Adjuvant proton beam therapy in patients with grade 2 meningiomas.

Background: The World Health Organization (WHO) grade 2 meningiomas behave aggressively with a high proclivity toward recurrence despite maximal surgical resection. Our institution, a pioneer of proton therapy, uses exclusively proton beam radiation, and thus, we present a retrospective cohort analysis of patients with WHO grade 2 meningiomas treated with adjuvant proton beam therapy (PBT) at our institution between 2007 and 2019. The effects of adjuvant PBT were evaluated. Methods: Data collected include diagnosis, gender, histological subtype, WHO grade, the extent of surgical resection, adjuvant PBT radiation, details of the PBT radiation, recurrence, any additional PBT radiation, systemic medical therapy, and disease-specific survival. Results: Among the WHO grade 2 meningiomas (n = 50) recommended PBT, 80% and 78% of patients with gross-total resection (GTR) and subtotal resection (STR), respectively, followed through with PBT. The median radiation dose of PBT was 59.5 Gy and 59.92 Gy for patients with GTR and STR, respectively, with a median of 33 fractions delivered in 1.8 Gy doses for both groups. Combined 3-year progression-free survival (PFS) was 96%, and 5-year PFS was 92%. Combined overall survival was 95% at five years. Minimal radiation side effects were reported with no grade 3 or higher toxicities. Conclusion: Our results suggest that adjuvant PBT is well tolerated with minimal radiation toxicity. Alternative to photon radiation, PBT may be considered at least as safe and effective for adjuvant treatment of WHO grade 2 meningiomas when it is available.

Building knowledge using a novel web-based intervention to promote HPV vaccination in a diverse, low-income population.

OBJECTIVES: HPV vaccination rates remain suboptimal despite proven efficacy. Data suggest misconceptions or lack of knowledge are leading barriers. Our study aimed to develop and pilot a novel interactive education resource designed to educate parents and patients about HPV vaccines. METHODS: This is a prospective pilot study conducted in an urban teaching hospital pediatric clinic. The Patient Activated Learning System (PALS) intervention included 3 web-based videos with HPV vaccine-related educational content. Participants were parents of adolescent patients, aged 11-17 years, and young adult patients, aged 18-26 years. Enrolled participants completed an HPV vaccine knowledge survey before and after watching PALS; paired scores were evaluated. Acceptability and participant-reported impact of PALS modules were measured via Likert-scale surveys. RESULTS: 132 individuals were approached; 101 (76%) enrolled and completed the study. Participants self-identified as Hispanic (50%), non-Hispanic Black (23%), non-Hispanic White (7%), Asian (6%), American/Alaskan/Hawaiian Native or Pacific Islander (5%). Half reported earning ≤$40,000 annually; 57% had only a high school education. Post-intervention knowledge scores were increased compared to baseline (9.87/27 points vs 17.53/27 points, p < 0.01). PALS modules were reported as enjoyable to use and understandable (89% and 93%, respectively), and improved participants' understanding of the importance of HPV vaccination (90%). Of the 18 patients unvaccinated at baseline, 39% received 1 shot of the HPV vaccine within one month. CONCLUSION: The PALS HPV vaccine educational intervention was feasible, acceptable, and improved knowledge among a diverse, underserved population. Our intervention may positively influence HPV vaccination rates, with potential to overcome HPV vaccine hesitancy.

Multifractality in stride-to-stride variations reveals that walking involves more movement tuning and adjusting than running.

