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Walking in daily life requires humans to adapt to environments that can influence one's fear of falling and anxiety about a potential fall. In such environments, individuals may adopt compensatory locomotor and balance changes to maintain a constant expected risk function equal to the product of the probability of some event (e.g., a fall) and the cost of that event (e.g., injury or death). Here, we tested whether locomotor behaviors broadly align with this risk model in two experiments with height-related threats in immersive virtual reality. In Experiment 1, we examined how individuals change their locomotor trajectory while walking along a straight high-elevation walkway. In Experiment 2, we examined how individuals change trajectory and balance control during curved walking where the location of high elevation threat varied. Participants adopted two behaviors that decreased their probability of falling off the edge and aligned with the risk-based model: participants altered their proximity to perceived threats that pose high costs (e.g., a high-elevation ledge), and decreased mediolateral center of mass velocity when that was not possible. Taken together, our results suggest that individuals alter locomotor behavior to change the probability of falling based on the perceived cost of that fall.

Chronic stress mediates cellular changes that can contribute to human disease. However, fluctuations in RNA metabolism caused by chronic stress have been largely neglected in the field. Stress granules (SGs) are cytoplasmic ribonucleoprotein condensates formed in response to stress-induced inhibition of mRNA translation and polysome disassembly. Despite the broad interest in SG assembly and disassembly in response to acute stress, SG assembly in response to chronic stress has not been extensively investigated. In this study, we show that cells pre-conditioned with low dose chronic (24-hour exposure) stresses such as oxidative stress, endoplasmic reticulum stress, mitochondrial stress, and starvation, fail to assemble SGs in response to acute stress. While translation is drastically decreased by acute stress in pre-conditioned cells, polysome profiling analysis reveals the partial preservation of polysomes resistant to puromycin-induced disassembly. We showed that chronic stress slows down the rate of mRNA translation at the elongation phase and triggers phosphorylation of translation elongation factor eEF2. Polysome profiling followed by RNase treatment confirmed that chronic stress induces ribosome stalling. Chronic stress-induced ribosome stalling is distinct from ribosome collisions that are known to trigger a specific stress response pathway. In summary, chronic stress triggers ribosome stalling, which blocks polysome disassembly and SG formation by subsequent acute stress., Significant Statements: Stress granules (SGs) are dynamic cytoplasmic biocondensates assembled in response to stress-induced inhibition of mRNA translation and polysome disassembly. SGs have been proposed to contribute to the survival of cells exposed to toxic conditions. Although the mechanisms of SG assembly and disassembly in the acute stress response are well understood, the role of SGs in modulating the response to chronic stress is unclear. Here, we show that human cells pre-conditioned with chronic stress fail to assemble SGs in response to acute stress despite inhibition of mRNA translation. Mechanistically, chronic stress induces ribosome stalling, which prevents polysome disassembly and subsequent SG formation. This finding suggests that chronically stressed or diseased human cells may have a dysfunctional SG response that could inhibit cell survival and promote disease.

