Treatment Gaps and Emerging Therapies in Lumbar Disc Herniation.

BACKGROUND: Lumbar disc herniation (LDH) occurs when the central disc material, primarily the nucleus pulposus, is displaced beyond the outer annulus, compressing the spinal nerve roots. LDH symptoms, including radicular leg pain, radiculopathy, and low back pain, are associated with considerable disease burden and the significant utilization of health care resources. OBJECTIVES: Provide overview of the current treatment landscape for LDH, identify unmet needs, and describe emerging treatments. STUDY DESIGN: Narrative literature review. METHODS: A review of literature concerning available LDH treatments and associated outcomes was conducted in PubMed to identify areas of unmet need. Some key words included "lumbar disc herniation," "radicular leg pain," "sciatica," "treatment," "therapy," and "burden." RESULTS: For patients who do not respond to conservative therapy, epidural steroid injections (ESIs) are widely used for persistent LDH symptoms. While ESIs provide short-term improvements in radicular pain, evidence that ESIs bestow sustained benefits is limited. ESIs are not approved by the US Food and Drug Administration (FDA) and, in rare cases, carry risks of infection and neurological injury, as well as the potential for long-term systemic effects of glucocorticoids. In cases when nonsurgical treatment fails to relieve symptoms, lumbar discectomy can provide rapid pain relief; however, in addition to the risk of intraoperative complications, the long-term consequences of lumbar discectomy may include recurrent pain or herniation, revision discectomy, loss of disc height, and Modic changes. Treatments for LDH in late-stage clinical development include sustained-release ESI formulations and a novel agent for chemonucleolysis, a nonsurgical method of minimizing the volume of the displaced nucleus pulposus. Emerging minimally invasive therapies that address the underlying pathophysiology of the disease have the potential to bridge the gap between symptomatic treatments and surgery. LIMITATIONS: Because this paper was a narrative review, literature search and selection processes were not systematic in nature. The evidence regarding the long-term efficacy of some treatments, such as discectomy, was limited by the high rates of crossover between the treatment groups. CONCLUSIONS: The lack of sustained benefits associated with ESIs and the risks associated with surgery underscore the unmet need for novel, minimally invasive interventional therapies able to address the underlying nerve root compression in LDH.

Navigating the Discrepancy: How Cost of Living (COL) Adjustments Impact Otolaryngology Residents' Salaries.

OBJECTIVE: To compare differences in otolaryngology residents' salaries in different cities and states before and after adjusting for the cost of living. STUDY DESIGN: Cross-sectional analysis. SETTING: Accreditation Council for Graduate Medical Education (ACGME) otolaryngology residency program websites. METHODS: US otolaryngology residency programs were identified via the ACGME database in December 2023. Stipends posted by each residency program were compared to the cost of living (COL) for related states and major cities. A baseline value of 100 was used as the mean COL, values over 100 indicate above-mean COL. The weighted salary by state and cities for postgraduate year (PGY) 1 to 5 combined was expressed as mean (SD). Comparisons between salaries before and after adjustment for the COL were assessed using t tests. RESULTS: The mean otolaryngology residency stipend across the nation, by city, was $70,572 (n = 1290, range: $58,100-$93,402; SD = $8370), with a post-COL adjustment mean stipend of $64,055 (range: $39,193-$76,674, SD = $10,094, p < .001). Otolaryngology residents in Manhattan, New York State faced a mean decrease from $89,282 to $39,193 (-56%) post-COL adjustments. Following that were Boston and Los Angeles programs which saw a -$26,402 (-32%) and -$24,761 (-32%) mean decrease after COL adjustments, respectively. CONCLUSION: Otolaryngology residents in high-cost areas experience significant salary reductions because of COL adjustments, resulting in financial strain. Residents in such regions endure increased financial pressure compared to those in low-cost areas, as current salaries fail to align with living expenses.

Cost-effective quantification of uric acid using niobium oxide and graphene oxide-modified pencil-drawn electrodes on PVC substrates.

