Hearing Loss, Incident Parkinson Disease, and Treatment With Hearing Aids.

Importance: The risk of developing Parkinson disease (PD) after objective hearing loss is unknown. PD studies using self-reported hearing loss are insensitive, and objective data are lacking. Objective: To examine the association of hearing loss with incident PD in US veterans and its effect modification by well-established prodromal conditions and hearing aids. Design, Setting, and Participants: This cohort study analyzed electronic health record data from the US Department of Veterans Affairs for veterans who had an audiogram from January 1, 1999, to December 30, 2022. Individuals with data missing or a preexisting PD diagnosis were excluded. Exposure: Audiogram-confirmed hearing loss. Main Outcomes and Measures: Cumulative incidence of PD was calculated with adjustment for competing risk of death. Results: Among 7 296 051 veterans with an audiogram, 3 596 365 were included. They were mostly male (n = 3 452 898 [96%]) and had a mean (SD) age of 67 (10.3) years. A total of 750 010 individuals (20.8%) had normal hearing at the time of audiometry examination; among those with hearing loss, 1 080 651 (30.0%), 1 039 785 (28.9%), 568 296 (15.8%), and 157 623 (4.3%) individuals had mild (20-<35 dB), moderate (35-<50 dB), moderate to severe (50-<65 dB), and severe to profound (65-120 dB) hearing loss, respectively. Age, gender, and smoking history were balanced between all exposed and unexposed groups with further adjustment for race, ethnicity, and frailty. At 10 years after the baseline audiogram, the numbers of additional cases of PD were 6.1 (95% CI, 4.5-7.79, 15.8 (95% CI, 12.8-18.8), 16.2 (95% CI, 11.9-20.6), and 12.1 (95% CI, 4.5-19.6) among veterans with mild, moderate, moderate to severe, and severe to profound hearing loss, respectively, compared with those with normal hearing. When combined with established prodromal conditions, hearing loss was associated with 5.7 (95% CI, 2.2-9.2) additional cases of PD at 10 years compared with either condition alone. With prompt hearing aid dispensation, incident cases of PD decreased by 21.6 cases (95% CI, 19.5-23.6) at 10 years. Conclusions and Relevance: Hearing loss appears to be an independent risk factor for later development of PD. Hearing aids attenuate this risk, and therefore widespread screening for hearing loss and appropriate use of hearing aids may reduce the incidence of PD. Additional studies are needed to examine the mechanisms underlying the association between hearing loss and PD.

Influence of septal deviation side on preoperative eustachian tube dysfunction and the effectiveness of septoplasty in alleviating eustachian tube dysfunction.

BACKGROUND: The Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7) serves as a valuable tool for assessing eustachian tube dysfunction (ETD). We investigated the impact of septal deviation side on ETD using preoperative ETDQ-7 scores and evaluated the effectiveness of septoplasty based on postoperative ETDQ-7 scores. METHODOLOGY: We conducted a retrospective analysis of patients with septal deviation who were scheduled for septoplasty. ETDQ-7 surveys were conducted preoperative and 1 and 3 months postoperative. RESULTS: 120 patients were included, with 72 completing the ETDQ-7 at all three time points. The average prevalence of ETD was 29.2%. Preoperative ETDQ-7 scores showed no significant difference between convex and concave nasal sides. However, the prevalence of ETD was significantly higher on the convex side (28.3% vs. 15.8%), especially in unilateral ETD cases. Preoperatively, the positive ETD group had significantly higher ETDQ-7 scores on the convex side while no significant difference was found between concave and convex sides in the negative ETD group. Postoperatively, the positive ETD group showed significant improvement in ETDQ-7 scores with significantly higher on the convex side (66.7% vs. 33.3%). ETDQ-7 scores improved after septoplasty, with more improvement in the positive ETD group. CONCLUSIONS: Septoplasty significantly improves ETD, particularly in the preoperative positive ETD group, by reducing ETDQ-7 scores. The prevalence of ETD was higher on the convex side preoperatively, and the positive ETD group exhibited significant postoperative improvements, especially on the convex side. This suggests that the direction of septal deviation influences ETD prevalence and surgery outcomes, although septoplasty alleviates ETD on both sides.

Glia in Tissue Engineering: From Biomaterial Tools to Transplantation.