Background: There is a paucity of research on the effects of commonly used substances, such as cannabis and other drugs, on quality of life as a contributor to head and neck cancer (HNC) prognosis. We examined associations between non-alcohol or tobacco substance use (cannabis and other illicit drug) and self-reported quality of life in patients with HNC prior to starting treatment., Methods: This was a cross-sectional study of patients who presented for routine psych-oncologevaluation prior to treatment between 11/2015 and 9/2022. Primary exposures were cannabis use (never, past, or current users) and current illicit drug use (yes/no). The primary outcome measure was the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) subscales (physical, social/family, functional and emotional). Linear regression models examined associations between pretreatment substance use and FACT-HN subscales adjusting for demographic, socioeconomic, and clinical factors., Results: Of 570 patients, 13.9% endorsed current cannabis and 13.9% current illicit drug use. The mean (SD) scores for FACT-HN subscales were physical well-being = 22.8 (5.0), social well-being = 22.7 (5.5), emotional well-being = 17.5 (4.5), and functional well-being = 18.7 (6.9). In the adjusted models, cannabis use was not independently associated with any FACT-HN subscales. However, patients who currently used illicit drugs reported worse emotional well-being (β = -1.32; 95% CI -2.45 to -0.20). No independent association was found between current illicit drug use and other subscales (physical, social, and functional)., Conclusions: Illicit drug use, but not cannabis use, is negatively associated with pretreatment emotional well-being in patients with HNC. Further research exploring the relationships between longitudinal cannabis and illicit drug use and methods of consumption on QoL and cancer outcomes in patients with head and neck cancer is warranted., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Neurocognitive impairments are sequelae of childhood cancer treatment, however little guidance is given to clinicians on common phenotypes of impairment or modifiable risk factors that could lead to personalized interventions in survivorship., Methods: Standardized clinical testing of neurocognitive function was conducted in 2958 (74.1%) eligible survivors, who were at least 5 years postdiagnosis and aged older than 18 years, and 477 community controls. Impairment was examined across 20 measures, and phenotypes were determined by latent class analysis. Multinomial logistic regression was used to estimate risk for phenotype, predicted by cancer diagnosis and treatment exposures, chronic health conditions, and lifestyle, adjusted for sex and age. Associations between phenotypes and social attainment were examined., Results: Five neurocognitive phenotypes were identified in survivors (global impairment 3.7%, impaired attention 5.0%, memory impairment 7.2%, processing speed and executive function impairment 9.3%, no impairment 74.8%). Risk of global impairment was associated with severe chronic health condition burden (odds ratio [OR] = 20.17, 95% confidence interval [CI] = 11.41 to 35.63) including cerebrovascular disease (OR = 14.5, 95% CI = 5.47 to 38.44) and cerebrovascular accident (OR = 14.7, 95% CI = 7.50 to 26.40). Modifiable risk factors, such as quitting smoking, reduced risk for global impairment (OR = 0.21, 95% CI = 0.06 to 0.66). Low physical activity increased risk for global impairment (OR = 4.54, 95% CI = 2.86 to 7.21), attention impairment (OR = 2.01, 95% CI = 1.41 to 2.87), processing speed and executive function impairment (OR = 1.90, 95% CI = 1.46 to 2.48), and memory impairment (OR = 2.09, 95% CI = 1.54 to 2.82)., Conclusions: Results support the clinical utility of neurocognitive phenotyping to develop risk profiles and personalized clinical interventions, such as preventing cerebrovascular disease in anthracycline-treated survivors by preventing hypercholesterolemia, smoking, and sedentary lifestyle, to reduce the risk for global impairment., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: 2017 blood pressure (BP) categories focus on cardiac risk. We hypothesize that studying the balance between mechanisms that increase or decrease BP across the medical phenome will lead to new insights. We devised a classifier that uses BP measures to assign individuals to mutually exclusive categories centered in the upper (Htn), lower (Hotn) and middle (Naf) zones of the BP spectrum; and examined the epidemiologic and phenotypic patterns of these BP-categories., Methods: We classified a cohort of 832,560 deidentified electronic health records by BP-category; compared the frequency of BP-categories and four subtypes of Htn and Hotn by sex and age-decade; visualized the distributions of systolic, diastolic, mean arterial and pulse pressures stratified by BP-category; and ran Phenome-wide Association Studies (PheWAS) for Htn and Hotn. We paired knowledgebases for hypertension and hypotension and computed aggregate knowledgebase status (KB-status) indicating known associations. We assessed alignment of PheWAS results with KB-status for phecodes in the knowledgebase, and paired PheWAS correlations with KB-status to surface phenotypic patterns., Results: BP-categories represent distinct distributions within the multimodal distributions of systolic and diastolic pressure. They are centered in the upper, lower, and middle zones of mean arterial pressure and provide a different signal than pulse pressure. For phecodes in the knowledgebase, 85% of positive correlations align with KB-status. Phenotypic patterns for Htn and Hotn overlap for several phecodes and are separate for others. Our analysis suggests five candidates for hypothesis testing research, two where the prevalence of the association with Htn or Hotn may be under appreciated, three where mechanisms that increase and decrease blood pressure may be affecting one another's expression., Conclusion: PairedPheWAS methods may open a phenome-wide path to disentangling hypertension and chronic hypotension. Our classifier provides a starting point for assigning individuals to BP-categories representing the upper, lower, and middle zones of the BP spectrum. 4.7 % of individuals matching 2017 BP categories for normal, elevated BP or isolated hypertension, have diastolic pressure < 60. Research is needed to fine-tune the classifier, provide external validation, evaluate the clinical significance of diastolic pressure < 60, and test the candidate hypotheses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: William Stead and Lisa Bastarache report financial support was provided by National Center for Advancing Translational Sciences. Lisa Bastarache reports financial support was provided by National Library of Medicine. William Stead reports a relationship with National Heart Lung and Blood Institute that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Loss to follow-up (LTFU) in primary open-angle glaucoma (POAG) can lead to undertreatment, disease progression, and irreversible vision loss. Patients who become LTFU either eventually re-establish glaucoma care after a lapse or never return to the clinic. The purpose of this study is to examine a large population of patients with POAG who became LTFU to determine the proportion that return to care and to identify demographic and clinical factors associated with nonreturn after LTFU., Design: Retrospective longitudinal cohort study., Participants: Patients with a diagnosis of POAG with a clinical encounter in 2014 in the IRIS® Registry (Intelligent Research in Sight)., Methods: We examined follow-up patterns for 553 663 patients with POAG who had an encounter in the IRIS Registry in 2014 by following their documented clinic visits through 2019. LTFU was defined as exceeding 1 calendar year without an encounter. Within the LTFU group, patients were classified as returning after a lapse in care (return after LTFU) or not (nonreturn after LTFU)., Main Outcome Measures: Proportion of patients with nonreturn after LTFU and baseline demographic and clinical characteristics associated with nonreturn among LTFU patients with POAG., Results: Among 553 663 patients with POAG, 277 019 (50%) had at least 1 episode of LTFU over the 6-year study period. Within the LTFU group, 33% (92 471) returned to care and 67% (184 548) did not return to care. Compared to those who returned to care, LTFU patients with nonreturn were more likely to be older (age >80 years; relative risk [RR] = 1.48; 95% confidence interval [CI]: 1.47-1.50), to have unknown/missing insurance (RR = 1.31; 95% CI: 1.30-1.33), and to have severe-stage POAG (RR = 1.13; 95% CI: 1.11-1.15). Greater POAG severity and visual impairment were associated with nonreturn with a dose-dependent relationship in the adjusted model that accounted for demographic characteristics. Among those with return after LTFU, almost all returned within 2 years of last appointment (82 201; 89%) rather than 2 or more years later., Conclusions: Half of patients with POAG in the IRIS Registry had at least 1 period of LTFU, and two thirds of LTFU patients with POAG did not return to care. More effort is warranted to re-engage the vulnerable patients with POAG who become LTFU., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the landscape of policies that determine eligibility for family planning services through Medicaid programs and describe trends in eligibility and its determinants over time., Data Sources and Study Setting: Secondary data were collected for all states in the United States for the years 2008 through 2023. Data on economic and demographic characteristics came from the American Community Survey (ACS)., Study Design: Our descriptive study characterized state adoptions of Medicaid family planning section 1115 waivers and state plan amendments (SPA) and their eligibility criteria. We then estimated the proportion of women aged 19-44 years who were eligible for family planning services through Medicaid and identified the key determinants of changes in eligibility, by state and year., Data Collection/extraction Methods: Information on state Medicaid policies was extracted from documentation on the Centers for Medicare & Medicaid Services website. When estimating the eligible population sizes, the denominator was women aged 19-44 years, the group most likely to be eligible for Medicaid family planning programs. Supplemental data on program enrollment or utilization were collected from states' websites and reports., Principal Findings: Though eligibility limits for family planning through Medicaid generally increased over time, the proportion of women aged 19-44 years eligible for at least limited benefits decreased from 45.0% in 2012 to 39.4% in 2022, largely because of increases in household income. Trends varied considerably across states and by eligibility pathway. Among women with incomes below the poverty level, the proportion who were not eligible for Medicaid family planning services decreased from 6.3% in 2013 to 1.5% in 2022., Conclusions: Our data demonstrated substantial geographic and temporal variation in eligibility for family planning services through Medicaid. We identified key drivers of eligibility changes that may have important implications for health services analyses of means-tested public programs., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Premature aging is a significant concern in adult survivors of childhood cancer as they develop aging-related conditions at a younger age than their peers with no history of childhood cancer. Although modifiable lifestyle factors, such as diet, are postulated to affect aging process, supporting evidence is sparse., Methods: We examined if the consumption of sugar and sugar-sweetened beverages was related to premature aging in 3322 adult survivors of childhood cancer in the St. Jude Lifetime Cohort. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 44 conditions total. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: There were 46% of childhood cancer survivors consumed SSBs once or more times per day. High intake of sugar, especially sugars added to foods during preparation or processing, and habitual consumption of sugar-sweetened beverage were associated with an increased risk of premature aging., Discussion: Our findings support a need to include strategies to reduce sugar and sugar-sweetened beverages consumption in lifestyle interventions to promote healthy aging in adult survivors of childhood cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We recently explored the cardiopulmonary interactions during partial unloading of the respiratory muscles during exercise. Expanding upon this work, we present a noteworthy case study whereby we eliminated the influence of respiration on cardiac function in a conscious but mechanically ventilated human during exercise. This human was a young healthy endurance-trained male who was mechanically ventilated during semi-recumbent cycle exercise at 75 Watts (W) (∼30% W max ). During mechanically ventilated exercise, esophageal pressure was reduced to levels indistinguishable from the cardiac artefact which led to a 94% reduction in the power of breathing. The reduction in respiratory pressures and respiratory muscle work led to a decrease in cardiac output (-6%), which was due to a reduction in stroke volume (-13%), left ventricular end-diastolic volume (-15%), and left-ventricular end-systolic volume (-17%) that was not compensated for by heart rate. Our case highlights the influence of extreme mechanical ventilation on cardiac function while noting the possible presence of a maximal physiological limit to which respiration (and its associated pressures) impacts cardiac function when the power of breathing is maximally reduced., Competing Interests: The authors declare no competing interests.