This study introduces a cost-effective approach for quantifying uric acid (UA), the main antioxidant species in human physiology and implicated in inflammatory regulation. Using a PVC substrate and pencil drawing technique, electrodes were fabricated and modified with niobium oxide and graphene oxide via a straightforward "drop casting" method. The nanostructures of the substrate, electrode, and modified electrode were evaluated using SEM images. The synergistic effect between these materials significantly facilitated the uric acid oxidation process with a 400 mV peak potential shift and 45% current increase. The evaluation of the electrode's response to common blood and urine components showed minimal deviation. Among the components tested-ascorbic acid, glucose, nitrate, nitrite, cysteine, urea, creatinine, and ammonium ion-only the ammonium ion exhibited a 10% interference at concentrations commonly found in urine. The sensors showed a good detection limit of 8.7 µmol L-1, with a wide linear range from 8.7 to 2000 µmol L-1 with a correlation factor of 0.9993 for five different sensors. The reproducibility and repeatability of the produced sensors were estimated by the RSD at 4% and 1%, respectively. Synthetic urine samples spiked exhibited reliable analysis, with recovery values within a 5% error margin. This work presents a practical, simple, and affordable sensor platform for rapid and accurate UA quantification.

Unmasking Nasal Septal Hematoma/Abscess: A Systematic Review and Meta-analysis.

Objective: We aim to discuss the demographics, symptoms, bacteriology, treatment, and sequelae associated with nasal septal hematoma/nasal septal abscess (NSH/NSA). Data Sources: CINAHL, PubMed, and Scopus were searched from inception until October 15, 2023. Review Methods: Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines were followed. Inclusion criteria included patients who were diagnosed with a traumatic NSH/NSA. NSH/NSA due to surgical procedures was excluded. Demographics included N of patients, patient age, and gender. Symptoms, antibiotics given, bacteriology, and sequelae were analyzed. Meta-analysis of continuous measures (mean, median), and proportions (%) with a 95% confidence interval (CI) was conducted. Results: Thirty studies (N = 598) were included. In total, 72.1% were males (95% CI: 67-78). The total mean age was 21.6 years (range: 0.2-85, 95% CI: 17.2-26.1). The mean time from trauma to diagnosis was 8.2 days. Common symptoms at presentation included nasal obstruction/congestion at 60.3% (95% CI: 37.1-81.4), nasal pain at 30.0% (17.2-44.6), swelling at 20.4% (8.7-35.5), headache at 15.5% (7.3-26.0), and fever at 13.9% (7.3-22.2). The most common pathogens isolated included Staphylococcus aureus at 56.5% (49.0-63.8), Streptococcus species at 8.9% (5.2-14.0), and Klebsiella pneumoniae at 6.3% (3.2-10.8). Antibiotics given included amoxicillin-clavulanate at 10.3% (4.5-18.2), metronidazole at 9.5% (1.1-24.9), ampicillin-sulbactam at 8.9% (0.4-26.5), and unspecified antibiotics at 39.7% (13.8-69.2). The most common sequelae were nasal septal deformity/cartilage destruction at 14.3% (7.7-22.6). Conclusion: NSA/NSH has an 8-day delay in diagnosis from the time of trauma. First-line practitioners should be made aware of the signs and symptoms of this condition to minimize the risk of morbidity.

Call to Action: Quality and Simulation Professionals Should Collaborate.

SUMMARY STATEMENT: Simulation is underutilized as a tool to improve healthcare quality and safety despite many examples of its effectiveness to identify and remedy quality and safety problems, improve teamwork, and improve various measures of quality and safety that are important to healthcare organizations, eg, patient safety indicators. We urge quality and safety and simulation professionals to collaborate with their counterparts in their organizations to employ simulation in ways that improve the quality and safety of care of their patients. These collaborations could begin through initiating conversations among the quality and safety and simulation professionals, perhaps using this article as a prompt for discussion, identifying one area in need of quality and safety improvement for which simulation can be helpful, and beginning that work.