Glia are imperative in nearly every function of the nervous system, including neurotransmission, neuronal repair, development, immunity, and myelination. Recently, the reparative roles of glia in the central and peripheral nervous systems have been elucidated, suggesting a tremendous potential for these cells as novel treatments to central nervous system disorders. Glial cells often behave as 'double-edged swords' in neuroinflammation, ultimately deciding the life or death of resident cells. Compared to glia, neuronal cells have limited mobility, lack the ability to divide and self-renew, and are generally more delicate. Glia have been candidates for therapeutic use in many successful grafting studies, which have been largely focused on restoring myelin with Schwann cells, olfactory ensheathing glia, and oligodendrocytes with support from astrocytes. However, few therapeutics of this class have succeeded past clinical trials. Several tools and materials are being developed to understand and re-engineer these grafting concepts for greater success, such as extra cellular matrix-based scaffolds, bioactive peptides, biomolecular delivery systems, biomolecular discovery for neuroinflammatory mediation, composite microstructures such as artificial channels for cell trafficking, and graft enhanced electrical stimulation. Furthermore, advances in stem cell-derived cortical/cerebral organoid differentiation protocols have allowed for the generation of patient-derived glia comparable to those acquired from tissues requiring highly invasive procedures or are otherwise inaccessible. However, research on bioengineered tools that manipulate glial cells is nowhere near as comprehensive as that for systems of neurons and neural stem cells. This article explores the therapeutic potential of glia in transplantation with an emphasis on novel bioengineered tools for enhancement of their reparative properties. STATEMENT OF SIGNIFICANCE: Neural glia are responsible for a host of developmental, homeostatic, and reparative roles in the central nervous system but are often a major cause of tissue damage and cellular loss in insults and degenerative pathologies. Most glial grafts have employed Schwann cells for remyelination, but other glial with novel biomaterials have been employed, emphasizing their diverse functionality. Promising strategies have emerged, including neuroimmune mediation of glial scar tissues and facilitated migration and differentiation of stem cells for neural replacement. Herein, a comprehensive review of biomaterial tools for glia in transplantation is presented, highlighting Schwann cells, astrocytes, olfactory ensheating glia, oligodendrocytes, microglia, and ependymal cells.

Melatonin Improves Vasogenic Edema via Inhibition to Water Channel Aquaporin-4 (AQP4) and Metalloproteinase-9 (MMP-9) Following Permanent Focal Cerebral Ischemia.

Background: The efficacy of melatonin in reducing vasogenic and cytotoxic edema was investigated using a model of permanent middle cerebral artery occlusion (pMCAO). Methods: Rats underwent pMCAO, followed by intravenous administration of either melatonin (5 mg/kg) or a vehicle 10 min post-insult. Brain infarction and edema were assessed, and Western blot analyses were conducted to examine the expression levels of aquaporin-4 (AQP4), metalloproteinase-9 (MMP-9), and the neurovascular tight-junction protein ZO-1 upon sacrifice. The permeability of the blood-brain barrier (BBB) was measured using spectrophotometric quantification of Evans blue dye leakage. Results: Compared to controls, melatonin-treated rats exhibited a significant reduction in infarct volume by 26.9% and showed improved neurobehavioral outcomes (p < 0.05 for both). Melatonin treatment also led to decreased Evans blue dye extravasation and brain edema (p < 0.05 for both), along with lower expression levels of AQP4 and MMP-9 proteins and better preservation of ZO-1 protein (p < 0.05 for all). Conclusions: Therefore, melatonin offers neuroprotection against brain swelling induced by ischemia, possibly through its modulation of AQP4 and MMP-9 activities in glial cells and the extracellular matrix (ECM) during the early phase of ischemic injury.

Cancer prevention and control in the USAPI: Participatory development and partnership - the voyage.

Charting a course to achieve cancer prevention and control in several sovereign Pacific Island nations and US Pacific Island Territories has been a challenging and dynamic process. Partners and stakeholders from these communities have developed the infrastructure to achieve cancer control in the region. This narrative is about the Pacific Cancer Control voyagers in the region, who they are, where they hope to go, and the voyaging canoe on which they journey.

A Working Framework to Address Diversity, Equity, and Inclusion in Undergraduate Medical Education.

