Neurological Disorders

Objective: To analyze the post-re-RT progression-free survival (PFS) and incidence of radio-necrosis (BRN) in patients with recurrent primary brain tumors and to explore the associated factors.

Method: A retrospective cohort study that included 15 pediatric and adult patients with primary brain tumors who were treated with re-RT between 2011 and 2020. The study endpoints included the post-re-RT PFS, which were analyzed using Kaplan-Meier survival analysis, and the incidence of radio-necrosis. Baseline demographic and clinical data, primary radiation therapy (RT1) parameters and outcomes, and re-RT parameters and outcomes, were analyzed as factors for the two outcomes.

Result: Of the 15 participants, 7 had glioblastoma and 5 had anaplastic ependymoma. The mean interval from first RT to re-RT was 24 months (range=2-60 months). The mean total cumulative dose after re-RT as per EQD2 (equivalent dose in 2 Gy) fractions was 101.97 Gy (max 135.6 Gy). The total mean (max) cumulative doses for organs at risk as per EQD2 after re-RT were 54.05 (92.93) Gy for brain stem, 41.19 (87.94) Gy for optic chiasma, and 28.79 (77.18) Gy and 28.6 (88.71) Gy for left and right optic nerves respectively. Disease progression occurred in 10/15 patients, and the median PFS was 4 months (95%CI=0-9.1). Although not statistically significant, PFS was likely to be prolonged in case of low-grade tumors, longer RT1-re-RT time. Radiation necrosis occurred in 2 patients.

Conclusion: The expected clinical benefits against the adverse effects should be contemplated for re-irradiation in primary brain tumors.

Transcranial Magnetic Stimulation (TMS) is a neuromodulation technique that has been approved by the Food and Drug Administration for several neuropsychiatric disorders, including major depression and obsessive compulsive disorder. It is also applied as a research tool for neurological disorders. However, the therapeutic efficacy of TMS treatment has been modest, despite of decades of research. While there are many potential reasons as to why, one of the most obvious is the technological limitations of current technologies. One prominent example is the penetration depth focality tradeoff of existing TMS coils. The most widely used Figure of 8 coils stimulate brain regions just superficially under the coil, missing deep brain regions known to be critically involved in psychiatric disorders; while ring type coils can stimulate deep into the brain, but stimulate a large brain volume (lack of focality). A new coil design strategy is proposed: magnetic materials encompassing the human head are optimized to shape the electromagnetic field generated by the primary coil. Specifically, a mathematical model was developed to describe the physical problem; the magnetic materials were discretized into unit blocks; Newton’s gradient descent method was applied to iteratively optimize the spatial distribution of the unit blocks to achieve a desired electric field distribution inside a head model. Results reveal that the proposed design achieves a coil penetration depth equal to or better than state of the art commercial coils, while improving the depth focality tradeoff by a factor of 2.2 to 2.7. As a proof of concept, a prototype coil and a spherical head model were constructed; the spatial distribution of the induced electric field inside the head model was mapped. Results validated the proposed coil design. TMS coils based on this novel design strategy could potentially lead to better therapeutic outcome.

Aim: DE is a chronic central nervous system complication caused by DM. Aβ^² deposition has been considered as the main cause of cognitive impairment in DE. Our study explored the function of non-inflammatory pathway of TLR9, that acting on Sirt1 related Aβ² deposition and cognitive function in DE.

Methods: Wide type and TLR9 knockout C57BL/6J mice were randomly divided into a control and a DM group. The DM rat was produced by intraperitoneal injection of STZ. And adeno associated virus was injected into their hippocampi to inhibit Sirt1. 12 weeks later, the rats were tested in water maze and then sacrificed. Hippocampi were for immunohistochemistry, Western blot, and RT-PCR. In vitro HT22 cells were incubated with or without high glucose medium and further intervened with TLR9 antagonist ODN2088 and p53 over expressed lent viral infection. The detection method was almost the same as in vivo, except for flow cytometry.

Results: We found that, compared with DM mice, TLR9-/-DM mice performed better in learning ability and short term memory and contained lower Aβ², but could be reversed by Sirt1 inhibition. Furthermore, in vitro, after intervention with high glucose and p53 over expressed lentiviral infection, we observed the positive results of TLR9 inhibition, such as Sirt1 up regulation, Aβ^² reduction or cognitive improvement, were reversed (all P<0.05).

Conclusions: We considered that TLR9/p53/Sirt1 signalling pathway induced by high glucose are one of molecular mechanisms underlying DE. These results not only confirm the importance of blood glucose management but also provide new insights for treatment of DE.

Background: The critical issue of treating Treatment Resistant Depression (TRD) is to improve antidepressant effect rapid onset and the recovery rates. Significant antidepressant effects of ketamine onset rapidly, but decays rapidly and repeated dosing increases the risks. This study aimed to explore the efficacy and safety of single intravenous ketamine, combined with venlafaxine’s hydrochloride for TRD.

Methods: 32 patients with treatment resistant depression will be randomly selected to undergo a four weeks double blind treatment with single dose ketamine (0.5 mg/kg over 40 min) and venlafaxine hydrochloride (4 weeks) or midazolam maleate (0.045 mg/kg over 40 min) and venlafaxine hydrochloride (4 weeks). Depressive symptoms will be measured by the Montgomery–Asberg Depression Rating Scale (MADRS) and the 16 item Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16). Adverse effects will be measured by the Brief Psychiatric Rating Scale-4 (BPRS-4), Young Manic Rating Scale (YMRS), the Clinician Administered Dissociative States Scale (CADSS), Frequency and Intensity of Side Effects Rating/Global Rating of Side Effects Burden (FISER/GRSEB) and Patient Rated Inventory of Side Effects (PRISE). Patients will be assessed at baseline, after intervention 1, 2, 4, 24, 48, 72 hours and 7, 14, 21 and 28 days.

Discussion: This study will provide important information on whether this new combined intervention can rapidly relieve the symptoms of depression and improve the remission rates of treatment resistant depression.

Purpose: To examine: (i) depression as a mediator in effects of sleep duration and quality on life satisfaction (LS), (ii) source of endogeneity in self-reported data on sleep, and (iii) predictive power of sleep duration and quality on LS.

Methods: Panel data of 22,674 observations from the China Health and Retirement Longitudinal Survey (2015 and 2018) was used. Sleep was assessed with self-reported duration and quality. Depression was measured by the 10-question version of the Center for Epidemiological Survey Depression. LS was rated by five scales. Fixed effects ordered logit models were used to determine the effect of sleep duration and quality on life satisfaction and the mediating role of depression. We used instrumental variable strategy to explore the source of endogeneity. Information value and random forest model were used to examine the predictive power of sleep measures duration and quality.

Results: Sleep duration and quality were found to improve life satisfaction via lower depression score. Non-agricultural employed population with urban hukou (household registration) accounted for the endogeneity, but the instrument variable sunset failed the weak instrument test. Sleep measures were found to predict life satisfaction, especially for the lower life satisfaction groups.

Conclusion: Our findings suggest the importance of sleep and the study of the associations between solar cues, social schedules, and sleep. Policy makers of social care of older adults might consider sleep intervention among this population.