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever ( P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (β = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change β = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (β = 9.3 [95% CI, 4.7 to 11.5]; P < .001).CONCLUSIONThese data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (r s ), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (r s  = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (r s  = -0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates., Competing Interests: None., (© 2024 Published by Elsevier Inc.)

Importance: Approximately 31 000 cases of human papillomavirus (HPV)-associated cancers are diagnosed annually in the US. The HPV vaccine can prevent more than 90% of these cancers, yet national uptake remains lower than the Healthy People 2030 target of 80% completion. To devise targeted interventions to increase the uptake of HPV vaccines, it is crucial to understand the vaccination rates across various health care settings., Objective: To examine the association between health care facility type and adolescent HPV vaccine uptake and clinician recommendation for the vaccine in the US., Design, Setting, and Participants: This cross-sectional study uses a complex sampling design of data from the 2020 National Immunization Survey-Teen. The study included adolescents aged 13 to 17 years. The data analysis was completed between March 1 and May 31, 2022., Exposure: Health care facility type classified as public, hospital-based, private, mixed (more than 1 type), and other facilities (eg, military health care facility; Women, Infants, and Children clinic; school-based health center; pharmacy)., Main Outcomes and Measures: Initiation of HPV vaccination was defined as the receipt of at least 1 dose of the HPV vaccine and completion as receipt of at least 2 or 3 doses, depending on age of initiation. Parent or guardian self-reported clinician recommendation was categorized as yes or no. Weighted, multivariable logistic regression models were used to estimate the odds of initiating and completing the HPV vaccine series and receiving clinician recommendation by health care facility type adjusted for adolescent and maternal characteristics., Results: A total of 20 162 adolescents (mean [SD] age, 14.9 [1.4] years; 51.0% male) were included. Clinician recommendation for the HPV vaccine was received by 81.4% of adolescents, and 75.1% initiated and 58.6% completed the HPV vaccine series. In the adjusted analyses, adolescents who received recommended vaccinations at public facilities had lower odds of initiating (adjusted odds ratio [AOR], 0.71; 95% CI, 0.58-0.88) and completing (AOR, 0.62; 95% CI, 0.51-0.76) HPV vaccination compared with those who received recommended vaccinations at private facilities. Similarly, adolescents who received recommended vaccinations at public facilities (AOR, 0.62; 95% CI, 0.51-0.77) had lower odds of receiving a clinician recommendation for the HPV vaccine compared with those who received recommended vaccinations at private facilities., Conclusions and Relevance: These findings reveal health disparities in HPV vaccination among adolescent populations served by public health care facilities, suggesting that a greater focus is needed on vaccine recommendations and uptake in public facilities.

