Opioid use and disposal at 2 weeks post-surgery: Brief communication regarding excess opioids and disposal habits.

OBJECTIVE: To measure the number of unused prescription opioids and disposal habits of patients following orthopedic shoulder surgery. DESIGN: A prospective observational study. SETTING: Academic orthopedic sports medicine department. PATIENTS: Sixty-seven patients undergoing shoulder surgery. INTERVENTIONS: Nine-question opioid use questionnaire. MAIN OUTCOME MEASURES: Responses to an opioid use questionnaire were collected at 2 weeks post-surgery. Outcomes of interest included the amount of initial opioid prescription used and the disposal of excess opioids. RESULTS: Sixty-seven patients completed the opioid use questionnaire. Forty-six (68.7 percent) patients reported having excess opioids at 2 weeks. Of the 46 patients with excess opioids, 57 percent disposed of the excess, and 43 percent planned to keep their opioids. CONCLUSION: Two-thirds of the patients reported having excess opioids, highlighting the issue of an overabundance of unused prescription opioids in America. Utilization of opioid-free pain management strategies and drug disposal kits should be explored to reduce the number of unused and improperly disposed opioids.

Postoperative Negative Pain Thoughts and Their Correlation With Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair: An Observational Cohort Study.

BACKGROUND: Pain and pain perception are influenced by patients' thoughts. The short form Negative Pain Thoughts Questionnaire (NPTQ-SF) can be used to quantify unhelpful negative cognitive biases about pain, but the relationship between NPTQ-SF scores and orthopaedic surgery outcomes is not known. PURPOSE/HYPOTHESIS: The purpose was to assess the relationship between negative pain thoughts, as measured by the NPTQ-SF, and patient-reported outcomes in patients undergoing arthroscopic rotator cuff repair, as well as to compare NPTQ-SF scores and outcomes between patients with and without a history of chronic pain and psychiatric history. It was hypothesized that patients with worse negative pain thoughts would have worse patient-reported outcomes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: In total, 109 patients undergoing arthroscopic rotator cuff repair were administered the 4-item NPTQ-SF, 12-item Short Form Health Survey (SF-12), American Shoulder and Elbow Surgeons (ASES) Shoulder Evaluation Form, and visual analog scale pain survey preoperatively between July 2021 and August 2022. The same surveys were completed ≥6 months postoperatively by 74 patients confirmed to have undergone arthroscopic rotator cuff repair. RESULTS: Preoperative NPTQ-SF scores did not show any correlation with the postoperative patient-reported outcomes measured in this study. Postoperative NPTQ-SF scores were statistically significantly negatively correlated with postoperative SF-12 Physical Health Score, SF-12 Mental Health Score, ASES, and satisfaction scores (P < .05). Postoperative NPTQ-SF scores were statistically significantly positively correlated with postoperative visual analog scale scores (P < .001). Moreover, postoperative NPTQ-SF scores were statistically significantly negatively correlated with achieving a Patient Acceptable Symptom State and the minimal clinically important difference on the postoperative ASES form (P < .001 and P = .009, respectively). CONCLUSION: Postoperative patient thought patterns and their perception of pain are correlated with postoperative outcomes after rotator cuff repair. This correlation suggests a role for counseling and expectation management in the postoperative setting. Conversely, preoperative thought patterns regarding pain, as measured by the NPTQ-SF, do not correlate with postoperative patient-reported outcome measures. Therefore, the NPTQ-SF should not be used as a preoperative tool to aid the prediction of outcomes after rotator cuff repair.

The Asymmetry Within: A Renewed Look at Cupids Bow in Unilateral Cleft Lip.

The purpose of this study is to analyze the angular variations within Cupid's bow in patients with unoperated unilateral cleft lip (UCL). Angular features of Cupid's bow were quantified in standardized presurgical photographs of children with UCL by 5 medical professionals specializing in craniofacial anomalies. The peaks and valley of Cupid's bow were identified. A cleft side (CSA) and a noncleft side angle (NCSA) were delineated and measured by each expert. The data was pooled, and the angles were analyzed for symmetry. Cupid's bow asymmetry was defined as a difference between NCSA and CSA ≥3°. Of the 37 patients studied, 29 were found to have asymmetry of Cupid's bow with an average angle difference of 8.0° (95% CI: 6.6°-9.5°). Within this group,15 patients were found with acute asymmetry and 14 with obtuse asymmetry. Geometric analysis was performed on an example of a patient with acute asymmetry to demonstrate how correction of asymmetry can be considered during surgical repair. There is an asymmetry that exists in the Cupid's bow of a significant number of patients with unoperated UCL. This finding not only adds to our understanding of UCL but may also have important implications when selecting the method/technique of surgical repair.