Patient-Reported Outcome Measures for Pelvic Organ Prolapse: A Systematic Review Using the COnsensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Checklist.

BACKGROUND: Patient-reported outcome measures (PROMs) are recommended to measure the impact of a health condition or intervention effectiveness as they aim to capture what is most meaningful to patients. Several PROMs are used to evaluate pelvic organ prolapse (POP)-related domains, yet the measurement properties of these instruments have not been fully explored with a rigorous analysis of the methodological quality and quality of evidence. OBJECTIVE: To conduct a systematic review reporting on the measurement properties of PROMs used for the assessment of POP-related domains in accordance with the COSMIN guidelines. SEARCH STRATEGY: Five databases were searched from inception to December 2023. SELECTION CRITERIA: Studies were eligible if they involved (1) at least one group of female adults diagnosed with or presenting with symptoms of POP; (2) a self-reported outcome measure (PROMs, questionnaires) to evaluate POP-related domains; and (3) at least one measurement property. DATA COLLECTION AND ANALYSIS: Methodological quality and measurement quality were assessed using the COSMIN risk of bias (ROB) checklist and the COSMIN criteria for good measurement properties. MAIN RESULTS: A total of 13 PROMs were included. The BIPOP had the lowest ROB for Content Validity. The POP-SS was the only PROM with sufficient evidence of adequate construct validity and responsiveness to be used in both surgical and conservative management settings. CONCLUSION: This original work identified a gap in evidence regarding the measurement qualities of identified PROMs used in the POP population.

The role of single case experimental designs in evidence creation in rehabilitation.

Randomized controlled trials (RCTs) are considered the gold standard of evidence guiding intervention selection in rehabilitation. However, conduct of sufficiently powered RCTs in rehabilitation can be expensive, pose ethical and attrition concerns when participants are assigned to ineffective treatment as usual conditions, and are infeasible with low-incidence populations. Single-case experimental designs (SCEDs), including N-of-1 RCTs are causal inference studies for small numbers of participants and not necessarily one participant as the name implies. These designs are increasingly used to evaluate the effectiveness of rehabilitation interventions in diverse clinical settings and employ design features including but not limited to randomization and each participant serving as their own control. These and other internal validity enhancements can increase the confidence in study results coming from these designs. This manuscript discusses the expanded application of SCEDs in rehabilitation contexts to answer everyday clinical rehabilitation research questions with emphasis on strategies to use: 1) to maximize internal validity of this family of designs; 2) improve utility, effectiveness, and acceptability of these designs for rehabilitation end-users (clinicians, policymakers, and participants); 3) build evidence bases in areas of rehabilitation where RCTs are uncommonly used. Primary considerations for situating SCEDs within the continuum of experimental designs include increasing internal validity within designs, improving transparency in conduct and reporting of these studies, and increasing access to advanced research methods training for rehabilitation professionals.

Protocol for a pilot study: Feasibility of a web-based platform to improve nutrition, mindfulness, and physical function in people living with Post COVID-19 condition (BLEND).

Individuals with Post COVID-19 condition (PCC), or long COVID, experience symptoms such as fatigue, muscle weakness, and psychological distress, including anxiety, depression, or sleep disorders that persist after recovery from COVID-19. These ongoing symptoms significantly compromise quality of life and diminish functional capacity and independence. Multimodal digital interventions targeting behavioural factors such as nutrition and mindfulness have shown promise in improving health outcomes of people with chronic health conditions and may be beneficial for those with PCC. The BLEND study (weB-based pLatform to improve nutrition, mindfulnEss, and physical function, in patients with loNg COVID) study is an 8-week pilot randomized controlled trial evaluating the feasibility of a digital wellness platform compared to usual care among individuals with PCC. The web-based wellness platform employed in this study, My Viva Plan (MVP)®, integrates a holistic, multicomponent approach to promote wellness. The intervention group receives access to the digital health platform for 8 weeks with encouragement for frequent interactions to improve dietary intake and mindfulness. The control group receives general content focusing on improvements in dietary intake and mindfulness. Assessments are conducted at baseline and week 8. The primary outcome is the feasibility of platform use. Secondary and exploratory outcomes include a between-group comparison of changes in body composition, nutritional status, quality of life, mindfulness, physical activity, and physical performance after 8 weeks. Findings of this study will inform the development of effective web-based wellness programs tailored for individuals with PCC to promote sustainable behavioural changes and improved health outcomes.