Introduction: The seemingly periodic human gait exhibits stride-to-stride variations as it adapts to the changing task constraints. The optimal movement variability hypothesis (OMVH) states that healthy stride-to-stride variations exhibit "fractality"-a specific temporal structure in consecutive strides that are ordered, stable but also variable, and adaptable. Previous research has primarily focused on a single fractality measure, "monofractality." However, this measure can vary across time; strideto-stride variations can show "multifractality." Greater multifractality in stride-tostride variations would highlight the ability to tune and adjust movements more. Methods: We investigated monofractality and multifractality in a cohort of eight healthy adults during self-paced walking and running trials, both on a treadmill and overground. Footfall data were collected through force-sensitive sensors positioned on their heels and feet. We examined the effects of self-paced walking vs. running and treadmill vs. overground locomotion on the measure of monofractality, α-DFA, in addition to the multifractal spectrum width, W, and the asymmetry in the multifractal spectrum, WAsym, of stride interval time series. Results: While the α-DFA was larger than 0.50 for almost all conditions, α-DFA was higher in running and locomoting overground than walking and locomoting on a treadmill. Similarly, W was greater while locomoting overground than on a treadmill, but an opposite trend indicated that W was greater in walking than running. Larger WAsym values in the negative direction suggest that walking exhibits more variation in the persistence of shorter stride intervals than running. However, the ability to tune and adjust movements does not differ between treadmill and overground, although both exhibit more variation in the persistence of shorter stride intervals. Discussion: Hence, greater heterogeneity in shorter than longer stride intervals contributed to greater multifractality in walking compared to running, indicated by larger negative WAsym values. Our results highlight the need to incorporate multifractal methods to test the predictions of the OMVH.

The Effectiveness of a Mobile Health Clinic Delivering Mandatory and Elective Middle School Immunizations: A Descriptive Analysis.

INTRODUCTION: Mobile health clinics serve a unique role in which they can offer affordable and adaptable care to the population they serve. The Edward Via College of Osteopathic Medicine (VCOM) mobile clinics began in 2020 as a partnership with the South Carolina Department of Health and Environmental Control (SCDHEC) to address the low vaccination rates that resulted from the COVID-19 pandemic. METHODS:  This study is a descriptive analysis that examines the number of vaccinations of tetanus, diphtheria, and pertussis (Tdap) and human papillomavirus (HPV) at different locations of administration including pediatrician offices, the novel VCOM mobile vaccination clinic, and the Spartanburg Health Department. The variables of interest and the study endpoints focused on Tdap and HPV vaccinations among students aged 11-12 years old in Spartanburg County according to the type of healthcare delivery location. RESULTS: From April to May of 2021, the VCOM mobile clinic was able to administer 279 Tdap vaccines and 189 HPV vaccines to students at local middle schools, which surpasses the number of vaccines administered at other sites from August 2020 to May 2021 when compared individually for both Tdap and HPV vaccinations. CONCLUSIONS: By assessing the total volume of vaccines administered by each group, the VCOM mobile clinic was established as an effective method of delivery and played a crucial role in the vaccination efforts of the Spartanburg community. Mobile medical units should be considered for similar efforts in providing care to resource-limited communities and those with limited access to care.

Baseline innate and T cell populations are correlates of protection against symptomatic influenza virus infection independent of serology.

Evidence suggests that innate and adaptive cellular responses mediate resistance to the influenza virus and confer protection after vaccination. However, few studies have resolved the contribution of cellular responses within the context of preexisting antibody titers. Here, we measured the peripheral immune profiles of 206 vaccinated or unvaccinated adults to determine how baseline variations in the cellular and humoral immune compartments contribute independently or synergistically to the risk of developing symptomatic influenza. Protection correlated with diverse and polyfunctional CD4+ and CD8+ T, circulating T follicular helper, T helper type 17, myeloid dendritic and CD16+ natural killer (NK) cell subsets. Conversely, increased susceptibility was predominantly attributed to nonspecific inflammatory populations, including γδ T cells and activated CD16- NK cells, as well as TNFα+ single-cytokine-producing CD8+ T cells. Multivariate and predictive modeling indicated that cellular subsets (1) work synergistically with humoral immunity to confer protection, (2) improve model performance over demographic and serologic factors alone and (3) comprise the most important predictive covariates. Together, these results demonstrate that preinfection peripheral cell composition improves the prediction of symptomatic influenza susceptibility over vaccination, demographics or serology alone.

Running gait produces long range correlations: A systematic review.

