Molecular Dynamics Investigations of Dienolate [4 + 2] Reactions.

We report quantum mechanics calculations and quasiclassical trajectory simulations of [4 + 2] reactions using three common dienolate substrates: siloxy dienes, Li dienolates, and conjugated Pd enolates. Asynchronous transition structures and unequal bond formation were invariably found, with average time gaps of developing bonds ranging from 26.5 to >251.0 fs. The results display a spectrum of dynamically concerted and stepwise [4 + 2] reactions, offering insights into the origin of the stereochemical outcomes of such reactions.

Divergent Catalysis: Catalytic Asymmetric [4+2] Cycloaddition of Palladium Enolates.

An asymmetric decarboxylative [4+2] cycloaddition from a catalytically generated chiral Pd enolate was developed, forging four contiguous stereocenters in a single transformation. This was achieved through a strategy termed divergent catalysis, wherein departure from a known catalytic cycle enables novel reactivity of a targeted intermediate prior to re-entry into the original cycle. Mechanistic studies including quantum mechanics calculations, Eyring analysis, and KIE studies offer insight into the reaction mechanism.

Letter to the Editor Response: Exploring COVID-19 Vaccine Hesitancy Among Stakeholders in African American and Latinx Communities in the Deep South Through the Lens of the Health Belief Model.

The purpose of this submission to respond to a Letter to the Editor recently submitted regarding our manuscript, "Exploring COVID-19 Vaccine Hesitancy among Stakeholders in African American and Latinx Communities in the Deep South through the Lens of the Health Belief Model" published in the American Journal of Health Promotion in February, 2022. The manuscript reported on a study that had as its purpose to qualitatively explore perceptions related to COVID-19 vaccination intention among African American and Latinx participants and suggest potential intervention strategies.

Exploring COVID-19 Vaccine Hesitancy Among Stakeholders in African American and Latinx Communities in the Deep South Through the Lens of the Health Belief Model.

PURPOSE: The purpose of this study was to qualitatively explore perceptions related to COVID-19 vaccination intention among African American and Latinx participants and suggest intervention strategies. APPROACH: Ninety minute virtual focus groups (N = 8), segmented by county, race and ethnicity were conducted with stakeholders from 3 vulnerable Alabama counties. PARTICIPANTS: Participants (N = 67) were primarily African American and Latinx, at least 19 years, and residents or stakeholders in Jefferson, Mobile, and Dallas counties. SETTING: Focus groups took place virtually over Zoom. METHODS: The semi-structured guide explored perceptions of COVID-19, with an emphasis on barriers and facilitators to vaccine uptake. Focus groups lasted approximately 90 minutes and were audio recorded, transcribed, and analyzed by a team of 3 investigators, according to the guidelines of Thematic Analysis using NVivo 12. To provide guidance in the development of interventions to decrease vaccine hesitancy, we examined how themes fit with the constructs of the Health Belief Model. RESULTS: We found that primary themes driving COVID-19 vaccine hesitancy, ordered from most to least discussed, are mistrust, fear, and lack of information. Additionally, interventions to decrease vaccine hesitancy should be multi-modal, community engaged, and provide consistent, comprehensive messages delivered by trusted sources.

In vivo Probabilistic Structural Atlas of the Inferior and Superior Colliculi, Medial and Lateral Geniculate Nuclei and Superior Olivary Complex in Humans Based on 7 Tesla MRI.

Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T2-weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an in vivo human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.

A probabilistic template of human mesopontine tegmental nuclei from in vivo 7T MRI.

Mesopontine tegmental nuclei such as the cuneiform, pedunculotegmental, oral pontine reticular, paramedian raphe and caudal linear raphe nuclei, are deep brain structures involved in arousal and motor function. Dysfunction of these nuclei is implicated in the pathogenesis of disorders of consciousness and sleep, as well as in neurodegenerative diseases. However, their localization in conventional neuroimages of living humans is difficult due to limited image sensitivity and contrast, and a stereotaxic probabilistic neuroimaging template of these nuclei in humans does not exist. We used semi-automatic segmentation of single-subject 1.1mm-isotropic 7T diffusion-fractional-anisotropy and T2-weighted images in healthy adults to generate an in vivo probabilistic neuroimaging structural template of these nuclei in standard stereotaxic (Montreal Neurological Institute, MNI) space. The template was validated through independent manual delineation, as well as leave-one-out validation and evaluation of nuclei volumes. This template can enable localization of five mesopontine tegmental nuclei in conventional images (e.g. 1.5T, 3T) in future studies of arousal and motor physiology (e.g. sleep, anesthesia, locomotion) and pathology (e.g. disorders of consciousness, sleep disorders, Parkinson's disease). The 7T magnetic resonance imaging procedure for single-subject delineation of these nuclei may also prove useful for future 7T studies of arousal and motor mechanisms.

