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Objective: Training programs exist that prepare college students, faculty, and staff to identify and support students potentially at risk for suicide. Kognito is an online program that trains users through simulated interactions with virtual humans. This study evaluated Kognito's effectiveness in preparing users to intervene with at-risk students. Participants: Training was completed by 2,727 university students, faculty, and staff from April, 2014 through September, 2015. Methods: Voluntary and mandatory participants at a land-grant university completed Kognito modules designed for higher education, along with pre- and post-assessments. Results: All modules produced significant gains in reported Preparedness, Likelihood, and Self-Efficacy in intervening with troubled students. Despite initial disparities in reported abilities, after training participants reported being similarly capable of assisting at-risk students, including LGBTQ and veteran students. Conclusions: Kognito training appears to be effective, on a large scale, in educating users to act in a facilitative role for at-risk college students.

Background Microdeletion of the human 16p11.2 gene locus confers risk for autism spectrum disorders and intellectual disability. How 16p11.2 deletion is linked to these neurodevelopmental disorders and whether there are treatment avenues for the manifested phenotypes remain to be elucidated. Emerging evidence suggests that epigenetic aberrations are strongly implicated in autism. Methods We performed behavioral and electrophysiological experiments to examine the therapeutic effects of epigenetic drugs in transgenic mice carrying 16p11.2 deletion (16p11 del/+ ). Results We found that 16p11 del/+ mice exhibited a significantly reduced level of histone acetylation in the prefrontal cortex (PFC). A short (3-day) treatment with class I histone deacetylase (HDAC) inhibitor MS-275 or Romidepsin led to the prolonged (3–4 weeks) rescue of social and cognitive deficits in 16p11 del/+ mice. Concomitantly, MS-275 treatment reversed the hypoactivity of PFC pyramidal neurons and the hyperactivity of PFC fast-spiking interneurons. Moreover, the diminished N-methyl-D-aspartate (NMDA) receptor-mediated synaptic currents and the elevated GABAA receptor-mediated synaptic currents in PFC pyramidal neurons of 16p11 del/+ mice were restored to control levels by MS-275 treatment. Conclusions Our results suggest that HDAC inhibition provides a highly effective therapeutic strategy for behavioral deficits and excitation/inhibition imbalance in 16p11 del/+ mice, likely via normalization of synaptic function in the PFC. [ABSTRACT FROM AUTHOR]

ADNP and POGZ are two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. Both ADNP and POGZ are chromatin regulators, which could profoundly affect gene transcription and cellular function in the brain. Using post-mortem tissue from patients with autism spectrum disorder, we found diminished expression of ADNP and POGZ in the prefrontal cortex, a region highly implicated in neurodevelopmental disorders. To understand the functional role of these neurodevelopmental disorder risk factors, we used viral-based gene transfer to investigate how Adnp or Pogz deficiency in mouse prefrontal cortex affects behavioural, transcriptomic and synaptic function. Mice with prefrontal cortex deficiency of Adnp or Pogz exhibited specific impairment of cognitive task performance. RNA-sequencing revealed that Adnp or Pogz deficiency induced prominent upregulation of overlapping genes enriched in neuroinflammation, similar to the elevation of pro-inflammatory genes in humans with neurodevelopmental disorders. Concomitantly, Adnp or Pogz deficiency led to the significant increase of pro-phagocytic microglial activation in prefrontal cortex, as well as the significant decrease of glutamatergic transmission and postsynaptic protein expression. These findings have uncovered the convergent functions of two top risk factors for autism spectrum disorder and intellectual disability in prefrontal cortex, providing a mechanism linking chromatin, transcriptional and synaptic dysregulation to cognitive deficits associated with neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

