Probing the Neurophysiology of Temporal Sensitivity in the Somatosensory System Using the Mismatch Negativity (MMN) Sensory Memory Paradigm.

Duration is an amodal feature common to all sensory experiences, but low-level processing of the temporal qualities of somatosensation remains poorly understood. The goal of the present study was to evaluate electrophysiological discrimination of parametric somatosensory stimuli to better understand how the brain processes the duration of tactile information. This research used a somatosensory mismatch negativity (sMMN) paradigm to evaluate electrophysiological sensitivity to differences in the duration of vibrotactile stimuli in healthy young adults. Specifically, a 100 ms standard vibration was presented 80% of the time while the remaining 20% of presentations were made up of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. When a deviation from the anticipated tactile input is detected, the distinct electrophysiological signature of the sMMN is present. A companion behavioral task assessed individual thresholds for cognizant awareness of the standard and deviant vibrotactile stimuli. The results of the present study demonstrated a sMMN response when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. This suggests that on average the participants did not electrophysiologically discriminate between the 100 and 115 ms. Future work may apply this paradigm to better understand atypical tactile sensitivity in various clinical conditions.

No Taxation Without Representation: Addressing the "Deaf Tax" in Academic Medicine.

Minority faculty and trainees experience unique factors that can hinder their success in academic medicine-collectively referred to as "minority tax." The authors argue that a similar "deaf tax" of unique barriers, experiences, and responsibilities disproportionately burdens deaf trainees and faculty. The cumulative effects of these deaf tax experiences represent a significant disadvantage for deaf professionals in academic medicine. Through a combination of relevant literature and the authors' personal experiences as deaf professionals, several causative domains of deaf tax are outlined, including the fight for reasonable accommodations, prejudice and discrimination, training and diversity barriers, and a lack of deaf mentorship. In addition, a number of practical steps are offered for institutional leaders to consider implementing to improve equity and inclusion in academic medicine, including facilitating language equity and communication access, implementing deaf awareness training, fostering effective deaf mentorship, and promoting deaf professionals into leadership positions. Addressing these issues would help remove the obstacles that create the high deaf tax burden and lower the near-insurmountable barrier of entry, advancement, and retention in academic medicine for deaf professionals.

Patient and Health Care Worker Perceptions of Communication and Ability to Identify Emotion When Wearing Standard and Transparent Masks.

Importance: Adoption of mask wearing in response to the COVID-19 pandemic alters daily communication. Objective: To assess communication barriers associated with mask wearing in patient-clinician interactions and individuals who are deaf and hard of hearing. Design, Setting, and Participants: This pilot cross-sectional survey study included the general population, health care workers, and health care workers who are deaf or hard of hearing in the United States. Volunteers were sampled via an opt-in survey panel and nonrandomized convenience sampling. The general population survey was conducted between January 5 and January 8, 2021. The health care worker surveys were conducted between December 3, 2020, and January 3, 2021. Respondents viewed 2 short videos of a study author wearing both a standard and transparent N95 mask and answered questions regarding mask use, communication, preference, and fit. Surveys took 15 to 20 minutes to complete. Main Outcomes and Measures: Participants' perceptions were assessed surrounding the use of both mask types related to communication and the ability to express emotions. Results: The national survey consisted of 1000 participants (mean [SD] age, 48.7 [18.5] years; 496 [49.6%] women) with a response rate of 92.25%. The survey of general health care workers consisted of 123 participants (mean [SD] age, 49.5 [9.0] years; 84 [68.3%] women), with a response rate of 11.14%. The survey of health care workers who are deaf or hard of hearing consisted of 45 participants (mean [SD] age, 54.5 [9.0] years; 30 [66.7%] women) with a response rate of 23.95%. After viewing a video demonstrating a study author wearing a transparent N95 mask, 781 (78.1%) in the general population, 109 general health care workers (88.6%), and 38 health care workers who are deaf or hard of hearing (84.4%) were able to identify the emotion being expressed, in contrast with 201 (20.1%), 25 (20.5%), and 11 (24.4%) for the standard opaque N95 mask. In the general population, 450 (45.0%) felt positively about interacting with a health care worker wearing a transparent mask; 76 general health care workers (61.8%) and 37 health care workers who are deaf or hard of hearing (82.2%) felt positively about wearing a transparent mask to communicate with patients. Conclusions and Relevance: The findings of this study suggest that transparent masks could help improve communication during the COVID-19 pandemic, particularly for individuals who are deaf and hard of hearing.

For the further training of individuals in neurosurgery: a history of the William P. Van Wagenen Fellowship.

