The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn.

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.

Peripheral Mechanosensory Neuron Dysfunction Underlies Tactile and Behavioral Deficits in Mouse Models of ASDs.

Patients with autism spectrum disorders (ASDs) commonly experience aberrant tactile sensitivity, yet the neural alterations underlying somatosensory dysfunction and the extent to which tactile deficits contribute to ASD characteristics are unknown. We report that mice harboring mutations in Mecp2, Gabrb3, Shank3, and Fmr1 genes associated with ASDs in humans exhibit altered tactile discrimination and hypersensitivity to gentle touch. Deletion of Mecp2 or Gabrb3 in peripheral somatosensory neurons causes mechanosensory dysfunction through loss of GABAA receptor-mediated presynaptic inhibition of inputs to the CNS. Remarkably, tactile defects resulting from Mecp2 or Gabrb3 deletion in somatosensory neurons during development, but not in adulthood, cause social interaction deficits and anxiety-like behavior. Restoring Mecp2 expression exclusively in the somatosensory neurons of Mecp2-null mice rescues tactile sensitivity, anxiety-like behavior, and social interaction deficits, but not lethality, memory, or motor deficits. Thus, mechanosensory processing defects contribute to anxiety-like behavior and social interaction deficits in ASD mouse models. PAPERCLIP.

The unseen impact - a deep dive into neurocognitive impairment among patients with intracranial meningiomas: a comprehensive systematic review of the literature.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life.

Rehabilitation of Neuropsychiatric Symptoms in Patients With Long COVID: Position Statement.

Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.

Conversion of Schedule II Opioids to Buprenorphine Buccal Film: A Retrospective Analysis.

OBJECTIVE: To provide clinical data for the conversion of Schedule II opioids to buprenorphine buccal film and to demonstrate sustained analgesia and a reduction in morphine milligram equivalents after conversion. DESIGN: Retrospective review of electronic medical records. SETTING: Group clinical practice providing outpatient chronic pain management care in Winston-Salem, North Carolina. SUBJECTS: Patients who received opioids for chronic pain between January 1, 2016, and June 30, 2019, were selected for chart review if they were converted to buprenorphine buccal film from a Schedule II opioid. METHODS: Patients who met inclusion criteria were stratified into subgroups on the basis of preconversion morphine milligram equivalents, whether they remained on opioids for breakthrough pain postconversion, and pre- and postconversion numerical rating scale pain scores. Outcomes of interest included the differences between pre- and postconversion numerical rating scale pain scores and daily morphine milligram equivalents for each subgroup. RESULTS: Of 157 patients reviewed, 87.9% were successfully converted to buprenorphine buccal film. Overall, numerical rating scale pain scores were stable after conversion. Statistically significant reductions were demonstrated in the <90 daily morphine milligram equivalent subgroup. Postconversion daily morphine milligram equivalents decreased by 85.4% from baseline. Change in daily morphine milligram equivalents is representative of patients who remained on breakthrough pain medication. CONCLUSIONS: Results demonstrate continued analgesia after conversion to buprenorphine buccal film despite reductions in daily morphine milligram equivalents. Most patients were able to convert directly from their long-acting opioid to buprenorphine buccal film and stabilized without the use of concomitant opioids for breakthrough pain. Aggressive titration strategies were associated with greater success.

Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS): Rationale and design of a cluster-randomized trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) reported that intensive blood pressure (BP) treatment reduced cardiovascular disease and mortality compared to standard BP treatment in hypertension patients. The next important question is how to implement more intensive BP treatment in real-world clinical practice. We designed an effectiveness-implementation hybrid trial to simultaneously test the effectiveness of a multifaceted intervention for intensive BP treatment and its feasibility, fidelity, and sustainability in underserved hypertension patients. METHODS: Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS) is a cluster randomized trial conducted in 36 Federally Qualified Health Center clinics in Louisiana and Mississippi. Federally Qualified Health Center clinics were randomized to either a multifaceted intervention for intensive BP treatment, including protocol-based treatment using the SPRINT intensive BP management algorithm, dissemination of SPRINT findings, BP audit and feedback, home BP monitoring, and health coaching, or enhanced usual care. Difference in mean systolic BP change from baseline to 18 months is the primary clinical effectiveness outcome, and intervention fidelity, measured by treatment intensification and medication adherence, is the primary implementation outcome. The planned sample size of 1,260 participants (36 clinics with 35 participants each) has 90% power to detect a 5.0-mm Hg difference in systolic BP at a .05 significance level and 80% follow-up rate. CONCLUSIONS: IMPACTS will generate critical data on the effectiveness and implementation of a multifaceted intervention for intensive BP treatment in real-world clinical practice and could directly impact the BP-related disease burden in minority and low-income populations in the United States.