BACKGROUND: Walking and running are common forms of locomotion, both of which exhibit variability over many gait cycles. Many studies have investigated the patterns generated from that ebb and flow, and a large proportion suggests human gait exhibits Long Range Correlations (LRCs). LRCs refer to the observation that healthy gait characteristic, like stride times, are positively correlated to themselves over time. Literature on LRCs in walking gait is well known but less attention has been given to LRCs in running gait. RESEARCH QUESTION: What is the state of the art concerning LRCs in running gait? METHODS: We conducted a systematic review to identify the typical LRC patterns present in human running gait, in addition to disease, injury, and running surface effects on LRCs. Inclusion criteria were human subjects, running related experiments, computed LRCs, and experimental design. Exclusion criteria were studies on animals, non-humans, walking only, non-running, non-LRC analysis, and non-experiments. RESULTS: The initial search returned 536 articles. After review and deliberation, our review included 26 articles. Almost every article produced strong evidence for LRCs apparent in running gait and in all running surfaces. Additionally, LRCs tended to decrease due to fatigue, past injury, increased load carriage and seem to be lowest at preferred running speed on a treadmill. No studies investigated disease effects on LRCs in running gait. SIGNIFICANCE: LRCs seem to increase with deviations away from preferred running speed. Previously injured runners produced decreased LRCs compared to non-injured runners. LRCs also tended to decrease due to an increase in fatigue rate, which has been associated with increased injury rate. Lastly, there is a need for research on the typical LRCs in an overground environment, for which the typical LRCs found in a treadmill environment may or may not transfer.

Lipid Deposition Profiles Influence Foreign Body Responses.

Fibrosis remains a significant cause of failure in implanted biomedical devices and early absorption of proteins on implant surfaces has been shown to be a key instigating factor. However, lipids can also regulate immune activity and their presence may also contribute to biomaterial-induced foreign body responses (FBR) and fibrosis. Here it is demonstrated that the surface presentation of lipids on implant affects FBR by influencing reactions of immune cells to materials as well as their resultant inflammatory/suppressive polarization. Time-of-flight secondary ion mass spectroscopy (ToF-SIMS) is employed to characterize lipid deposition on implants that are surface-modified chemically with immunomodulatory small molecules. Multiple immunosuppressive phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin) are all found to deposit preferentially on implants with anti-FBR surface modifications in mice. Significantly, a set of 11 fatty acids is enriched on unmodified implanted devices that failed in both mice and humans, highlighting relevance across species. Phospholipid deposition is also found to upregulate the transcription of anti-inflammatory genes in murine macrophages, while fatty acid deposition stimulated the expression of pro-inflammatory genes. These results provide further insights into how to improve the design of biomaterials and medical devices to mitigate biomaterial material-induced FBR and fibrosis.

Molecular hydrogen therapy for neurological diseases: a review of current evidence.

Reactive oxygen species and other free radicals cause oxidative stress which is the underlying pathogenesis of cellular injury in various neurological diseases. Molecular hydrogen therapy with its unique biological property of selectively scavenging pathological free radicals has demonstrated therapeutic potential in innumerable animal studies and some clinical trials. These studies have implicated several cellular pathways affected by hydrogen therapy in explaining its anti-inflammatory and antioxidative effects. This article reviews relevant animal and clinical studies that demonstrate neuroprotective effects of hydrogen therapy in stroke, neurodegenerative diseases, neurotrauma, and global brain injury.

Winnipeg's North End Wellbeing Measure: Using Social Innovation to Drive Community Measurements.