Purpose: To identify prevalence of and risk factors for loss to follow up (LTFU) among a national cohort of patients with primary open-angle glaucoma (POAG)., Methods: This retrospective cohort study analyzed data from the IRIS® Registry (Intelligent Research in Sight) database from 2014 through 2019 to assess LTFU among adult patients with POAG. POAG patients with at least one clinical encounter in 2014 were included. LTFU was defined as exceeding one year without a clinical encounter during the study period., Results: Among 553,663 glaucoma patients, 277,019 (50%) became LTFU, of whom 184,548 (67%) never returned to care and 92,471 (33%) re-established follow-up after a lapse. Risk of LTFU was greatest among those younger than 60 years (RR = 1.38; 95% CI: 1.36-1.39) or older than 80 years (RR = 1.39; 95% CI: 1.38-1.40) compared to those in their 60s. Compared to White race, risk for LTFU was highest among Native Hawaiian/Pacific Islander (RR = 1.24; 95% CI: 1.17-1.31), Hispanic ethnicity (RR = 1.19; 95% CI: 1.18-1.20), and Black race (RR = 1.10; 95% CI: 1.09-1.11). Medicare insurance was associated with lower risk of LTFU (RR = 0.79; 95% CI: 0.78-0.79), whereas unknown/missing/no insurance was associated with greater risk (RR = 1.33; 95% CI: 1.32-1.34), compared to private insurance. Compared to mild-stage POAG, risk of LTFU was higher for moderate-stage (RR = 1.10; 95% CI: 1.08-1.13) and severe-stage disease (RR = 1.35; 95% CI: 1.32-1.38)., Conclusion: We found a 50% prevalence of LTFU among POAG patients in the IRIS Registry over a 6-year study period, with greater risk among minority groups and those with more advanced disease.

Importance: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons at the spinal or bulbar level., Objective: We aim to describe the most frequent otolaryngology (ORL) complaints and voice disturbances in patients with bulbar onset ALS., Design: Retrospective cohort study., Setting: Single-center study with combined ORL and ALS clinic evaluation., Participants: Patients with a confirmed diagnosis of ALS following an ORL visit and who underwent comprehensive voice assessments between January 2021 and January 2023., Exposure: Objective voice assessments., Main Outcomes and Measures: Glottal functional index (GFI), voice handicap index (VHI), reflux system index (RSI), and voice quality characteristics such as shimmer, jitter, maximum phonation time (MPT), and other essential parameters were assessed., Results: One hundred and thirty-three patients (age 62.17 ± 10.79, 54.48% female) were included. Three patients were referred from the ORL department to the ALS clinic. The most frequent symptoms were; dysphagia, dysarthria, facial weakness, pseudobulbar affect, and sialorrhea. The mean of forced vital capacity was 59.85%, EAT-10 15.91 ± 11.66, RSI 25.84 ± 9.03, GFI 14.12 ± 5.58, VHI-10 42.81 ± 34.94, MPT 15.22 s ± 8.06. Many patients reported voice impairments mainly related to spastic dysarthria and the combination of lower and upper motor neuron dysarthria, hypernasality, reduced verbal expression, and articulatory accuracy. Shimmer was increased to 8.46% ± 7.20, and jitter to 2.26% ± 1.39., Conclusions and Relevance: Based on our cohort, this population with bulbar onset ALS has a higher frequency of voice disturbance characterized by hypernasality, spastic dysarthria, and reduced verbal expression., Level of Evidence: Level 3., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amy Rutt reports administrative support was provided by Mayo Clinic in Florida. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Energetic resources fuel immune responses and parasite growth within organisms, but it is unclear whether energy allocation is sufficient to explain changes in infection outcomes under the threat of multiple parasites. We manipulated diet in flour beetles ( Tribolium confusum ) infected with two natural parasites to investigate the role of resources in shifting metabolic and immune responses after single and co-infection. Our results suggest that gregarine parasites alter the within-host energetic environment, and by extension juvenile development time, in a diet-dependent manner. Gregarines do not affect host resistance to acute bacterial infection but do stimulate the expression of an alternative set of immune genes and promote damage to the gut, ultimately contributing to reduced survival regardless of diet. Thus, energy allocation is not sufficient to explain the immunological contribution to coinfection outcomes, emphasizing the importance of mechanistic insight for predicting the impact of coinfection across levels of biological organization.