Improvement in Existing Chest Wall Irregularities During Breast Reconstruction.

Mastectomies for both cancer resection and risk reduction are becoming more common. Existing chest wall irregularities are found in these women presenting for breast reconstruction after mastectomy and can pose reconstructive challenges. Women who desired breast reconstruction after mastectomy were evaluated preoperatively for existing chest wall irregularities. Case reports were selected to highlight common irregularities and methods for improving cosmetic outcome concurrently with breast reconstruction procedures. Muscular anomalies, pectus excavatum, scoliosis, polythelia case reports are discussed. Relevant data from the literature are presented. Chest wall irregularities are occasionally encountered in women who request breast reconstruction. Correction of these deformities is possible and safe during breast reconstruction and can lead to improved cosmetic outcome and patient satisfaction.

In the Age of Breast Augmentation, Breast Reconstruction Provides an Opportunity to Augment the Breast.

BACKGROUND: Augmentation mammoplasty remains the most common cosmetic surgery procedure performed. The objective of this article is to evaluate the impact of augmented volume of the reconstructed breast in patients that undergo nipple-sparing mastectomy and patients previously augmented who undergo mastectomy with tissue expander/implant-based reconstruction. METHODS: Patients undergoing skin-sparing mastectomy, nipple-sparing mastectomy, and mastectomy after previous augmentation followed by tissue expander/implant-based reconstruction between June 2011 and April 2015 by 2 surgeons at the same institution were included. Retrospective chart review of the patients identified using these criteria was performed to record patient characteristics, complications, breast volume, implant volume, and percentage change in volume at the time of reconstruction. Percentage change of breast volume was calculated using the formula (implant breast weight)/(breast weight) for skin-sparing and nipple-sparing mastectomy patients and (final breast implant weight - [breast weight + augmentation breast implant weight])/([breast weight + augmentation breast implant]) for patients undergoing mastectomy following previous augmentation. RESULTS: A total of 293 patients were included in the study with 63 patients who underwent nipple-sparing mastectomy, 166 patients who underwent skin-sparing mastectomy, and 64 patients who underwent previous augmentation with subsequent mastectomy. Mean percentage change in breast volume was 66% in the nipple-sparing mastectomy group, 15% for the right breast and 18% for the left breast in the skin-sparing mastectomy group, and 81% for the right breast and 72% for the left breast in the mastectomy following previous augmentation group. Complication rate for nipple-sparing mastectomy was 27%, mastectomy following previous augmentation was 20.3%, and skin-sparing mastectomy group was 18.7%. CONCLUSION: Patients who undergo nipple-sparing mastectomy or mastectomy following previous augmentation have the ability to achieve greater volume in their reconstructed breast via tissue expander/implant-based reconstruction.

Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets.

The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to "unclassified" cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.

Recurrent Systemic Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant-Associated Lesion.

A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease.

Plastic Surgery Response in Natural Disasters.

Disasters cause untold damage and are often unpredictable; however, with proper preparation, these events can be better managed. The initial response has the greatest impact on the overall success of the relief effort. A well-trained multidisciplinary network of providers is necessary to ensure coordinated care for the victims of these mass casualty disasters. As members of this network of providers, plastic surgeons have the ability to efficiently address injuries sustained in mass casualty disasters and are a valuable member of the relief effort. The skill set of plastic surgeons includes techniques that can address injuries sustained in large-scale emergencies, such as the management of soft-tissue injury, tissue viability, facial fractures, and extremity salvage. An approach to disaster relief, the types of disasters encountered, the management of injuries related to mass casualty disasters, the role of plastic surgeons in the relief effort, and resource management are discussed. In order to improve preparedness in future mass casualty disasters, plastic surgeons should receive training during residency regarding the utilization of plastic surgery knowledge in the disaster setting.