NMDARs are ionotropic glutamate receptors widely expressed in the CNS, where they mediate phenomena as diverse as neurotransmission, information processing, synaptogenesis, and cellular toxicity. They function as glutamate-gated Ca2+-permeable channels, which require glycine as coagonist, and can be modulated by many diffusible ligands and cellular cues, including mechanical stimuli. Previously, we found that, in cultured astrocytes, shear stress initiates NMDAR-mediated Ca2+ entry in the absence of added agonists, suggesting that more than being mechanosensitive, NMDARs may be mechanically activated. Here, we used controlled expression of rat recombinant receptors and noninvasive on-cell single-channel current recordings to show that mild membrane stretch can substitute for the neurotransmitter glutamate in gating NMDAR currents. Notably, stretch-activated currents maintained the hallmark features of the glutamate-gated currents, including glycine-requirement, large unitary conductance, high Ca2+ permeability, and voltage-dependent Mg2+ blockade. Further, we found that the stretch-gated current required the receptor's intracellular domain. Our results are consistent with the hypothesis that mechanical forces can gate endogenous NMDAR currents even in the absence of synaptic glutamate release, which has important implications for understanding mechanotransduction and the physiological and pathologic effects of mechanical forces on cells of the CNS. [ABSTRACT FROM AUTHOR]

Microdeletion of the human 16p11.2 gene locus has been linked to autism spectrum disorder (ASD) and intellectual disability and confers risk for a number of other neurodevelopmental deficits. Transgenic mice carrying 16p11.2 deletion (16p11+/-) display phenotypes reminiscent of those in human patients with 16p11.2 deletion syndrome, but the molecular mechanisms and treatment strategies for these phenotypes remain unknown. In this study, we have found that both male and female 16p11+/- mice exhibit deficient NMDA receptor (NMDAR) function in the medial prefrontal cortex (mPFC), a brain region critical for high-level "executive" functions. Elevating the activity of mPFC pyramidal neurons with a CaMKII-driven Gq-DREADD (Gq-coupled designer receptors exclusively activated by designer drugs) led to the significant increase of NR2B subunit phosphorylation and the restoration of NMDAR function, as well as the amelioration of cognitive and social impairments in 16p11+/- mice. These results suggest that NMDAR hypofunction in PFC may contribute to the pathophysiology of 16p11.2 deletion syndrome and that restoring PFC activity is sufficient to rescue the behavioral deficits. [ABSTRACT FROM AUTHOR]

A bioimpedance-controlled concept for bone cement milling during revision total hip replacement is presented. Normally, the surgeon manually removes bone cement using a hammer and chisel. However, this procedure is relatively rough and unintended harm may occur to tissue at any time. The proposed bioimpedance-controlled surgical instrumentation improves this process because, for example, most risks associated with bone cement removal are avoided. The electrical bioimpedance measurements enable online process-control by using the milling head as both a cutting tool and measurement electrode at the same time. Furthermore, a novel integrated surgical milling tool is introduced, which allows acquisition of electrical bioimpedance data for online control; these data are used as a process variable. Process identification is based on finite element method simulation and on experimental studies with a rapid control prototyping system. The control loop design includes the identified process model, the characterization of noise as being normally distributed and the filtering, which is necessary for sufficient accuracy (\pm 0.5~mm). Also, in a comparative study, noise suppression is investigated in silico with a moving average filter and a Kalman filter. Finally, performance analysis shows that the bioimpedance-controlled surgical instrumentation may also performs effectively at a higher feed rate (e.g., 5 mm/s). [ABSTRACT FROM PUBLISHER]

One of the core symptoms of autism spectrum disorder (ASD) is impaired social interaction. Currently, no pharmacotherapies exist for this symptom due to complex biological underpinnings and distinct genetic models which fail to represent the broad disease spectrum. One convincing hypothesis explaining social deficits in human ASD patients is amotivation, however it is unknown whether mouse models of ASD represent this condition. Here we used two highly trusted ASD mouse models (male Shank3‐deficient [Shank3+/ΔC] mice modeling the monogenic etiology of ASD, and inbred BTBR mice [both male and female] modeling the idiopathic and highly polygenic pathology for ASD) to evaluate the level of motivation to engage in a social interaction. In the behavioral paradigms utilized, a social stimulus was placed in the open arm of the elevated plus maze (EPM), or the light compartment of the light‐dark box (LDB). To engage in a social interaction, mice were thus required to endure innately aversive conditions (open areas, height, and/or light). In the modified EPM paradigm, both Shank3+/ΔC and BTBR mice demonstrated decreased open‐arm engagement with a social stimulus but not a novel object, suggesting reduced incentive to engage in a social interaction in these models. However, these deficits were not expressed under the less severe aversive pressures of the LDB. Collectively, we show that ASD mouse models exhibit diminished social interaction incentive, and provide a new investigation strategy facilitating the study of the neurobiological mechanisms underlying social reward and motivation deficits in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