Preoperative Predictors of Patient-Reported Outcomes Following Arthroscopic Partial Meniscectomy.

The purpose of this study is to evaluate the effect of patient demographics and injury characteristics on post-arthroscopic partial meniscectomy (post-APM) patient-reported outcomes (PROs). We hypothesize that the presence of high-grade (Kellgren-Lawrence grades 3-4) arthritis at any location of the knee (medial and lateral compartments, patella, trochlea), comorbidities (psychiatric history, chronic pain, diabetes, smoking, body mass index [BMI] ≥ 30), and lower scores on preoperative patient-reported measures (36-Item Short Form Health Survey [SF-36]) would predict poor outcomes after APM. We conducted a single-center prospective study of 92 patients who underwent APM surgery for associated knee pain. General demographic information and PROs were prospectively collected using SF-12, SF-36, and International Knee Documentation Committee (IKDC) surveys presurgery and at 6-month follow-up. Postsurgery outcomes were patient-reported satisfaction (yes/no) and obtaining a patient-acceptable symptom state (PASS) on IKDC. Data were analyzed with odds ratios (ORs), binomial logistic regression, and Mann-Whitney U test using IBM SPSS software. Demographic and injury characteristics that were poor prognostic indicators (had a decreased likelihood of obtaining PASS on IKDC postsurgery) included having Medicaid insurance (OR: 0.056; 0.003-1.00), chronic pain (OR: 0.106; 0.013-0.873), acute injury (OR: 0.387; 0.164-0.914), and high-grade (KL grades 3-4) medial compartment arthritis (OR: 0.412; 0.174-0.980), and preoperative SF-36 physical health score (PHS; p = 0.023) and mental health score (MHS; p = 0.006) values less than 47 and 48, respectively. Additionally, former smoking history (OR: 0.271; 0.079-0.928) showed a lower likelihood of being satisfied postsurgery. Not having psychiatric history (OR: 14.925; p < 0.001; increased likelihood of obtaining PASS on IKDC score postsurgery) and not having patellar arthritis (OR: 4.082; p = 0.025; increased likelihood of PASS on IKDC) were positive prognostic indicators. This study identifies predictive factors of poor outcomes post-APM; particularly, it highlights the usefulness of SF-36 surveys prior to APM surgery. Patients with low SF-36 score preoperatively may not find APM acceptable. Additional attention should be put on patient demographics (such as psychiatric history, chronic pain, and insurance type) and injury characteristics (presence of arthritis and acute injury) prior to performing APM. LEVEL OF EVIDENCE: II.

Delays in the diagnosis and surgical treatment of drug-resistant epilepsy: A cohort study.

OBJECTIVE: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. METHODS: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. RESULTS: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st-3rd quartile) intervals observed were 10.1 (3.8-21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5-28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6-4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001). SIGNIFICANCE: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.

Evaluation of IVIM in the Spinal Cord of Multiple Sclerosis Patients.

PURPOSE: To evaluate the ability of intravoxel incoherent motion (IVIM), a perfusion-weighted imaging technique, to differentiate microcirculation changes in the spinal cord of patients with multiple sclerosis (MS) compared with healthy individuals. METHODS: Fifteen healthy individuals and 15 individuals with MS underwent IVIM magnetic resonance (MR) imaging using a 3 T scanner with 2-D axial gradient recalled echo and 2-D axial diffusion-weighted imaging (DWI) sequences. The MR images underwent segmentation to produce white matter and gray matter regions of interest. IVIM metrics for perfusion fraction, pseudo-diffusion coefficients, water-diffusion coefficients, and signal without diffusion encoding were calculated using DWI data. An unpaired t test was performed on these IVIM metrics to compare imaging of healthy individuals with imaging of individuals with MS. RESULTS: No significant differences between images from healthy individuals and individuals with MS were found for any IVIM metric. The lowest P values calculated (.082 and .055) were in the white matter region of interest perfusion fraction and pseudo-diffusion measurements. The gray matter region of interest had the highest P value. DISCUSSION: The findings in this study are consistent with current perfusion-weighted imaging literature focused on MS in the brain. The gray matter in MS patients in this study showed reduced perfusion compared with healthy individuals. CONCLUSION: IVIM is a promising imaging technique for the evaluation of the spinal cord in MS patients. It has the potential to provide valuable information on microvascular perfusion and diffusion in the spinal cord, which might be related to disease progression and response to treatment.