BACKGROUND: The Winnipeg Boldness Project, a social innovation initiative addressing early childhood outcomes in the underserved community of Point Douglas, worked alongside the community to develop a meaningful measurement tool, the North End Wellbeing Measure (NEWM). This article describes the context, the research and pilot, and the lessons learned. OBJECTIVES: To develop a community-based tool called the NEWM, which evaluates what is important to Point Douglas families. METHODS: We used community-based participatory research methods and surveys for data collection. LESSONS LEARNED: We learned that 1) the language used in relation to notions of well-being and satisfaction could be more precise, 2) our assumptions about strengths-based measurement did not always align with community perspectives, 3) hiring Indigenous people as data collectors is essential, and 4) we need to remain vigilant in our attention to respecting the participants' lived experiences. We also learned that, given the opportunity, the community has a desire to participate in research involving their experiences and well-being and greatly benefit from self-voicing and agency in research development. CONCLUSIONS: The pilot NEWM demonstrates the benefits and challenges of Indigenous social innovation and will benefit future iterations of the measure, as well as other community-based well-being measures.

Common Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T-cell Receptor Lineages.

Current chimeric antigen receptor-modified (CAR) T-cell products are evaluated in bulk, without assessing functional heterogeneity. We therefore generated a comprehensive single-cell gene expression and T-cell receptor (TCR) sequencing data set using pre- and postinfusion CD19-CAR T cells from blood and bone marrow samples of pediatric patients with B-cell acute lymphoblastic leukemia. We identified cytotoxic postinfusion cells with identical TCRs to a subset of preinfusion CAR T cells. These effector precursor cells exhibited a unique transcriptional profile compared with other preinfusion cells, corresponding to an unexpected surface phenotype (TIGIT+, CD62Llo, CD27-). Upon stimulation, these cells showed functional superiority and decreased expression of the exhaustion-associated transcription factor TOX. Collectively, these results demonstrate diverse effector potentials within preinfusion CAR T-cell products, which can be exploited for therapeutic applications. Furthermore, we provide an integrative experimental and analytic framework for elucidating the mechanisms underlying effector development in CAR T-cell products. SIGNIFICANCE: Utilizing clonal trajectories to define transcriptional potential, we find a unique signature of CAR T-cell effector precursors present in preinfusion cell products. Functional assessment of cells with this signature indicated early effector potential and resistance to exhaustion, consistent with postinfusion cellular patterns observed in patients. This article is highlighted in the In This Issue feature, p. 2007.

Comparing the structural dynamics of the human KCNE3 in reconstituted micelle and lipid bilayered vesicle environments.

KCNE3 is a single transmembrane protein of the KCNE family that modulates the function and trafficking of several voltage-gated potassium channels, including KCNQ1. Structural studies of KCNE3 have been previously conducted in a wide range of model membrane mimics. However, it is important to assess the impact of the membrane mimics used on the observed conformation and dynamics. In this study, we have optimized a method for the reconstitution of the KCNE3 into POPC/POPG lipid bilayer vesicles for electron paramagnetic resonance (EPR) spectroscopy. Our CD spectroscopic data suggested that the degree of regular secondary structure for KCNE3 protein reconstituted into lipid bilayered vesicle is significantly higher than in DPC detergent micelles. Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling (SDSL) was used to probe the structural dynamics of S49C, M59C, L67C, V85C, and S101C mutations of KCNE3 in both DPC micelles and in POPC/POPG lipid bilayered vesicles. Our CW-EPR power saturation data suggested that the site S74C is buried inside the lipid bilayered membrane while the site V85C is located outside the membrane, in contrast to DPC micelle results. These results suggest that the KCNE3 micelle structures need to be refined using data obtained in the lipid bilayered vesicles in order to ascertain the native structure of KCNE3. This work will provide guidelines for detailed structural studies of KCNE3 in a more native membrane environment and comparing the lipid bilayer results to the isotropic bicelle structure and to the KCNQ1-bound cryo-EM structure.

Pediatric abusive head trauma: ThinkFirst national injury prevention foundation.