Health disparities exist among groups that are based on race, ethnicity, gender, socioeconomic status, and geography. Often, interventions directed at addressing these disparities are episodically incorporated into health professions education as opposed to a more uniform integration throughout a curriculum. Thus, a working framework for integrating and assessing diversity, equity, and inclusion (DEI) specifically into foundational science teaching in health professions' education is needed. Current frameworks are theoretically based and often bereft of practical examples that basic science and clinical educators would find useful in educational settings. Here we analyzed examples in pharmacology, therapeutics, and clinical medicine to create a tool aimed at identifying and remediating biases and disparities across the undergraduate medical education (UME) curriculum. We initially focused on pharmacology examples and performed a literature search followed by an in-depth analysis of the literature together with our experiences teaching topics with a DEI component. It became clear that, in addition to pure pharmacology topics, there are many pharmacology- and therapeutics-related topics that also involve race, gender, and sexual orientation. These include clinical guidelines and clinical screening criteria. Further analysis of all of the examples derived from our multi-faceted analysis revealed common themes that we, in turn, compiled into a framework. This framework can be used by foundational science and clinical educators to help both students and faculty understand how to navigate DEI-associated foundational science content.

Single-cell profiling reveals a conserved role for hypoxia-inducible factor signaling during human craniotomy infection.

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The importance of HIF signaling was validated using a mouse model of Staphylococcus aureus craniotomy infection, where HIF inhibition increases chemokine production and leukocyte recruitment, exacerbating tissue pathology. These findings establish conserved metabolic and transcriptional signatures that may represent promising future therapeutic targets for human craniotomy infection in the face of increasing antimicrobial resistance.

Epidural Spinal Cord Recordings (ESRs): sources of neural-appearing artifact in stimulation evoked compound action potentials.

Evoked compound action potentials (ECAPs) measured during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain and inform closed-loop control of SCS. Previous studies have used ECAPs to characterize neural responses to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model. We characterized sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode™ lead. Spinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby muscles of the back, and motion artifact. The capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. EMG bleed-through can have phase shifts across the electrode array, similar to the phase shift anticipated by propagation of an evoked A-beta fiber response. The short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in CSF between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of recorded ECAPs. Controls must be implemented to separate neural signal from sources of artifact in SCS ECAPs. We suggest experimental procedures and reporting requirements necessary to disambiguate underlying neural response from these confounds. These data are important to better understand the framework for recorded ESRs, with components such as ECAPs, EMG, and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.

Decision regret following surgical management of pilonidal disease.

AIM: Surgical decision making in the context of pilonidal disease (PD) can be challenging. Current evidence for the management of PD is inadequate and optimum treatment is not clear. This paper reports on patient experience of shared decision making (SDM) and decision regret following surgical management of PD. METHOD: The Pilonidal Trial. Studying the Treatment Options (PITSTOP) study (ISRCTN95551898) is a prospective cohort study of patients with PD treated between May 2019 and March 2022. This subanalysis reports the results of quantitative data capture between baseline and 6 months post-procedure. Baseline data consisted of patient and disease characteristics, surgical procedure and impression of SDM. Post-procedure data consisted of operative outcomes and decision regret. Multiple linear regression analysis was used to analyse the relationship between clinical outcomes and decision regret. RESULTS: Overall, 677 patients were included, and follow-up data to 6 months were available for 476 (71%). Most (59.5%) patients underwent major excisional surgery; 45.1% of patients experienced a postoperative complication. Participant impression of SDM was positive, with a median CollaboRATE mean-score response of 3 (interquartile range: 3-4). Of the patients who underwent a 'leave open' approach, 20.6% were dissatisfied or very dissatisfied with their treatment. Postoperative complications (ß = 3.21, 95% CI: -12.75 to 7.25, p < 0.001) and disease recurrence (ß = 11.5, 95% CI: -10.6 to 9.4, p < 0.001) were both associated with higher rates of decision regret. CONCLUSION: The clinical outcomes, postoperative complications and recurrence, were associated with higher levels of decision regret. Surgeons treating patients with PD should practice SDM and ensure that patient priorities inform treatment approach.

Clinical and Neuropathological Correlates of Substance Use in American Football Players.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. Objective: To examine the association between substance use and clinical and neuropathological endpoints of CTE. Methods: Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Results: Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04-0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02-0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Conclusions: Among deceased football players, substance use was common and associated with clinical symptoms.