Automated differentiation of mixed populations of free-flying female mosquitoes under semi-field conditions.

Great advances in automated identification systems, or 'smart traps', that differentiate insect species have been made in recent years, yet demonstrations of field-ready devices under free-flight conditions remain rare. Here, we describe the results of mixed-species identification of female mosquitoes using an advanced optoacoustic smart trap design under free-flying conditions. Point-of-capture classification was assessed using mixed populations of congeneric (Aedes albopictus and Aedes aegypti) and non-congeneric (Ae. aegypti and Anopheles stephensi) container-inhabiting species of medical importance. Culex quinquefasciatus, also common in container habitats, was included as a third species in all assessments. At the aggregate level, mixed collections of non-congeneric species (Ae. aegypti, Cx. quinquefasciatus, and An. stephensi) could be classified at accuracies exceeding 90% (% error = 3.7-7.1%). Conversely, error rates increased when analysing individual replicates (mean % error = 48.6; 95% CI 8.1-68.6) representative of daily trap captures and at the aggregate level when Ae. albopictus was released in the presence of Ae. aegypti and Cx. quinquefasciatus (% error = 7.8-31.2%). These findings highlight the many challenges yet to be overcome but also the potential operational utility of optoacoustic surveillance in low diversity settings typical of urban environments.

Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many contradictory findings. Since correctly identifying the underlying neuroanatomical changes is critical to advancing TBI research, we compared three commonly used markers for their ability to detect TBI pathological structures: Fluoro-Jade C, the rabbit monoclonal antibody Y188 against amyloid precursor protein and the NeuroSilver kit were used to stain adjacent slices from naïve or injured mouse brains harvested at different time points from 30 min to 3 months after lateral fluid percussion injury. Although not all pathological structures were stained by all markers at all time points, we found damaged neurons and deformed dendrites in gray matter, punctate and perivascular structures in white matter, and axonal blebs and Wallerian degeneration in both gray and white matter. The present study demonstrates the temporal and structural sensitivities of the three biomarkers: each marker is highly effective for a set of pathological structures, each of which in turn emerges at a particular time point. Furthermore, the different biomarkers showed different abilities at detecting identical types of pathological structures. In contrast to previous studies that have used a single biomarker at a single time range, the present report strongly recommends that a combination of different biomarkers should be adopted and different time points need to be checked when assessing neuropathology after TBI.

The nurse educator multiplier: Mobile-friendly, bite-sized training.

This learning solution shortens orientation times, reduces costs, and improves outcomes.

Spatially Dependent Tissue Distribution of Thyroid Hormones by Plasma Thyroid Hormone Binding Proteins.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings. (1) Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 in Liver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate. (2) Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions. (3) The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end. (4) Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution.

Age-Related Differences in Motor Skill Transfer with Brief Memory Reactivation.

Motor memories can be strengthened through online practice and offline consolidation. Offline consolidation involves the stabilization of memory traces in post-practice periods. Following initial consolidation of a motor memory, subsequent practice of the motor skill can lead to reactivation and reconsolidation of the memory trace. The length of motor memory reactivation may influence motor learning outcomes; for example, brief, as opposed to long, practice of a previously learned motor skill appears to optimize intermanual transfer in healthy young adults. However, the influence of aging on reactivation-based motor learning has been scarcely explored. Here, the effects of brief and long motor memory reactivation schedules on the retention and intermanual transfer of a visuomotor tracing task are explored in healthy older adults. Forty older adults practiced a virtual star-tracing task either three ("brief reactivation") or ten ("long reactivation") times per session over a two-week period. Comparison with a previously reported group of younger adults revealed significant age-related differences in the effect of the motor memory reactivation schedule on the intermanual transfer of the motor task. In older adults, unlike younger adults, no significant between-group differences were found by practice condition in the speed, accuracy, or skill of intermanual task transfer. That is, motor task transfer in healthy younger, but not older, adults appears to benefit from brief memory reactivation. These results support the use of age-specific motor training approaches and may inform motor practice scheduling, with possible implications for physical rehabilitation, sport, and music.

Spatial-temporal pattern of change in production-living-ecological space of Nanchong City from 2000 to 2020 and underlying factors.

This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.

Adult stem cell activity in naked mole rats for long-term tissue maintenance.