Safe Management of Adverse Effects Associated with Prescription Opioids in the Palliative Care Population: A Narrative Review.

In the palliative care population, prescription opioids are often considered viable pain relief options. However, in this complex patient population, the adverse effects of opioid medications should be identified and managed without delay. Common adverse effects can include constipation, nausea, somnolence, dizziness, vomiting, and pruritus. Less common adverse effects can include potentially lethal respiratory depression and cardiovascular effects. Critical aspects of safe opioid prescribing are recognition of side effects and knowledge of effective management strategies; prompt management is necessary for uninterrupted pain relief. Most complications are managed with general approaches such as dose reduction, opioid rotation, alternate routes of administration, and symptomatic management. The only opioid-induced complication for which US Food and Drug Administration-approved treatments currently exist is constipation. Treating laxative-refractory opioid-induced constipation (OIC) with peripherally acting mu-opioid receptor antagonists (PAMORAs), which block gastrointestinal opioid receptors, can restore gastrointestinal motility and fluid secretion. This narrative review discusses key complications of prescription opioid treatment and their management in the palliative care setting.

Frontline Perspectives on Buprenorphine for the Management of Chronic Pain.

Due to the prevalence of chronic pain and high-impact chronic pain in the US, a significant percentage of the population is prescribed opioids for pain management. However, opioid use disorder is associated with reduced quality of life, along with fatal opioid overdoses, and is a significant burden on the US economy. Considering the clinical needs of patients with intractable chronic pain and the potential harms associated with prescribed and illicit opioids in our communities, having a deep understanding of current treatment options, supporting evidence, and clinical practice guidelines is essential for optimizing treatment selections. Buprenorphine is a Schedule III opioid with a unique mechanism of action, allowing effective and long-lasting analgesia at microgram doses with fewer negative side effects and adverse events, including respiratory depression, when compared with other immediate-release, long-acting, and extended-release prescription opioids. Due to its relatively lower risk for overdose and misuse, buprenorphine was recently added to the Clinical Practice Guideline for the Use of Opioids in the Management of Chronic Pain as a first-line treatment for chronic pain managed by opioids by the US Departments of Defense and Veterans Affairs, and the Department of Health and Human Services recommends that buprenorphine be made available for the treatment of chronic pain. In this narrative review, we discuss the different buprenorphine formulations, clinical efficacy, advantages for older adults and other special populations, clinical practice guideline recommendations, and payer considerations of buprenorphine and suggest that buprenorphine products approved for chronic pain should be considered as a first-line treatment for this indication.

Mobility and bioaccessibility of arsenic (As) bound to titanium dioxide (TiO2) water treatment residuals (WTRs).

This work systematically describes arsenic mobility and potential bioaccessibility of arsenic-enriched titanium dioxide water treatment residuals (TiO2 WTRs) by employing a suite of wet chemical experiments and spectroscopic measurements. Specifically, Environmental Protection Agency (EPA) digestion method 3051a indicated <3% of total arsenic in the solid phase was released, and arsenic assessed by EPA method 1340 for bioaccessibility was below detection limits. A novel finding is while the arsenic appeared to be stable under highly acidic digestion conditions, it is in fact highly mobile when exposed to simple phosphate solutions. On average, 55% of arsenic was extracted from all samples during a 50-day replenishment study. This was equivalent to 169 mg kg-1 arsenic released from the solid phase. Macroscopic desorption experiments indicated arsenic likely formed inner-sphere bonds with the TiO2 particles present in the samples. This was confirmed with X-ray absorption spectroscopy (XAS), where an interatomic distance of 3.32 Å and a coordination number (CN) of 1.79 titanium atoms were determined. This translates to a configuration of arsenic on TiO2 surfaces as a bidentate binuclear inner-sphere complex. Thus, both macroscopic and spectroscopic data are in agreement. During incubation experiments, arsenic(V) was actively reduced to arsenic(III); the amount of arsenic(III) in solution varied from 8 to 38% of total dissolved arsenic. Lastly, elevated concentrations and mobility of vanadium in these systems merit further investigation. The high mobility of arsenic and its potential for reduction when reintroduced into the environment, particularly in agriculturally important areas, presents an important risk when waste products are not properly managed.