Introduction: Various factors impact outcomes following bariatric surgery. Lack of access to healthy food options (food insecurity [FI]) is another potential factor affecting outcomes. No prior studies have directly explored the relationship between residing in a high FI zip code and patient outcomes relating to weight loss after bariatric surgery. We hypothesized that living in a high FI zip code would be associated with decreased weight loss postsurgery., Methods: We conducted a retrospective study with 210 bariatric surgery patients at a tertiary referral center from January to December 2020. Patient weight and body mass index (BMI) were recorded at three time points: surgery date, 1 mo, and 12 mo postoperative. Residential addresses were collected, and FI rates for the corresponding Zip Code Tabulation Areas were obtained from the 2022 Feeding America Map the Meal Gap study (2020 data)., Results: The FI rate showed a negative correlation of -18.3% (95% confidence interval: -35% to -0.5%; P = 0.039) with the percentage of excess weight loss (%EWL) at 1 y. In multivariate analysis, preoperative BMI (P = 0.001), presence of diabetes mellitus (P = 0.008), and bariatric procedure type (P = 0.000) were significant predictors of %EWL at 1 y. After adjusting for confounding factors, including sex, preoperative BMI, insurance status, primary bariatric procedure, and emergency department visits, the increased FI rate (P = 0.047) remained significantly associated with a decreased %EWL at 1 y., Conclusions: Residing in a high FI, Zip Code Tabulation Areas correlated with a decreased %EWL at 1 y after bariatric surgery. These findings highlight the importance of assessing FI status in pre-bariatric surgery patients and providing additional support to individuals facing FI., (Published by Elsevier Inc.)

Purpose: Although spurts in physical capacities during adolescence are well known, little is known about the existence of such spurts in sport-specific skill development, especially during the period of rapid growth in stature. Our aims were to examine the timing, intensity, and sequence of basketball-specific skill spurts aligned with biological (years from peak height velocity (PHV)) rather than chronological age. We then defined putative sensitive periods (windows of optimal development) for each skill aligned to the adolescent growth spurt., Methods: Altogether, 160 adolescent male basketballers aged 11-15 yr were tested biannually over 3 consecutive years. The years from attainment of PHV was estimated, and six skill tests were aligned to each year from PHV in 3-month intervals. Skill velocities were estimated using a nonsmooth polynomial model., Results: Maximal gains in slalom dribble occurred 12 months before PHV attainment (intensity, 0.18 m·s -1 ·yr -1 ), whereas in speed shot shooting (intensity, 9.91 pts·yr -1 ), passing (intensity, 19.13 pts·yr -1 ), and slalom sprint (intensity, 0.19 m·s -1 ·yr -1 ), these skill spurts were attained 6 months before PHV attainment. The mean gains in control dribble (intensity, 0.10 m·s -1 ·yr -1 ) and defensive movement (intensity, 0.12 m·s -1 ·yr -1 ) peaks coincided with attainment of PHV. We identified different sized windows for optimal development for each skill., Conclusions: Peak spurts in skill development, for most basketball skills, were attained at the same time as PHV. The multiple peaks observed within the defined windows of optimal development suggest that there is room for skill improvement even if gains might be greater earlier rather than later in practice. Our findings highlight the need to make coaches aware of where their players are relative to the attainment of PHV because different skills appear to develop differently relative to PHV. Such knowledge may help in designing more relevant training regimes that incorporate the athlete's current growth status so that skill development can be maximized., (Copyright © 2024 by the American College of Sports Medicine.)

Purpose: The primary goal of this scoping review was to summarize the literature published after the 2018 National Cancer Institute think tank, "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors," on physical and cognitive functional outcomes among cancer survivors treated with chemotherapy. We focused on the influence of chemotherapy on aging-related outcomes (i.e., physical functional outcomes, cognitive functional outcomes, and frailty), given the known associations between chemotherapy and biologic mechanisms that affect aging-related physiologic processes., Methods: A search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, for manuscripts published between August 2018 and July 2023. Eligible studies: 1) included physical function, cognitive function, and/or frailty as outcomes; 2) included cancer survivors (as either the whole sample or a subgroup); 3) reported on physical or cognitive functional outcomes and/or frailty related to chemotherapy treatment (as either the whole sample or a subgroup); and 4) were observational in study design., Results: The search yielded 989 potentially relevant articles, of which 65 met the eligibility criteria. Of the 65 studies, 49 were longitudinal, and 16 were cross-sectional; 30 studies (46%) focused on breast cancer, 20 studies (31%) focused on the age group 60 + years, and 17 (26%) focused on childhood cancer survivors. With regards to outcomes, 82% of 23 studies reporting on physical function showed reduced physical function, 74% of 39 studies reporting on cognitive functional outcomes found reduced cognitive function, and 80% of 15 studies reporting on frailty found increasing frailty among cancer survivors treated with chemotherapy over time and/or compared to individuals not treated with chemotherapy. Fourteen studies (22%) evaluated biologic mechanisms and their relationship to aging-related outcomes. Inflammation was consistently associated with worsening physical and cognitive functional outcomes and epigenetic age increases. Further, DNA damage was consistently associated with worse aging-related outcomes., Conclusion: Chemotherapy is associated with reduced physical function, reduced cognitive function, and an increase in frailty in cancer survivors; these associations were demonstrated in longitudinal and cross-sectional studies. Inflammation and epigenetic age acceleration are associated with worse physical and cognitive function; prospective observational studies with multiple time points are needed to confirm these findings., Implications for Cancer Survivors: This scoping review highlights the need for interventions to prevent declines in physical and cognitive function in cancer survivors who have received chemotherapy., (© 2024. The Author(s).)