BACKGROUND: Pediatric abusive head trauma (AHT) represents 80% of nonaccidental trauma deaths, remaining a lead cause of death among infants and young children. Furthermore, neurosurgical intervention can ameliorate damage from secondary injury, but we are currently unable to alter the impact of the primary injury. Thus, prevention through increased public awareness is imperative. This study identifies injuries and predictors of outcomes in pediatric AHT and highlights the importance of partnering with our community through ThinkFirst, a national injury prevention foundation, to educate parents and caregivers about prevention. METHODS: This single-institution retrospective review identifies injuries and predictors of outcomes in pediatric AHT and highlights the importance of partnering with our community to raise awareness and educate parents and caregivers about prevention. RESULTS: The number of pediatric AHT cases continues to steadily increase over time (P < 0.001), and over 70% of these patients are <1 year of age (P < 0.001). Patients suffering AHT have a mortality rate of nearly 10%. In addition to morbidity and mortality, the economic burden of caring for abused children is high as they often require high levels of care, long hospital stays, and extensive rehabilitation. Furthermore, Medicaid pays for nearly 80% of these patients. CONCLUSION: The population of patients with AHT is unique, and one that will benefit from continued efforts at increased multidisciplinary and public awareness. Prevention of AHT through awareness is critical. Through partnering with ThinkFirst, a national injury prevention foundation, we aim to educate parents and caregivers about prevention.

Thoracic ventral spinal cord herniation with progressive myelopathy - A case report and review of the literature.

BACKGROUND: Idiopathic spinal cord herniation (ISCH) is a rare, underrecognized, and often misdiagnosed entity of unclear pathogenesis that typically presents as a slowly progressive thoracic myelopathy. There are less than 200 such cases reported in the literature. ISCH diagnosis and treatment are often delayed contributing to greater fixed neurological deficits, often leading to costly, unnecessary imaging studies, and inappropriate surgery. CASE DESCRIPTION: Here, a 48-year-old female presented with trauma-induced ISCH characterized by gradually worsening lower extremity myelopathy. CONCLUSION: Idiopathic spinal cord herniation (ISCH) is rare, often underdiagnosed posttraumatic myelopathy that, when accurately diagnosed and treated, can result in good outcomes.

Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells.

Immune cells regulate tumor growth by mirroring their function as tissue repair organizers in normal tissues. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunologic manipulation with noninvasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4+ and myeloid populations colocalized within the tumor parenchyma, while CD8+ T cells and B cells were peripherally dispersed. Depletion of CD4+ T cells or CCR2+ macrophages, but not B cells, CD8+ T cells, or natural killer (NK) cells, prevented tumor formation. Tumor CD4+ T cells displayed unconventional phenotypes and were clonotypically diverse and antigen independent. Within the myeloid fraction, tumor growth required myeloid cells expressing arginase-1. Overall, these results demonstrate how arginine-metabolizing myeloid cells conspire with pathogenic CD4+ T cells to create permissive conditions for tumor formation, suggesting that these protumorigenic pathways could be disabled by targeting myeloid arginine metabolism. SIGNIFICANCE: A new model of human neuroblastoma provides ways to track tumor formation and expansion in living animals, allowing identification of CD4+ T-cell and macrophage functions required for oncogenesis.

The ripple effect: Examining the impact on parents of an Abecedarian early child care intervention in an urban social housing development.

The Abecedarian Approach is an internationally recognised early childhood intervention program that has shown long-term positive outcomes for children living in low SES communities. However, there are few studies examining the broader influence of such interventions for young children on the lives of their parents. This article describes the findings of a qualitative study exploring the perceptions and experiences of parents whose children attend an Abecedarian early intervention program located in an urban social housing complex. Eighteen parents whose children had attended the program for a minimum of one year were interviewed. The main themes that emerged were: strengthened relationships between parents and program staff, as well as between parents themselves, particularly supported through the home visitor; increased awareness among parents about early development and of their role in supporting child development; and opportunities for parents' personal growth. The findings suggest that high quality early child intervention programs, such as the Abecedarian Approach, can positively impact the lives of parents.

Intracranial Venous Sinus Stenting in Idiopathic Intracranial Hypertension: A Case Report and Review of the Literature.

