβ)‏‎ proteins have been evaluated. Finally, the cutoff points, receiver operating characteristic (ROC), sensitivity, and specificity have been calculated to find accurate and detectable biomarkers.
UNASSIGNED: Findings showed that the salivary level of Aβ was higher in both PD (p < 0.01) and AD (p < 0.001) patients than in controls. Moreover, the level of α-syn in both PD and AD patients was similarly lower than in controls (p < 0.05). However, the level of p-tau was only ‎higher in the AD group than in the control (p < 0.01). Salivary Aβ 1-42 level at a 60.3 pg/ml cutoff point revealed an excellent performance for diagnosing AD (AUC: 0.81).
UNASSIGNED: Evaluation of p-tau, α-syn, and Aβ 1-42 levels in the saliva of AD and PD patients could help the early diagnosis. The p-tau level might be valuable for differentiation between AD and PD. Therefore, these hopeful investigations could be done to reduce the usage of invasive diagnostic methods, which alone is a success in alleviating the suffering of AD and PD patients. Moreover, introducing accurate salivary biomarkers according to the pathophysiology of AD and PD should be encouraged.

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB. Since MPS IIIB is a pediatric disease the safety/toxicity, pharmacokinetics and biodistribution of TA were evaluated in juvenile non-human primates that were administered up to 5 weekly intracerebroventricular (ICV) or single intravenous (IV) infusions of TA. TA administered by ICV slow-, ICV isovolumetric bolus- or IV-infusion was well-tolerated, and no effects were observed on clinical observations, electrocardiographic or ophthalmologic parameters, or respiratory rates. The drug-related changes observed were limited to increased cell infiltrates in the CSF and along the ICV catheter track after ICV administration. These findings were not associated with functional changes and are associated with the use of ICV catheters. The CSF PK profiles were consistent across all conditions tested and TA distributed widely in the CNS after ICV administration. Anti-drug antibodies were observed but did not appear to significantly affect the exposure to TA. Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB.

A 78-year-old man developed paresthesias in the extremities. He was referred to our hospital because of positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies in the serum and the presence of abnormal lymphocytes. He was diagnosed as chronic-type adult T-cell leukemia/lymphoma. Neurological examination revealed sensory impairment in the distal parts of the extremities with loss of deep tendon reflexes. Nerve conduction study showed motor and sensory demyelinating polyneuropathy, indicating a diagnosis of HTLV-1-associated demyelinating neuropathy. Corticosteroid therapy followed by intravenous immunoglobulin therapy improved his symptoms. Since demyelinating neuropathy associated with HTLV-1 infection is not well recognized, we here report its characteristics and clinical course through our case report and literature review.

UNASSIGNED: Conventional computed tomography (CT) images are severely affected by metal artifacts in patients with intracranial coils. Monoenergetic images have been suggested to reduce metal artifacts.The aim of this study was to assess metal artifacts in virtual monoenergetic images (VMIs) reconstructed from spectral brain CT.
UNASSIGNED: Thirty-two consecutive patients with intracranial coils examined by spectral non contrast brain CT (NCCT) at our center between November 2017 and April 2019 were included. Attenuation and standard deviations were measured in regions of interest (ROIs) at predefined areas in artifact-free and artifact-affected areas. Measurements were performed in conventional polyenergetic images (CIs) and the corresponding data for VMIs were retrieved through spectral diagrams for the each ROI. Subjective analysis was performed by visual grading of CIs and specific VMIs by two neuroradiologists, independently.
UNASSIGNED: In artefact-affected image areas distal from the metal objects, the attenuation values decreased with higher energy level VMIs. The same effect was not seen for artefact-affected image areas close to the metal.Subjective rating of the artefact severity was significantly better in VMIs at 50 keV for one of the two reviewers compared to the CIs. Overall image quality and tissue differentiation scores were significantly higher for both reviewers in VMIs at 60 and 70 keV compared to CIs.
UNASSIGNED: Our quantitative and qualitative image analysis shown that there is a small significant reduction of intracranial coils artifacts severity by all monoenergetic reconstructions from 50 to 200 keV with preserved or increased overall subjective image quality compared to conventional images.

UNASSIGNED: Complex anterior skull base defects produced by resection of mass lesions vary in size and configuration and may be extensive. We analyzed the largest single-center series of midline craniofacial lesions extending intra- and extracranially. The study aims at the development of a predictive model for preoperative measurement of the risk of the postoperative cerebrospinal fluid (CSF) leak based on patients\' characteristics and surgical plans.
UNASSIGNED: 166 male and 149 female patients with mean age 40,5 years (1 year and - 81 years) operated for benign and tumor-like midline craniofacial mass lesions were retrospectively analyzed using logistic regression method (Ridge regression algorithm was selected). The overall CSF leak rate was 9.6%. The ROSE algorithm and \'glmnet\' software suite in R were used to overcome the cohort\'s disbalance and avoid overtraining the model.
UNASSIGNED: The most influential modifiable negative predictor of the postoperative CSF leak was the use of extracranial and combined approaches. Use of transbasal approaches, gross total resection, utilization of one or two vascularized flaps for skull base reconstruction were the foremost modifiable predictors of a good outcome. Criterium of elevated risk was established at 50% with a specificity of the model as high as 0.83.
UNASSIGNED: The performed study has allowed for identifying the most significant predictors of postoperative CSF leak and developing an effective formula to estimate the risk of this complication using data known for each patient. We believe that the suggested web-based online calculator can be helpful for decision making support in off-pattern clinical situations.

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