A place to call our home: innovative rural physical therapy training in Canada.

BACKGROUND: To promote rural practice and increase enrollment in the entry-level Master of Science Physical Therapy program at the University of Alberta, the Department of Physical Therapy developed a rural physical therapy satellite campus located in a farming region in central Alberta. A distributed learning format was used to connect the rural cohort to the main urban campus. Real time video conferencing was used to connect the two campuses for all lectures, seminars and clinical skills classes. This evaluation aimed to describe a unique rural training program for physical therapy students and its effectiveness in promoting work in rural communities after graduation. METHODS: Physical Therapy students in the first three years (2012-2015) of commencing the rural satellite program (n = 280) were surveyed, and six focus groups were held to capture student experiences, satisfaction and engagement. Data were collected on employment locations of the 2012-2019 graduates' first physical therapy position and current employment. RESULTS: Survey results suggested comparable levels of satisfaction and engagement for all physical therapy students regardless of campus. Focus group data revealed that students quickly accepted the distributed learning technological interface, enjoyed their local campuses, and felt connected to instructors and student colleagues. Compared to the overall physical therapy workforce, a higher percentage of physical therapists graduating from the rural campus reported working in rural centers for both their first and current jobs. CONCLUSION: Regardless of campus, students were satisfied and equally engaged in the physical therapy program. Students who completed the physical therapy program in a rural setting tended to work rurally after graduation. A distributed learning model may be useful for other healthcare training programs to promote engagement in rural health.

Evaluation of the Deletion of African Swine Fever Virus E111R Gene from the Georgia Isolate in Virus Replication and Virulence in Domestic Pigs.

African swine fever virus (ASFV) is the causative agent of an often lethal disease in domestic pigs, African swine fever (ASF). ASF is currently a pandemic disease challenging pig production in Eurasia. While the ASFV genome encodes for over 160 proteins, the function of most of them are still not characterized. Among those ASF genes with unknown functions is the E111R gene. It has been recently reported that the deletion of the E111R gene from the genome of the virulent Chinese field isolate SY18 strain produced a reduction of virus virulence when pigs were inoculated at relatively low doses. Conversely, we report here that deletion of the ASFV gene E111R in the Georgia 2010 isolate does not alter the virulence of the parental virus in experimentally inoculated pigs. A recombinant virus lacking the E111R gene, ASFV-G-∆E111R was intramuscularly (IM) inoculated in domestic pigs at a dose of 102 HAD50 of ASFV-G-∆E111R and compared with animals that received a similar dose of virulent ASFV-G. Both, animals inoculated with either the recombinant ASFV-G-∆E111R or the parental virus developed a fatal form of the disease and were euthanized around the 6th-7th day post-inoculation (dpi).

Challenges and recommendations for the translation of biomarkers of aging.

Biomarkers of aging (BOA) are quantitative parameters that predict biological age and ideally its changes in response to interventions. In recent years, many promising molecular and omic BOA have emerged with an enormous potential for translational geroscience and improving healthspan. However, clinical translation remains limited, in part due to the gap between preclinical research and the application of BOA in clinical research and other translational settings. We surveyed experts in these areas to better understand current challenges for the translation of aging biomarkers. We identified six key barriers to clinical translation and developed guidance for the field to overcome them. Core recommendations include linking BOA to clinically actionable insights, improving affordability and availability to broad populations and validation of biomarkers that are robust and responsive at the level of individuals. Our work provides key insights and practical recommendations to overcome barriers impeding clinical translation of BOA.

