Tirzepatide for Obesity Treatment and Diabetes Prevention.

Background: Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.

Excitatory and Inhibitory Descending Commissural Interneurons Differentially Integrate Supraspinal and Segmental Sensory Signals.

The limited information about how descending inputs from the brain and sensory inputs from the periphery use spinal cord interneurons (INs) is a major barrier to understanding how these inputs may contribute to motor functions under normal and pathologic conditions. Commissural interneurons (CINs) are a heterogeneous population of spinal INs that has been implicated in crossed motor responses and bilateral motor coordination (ability to use the right and left side of the body in a coordinated manner) and, therefore, are likely involved in many types of movement (e.g.

Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study.

Purpose: To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis.

Methods: We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461).

Segmental organization of vestibulospinal inputs to spinal interneurons mediating crossed activation of thoracolumbar motoneurons in the neonatal mouse.

Vestibulospinal pathways activate contralateral motoneurons (MNs) in the thoracolumbar spinal cord of the neonatal mouse exclusively via axons descending ipsilaterally from the vestibular nuclei via the lateral vestibulospinal tract (LVST; Kasumacic et al., 2010). Here we investigate how transmission from the LVST to contralateral MNs is mediated by descending commissural interneurons (dCINs) in different spinal segments.

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse.

Using optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi- and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively.

Glutamatergic reticulospinal neurons in the mouse: developmental origins, axon projections, and functional connectivity.

Subcortical descending glutamatergic neurons, such as reticulospinal (RS) neurons, play decisive roles in the initiation and control of many motor behaviors in mammals. However, little is known about the mechanisms used by RS neurons to control spinal motor networks because most of the neuronal elements involved have not been identified and characterized. In this review, we compare, in the embryonic mouse, the timing of developmental events that lead to the formation of synaptic connections between RS and spinal cord neurons.

Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain.

A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation.

Contribution of morphology and membrane resistance to integration of fast synaptic signals in two thalamic cell types.

Thalamocortical cells (TCs) and interneurons (INs) in the lateral geniculate nucleus process visual information from the retina. The TCs have many short dendrites, whereas the INs have fewer and longer dendrites. Because of these morphological differences, it has been suggested that transmission of synaptic signals from dendritic synapses to soma is more efficient in TCs than in INs.

C fragment of tetanus toxin hybrid proteins evaluated for muscle-specific transsynaptic mapping of spinal motor circuitry in the newborn mouse.

We investigated whether the non-toxic C fragment of tetanus toxin (TTC) fused to either beta-galactosidase or green fluorescent protein could be utilized to transsynaptically trace muscle-specific spinal circuitry in the neonatal mouse after i.m. injection into a single hindlimb muscle.

Motoneurons have different membrane resistance during fictive scratching and weight support.

The passive membrane properties of motoneurons may be affected in a behavior-specific manner because of differences in synaptic drive during different motor behaviors. To explore this possibility, the changes in input resistance (R(in)) and membrane time constant (tau(m)) of single extensor motoneurons were compared during two different types of motor activities: fictive scratching and fictive weight support. These two activities were selected because the membrane potential of extensor motoneurons follows a very different trajectory during fictive scratching (multiphasic, mostly rhythmic trajectory) and fictive weight support (monophasic, tonic trajectory).

Proprioceptive control of extensor activity during fictive scratching and weight support compared to fictive locomotion.

At rest, extensor group I afferents produce oligosynaptic inhibition of extensor motoneurons. During locomotor activity, however, such inhibition is replaced by oligosynaptic excitation. Oligosynaptic excitation from extensor group I afferents plays a crucial role in the regulation of extensor activity during walking.