The Evolving Need for Neuropsychology in Neurosurgical Settings: Challenges Facing Transformative Care.

Clinical neuropsychology has been a valuable asset to neurologic surgery, contributing to lateralization and localization of pathologic brain tissue, identification of eloquent cortex, and evaluation of postoperative neuropsychological functioning. Moreover, neuropsychologists provide empirically driven interventions aimed at supporting preparation and/or recovery of neurosurgery patients. Nonetheless, several challenges may limit the reliability, validity, and generalizability of the assessment data obtained and reduce the usefulness of other neuropsychological services provided. Specifically, linguistic, cultural, educational, and other biases associated with demographic characteristics can lead to a narrowed view of an individual's life experiences, which must be confronted to fulfill the mission of ensuring that all patients have access to care that is appropriate to their needs. Instead of perceiving these challenges as insurmountable barriers, such issues can be viewed as opportunities to catalyze change and foster innovation for the future of neuropsychological care in neurosurgical settings. In addition to reviewing the possible mechanisms of these obstacles, the current article offers tangible solutions at both a macro level (e.g., discipline-wide transformations) and micro level (e.g., individualized patient-centric approaches). Outlined are practical techniques to potentially improve consensus and standardization of methods, advance and globalize research, expand representativeness of measures and practices to serve diverse individuals, and increase treatment adherence through engagement of patients and their families.

Foundations of Neuropsychology: Collaborative Care in Neurosurgery.

The disciplines of neuropsychology and neurosurgery have a history of partnership that has improved prognoses for patients with neurologic diagnoses that once had poor outcomes. This article outlines the evolution of this relationship and describes the current role that clinical neuropsychology has within a department of neurological surgery across the preoperative, intraoperative, and postoperative stages of treatment. Understanding the foundations of collaboration between neuropsychology and neurosurgery contextualizes present challenges and future innovations for advancing excellence along the continuum of care for all neurosurgical patients.

Innovations in Neuropsychology: Future Applications in Neurosurgical Patient Care.

Over the last century, collaboration between clinical neuropsychologists and neurosurgeons has advanced the state of the science in both disciplines. These advances have provided the field of neuropsychology with many opportunities for innovation in the care of patients prior to, during, and following neurosurgical intervention. Beyond giving a general overview of how present-day advances in technology are being applied in the practice of neuropsychology within a neurological surgery department, this article outlines new developments that are currently unfolding. Improvements in remote platform, computer interface, "real-time" analytics, mobile devices, and immersive virtual reality have the capacity to increase the customization, precision, and accessibility of neuropsychological services. In doing so, such innovations have the potential to improve outcomes and ameliorate health care disparities.

Synthesis, structure, and reactivity of a nickel dihydrogen complex.

Hydrogen activation by nickel: A tBuPCP pincer ligand facilitates formation of cationic Ni(II) dihydrogen and terminal dinitrogen complexes. The compounds have been characterized by X-ray crystallography and NMR spectroscopy. Addition of base promotes heterolytic cleavage of H(2) to form the corresponding neutral hydride complex.

The delayed appearance of neurological signs in intrathecal granuloma warrants imaging surveillance: a case series and review of the literature.

Intrathecal pump therapy (ITP) has become a mainstay of treatment for the chronic, refractory nonmalignant pain patient. Increasingly, ITP therapy is being instituted for the failed back pain population. Inflammatory mass or granuloma is a complication that is considered "rare" or "uncommon." In this patient population, the symptoms of granuloma can often mimic the symptoms for which the patient is being treated. The case series reported here illustrates 4 cases of inflammatory mass. One patient presented with paralysis before she was diagnosed, and the remainder of the patients were asymptomatic at the time of diagnosis. The cases presented illustrate the need for broader education of inflammatory mass among nonpain specialists. Etiology, diagnosis and treatment guidelines of inflammatory mass are reviewed. The literature reviewed highlights the number of patients who present with paralysis as well as the need for regular screening of ITP patients.