The William P. Van Wagenen Fellowship, celebrating its 50th anniversary, is an annual award given by the AANS and administered by the Neurosurgery Research and Education Foundation (NREF). Named after its benefactor, Dr. William Van Wagenen, the fellowship continues his legacy of mentorship and innovation. As the premier research award for young neurosurgeons, it has provided a foundation for career development for many thought leaders in the field. The award was created in the spirit of Van Wagenen's belief in collaboration with other institutions as a means of refining neurosurgical technique, creating new research initiatives, and improving patient outcomes. Van Wagenen's commitment was informed by his early experiences in neurosurgery with his mentor Dr. Harvey Cushing, who helped to fund Van Wagenen's scientific endeavors in Europe. This journey catalyzed Van Wagenen's lifelong commitment to mentorship, which is exemplified by his instrumental role in the creation of the Harvey Cushing Society, now the AANS. Over the last 50 years, the recipients of this award have used the endowment to lay the groundwork for many scientific and technical innovations in neurosurgery. The fellowship remains an unmatched opportunity to explore new lines of investigation, foster academic and research goals, incorporate new technology and skills into American neurosurgical practice, and motivate young neurosurgeons to transform the field. The legacy of mentorship, scientific inquiry, and clinical excellence personified by Cushing and Van Wagenen is memorialized in the William P. Van Wagenen Fellowship.

Risk factors associated with venous thromboembolism in patients undergoing spine surgery.

OBJECTIVE Patients undergoing spinal surgery are at risk for developing venous thromboembolism (VTE). The authors sought to identify risk factors for VTE in these patients. METHODS The American College of Surgeons National Surgical Quality Improvement Project database for the years 2006-2010 was reviewed for patients who had undergone spinal surgery according to their primary Current Procedural Terminology code(s). Clinical factors were analyzed to identify associations with VTE. RESULTS Patients who underwent spinal surgery (n = 22,434) were identified. The rate of VTE in the cohort was 1.1% (pulmonary embolism 0.4%; deep vein thrombosis 0.8%). Multivariate binary logistic regression analysis revealed 13 factors associated with VTE. Preoperative factors included dependent functional status, paraplegia, quadriplegia, disseminated cancer, inpatient status, hypertension, history of transient ischemic attack, sepsis, and African American race. Operative factors included surgery duration > 4 hours, emergency presentation, and American Society of Anesthesiologists Class III-V, whereas postoperative sepsis was the only significant postoperative factor. A risk score was developed based on the number of factors present in each patient. Patients with a score of ≥ 7 had a 100-fold increased risk of developing VTE over patients with a score of 0. The receiver-operating-characteristic curve of the risk score generated an area under the curve of 0.756 (95% CI 0.726-0.787). CONCLUSIONS A risk score based on race, preoperative comorbidities, and operative characteristics of patients undergoing spinal surgery predicts the postoperative VTE rate. Many of these risks can be identified before surgery. Future protocols should focus on VTE prevention in patients who are predisposed to it.

Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands.

The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.

The carbonate analogues of 5'-halogenated resiniferatoxin as TRPV1 ligands.

A series of carbonate analogues of 5'-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I>Br>Cl>F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with Ki(ant)=2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism.

New transient receptor potential vanilloid subfamily member 1 positron emission tomography radioligands: synthesis, radiolabeling, and preclinical evaluation.

The transient receptor potential vanilloid subfamily member 1 (TRPV1) cation channel is known to be involved in pain nociception and neurogenic inflammation, and accumulating evidence suggests that it plays an important role in several central nervous system (CNS)-related disorders. TRPV1-specific positron emission tomography (PET) radioligands can serve as powerful tools in TRPV1-related (pre)clinical research and drug design. We have synthesized several potent TRPV1 antagonists and accompanying precursors for radiolabeling with carbon-11 or fluorine-18. The cinnamic acid derivative [(11)C]DVV24 and the aminoquinazoline [(18)F]DVV54 were successfully synthesized, and their biological behavior was studied. In addition, the in vivo behavior of a (123)I-labeled analogue of iodo-resiniferatoxin (I-RTX), a well-known TRPV1 antagonist, was evaluated. The binding affinities of DVV24 and DVV54 for human TRPV1 were 163 ± 28 and 171 ± 48 nM, respectively. [(11)C]DVV24, but not [(18)F]DVV54 or (123)I-RTX, showed retention in the trigeminal nerve, known to abundantly express TRPV1. Nevertheless, it appears that ligands with higher binding affinities will be required to allow in vivo imaging of TRPV1 via PET.

2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region.

A series of N-(2-amino-6-trifluoromethylpyridin-3-ylmethyl)-2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were designed combining previously identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR analysis indicated that specific hydrophobic interactions of the 2-amino substituents in the C-region of the ligand were critical for high hTRPV1 binding potency. In particular, compound 49S was an excellent TRPV1 antagonist (K(i(CAP)) = 0.2 nM; IC(50(pH)) = 6.3 nM) and was thus approximately 100- and 20-fold more potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism. Furthermore, it demonstrated strong analgesic activity in the rat neuropathic model superior to 2 with almost no side effects. Compound 49S antagonized capsaicin induced hypothermia in mice but showed TRPV1-related hyperthermia. The basis for the high potency of 49S compared to 2 is suggested by docking analysis with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C-region of 49S made additional hydrophobic interactions with the hydrophobic region.