Purpose of Review: Family/unpaid caregivers play an important role in cancer care. This review aims to summarize caregiver communication experiences with healthcare professionals (HCPs)., Recent Findings: The Caregiver-Centered Communication model defines five core functions that HCPs should achieve when interacting with caregivers, including fostering relationships, exchanging information, recognizing and responding to caregiver emotions, aiding in decision making, and assisting in patient care management. The literature shows that caregivers have both positive and negative communication experiences with HCPs with respect to these five core functions. Factors at the caregiver (e.g., demographic characteristics, information sources, caregiving duration, health status), patient (e.g., demographic and clinical characteristics), and HCP levels (e.g., time constraints in clinical settings, communication skills) are associated with caregiver-HCP communication quality. Studies further show that these communication experiences may affect caregiver outcomes, including quality of life, mental health, resilience, and satisfaction with cancer care. Moreover, poor quality caregiver-HCP communication is associated with patient readmission to the hospital and unmet care needs. Interventions for caregivers or patient-caregiver dyads have been shown to enhance caregiver confidence and increase their engagement in communication with HCPs. Interventions for HCPs have shown efficacy in improving their communication skills, particularly in involving caregivers in decision-making discussions. Given time constraints during medical visits, we suggest conducting a caregiver assessment by navigators prior to visits to understand their communication needs. Additionally, reimbursing HCPs for time spent communicating with caregivers during visits could be beneficial. More research is needed to better understand how to enhance caregiver-HCP communication quality., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To assess the efficacy of electronic health record (EHR) messaging for re-engaging patients with ophthalmology care after a missed appointment., Design: Prospective, randomized clinical trial., Methods: The study setting was an academic ophthalmology department. The patient population comprised of return patients age 18 years or older with an appointment "no show," or missed appointment. Over 2 phases of recruitment, 362 patients with an active patient portal in the EHR were selected consecutively each business day. Patients were randomized using a web-based tool to receive a reminder to reschedule via a standard mailed letter only (control) or the mailed letter plus an electronic message through the EHR within 1 business day of the missed appointment (intervention). Reengagement with eye care was defined as attendance of a rescheduled appointment within 30 days of the no-show visit. Patient charts were reviewed for demographic and clinical data., Results: The average age of recruited patients was 59.9 years, just under half of the sample was male (42.5%, 154/362), and most patients were White (56.9%, 206/362) or Black (36.2%, 131/362). Patients were most commonly recruited from the retina service (39.2%, 142/362) followed by the glaucoma service (29.3%, 106/362). Many patients in this study had previous no-show appointments, with an average no-show rate of 18.8% out of all scheduled visits across our health system. In total, 22.2% (42/189) of patients in the intervention group attended a follow-up appointment within 30 days of their no-show visit compared to 11.6% (20/173) of the control group (OR, 2.186; 95% CI, 1.225-3.898; P = .008). When including only the 74 patients in the intervention group who read the intervention message in the patient portal, 28.4% (21/74) attended a follow-up compared to 11.6% (20/173) of the control group (P = .001)., Conclusions: EHR-based reminder messages sent within a business day of a missed appointment may promote re-engagement in ophthalmology care after appointment no-show., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context/objective: The risk for cardiovascular disease is amplified following spinal cord injury, but whether risk differs between the sexes remains unknown. Here, we evaluated sex differences in the prevalence of heart disease among individuals with spinal cord injury, and compared sex differences with able-bodied individuals., Design: The design was a cross-sectional study. Multivariable logistic regression analysis was conducted, using inverse probability weighting to account for the sampling method and to adjust for confounders., Setting: Canada., Participants: Individuals who participated in the national Canadian Community Health Survey., Interventions: Not applicable., Outcome Measures: Self-reported heart disease., Results: Among 354 individuals with spinal cord injury, the weighted prevalence of self-reported heart disease was 22.9% in males and 8.7% in females, with an inverse-probability weighted odds ratio of 3.44 (95% CI 1.70-6.95) for males versus females. Among 60,605 able-bodied individuals, the prevalence of self-reported heart disease was 5.8% in males and 4.0% in females, with an inverse probability weighted odds ratio of 1.62 (95% CI 1.50-1.75) for males versus females. The effect of male sex on increasing heart disease prevalence was about two times higher among individuals with spinal cord injury than able-bodied individuals (relative difference in inverse probability weighted odds ratios = 2.12, 95% CI 1.08-4.51)., Conclusion: Males with spinal cord injury exhibit a significantly higher prevalence of heart disease, compared with females with spinal cord injury. Moreover, relative to able-bodied individuals, spinal cord injury amplifies sex-related differences in heart disease. Overall, this work will inform targeted cardiovascular prevention strategies, and may also inform a better understanding of cardiovascular disease progression in both able-bodied and individuals with spinal cord injury.