Computed Tomographic Characterization for Basivertebral Nerve Ablation Utilizing a Radiofrequency Multitined Expandable Electrode.

Background: A growing body of clinical evidence has demonstrated that intraosseous minimally invasive basivertebral nerve (BVN) ablation results in significant and durable improvements in vertebrogenic back pain. Thus, it is important to develop, refine and validate new and additional devices to accomplish this procedure. Methods: Using reconstructions of 31 patient computed tomography (CT) scans of the lumbosacral spine (L1-S1), the primary objective was to simulate the intravertebral placement of a novel multitined expandable electrode in bipolar configuration at the targeted ablation site and determine if the proper trajectories could be achieved in order for the device tips to be in the correct position for lesion formation at the BVN plexus. Successful device deployment required that the distance between tips was between 10 mm and 20 mm. Results: The mean distances between device tips ranged from 11.35 mm (L5) to 11.87 mm (L3), and there were no statistically significance differences across the six vertebral levels (F = 0.72, p = 0.61). The percentage of successful intraosseous device placements within the tip distance acceptable range (≥ 10 mm to ≤ 20 mm) was 90% (162 of 180), with no tip-to-tip distances > 20 mm. There was a notable association between decreasing vertebral level and mean degree of angulation between contralateral devices ranging from 50.90° at L1 to 91.51° at S1, and the difference between across the six vertebral levels was significant (F = 89.5, p < 0.01). Conclusion: Feasibility evidence is provided from real world CT imaging data that validates using the multitined electrode for proper intraosseous placement within the vertebral body to effectively ablate the BVN plexus.

Calibration-Free Analysis with Chronoamperometry at Microelectrodes.

Analytical methods are crucial for monitoring and assessing the concentration of important chemicals, and there is now a growing demand for methodologies that allow miniaturization, require lower sample volumes, and enable real-time analysis in the field. Most electroanalytical techniques depend on calibrations or standards, and this has several limitations, ranging from matrix interference, to stability problems, time required, cost and waste. Therefore, strategies that do not require standards or calibration curves greatly interest the analytical chemistry community. Here, we propose a new quantification method that does not rely on calibration and is only based on a single chronoamperometric curve recorded with a microelectrode. We show that satisfactory analytical information is obtained with just one chronoamperometric experiment that only takes a few seconds. We propose different data treatments to determine the unknown concentration, we consider the experimental conditions and instrument parameters, we report how parallel reactions affect the results, and we recommend procedures to implement the method in autonomous sensors. We also show that the concentration of several species can be derived if their E° values are sufficiently far apart or the sum of all concentrations if the E° values are too close. The proposed method was validated with a model redox system then further evaluated by determining ascorbic acid concentrations in standard solutions and food supplements, and paracetamol in a pain killer. The results for ascorbic acid were compared with those obtained by coulometry, and a good agreement was found, with a maximum deviation ca. 10.8%. The approach was also successfully applied to ascorbic acid quantification in solutions with different viscosity using ethylene glycol as a thickener.

Comparative analysis of sport-related concussion: how do 8- to 12-year-old athletes differ from 13- to 17-year-old athletes?