ADNP and POGZ are two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. Both ADNP and POGZ are chromatin regulators, which could profoundly affect gene transcription and cellular function in the brain. Using post-mortem tissue from patients with autism spectrum disorder, we found diminished expression of ADNP and POGZ in the prefrontal cortex, a region highly implicated in neurodevelopmental disorders. To understand the functional role of these neurodevelopmental disorder risk factors, we used viral-based gene transfer to investigate how Adnp or Pogz deficiency in mouse prefrontal cortex affects behavioural, transcriptomic and synaptic function. Mice with prefrontal cortex deficiency of Adnp or Pogz exhibited specific impairment of cognitive task performance. RNA-sequencing revealed that Adnp or Pogz deficiency induced prominent upregulation of overlapping genes enriched in neuroinflammation, similar to the elevation of pro-inflammatory genes in humans with neurodevelopmental disorders. Concomitantly, Adnp or Pogz deficiency led to the significant increase of pro-phagocytic microglial activation in prefrontal cortex, as well as the significant decrease of glutamatergic transmission and postsynaptic protein expression. These findings have uncovered the convergent functions of two top risk factors for autism spectrum disorder and intellectual disability in prefrontal cortex, providing a mechanism linking chromatin, transcriptional and synaptic dysregulation to cognitive deficits associated with neurodevelopmental disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Microdeletion of the human 16p11.2 gene locus has been linked to autism spectrum disorder (ASD) and intellectual disability and confers risk for a number of other neurodevelopmental deficits. Transgenic mice carrying 16p11.2 deletion ( 16p11 +/- ) display phenotypes reminiscent of those in human patients with 16p11.2 deletion syndrome, but the molecular mechanisms and treatment strategies for these phenotypes remain unknown. In this study, we have found that both male and female 16p11 +/- mice exhibit deficient NMDA receptor (NMDAR) function in the medial prefrontal cortex (mPFC), a brain region critical for high-level "executive" functions. Elevating the activity of mPFC pyramidal neurons with a CaMKII-driven Gq-DREADD (Gq-coupled designer receptors exclusively activated by designer drugs) led to the significant increase of NR2B subunit phosphorylation and the restoration of NMDAR function, as well as the amelioration of cognitive and social impairments in 16p11 +/- mice. These results suggest that NMDAR hypofunction in PFC may contribute to the pathophysiology of 16p11.2 deletion syndrome and that restoring PFC activity is sufficient to rescue the behavioral deficits. SIGNIFICANCE STATEMENT The 16p11.2 deletion syndrome is strongly associated with autism spectrum disorder and intellectual disability. Using a mouse model carrying the 16p11.2 deletion, 16p11 +/- , we identified NMDA receptor hypofunction in the prefrontal cortex (PFC). Elevating the activity of PFC pyramidal neurons with a chemogenetic tool, Gq-DREADD, led to the restoration of NMDA receptor function and the amelioration of cognitive and social impairments in 16p11 +/- mice. These results have revealed a novel route for potential therapeutic intervention of 16p11.2 deletion syndrome., (Copyright © 2018 the authors 0270-6474/18/385939-10$15.00/0.)

We report on a frequency stabilized laser system with a variable linewidth at a wavelength of 404.7 nm used as an incoherent repump on the 6P3 0 ↔7S3 1 transition in mercury. By directly modulating the laser diode current with Gaussian white noise, the laser linewidth can be broadened up to 68 MHz. A Doppler-free dichroic atomic vapor laser lock spectroscopy provides an error signal suitable for frequency stabilization even for the broadened laser. Without the need of an acousto-optic modulator for the linewidth tuning or lock-in technique for frequency stabilization, this laser system provides an inexpensive approach for an incoherent and highly efficient repumper in atomic experiments.

We report on a solid-state-based laser system at 1028 nm. The light is generated by a diode laser seeded ytterbium fiber amplifier. In two build-up cavities, its frequency is doubled and quadrupled to 514 nm and 257 nm, respectively. At 514 nm, the system delivers up to 4.7 W of optical power. In the fourth harmonic, up to 173 mW are available limited by the nonlinear crystal. The frequency of the laser is mode-hop-free tunable by 16 GHz in 10 ms in the UV. Therefore, the system is suitable as a low maintenance, efficient, and tunable narrowband replacement for frequency doubled Ar + laser systems.