90-Day Complication and Readmission Rates for Geriatric Patients With Hip Fracture at Different Time Points From COVID-19 Positivity: A Database Study.

INTRODUCTION: Geriatric patients with hip fracture are at risk of having COVID-19 while needing fracture treatment. Understanding the associated risks of variable timing of COVID-19 before surgery may help direct care algorithms. METHODS: Geriatric patients with documented hip fracture surgery were identified within the PearlDiver M157 database. Patients with a preoperative COVID-19 diagnosis were classified based on time from diagnosis to surgery: ≤ 1 week, > 1 to ≤ 4 weeks, > 4 to ≤ 7 weeks, > 7 to ≤ 10 weeks, and > 10 to ≤ 13 weeks. The association of COVID-19 diagnoses with 90-day complications was evaluated. RESULTS: Overall, 263,771 patients with hip fracture were identified, of which COVID-19 within 13 weeks of surgery was documented for 976. On multivariable analysis, patients with COVID-19 infection within ≤ 1 week preoperatively demonstrated increased rates of minor adverse events (odds ratio (OR) = 1.50), all adverse events (OR = 1.59), sepsis (OR = 1.70), and pneumonia (OR = 2.35) (P ≤ 0.0007 for each). For time points greater than 1 week, there were no differences in complication rates. DISCUSSION: Patients with COVID-19 within 1 week of hip fracture surgery demonstrated greater odds of 90-day complications. Reassuringly, patients with COVID-19 diagnoses more than 1 week preoperatively were not associated with increased odds of any assessed complication.

Unsupervised, piecewise linear decoding enables an accurate prediction of muscle activity in a multi-task brain computer interface.

Objective: Creating an intracortical brain-computer interface (iBCI) capable of seamless transitions between tasks and contexts would greatly enhance user experience. However, the nonlinearity in neural activity presents challenges to computing a global iBCI decoder. We aimed to develop a method that differs from a globally optimized decoder to address this issue. Approach: We devised an unsupervised approach that relies on the structure of a low-dimensional neural manifold to implement a piecewise linear decoder. We created a distinctive dataset in which monkeys performed a diverse set of tasks, some trained, others innate, while we recorded neural signals from the motor cortex (M1) and electromyographs (EMGs) from upper limb muscles. We used both linear and nonlinear dimensionality reduction techniques to discover neural manifolds and applied unsupervised algorithms to identify clusters within those spaces. Finally, we fit a linear decoder of EMG for each cluster. A specific decoder was activated corresponding to the cluster each new neural data point belonged to. Main results: We found clusters in the neural manifolds corresponding with the different tasks or task sub-phases. The performance of piecewise decoding improved as the number of clusters increased and plateaued gradually. With only two clusters it already outperformed a global linear decoder, and unexpectedly, it outperformed even a global recurrent neural network (RNN) decoder with 10-12 clusters. Significance: This study introduced a computationally lightweight solution for creating iBCI decoders that can function effectively across a broad range of tasks. EMG decoding is particularly challenging, as muscle activity is used, under varying contexts, to control interaction forces and limb stiffness, as well as motion. The results suggest that a piecewise linear decoder can provide a good approximation to the nonlinearity between neural activity and motor outputs, a result of our increased understanding of the structure of neural manifolds in motor cortex.

Simulated herbicide drift alters native plant flowering phenology.

Data for herbicide effects on plant flowering are needed to determine potential impacts on plant reproduction. Thus, flowering phenology was determined for up to 12 weeks after herbicide treatment for native Willamette Valley plants growing in small plots on two Oregon State University experimental farms. Six perennial species were evaluated: Camassia leichtlinii (CALE), Elymus glaucus (ELGL), Eriophyllum lanatum (ERLA), Festuca idahoensis subsp. roemeri (FEID), Iris tenax (IRTE), and Prunella vulgaris var. lanceolata (PRVU). Effects of glyphosate and dicamba, alone and in combination, were determined using simulated drift rates of 0.1 or 0.2 x field application rates (FAR) of 1119 g ha-1 active ingredient (a.i.) (830 g ha-1 acid glyphosate) for glyphosate and 560 g ha-1 a.i. for dicamba. Flowering phenology was evaluated as stage of development on a scale from no buds (converted to 0), buds (1), pre-flowering (2), flowering (3), post-flowering (4), to mature seeds (5) before herbicide treatment and for 12 weeks after treatment. Flowering response to herbicides varied by species and farm; but, in general, dicamba and glyphosate resulted in earlier flowering stages (delayed or not full flowering) for the dicot ERLA, and to a lesser extent, PRVU; and glyphosate resulted in earlier flowering stages for the monocot IRTE. Based on these data, the concentration of herbicide affecting flowering stage was 0.1 x FAR. Once flowering stage was inhibited by dicamba and glyphosate, plants generally did not recover to full flowering. This study provided evidence that common herbicides can affect flowering phenology of native plants with implications for seed production.