The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in their native in vivo state, we find an expanded pool of Lgr5+ cells in NMRs, and these cells specifically at the crypt base (Lgr5+CBC) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5+CBC cells. Instead of entering quiescence (G0), NMR Lgr5+CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

Contributions of climate change and human activities to grassland degradation and improvement from 2001 to 2020 in Zhaosu County, China.

Grassland degradation poses a serious threat to biodiversity, ecosystem services, and human well-being. In this study, we investigated grassland degradation in Zhaosu County, China, between 2001 and 2020, and analyzed the impacts of climate change and human activities using the Miami model. The actual net primary productivity (ANPP) obtained with CASA (Carnegie-Ames-Stanford Approach) modeling, showed a decreasing trend, reflecting the significant degradation that the grasslands in Zhaosu County have experienced in the past 20 years. Grassland degradation was found to be highest in 2018, while the degraded area continuously decreased in the last 3 years (2018-2020). Climatic factors for found to be the dominant factor affecting grassland degradation, particularly the decrease in precipitation. On the other hand, human activities were found to be the main factor affecting improvement of grasslands, especially in recent years. This finding profoundly elucidates the underlying causes of grassland degradation and improvement and helps implement ecological conservation and restoration measures. From a practical perspective, the research results provide an important reference for the formulation of policies and management strategies for sustainable land use.

cloneRate: fast estimation of single-cell clonal dynamics using coalescent theory.

MOTIVATION: While evolutionary approaches to medicine show promise, measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. In cancer evolution, continuous observation of clonal architecture is impossible, and longitudinal samples from multiple timepoints are rare. Increasingly available DNA sequencing datasets at single-cell resolution enable the reconstruction of past evolution using mutational history, allowing for a better understanding of dynamics prior to detectable disease. There is an unmet need for an accurate, fast, and easy-to-use method to quantify clone growth dynamics from these datasets. RESULTS: We derived methods based on coalescent theory for estimating the net growth rate of clones using either reconstructed phylogenies or the number of shared mutations. We applied and validated our analytical methods for estimating the net growth rate of clones, eliminating the need for complex simulations used in previous methods. When applied to hematopoietic data, we show that our estimates may have broad applications to improve mechanistic understanding and prognostic ability. Compared to clones with a single or unknown driver mutation, clones with multiple drivers have significantly increased growth rates (median 0.94 versus 0.25 per year; P = 1.6×10-6). Further, stratifying patients with a myeloproliferative neoplasm (MPN) by the growth rate of their fittest clone shows that higher growth rates are associated with shorter time to MPN diagnosis (median 13.9 versus 26.4 months; P = 0.0026). AVAILABILITY AND IMPLEMENTATION: We developed a publicly available R package, cloneRate, to implement our methods (Package website: https://bdj34.github.io/cloneRate/). Source code: https://github.com/bdj34/cloneRate/.

A decision support tool for risk-benefit analysis of Japanese encephalitis vaccine in travellers.

BACKGROUND: During pre-travel consultations, clinicians and travellers face the challenge of weighing the risks verus benefits of Japanese encephalitis (JE) vaccination due to the high cost of the vaccine, low incidence in travellers (~1 in 1 million), but potentially severe consequences (~30% case-fatality rate). Personalised JE risk assessment based on the travellers' demographics and travel itinerary is challenging using standard risk matrices. We developed an interactive digital tool to estimate risks of JE infection and severe health outcomes under different scenarios to facilitate shared decision-making between clinicians and travellers. METHODS: A Bayesian network (conditional probability) model risk-benefit analysis of JE vaccine in travellers was developed. The model considers travellers' characteristics (age, sex, co-morbidities), itinerary (destination, departure date, duration, setting of planned activities) and vaccination status to estimate the risks of JE infection, the development of symptomatic disease (meningitis, encephalitis), clinical outcomes (hospital admission, chronic neurological complications, death) and adverse events following immunization. RESULTS: In low-risk travellers (e.g. to urban areas for <1 month), the risk of developing JE and dying is low (<1 per million) irrespective of the destination; thus, the potential impact of JE vaccination in reducing the risk of clinical outcomes is limited. In high-risk travellers (e.g. to rural areas in high JE incidence destinations for >2 months), the risk of developing symptomatic disease and mortality is estimated at 9.5 and 1.4 per million, respectively. JE vaccination in this group would significantly reduce the risk of symptomatic disease and mortality (by ~80%) to 1.9 and 0.3 per million, respectively. CONCLUSION: The JE tool may assist decision-making by travellers and clinicians and could increase JE vaccine uptake. The tool will be updated as additional evidence becomes available. Future work needs to evaluate the usability of the tool. The interactive, scenario-based, personalised JE vaccine risk-benefit tool is freely available on www.VaxiCal.com.