OBJECTIVE: Despite the growing literature on sport-related concussion (SRC) in high school and collegiate athletes, the understanding of how outcomes can vary in child athletes younger than 12 years of age remains limited. Therefore, the authors sought to compare injury characteristics and recovery in 8- to 12-year-old athletes with those of 13- to 17-year-old athletes following SRC. METHODS: A single-institution retrospective cohort study was undertaken including 8- to 12-year-old and 13- to 17-year-old athletes seen at a regional SRC between November 2017 and January 2022. Demographic information, injury characteristics, Post-Concussion Symptom Scale (PCSS) scores, and recovery (i.e., return to learn [RTL], symptom resolution, and return to play [RTP]) were compared between 8- to 12-year-old and 13- to 17-year-old athletes using the Mann-Whitney U-test and chi-square test. RESULTS: A total of 147 athletes (8- to 12-year-old athletes: n = 49; 13- to 17-year-old athletes: n = 98) were included. The mean ages for the younger and older groups were 10.9 ± 0.9 and 15.7 ± 1.3 years, respectively. Athletes aged 8-12 years and 13-17 years had similar median times to initial healthcare presentation (1 vs 2 days, p = 0.37). Athletes aged 8-12 years were more likely to present to the emergency department (ED) (44.9% vs 25.5%, p = 0.02) and receive head imaging (36.7% vs 19.4%, p = 0.02). Initial PCSS scores were similar between the groups (21.5 vs 22.0, p = 0.99). Athletes aged 8-12 years took longer to RTL (median 6.0 [IQR 4.0-13.0] days vs median 4.0 [IQR 2.0-8.0] days, p = 0.04). However, time to symptom resolution (median 16.0 [IQR 7.0-42.0] days vs median 13.5 [IQR 6.3-22.5] days, p = 0.34) and RTP (median 22.5 [IQR 10.0-54.8] days vs median 15.0 [IQR 10.0-24.0] days, p = 0.17) were not significantly different. CONCLUSIONS: Comparing 8- to 12-year-old with 13- to 17-year-old concussed athletes, the authors found that the initial PCSS score did not differ, although the younger group was more likely to present to the ED and receive head imaging. The 8- to 12-year-old athletes took more time to RTL, although no differences were found in time to symptom resolution or RTP.

Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: bone microarchitecture international consortium (BoMIC) prospective cohorts.

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9 years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height and weight, and then additionally adjusted for femoral neck (FN) aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 to -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, failure load and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.

Identifying individuals at risk for short-term fracture (within 2-years) is essential to offer prompt treatment. We examined bone microarchitecture at arm and lower leg for prediction of short-term fractures in 7327 older adults, independent of the common clinical practice measures ­ DXA-BMD and FRAX. After adjusting for other factors, we found that measures of failure load, cortical and trabecular bone microarchitecture and density predicted short-term risk of fracture beyond the usual clinical measures of DXA and FRAX. These measures of bone that indicate deficits in microarchitecture may be a useful adjunct to traditional assessment of fracture risk in older adults.

Image-based simulation of mitral valve dynamic closure including anisotropy.

Simulation of the dynamic behavior of mitral valve closure could improve clinical treatment by predicting surgical procedures outcome. We propose here a method to achieve this goal by using the immersed boundary method. In order to go towards patient-based simulation, we tailor our method to be adapted to a valve extracted from medical image data. It includes investigating segmentation process, smoothness of geometry, case setup and the shape of the left ventricle. We also study the influence of leaflet tissue anisotropy on the quality of the valve closure by comparing with an isotropic model. As part of the anisotropy analysis, we study the influence of the principal material direction by comparing methods to obtain them without dissection. Results show that our method can be scaled to various image-based data. We evaluate the mitral valve closure quality based on measuring bulging area, contact map, and flow rate. The results show also that the anisotropic material model more precisely represents the physiological characteristics of the valve tissue. Furthermore, results indicate that the orientation of the principal material direction plays a role in the effectiveness of the valve seal.

A systematic review of normal tissue neurovascular unit damage following brain irradiation-Factors affecting damage severity and timing of effects.

