Faculty Bibliography

STUDY OBJECTIVES/OBJECTIVE:A relationship between obstructive sleep apnea (OSA) and exposure to the World Trade Center (WTC) dust and fumes has been suggested in responders but little is known about a possible relationship in community members. We characterized sleep studies performed in community members with WTC dust exposure to improve our understanding of the relationship between the diagnosis and severity of OSA and WTC dust exposure in this population. METHODS:Single-center, retrospective study of patients enrolled in a clinical treatment program for community members with WTC dust exposure. Patients were included if they had undergone sleep studies for evaluation of possible OSA through September 2016 and provided written informed consent. RESULTS:. Most reported upper and lower respiratory symptoms. An apnea-hypopnea index (AHI) ≥ 5 events/h was measured in 66% of the patients, and respiratory disturbance index was ≥ 5 events/h in 97%. The proportion of patients with moderate-severe OSA (defined by the AHI 4% criteria) was 50%. Multivariate logistic regression revealed that acute WTC dust cloud exposure was associated with severity but not diagnosis of OSA. CONCLUSIONS:We identified a high rate of OSA in the WTC community cohort who were referred for sleep studies. Exposure to the massive WTC dust cloud caused by the WTC collapse was independently associated with the severity of OSA in this population. This finding highlights the role that environmental exposures may play in the development of OSA.

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

In this issue of Cell, Shin et al. report the first live-cell imaging of a fusion pore. Directly visualized pores in neuroendocrine cells can be much larger than expected yet not require vesicular full-collapse. These fusion-fission pores have diverse fates arising from opposing dynamin-driven pore constriction and F-actin-mediated pore expansion.

High-throughput electron microscopy has started to reveal synaptic connectivity maps of single circuits and whole brain regions, for example, in the Drosophila olfactory system. However, efficacy, timing, and frequency tuning of synaptic vesicle release are also highly diversified across brain synapses. These features critically depend on the nanometer-scale coupling distance between voltage-gated Ca²⁺ channels (VGCCs) and the synaptic vesicle release machinery. Combining light super resolution microscopy with in vivo electrophysiology, we show here that two orthogonal scaffold proteins (ELKS family Bruchpilot, BRP, and Syd-1) cluster-specific (M)Unc13 release factor isoforms either close (BRP/Unc13A) or further away (Syd-1/Unc13B) from VGCCs across synapses of the Drosophila olfactory system, resulting in different synapse-characteristic forms of short-term plasticity. Moreover, BRP/Unc13A versus Syd-1/Unc13B ratios were different between synapse types. Thus, variation in tightly versus loosely coupled scaffold protein/(M)Unc13 modules can tune synapse-type-specific release features, and "nanoscopic molecular fingerprints" might identify synapses with specific temporal features.

OBJECTIVE Since the first clinical application of the incisionless magnetic resonance-guided focused ultrasound (MRgFUS) technology only small series of patients have been reported, and thus only extrapolations of the procedure-related risks could be offered. In this study, the authors analyze side-effects and targeting accuracy in 180 consecutive treatments with MRgFUS for chronic therapy-resistant idiopathic Parkinson's disease (PD), essential tremor (ET), cerebellar tremor (CT), and neuropathic pain (NP), all performed in their dedicated center. METHODS A total of 180 treatments with MRgFUS for chronic therapy-resistant idiopathic PD, ET, CT, and NP were prospectively assessed for side-effects and targeting accuracy. Monitoring for later side-effects was continued for at least 3 months after the procedure in all but 1 case (0.6%); in that single case, the patient was lost to follow-up after an uneventful early postoperative course. The surgical targets were the pallidothalamic tract (pallidothalamic tractotomy, n = 105), the cerebellothalamic tract (cerebellothalamic tractotomy, n = 50), the central lateral nucleus (central lateral thalamotomy, n = 84), the centrum medianum (centrum medianum thalamotomy, n = 12), and the globus pallidus (pallidotomy, n = 2). Cognitive testing was performed before, 1-2 days after, and 1 year after the procedure. The Mini-Mental State Examination (MMSE) was used for the first 29 cases and was then replaced by the Montreal Cognitive Assessment (MoCA). Lesion reconstruction and measurement of targeting accuracy were done on 2-day posttreatment MR images for each performed target. To determine targeting accuracy measurement, 234 out of the 253 lesions depicted in the 2-day postoperative MR examination could be 3D-reconstructed. RESULTS The mean MoCA score was slightly improved 2 days postoperatively (p = 0.002) and remained stable at 1-year follow-up (p = 0.03). The mean MMSE score was also slightly improved 2 days postoperatively and at 1-year follow-up, but the improvement was not statistically significant (p = 0.06 and p = 0.2, respectively). The mean (± SD) accuracy was 0.32 ± 0.29 mm, 0.29 ± 0.28 mm, and 0.44 ± 0.39 mm for the mediolateral, anteroposterior, and dorsoventral dimensions, respectively. The mean 3D accuracy was 0.73 ± 0.39 mm. As to side-effects, 14 events over 180 treatments were documented. They were classified into procedure-related (n = 4, 2.2%), effect on neighboring structures (n = 3, 1.7%), and disease-related (n = 7, 3.9%). There was no bleeding. CONCLUSIONS The incisionless transcranial MRgFUS technology demonstrates a higher targeting accuracy and a lower side-effect profile than techniques requiring cerebral penetration. In the absence of penetration brain shift, this technique avoids the placement of a thermolesion away from the chosen target, thus suppressing the need for reversible therapeutic energy application. With the use of proper physiopathology-based targets, definitive therapeutic effects can be coupled with sparing of sensory, motor, and paralimbic/multimodal thalamocortical functions. Clinical efficacy, not analyzed in this investigation, will ultimately rest in proper target selection and optimized thermolesional coverage of the target.