Few-shot Algorithms for Consistent Neural Decoding (FALCON) Benchmark.

Intracortical brain-computer interfaces (iBCIs) can restore movement and communication abilities to individuals with paralysis by decoding their intended behavior from neural activity recorded with an implanted device. While this activity yields high-performance decoding over short timescales, neural data are often nonstationary, which can lead to decoder failure if not accounted for. To maintain performance, users must frequently recalibrate decoders, which requires the arduous collection of new neural and behavioral data. Aiming to reduce this burden, several approaches have been developed that either limit recalibration data requirements (few-shot approaches) or eliminate explicit recalibration entirely (zero-shot approaches). However, progress is limited by a lack of standardized datasets and comparison metrics, causing methods to be compared in an ad hoc manner. Here we introduce the FALCON benchmark suite (Few-shot Algorithms for COnsistent Neural decoding) to standardize evaluation of iBCI robustness. FALCON curates five datasets of neural and behavioral data that span movement and communication tasks to focus on behaviors of interest to modern-day iBCIs. Each dataset includes calibration data, optional few-shot recalibration data, and private evaluation data. We implement a flexible evaluation platform which only requires user-submitted code to return behavioral predictions on unseen data. We also seed the benchmark by applying baseline methods spanning several classes of possible approaches. FALCON aims to provide rigorous selection criteria for robust iBCI decoders, easing their translation to real-world devices. https://snel-repo.github.io/falcon/.

The effects of neuron morphology and spatial distribution on the selectivity of dorsal root ganglion stimulation.

Objective.For prosthesis users, sensory feedback that appears to come from the missing limb can improve function, confidence, and phantom limb pain. Numerous pre-clinical studies have considered stimulation via penetrating microelectrodes at the dorsal root ganglion (DRG) as a potential approach for somatosensory neuroprostheses. However, to develop clinically translatable neuroprosthetic devices, a less invasive approach, such as stimulation via epineural macroelectrodes, would be preferable. This work explores the feasibility of using such electrodes to deliver focal sensory feedback by examining the mechanisms of selective activation in response to stimulation via epineural electrodes compared with penetrating electrodes.Approach.We developed computational models of the DRG, representing the biophysical properties of the DRG and surrounding tissue to evaluate neural responses to stimulation via penetrating microelectrodes and epineural macroelectrodes. To assess the role of properties such as neuron morphology and spatial arrangement we designed three models, including one that contained only axons (axon only), one with pseudounipolar neurons arranged randomly (random), and one with pseudounipolar neurons placed according to a realistic spatial distribution (realistic).Main results.Our models demonstrate that activation in response to stimulation via epineural electrodes in a realistic model is commonly initiated in the axon initial segment adjacent to the cell body, whereas penetrating electrodes commonly elicit responses in t-junctions and axons. Moreover, we see a wider dynamic range for epineural electrodes compared with penetrating electrodes. This difference appears to be driven by the spatial organization and neuron morphology of the realistic DRG.Significance.We demonstrate that the anatomical features of the DRG make it a potentially effective target for epineural stimulation to deliver focal sensations from the limbs. Specifically, we show that epineural stimulation at the DRG can be highly selective thanks to the neuroanatomical arrangement of the DRG, making this a promising approach for future neuroprosthetic development.

Cervical Cancer Incidence in the US-Affiliated Pacific Islands.