Hypervascular glioblastoma multiforme or arteriovenous malformation associated Glioma? A diagnostic and therapeutic challenge: A case report.

BACKGROUND: Simultaneous presentation of arteriovenous malformation (AVM) and glioblastoma multiforme (GBM) is rarely reported in the literature and needs to be differentiated from "angioglioma", a highly vascular glioma and other differential diagnosis such as hypervascular glioblastoma. Incorporating critical features of both, malignant glioma and AVM, such lesions lack a standard algorithm for diagnosis and therapy due to their rare incidence as well as their complex radiological and highly individualized clinical presentation. CASE DESCRIPTION: We present a case of a 71-year-old female with newly developing motor deficits and radiographic findings of a heterogeneously contrast enhancing right-sided thalamic lesion with highly prominent vasculature. While computed tomography angiogram and cerebral digital subtraction angiography supported the diagnosis of AVM, contrast-enhancing magnetic resonance imaging (MRI) and MR-spectroscopy was suggestive of malignant glioma. A stereotactic biopsy revealed the diagnosis of a GBM (WHO IV) and the patient was treated accordingly. CONCLUSION: The coincidental presentation of vascular lesions such as AVM and malignant glioma is rare and presents a major challenge when establishing a diagnosis. The respective treatment decision is complicated by the fact that available treatment modalities (e.g. radiosurgery and/or open resection) carry disease specific complications for each entity. Finding a suitable solution for such cases requires standardization of early diagnostic and therapeutic management.

Surgical treatment options and management strategies of metastatic renal cell carcinoma to the lumbar spinal nerve roots.

Spinal nerve root metastasis of renal cell carcinoma is a rare occurrence. In addition to treatment of the primary lesion, surgical resection of the nerve root metastasis, occasionally with sacrifice of the involved nerve, is the accepted standard of treatment. Resection often resolves presenting motor and pain symptoms due to relief of neural compression. We describe two patients with nerve root metastasis of renal cell carcinoma and their management. While locally advanced and metastatic renal cell carcinoma has been shown to be chemo- and radio-resistant, immunotherapy is a promising treatment. Given the high prevalence of systemic disease in patients with intradural metastases, systemic (and possibly intracranial) imaging can be used to identify other potential areas of disease.

Beneficial effect of subsequent lesion procedures after nonresponse to initial cingulotomy for severe, treatment-refractory obsessive-compulsive disorder.

BACKGROUND: Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown. OBJECTIVE: To determine whether a second lesion procedure is beneficial after unsuccessful initial AC. METHODS: In this retrospective cohort study, we reviewed the records of 31 patients who were nonresponders to initial AC. Full response was defined as at least a 35% decrease and partial response as a 25% to 34% decrease in Yale-Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale change was compared between patients who underwent additional surgery and those treated nonsurgically. In addition, for patients who underwent additional surgery, we compared the benefit of subcaudate tractotomy with repeat AC (extension of the initial lesion) as the second procedure. RESULTS: Nineteen patients underwent a second surgery and 12 patients continued nonsurgical therapy. Fifty-three percent of patients who received additional surgery were full responders and 21% were partial responders at the most recent follow-up compared with 17% full responders and 25% partial responders among those who continued conventional therapy (P = .02). Of the patients who underwent an additional surgery, there were 64% full and 9% partial responders in the subcaudate tractotomy group compared with 38% full and 38% partial responders in the repeat AC group (P = .04). CONCLUSION: Second lesion surgery can be a safe and effective therapy for patients who do not respond to initial AC. Subcaudate tractotomy may confer a higher response rate than repeat cingulotomy.