Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here ...we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse model, ATV:TREM2 boosted brain microglial activity and glucose metabolism. Thus, ATV:TREM2 represents a promising approach to improve microglial function and treat brain hypometabolism found in patients with AD.
•There have been limited long-term studies on suicide in Chinese psychiatric settings.•After the initial psychiatric assessment, 3.7% subjects committed suicide during a period of 17 years, of which ...one-fifth of suicides occurred within one year and half within 5 years.•Deliberate self-harm and having a psychiatric disorder at the time of assessment are significant risk factors of suicide.
There are few long-term studies on suicide in psychiatric settings in China. The objective of this study was to evaluate the long term suicide risk and its associated factors after the initial psychiatric assessment. Demographic and clinical data of adult subjects receiving psychiatric assessment between 1996 and 2000 in a district hospital in Hong Kong were retrieved from the hospital computer system. Data were matched with completed suicides before June 30 2015 as recorded by the Coroner's Office. From a total of 4078 subjects identified, there were 152 (3.7%) recorded suicides; one-fifth of suicides occurred within one year, and half within 5 years. Cox regression analysis revealed that the risk of suicide after the initial psychiatric assessment was positively associated with deliberate self-harm (Hazard ratio = 2.1; 95%CI = 1.5–3.0; p < 0.001), and negatively associated with ‘no psychiatric disorder’ (Hazard ratio = 0.4; 95%CI = 0.2–0.6; p = 0.001). The overall suicide risk for those diagnosed to have a psychiatric disorder was 4.4%; 4.5% for men and 4.3% for women. Deliberate self-harm and having a psychiatric disorder at the time of assessment are significant risk factors of suicide. Appropriate treatment of psychiatric disorders and comprehensive management of deliberate self-harm are important for suicide prevention.
The impact of magnetic resonance imaging (MRI)-identified T2-weighted hyperintensities (unidentified bright objects) on the cognitive function of children with neurofibromatosis 1 is controversial. ...We recruited 32 right-handed children with neurofibromatosis 1 (22 boys, 10 girls) aged between 5 and 16 years (mean age 10.2 years) for magnetic resonance imaging examinations and neuropsychologic evaluation. Statistical analysis was performed to evaluate the significance of the hyperintensities. Twenty-four children had unidentified bright objects, whereas eight children did not. Using the t-test, thalamic lesions were associated with lower intellectual function (P = .031). Left globus pallidus hyperintensities were associated with a lower attention score (P = .04), and right middle cerebellar peduncle hyperintensities were associated with a lower sensorimotor score (P = .05). The size of the thalamic lesions correlated with cognitive function (P < .05). Among the group with unidentified bright objects, there was a significant association between more involved sites on the dominant hemisphere and impaired verbal function (r = -.55; P = .005). Unidentified bright objects in the thalamus, globus pallidus, and middle cerebellar peduncles and the laterality of the lesions had an impact on cognitive function.
The impact of magnetic resonance imaging (MRI)—identified T2-weighted hyperintensities (unidentified bright objects) on the cognitive function of children with neurofibromatosis 1 is controversial. ...We recruited 32 right-handed children with neurofibromatosis 1 (22 boys, 10 girls) aged between 5 and 16 years (mean age 10.2 years) for magnetic resonance imaging examinations and neuropsychologic evaluation. Statistical analysis was performed to evaluate the significance of the hyperintensities. Twenty-four children had unidentified bright objects, whereas eight children did not. Using the t-test, thalamic lesions were associated with lower intellectual function (P = .031). Left globus pallidus hyperintensities were associated with a lower attention score ( P = .04), and right middle cerebellar peduncle hyperintensities were associated with a lower sensorimotor score (P = .05). The size of the thalamic lesions correlated with cognitive function (P < .05). Among the group with unidentified bright objects, there was a significant association between more involved sites on the dominant hemisphere and impaired verbal function (r = —.55; P = .005). Unidentified bright objects in the thalamus, globus pallidus, and middle cerebellar peduncles and the laterality of the lesions had an impact on cognitive function. (J Child Neurol 2004; 19:853-858).
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