Importance: The World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI). Objective: To calculate age-standardized incidence rates for cervical cancer in the 6 USAPI and compare these rates with rates in the US (50 states and the District of Columbia). Design, Setting, and Participants: This cross-sectional study used population-based data from the Pacific Regional Central Cancer Registry for women aged 20 years or older who were diagnosed with invasive cervical cancer from January 1, 2007, to December 31, 2020. The registry comprises data on all cervical cancers from the USAPI, which include 3 US territories (American Samoa, Commonwealth of the Northern Mariana Islands, and Guam) and 3 freely associated states (Federated States of Micronesia [FSM], Republic of the Marshall Islands [RMI], and Republic of Palau). Data were analyzed from July 10, 2023, to November 28, 2023. Main Outcomes and Measures: The main outcome was age-standardized cervical cancer incidence rates, stratified by age, stage, and histologic code for the USAPI using population estimates from 3 different sources (US Census Bureau International Database, United Nations Population Division, and Pacific Data Hub). Rate ratios were calculated to compare incidence rates between the USAPI and the US. Results: From 2007 to 2020, 409 cases of cervical cancer were diagnosed in the USAPI (median age at diagnosis, 46.0 years [25th-75th percentile, 39.0-55.0 years]), with an age-standardized incidence rate ranging from 21.7 (95% CI, 19.6-23.9) to 22.1 (95% CI, 20.0-24.4) per 100 000 women, depending on the population estimate. Incidence rates were highest in RMI, ranging from 58.1 (95% CI, 48.0-69.7) to 83.4 (95% CI, 68.3-101.0) per 100 000 women, followed by FSM, ranging from 28.7 (95% CI, 23.4-34.9) to 29.8 (95% CI, 24.3-36.3) per 100 000 women. Compared with the US, incidence rates were highest in RMI (rate ratio, 5.7 [95% CI, 4.7-6.8] to 8.2 [95% CI, 6.7-9.9]) and FSM (rate ratio; 2.8; 95% CI, 2.3-3.4). Of all cases in the USAPI, 213 (68.2%) were diagnosed at a late stage. Conclusions and Relevance: In this cross-sectional study, cervical cancer remained a major public health issue in some USAPI, with RMI reporting the highest incidence rates. The findings suggest that improvements in human papillomavirus vaccination and cancer screening coverage through efforts tailored to the unique geographic, sociocultural, economic, and health care landscape of the USAPI may reduce the burden of cervical cancer.

A preliminary study exploring the effects of transcutaneous spinal cord stimulation on spinal excitability and phantom limb pain in people with a transtibial amputation.

Objective. Phantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes andF-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating PLP. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation.Approach. We recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5 d study. We measured pain using the McGill Pain Questionnaire (MPQ), visual analog scale (VAS), and pain pressure threshold (PPT) test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes andF-waves, respectively. We delivered tSCS for 30 min d-1for 5 d.Main Results. After 5 d of tSCS, MPQ scores decreased by clinically-meaningful amounts for all participants from 34.0 ± 7.0-18.3 ± 6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased PPTs across the residual limb (Day 1: 5.4 ± 1.6 lbf; Day 5: 11.4 ± 1.0 lbf).F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5 ± 6.1µC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 d of tSCS, reflex thresholds decreased significantly (38.6 ± 12.2µC;p< 0.001).Significance. These preliminary results in this non-placebo-controlled study suggest that, overall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.

X-ray Irradiation Reduces Live Aspergillus flavus Viability but Not Aflatoxin B1 in Naturally Contaminated Maize.

Food crops around the world are commonly contaminated with Aspergillus flavus, which can produce the carcinogenic mycotoxin aflatoxin B1 (AFB1). The objective of this study is to test an X-ray irradiation sterilization method for studying AFB1 in contaminated maize samples in the laboratory. Maize that had been naturally contaminated with 300 ppb AFB1 by the growth of aflatoxigenic A. flavus was ground and then irradiated at 0.0, 1.0, 1.5, 2.0, 2.5, and 3.0 kGy. A. flavus was quantified by dilution plating on potato dextrose agar (PDA) and modified Rose Bengal media (MDRB) for viability and qPCR for gene presence. AFB1 was quantified by HPLC and ELISA. A. flavus viability, but not gene copies, significantly decreased with increasing doses of radiation (PDA: p < 0.001; MDRB: p < 0.001; qPCR: p = 0.026). AFB1 concentration did not significantly change with increasing doses of radiation (HPLC: p = 0.153; ELISA: p = 0.567). Our results imply that X-ray irradiation is an effective means of reducing viable A. flavus without affecting AFB1 concentrations. Reducing the hazard of fungal spores and halting AFB1 production at the targeted dose are important steps to safely and reproducibly move forward research on the global mycotoxin challenge.