Applied strategies of neuroplasticity.

Various levels of somatotopic organization are present throughout the human nervous system. However, this organization can change when needed based on environmental demands, a phenomenon known as neuroplasticity. Neuroplasticity can occur when learning a new motor skill, adjusting to life after blindness, or following a stroke. Following an injury, these neuroplastic changes can be adaptive or maladaptive, and often occur regardless of whether rehabilitation occurs or not. But not all movements produce neuroplasticity, nor do all rehabilitation interventions. Here, we focus on research regarding how to maximize adaptive neuroplasticity while also minimizing maladaptive plasticity, known as applied neuroplasticity. Emphasis is placed on research exploring how best to apply neuroplastic principles to training environments and rehabilitation protocols. By studying and applying these principles in research and clinical practice, it is hoped that learning of skills and regaining of function and independence can be optimized.

Daily cannabis use may cause cannabis-induced hyperalgesia.

BACKGROUND AND OBJECTIVES: Public opinion about cannabis as a medical treatment is generally favorable. As many as 35% of primary care patients report medical use of cannabis, most commonly for pain treatment. We designed a way to test whether cannabis helps chronic pain. METHODS: A retrospective cohort study was conducted to explore whether daily long-term cannabis use was associated with increased pain sensitivity using the cold pressor test (CPT) to measure pain tolerance. Patients who used cannabis every day were compared to patients who inhaled tobacco and control patients who never used tobacco or cannabis. The effect of cannabis use on CPT was assessed using a generalized linear model. RESULTS: Patients using cannabis daily had a median CPT of 46 s, similar to those who did not use cannabis but who inhaled tobacco (median CPT 45 s). Patients who used both cannabis and tobacco had the lowest CPT (median 26 s). The control group had a median CPT of 105 s. Cannabis use was associated with a significantly decreased pain tolerance (χ²(1) = 8.0, p = .004). The effect of tobacco on CPT was only marginally significant (χ²(1) = 3.8, p = .052). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This suggests a phenomenon similar to opioid-induced hyperalgesia; a drug that reduces pain short term, induces pain long term-opponent process. Daily cannabis use may make chronic pain worse over time by reducing pain tolerance. In terms of risk/benefit, daily cannabis users risk addiction without any long-term benefit for chronic pain.

Neuronal somatic plasmalemmal permeability and dendritic beading caused by head rotational traumatic brain injury in pigs-An exploratory study.

Closed-head traumatic brain injury (TBI) is induced by rapid motion of the head, resulting in diffuse strain fields throughout the brain. The injury mechanism(s), loading thresholds, and neuroanatomical distribution of affected cells remain poorly understood, especially in the gyrencephalic brain. We utilized a porcine model to explore the relationships between rapid head rotational acceleration-deceleration loading and immediate alterations in plasmalemmal permeability within cerebral cortex, sub-cortical white matter, and hippocampus. To assess plasmalemmal compromise, Lucifer yellow (LY), a small cell-impermeant dye, was delivered intraventricularly and diffused throughout the parenchyma prior to injury in animals euthanized at 15-min post-injury; other animals (not receiving LY) were survived to 8-h or 7-days. Plasmalemmal permeability preferentially occurred in neuronal somata and dendrites, but rarely in white matter axons. The burden of LY+ neurons increased based on head rotational kinematics, specifically maximum angular velocity, and was exacerbated by repeated TBI. In the cortex, LY+ cells were prominent in both the medial and lateral gyri. Neuronal membrane permeability was observed within the hippocampus and entorhinal cortex, including morphological changes such as beading in dendrites. These changes correlated with reduced fiber volleys and synaptic current alterations at later timepoints in the hippocampus. Further histological observations found decreased NeuN immunoreactivity, increased mitochondrial fission, and caspase pathway activation in both LY+ and LY- cells, suggesting the presence of multiple injury phenotypes. This exploratory study suggests relationships between plasmalemmal disruptions in neuronal somata and dendrites within cortical and hippocampal gray matter as a primary response in closed-head rotational TBI and sets the stage for future, traditional hypothesis-testing experiments.

Recurrence patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.

OBJECTIVE: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). METHODS: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05). CONCLUSION: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS.