Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety.

There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy.

Development of an open hardware 3-D printed conveyor device for continuous cryopreservation of non-batched samples.

A great challenge among communities participating in germplasm repository development is to obtain suitable cryopreservation equipment and devices. Commercial programmable freezers are costly and thus unaffordable to many users. Self-made devices have substantial variability among users, resulting in few opportunities for standardization across communities.

Human IPSC-Derived Model to Study Myelin Disruption.

Myelin is of vital importance to the central nervous system and its disruption is related to a large number of both neurodevelopmental and neurodegenerative diseases. The differences observed between human and rodent oligodendrocytes make animals inadequate for modeling these diseases. Although developing human in vitro models for oligodendrocytes and myelinated axons has been a great challenge, 3D cell cultures derived from iPSC are now available and able to partially reproduce the myelination process.

Greater baseline connectivity of the salience and negative affect circuits are associated with natural improvements in anxiety over time in untreated participants.

Background: There is limited research examining the natural trajectories of depression and anxiety, how these trajectories relate to baseline neural circuit function, and how symptom trajectory-circuit relationships are impacted by engagement in lifestyle activities including exercise, hobbies, and social interactions. To address these gaps, we assessed these relations over three months in untreated participants.

Methods: 262 adults (59.

Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity.

Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential.

Reduced functional connectivity of default mode network subsystems in depression: Meta-analytic evidence and relationship with trait rumination.

Resting-state functional connectivity changes in the default mode network (DMN) of patients with major depressive disorder (MDD) have been linked to rumination. The DMN is divided into three subsystems: a midline Core, a dorsal medial prefrontal cortex (DMPFC) subsystem, and a medial temporal lobe (MTL) subsystem. We examined resting-state functional connectivity within and between DMN subsystems in MDD and its association with rumination.

Microfabrication of low-cost customisable counting chambers for standardised estimation of sperm concentration.

Evaluation of sperm concentration is essential for research and procedures involving AI, cryopreservation and sperm quality assessment. Microfabrication technologies have shown tremendous potential for rapid prototyping and fabrication of devices to assist reproduction and fertility research, but such utility has not yet been made available for most reproduction laboratories. The aim of this study was to evaluate the feasibility of using microfabrication techniques to produce counting chambers for estimation of sperm concentration.

Antidepressant Paroxetine Exerts Developmental Neurotoxicity in an iPSC-Derived 3D Human Brain Model.

Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy. Various concerns have been raised about the possible effects of these drugs on fetal development. Current developmental neurotoxicity (DNT) testing conducted in rodents is expensive, time-consuming, and does not necessarily represent human pathophysiology.

The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression.

Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally.

and Models to Study Mosquito-Borne Flavivirus Neuropathogenesis, Prevention, and Treatment.

Mosquito-borne flaviviruses can cause disease in the nervous system, resulting in a significant burden of morbidity and mortality. Disease models are necessary to understand neuropathogenesis and identify potential therapeutics and vaccines. Non-human primates have been used extensively but present major challenges.

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres.

Human induced pluripotent stem cells (iPSCs), together with 21st century cell culture methods, have the potential to better model human physiology with applications in toxicology, disease modeling, and the study of host-pathogen interactions. Several models of the human brain have been developed recently, demonstrating cell-cell interactions of multiple cell types with physiologically relevant 3D structures. Most current models, however, lack the ability to represent the inflammatory response in the brain because they do not include a microglial cell population.

Kirby-Bauer disc approximation to detect inducible third-generation cephalosporin resistance in Enterobacteriaceae.

Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect using standard methods of either Kirby-Bauer disc diffusion (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This difficulty is due to genetic differences in resistance determinants, differences in levels of gene expression, and variation in spectra of enzymatic activity against the substrate beta-lactams used for susceptibility testing. We have examined 95 clinical isolates reportedly susceptible to ceftazidime and ceftriaxone, as originally determined by either KBDD or MIC methods.

Reboxetine: functional inhibition of monoamine transporters and nicotinic acetylcholine receptors.

The present study determined whether repeated administration of the antidepressant and selective norepinephrine (NE) uptake inhibitor reboxetine resulted in an adaptive modification of the function of the NE transporters (NETs), serotonin (5-HT) transporters, or dopamine (DA) transporters. Because antidepressants may be effective tobacco smoking cessation agents and because antidepressants have recently been shown to interact with nicotinic acetylcholine receptors (nAChRs), the interaction of reboxetine with nAChRs was also evaluated. Repeated administration of reboxetine (10 mg/kg i.

Mitochondrial toxin inhibition of [(3)H]dopamine uptake into rat striatal synaptosomes.

Administration of the mitochondrial inhibitors malonate and 3-nitropropionic acid (3-NP) to rats provides useful models of Huntington's disease. Exposure to these inhibitors has been shown to result in increased extracellular concentrations of striatal dopamine (DA), which is neurotoxic at high concentrations. The cause of this increase is unknown.

Clorgyline and deprenyl attenuate striatal malonate and 3-nitropropionic acid lesions.

We have previously shown that dopamine depletion reduces striatal damage elicited by the mitochondrial neurotoxins malonate and 3-nitropropionic acid (3NP). Metabolism of dopamine by monoamine oxidase results in the formation of hydrogen peroxide, which may mediate dopamine toxicity. In this study, administration of the monoamine oxidase inhibitors clorgyline and deprenyl resulted in a 42% and 75% reduction in lesion volumes in malonate- and 3NP-treated animals, respectively, compared to controls.