Objective: Cartilaginous tumors of the larynx are rare, representing less than 1% of all laryngeal tumors. Chondromas are benign mesenchymal tumors characterized by a slow-paced growth, primarily originated in the cricoid cartilage, followed by the thyroid, arytenoid, and epiglottic cartilages. This scoping review aims to understand the extent of evidence on the epidemiology, clinical characteristics, morbidity, and recurrence of the laryngeal chondroma (LC)., Data Sources: MEDLINE (Ovid), Embase (Elsevier), Web of Science (Clarivate), Cochrane Central Register of Controlled Trials and Systematic Reviews, Lilacs, Scopus, and Google Scholar databases., Review Methods: The scoping review was conducted from 1816 to 2023, for observational studies describing LC. Titles and abstracts were screened for relevance, followed by an evaluation of the full text for eligibility. The data were collected from the qualifying articles, and a narrative summary of the outcomes was prepared., Results: One hundred and nineteen studies met the inclusion criteria. Ninety-four case reports, 22 case series, and 3 cohorts. Two hundred and four participants with a diagnosis of LC were described. Male:female ratio was 2.8:1. The most common localization was the cricoid (113; 47.08%), followed by the thyroid (45; 18.75%), and the arytenoid cartilage (27; 11.25%). Dyspnea (78.85%) and hoarseness (74.28%) were the most reported symptoms. The recurrence rate was 11.25%, and complications were uncommon following the resection., Conclusion: This scoping review found a low-frequency rate over all the cartilaginous laryngeal tumors. Most patients were treated with resection, with a low rate of malignancy conversion. This population has low attributable mortality, morbidity, and recurrence according to the current literature., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Gonorrhea's rapid development of antimicrobial resistance underscores the importance of new prevention modalities. Recent evidence suggests that a serogroup B meningococcal vaccine may be partially effective against gonococcal infection. However, the viability of vaccination and the role it should play in gonorrhea prevention are an open question., Methods: We modeled the transmission of gonorrhea over a 10-year period in a heterosexual population to find optimal patterns of year-over-year investment of a fixed budget in vaccination and screening programs. Each year, resources could be allocated to vaccinating people or enrolling them in a quarterly screening program. Stratifying by mode (vaccination vs. screening), sex (male vs. female), and enrollment venue (background screening vs. symptomatic visit), we consider 8 different ways of controlling gonorrhea. We then found the year-over-year pattern of investment among those 8 controls that most reduced the incidence of gonorrhea under different assumptions. A compartmental transmission model was parameterized from existing literature in the US context., Results: Vaccinating men with recent symptomatic infection, which selected for higher sexual activity, was optimal for population-level gonorrhea control. Given a prevention budget of $3 per capita, 9.5% of infections could be averted ($299 per infection averted), decreasing gonorrhea sequelae and associated antimicrobial use by similar percentages. These results were consistent across sensitivity analyses that increased the budget, prioritized incidence or prevalence reductions in women, or lowered screening costs. Under a scenario where only screening was implemented, just 5.5% of infections were averted., Conclusions: A currently available vaccine, although only modestly effective, may be superior to frequent testing for population-level gonorrhea control., Competing Interests: Conflict of interest and Sources of Funding: None declared., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Adolescents and young adults (AYAs) commonly receive cancer care in the community setting, but the availability of treatment options, resources, and support services for this population is not well known. The National Cancer Institute Community Oncology Research Program (NCORP) funds a network of practices whose mission is to increase access to cancer care and clinical trials in the community setting. We describe our interdisciplinary methodological approach to identify and characterize NCORP practices where AYAs receive cancer care. Methods: NCORP practices completed a cross-sectional Landscape Assessment to describe resources and practice characteristics. We established an interdisciplinary team of stakeholders to analyze the Landscape Assessment data relating to AYAs. Through an iterative process, we assessed NCORP practice responses to questions assessing AYA cancer care capacity, determined a threshold to define practices treating AYAs, and characterized these practices. Results: We determined that practices provide cancer care to AYAs if the following criteria were met: (1) endorsed having an AYA program ( n  = 20), (2) AYAs comprised ≥5% of annual cancer cases ( n  = 55), or (3) the practice treated ≥50 AYA cancer cases annually ( n  = 70). Of 271 NCORP practices, 100 (37%) met any criteria, whereas 87 (32%) did not; 84 (31%) could not be classified due to missing or unknown data. Conclusion: Using an interdisciplinary process, we define practices that treat AYAs in the community. We posit a uniform approach to examine resources and practice capacity for AYAs receiving cancer care across the United States to guide future AYA-focused cancer care delivery research development.

Objective: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas., Methods: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year., Results: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05)., Conclusion: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study investigated the performance of a generative artificial intelligence (AI) tool using GPT-4 in answering clinical questions in comparison with medical librarians' gold-standard evidence syntheses., Methods: Questions were extracted from an in-house database of clinical evidence requests previously answered by medical librarians. Questions with multiple parts were subdivided into individual topics. A standardized prompt was developed using the COSTAR framework. Librarians submitted each question into aiChat, an internally-managed chat tool using GPT-4, and recorded the responses. The summaries generated by aiChat were evaluated on whether they contained the critical elements used in the established gold-standard summary of the librarian. A subset of questions was randomly selected for verification of references provided by aiChat., Results: Of the 216 evaluated questions, aiChat's response was assessed as "correct" for 180 (83.3%) questions, "partially correct" for 35 (16.2%) questions, and "incorrect" for 1 (0.5%) question. No significant differences were observed in question ratings by question category (p=0.39). For a subset of 30% (n=66) of questions, 162 references were provided in the aiChat summaries, and 60 (37%) were confirmed as nonfabricated., Conclusions: Overall, the performance of a generative AI tool was promising. However, many included references could not be independently verified, and attempts were not made to assess whether any additional concepts introduced by aiChat were factually accurate. Thus, we envision this being the first of a series of investigations designed to further our understanding of how current and future versions of generative AI can be used and integrated into medical librarians' workflow.