Background: Radiotherapy is key in the treatment of primary and secondary brain tumors. However, normal tissue is inevitably irradiated, causing toxicity and contributing to cognitive dysfunction. The relative importance of vascular damage to cognitive decline is poorly understood. Here, we systematically review the evidence for radiation-induced damage to the entire neurovascular unit (NVU), particularly focusing on establishing the factors that influence damage severity, and timing and duration of vascular effects relative to effects on neural tissue. Methods: Using PubMed and Web of Science, we searched preclinical and clinical literature published between January 1, 1970 and December 1, 2022 and evaluated factors influencing NVU damage severity and timing of NVU effects resulting from ionizing radiation. Results: Seventy-two rodents, 4 canines, 1 rabbit, and 5 human studies met inclusion criteria. Radiation increased blood-brain barrier (BBB) permeability, reduced endothelial cell number and extracellular matrix proteoglycans, reduced tight junction proteins, upregulated cellular adhesion molecule expression, reduced activity of glucose and BBB efflux transporters and activated glial cells. In the brain parenchyma, increased metalloproteinases 2 and 9 levels, demyelination, cell death, and inhibited differentiation were observed. Effects on the vasculature and neural compartment were observed across acute, delayed, and late timepoints, and damage extent was higher with low linear energy transfer radiation, higher doses, lower dose rates, broader beams, and in the presence of a tumor. Conclusions: Irradiation of normal brain tissue leads to widespread and varied impacts on the NVU. Data indicate that vascular damage is in most cases an early effect that does not quickly resolve. More studies are needed to confirm sequence of damages, and mechanisms that lead to cognitive dysfunction.

Improving adherence through collaboration and care coordination in the management of food allergies and asthma.

Food allergies and asthma significantly impact individual health and global healthcare systems. Despite established management protocols for asthma and the emerging use of oral immunotherapy for food allergy, adherence to treatments remains a challenge for healthcare professionals and patients. This review explores the differences in adherence required of asthma and food allergy treatments and strategies to improve adherence. We highlight the role of collaborative care coordination among healthcare professionals in enhancing adherence in asthma and food allergy management and improving patient outcomes.

Perceived Chronic Traumatic Encephalopathy and Suicidality in Former Professional Football Players.

Importance: Participation in American-style football (ASF) has been linked to chronic traumatic encephalopathy neuropathological change (CTE-NC), a specific neuropathologic finding that can only be established at autopsy. Despite being a postmortem diagnosis, living former ASF players may perceive themselves to have CTE-NC. At present, the proportion and clinical correlates of living former professional ASF athletes with perceived CTE who report suicidality are unknown. Objective: To determine the proportion, clinical correlates, and suicidality of living former professional ASF players with perceived CTE. Design, Setting, and Participants: A cross-sectional study within the Football Players Health Study at Harvard University was conducted from 2017 to 2020. Using electronic and paper surveys, this population-based study included former ASF players who contracted with a professional league from 1960 to 2020 and volunteered to fill out a baseline survey. Data for this study were analyzed from June 2023 through March 2024. Exposures: Data included demographics, football-related exposures (eg, position, career duration), and current health problems (anxiety, attention-deficit/hyperactivity disorder, depression, diabetes, emotional and behavioral dyscontrol symptoms, headache, hyperlipidemia, hypertension, low testosterone level, pain, sleep apnea, and subjective cognitive function). Main Outcomes and Measures: The proportion of participants reporting perceived CTE. Univariable and multivariable models were used to determine clinical and suicidality correlates of perceived CTE. Results: Among 4180 former professional ASF players who volunteered to fill out a baseline survey, 1980 (47.4%) provided follow-up data (mean [SD] age, 57.7 [13.9] years). A total of 681 participants (34.4%) reported perceived CTE. Subjective cognitive difficulties, low testosterone level, headache, concussion signs and symptoms accrued during playing years, depressive/emotional and behavioral dyscontrol symptoms, pain, and younger age were significantly associated with perceived CTE. Suicidality was reported by 171 of 681 participants with perceived CTE (25.4%) and 64 of 1299 without perceived CTE (5.0%). After adjusting for established suicidality predictors (eg, depression), men with perceived CTE remained twice as likely to report suicidality (odds ratio, 2.06; 95% CI, 1.36-3.12; P < .001). Conclusions and Relevance: This study found that approximately one-third of living former professional ASF players reported perceived CTE. Men with perceived CTE had an increased prevalence of suicidality and were more likely to have health problems associated with cognitive impairment compared with men without perceived CTE. Perceived CTE represents a novel risk factor for suicidality and, if present, should motivate the diagnostic assessment and treatment of medical and behavioral conditions that may be misattributed to CTE-NC.