We describe a case of severe headaches, double vision, and progressive vision loss secondary to a ruptured intracranial cyst (IAC) in a 31-year-old woman with no relevant past medical history. The case is peculiar because drainage of the subdural hygroma led to a minimal improvement in vision with persistent elevated intracranial pressure (ICP). Further exploration revealed transverse sinus stenosis necessitating stenting. Evaluation post-stenting showed marked reduction of ICP and improvement in symptoms. This report underscores the importance of comprehensive work-up and suspicion of multiple underlying etiologies that may be crucial to complete resolution of presenting symptoms in some cases. We provide an overview of the clinical indications and evidence for venous sinus stenting in treating idiopathic intracranial hypertension (IIH).

Computer-assisted surgery in medical and dental applications.

INTRODUCTION: Computer-assisted surgery (CAS) is a broad surgical methodology that utilizes computer technology to both plan and execute surgical intervention. CAS is widespread in both medicine and dentistry as it allows for minimally invasive and precise surgical procedures. Key innovations in volumetric imaging, virtual surgical planning software, instrument tracking, and robotics have assisted in facilitating the transfer of surgical plans to precise execution of surgical procedures. CAS has long been used in certain medical specialties including neurosurgery, cardiology, orthopedic surgery, otolaryngology, and interventional radiology, and has since expanded to oral and maxillofacial application, particularly for computer-assisted implant surgery. AREAS COVERED: This review provides an updated overview of the most current research for CAS in medicine and dentistry, with a focus on neurosurgery and dental implant surgery. The MEDLINE electronic database was searched and relevant original and review articles from 2005 to 2020 were included. EXPERT OPINION: Recent literature suggests that CAS performs favorably in both neurosurgical and dental implant applications. Computer-guided surgical navigation is well entrenched as standard of care in neurosurgery. Whereas static computer-assisted implant surgery has become established in dentistry, dynamic computer-assisted navigation is newly poised to trend upward in dental implant surgery.

Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management.

Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas.

Optimizing Radiosurgery for Trigeminal Neuralgia: Impact of Radiation Dose and Anatomic Target on Patient Outcomes.

OBJECTIVE: Radiosurgery is an increasingly popular treatment for trigeminal neuralgia (TN); however, several treatment variables require further study. This meta-analysis was conducted to clarify ambiguity in the literature and optimize treatment parameters. METHODS: A random-effects proportions meta-analysis using subgroup analysis and meta-regression investigated the association of prescription dose and anatomic target on outcomes in patients with typical TN. The PRISMA guidelines were used. Radiation doses used ranged from 70 to 90 Gy and the anatomic targets were either the root entry zone or a more distal nerve location. Outcome measures were pain at last follow-up and the development of bothersome numbness. RESULTS: Increasing radiation prescription dose was associated with improved outcomes across all analyzed doses (P < 0.001). Patients treated at a distal trigeminal nerve target had better pain control compared with a root entry zone target (P < 0.001). Despite a higher median dose, a distal target was independently associated with improved pain control. There were similar rates of bothersome numbness across radiation doses and both treatment targets. CONCLUSIONS: Higher radiation dose was associated with superior pain control without increasing bothersome numbness. Independent of dose, the distal target was also associated with improved pain control. Bothersome numbness was not related to dose or target.

One hundred years of (influenza) immunopathology.

It has been over 100 years since the 1918 influenza pandemic, one of the most infamous examples of viral immunopathology. Since that time, there has been an inevitable repetition of influenza pandemics every few decades and yearly influenza seasons, which have a significant impact on human health. Recently, noteworthy progress has been made in defining the cellular and molecular mechanisms underlying pathology induced by an exuberant host response to influenza virus infection. Infection with influenza viruses is associated with a wide spectrum of disease, from mild symptoms to severe complications including respiratory failure, and the severity of influenza disease is driven by a complex interplay of viral and host factors. This chapter will discuss mechanisms of infection severity using concepts of disease resistance and tolerance as a framework for understanding the balance between viral clearance and immunopathology. We review mechanistic studies in animal models of infection and correlational studies in humans that have begun to define these factors and discuss promising host therapeutic targets to improve outcomes from severe influenza disease.