While multi-level theories and frameworks have become a cornerstone in broader efforts to address HIV inequities, little is known regarding their application in adolescent and young adult (AYA) HIV research. To address this gap, we conducted a scoping review to assess the use and application of multi-level theories and frameworks in AYA HIV prevention and care and treatment empirical research. We systematically searched five databases for articles published between 2010 and May 2020, screened abstracts, and reviewed eligible full-text articles for inclusion. Of the 5890 citations identified, 1706 underwent full-text review and 88 met the inclusion criteria: 70 focused on HIV prevention, with only 14 on care and treatment, 2 on both HIV prevention and care and treatment, and 2 on HIV-affected AYA. Most authors described the theory-based multi-level framework as informing their data analysis, with only 12 describing it as informing/guiding an intervention. More than seventy different multi-level theories were described, with 38% utilizing socio-ecological models or the eco-developmental theory. Findings were used to inform the adaptation of an AYA World Health Organization multi-level framework specifically to guide AYA HIV research., (© 2024. The Author(s).)

This study measures changes in condomless anal sex (CAS) among HIV-negative men who have sex with men (MSM) who are not taking pre-exposure prophylaxis (PrEP). It considers the 2014-2019 cycles of the American Men's Internet Survey, a serial, cross-sectional web-based survey of US cisgender MSM aged ≥ 15 years, in which ~ 10% of each year's sample is drawn from the previous year. Among those surveyed for 2 years who remained HIV-negative and off PrEP, reports of having any CAS and of CAS partner number were compared across years. We disaggregated by partner HIV status, and considered demographic predictors. The overall population saw a significant 2.2 percentage-point (pp) increase in reports of any CAS year-over-year. Sub-populations with the largest year-on-year increases were 15-24-year-olds (5.0-pp) and Hispanic respondents (5.1-pp), with interaction (young Hispanic respondents = 12.8-pp). On the relative scale, these numbers correspond to 3.2%, 7.2%, 7.3% and 18.7%, respectively. Absolute increases were concentrated among partners reported as HIV-negative. Multivariable analyses for CAS initiation found effects concentrated among Hispanic and White youth and residents of fringe counties of large metropolitan areas. CAS partner number increases were similarly predicted by Hispanic identity and young age. Although condom use remains more common than PrEP use, increasing CAS among MSM not on PrEP suggests potential new HIV transmission pathways. Concentration of increases among 18-24-year-old MSM portends future increases in the proportion of newly diagnosed HIV that occur among youth. Concentration among young Hispanic MSM will likely expand existing disparities. Although reducing barriers to PrEP remains vital, condom promotion for MSM remains a key public health practice and appears to be missing key audiences. LGBTQ+-inclusive sex education is one avenue for enhancing these efforts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To identify dietary factors that are related to premature aging in adult survivors of childhood cancer, we examined the associations between plant food intakes and age-related deficit accumulation., Methods: A total of 3,322 childhood cancer survivors (age 18-65 years, mean = 31, standard deviation = 8.4) in the St Jude Lifetime Cohort had total fruit, total vegetables and subgroups, whole grains, refined grains, nuts/seeds, and nutrients intake assessed using a food frequency questionnaire. Premature aging at baseline was assessed by the deficit accumulation index (DAI) and categorized as low, medium, and high risk. Multinomial logistic regressions (reference: low risk) adjusting for confounders estimated odds ratios (ORs) and 95% CIs. Multivariable linear regression of a continuous intake against a continuous DAI was also performed., Results: Dark green vegetable (OR high v low = 0.47 [95% CI, 0.28 to 0.78] per 1/2 cup/1,000 kcal increment) and nuts/seeds intakes (OR high v low = 0.71 [95% CI, 0.47 to 1.08] per 1 oz/1,000 kcal increment; coefficient linear = -0.0115, P = .02) were associated with a lower risk of premature aging. Conversely, refined grain intake was related to an increased risk of premature aging (OR high v low = 1.33 [95% CI, 0.99 to 1.78], per 1 oz/1,000 kcal increment; coefficient linear = 0.0093, P = .005). Fruit and whole grain intakes were not associated with premature aging risk. Among nutrients abundant in plant foods, dietary folate intake was associated with a lower risk of premature aging (OR high v low = 0.89 [95% CI, 0.80 to 0.99] per 50 mcg/1,000 kcal increase). Beta-carotene, lutein/zeaxanthin, and vitamin E intakes from foods were also related to a modestly lower, but not statistically significant, risk of premature aging., Conclusion: Specific plant foods are associated with lower risk of premature aging, providing targets for the interventions to promote healthy aging in childhood cancer survivors.

There is limited research on female football players, especially related to their physical and cognitive performance under different climactic conditions. We analyzed the impact of a hot environmental temperature on physical performance and anticipation in elite female football players during a fatigue-inducing intermittent protocol. Elite female players (n = 21) performed the countermovement jump (CMJ) and responded to filmed sequences of offensive play under two distinct environmental temperatures (i.e., mild environment temperature- 20°C and 30% rh versus hot environment temperature- 38°C and 80% rh), interspersed by 1-week interval. Linear mixed models were used. CMJ performance declined following the intermittent protocol on both temperature conditions (p < 0.05). Moreover, there were significant main effects for protocol on CMJ speed (m/s) (p = 0.001; η p 2  = 0.12), CMJ power (p = 0.002; η p 2  = 0.11), and CMJ Height max (p = 0.002; η p 2  = 0.12). After performing the intermittent protocol, exposure to a hot temperature caused a greater decline in anticipation accuracy (mild temperature = 64.41% vs. hot temperature = 53.44%; p < 0.001). Our study shows impaired performance in elite female football players following an intermittent protocol under hot compared with mild environmental conditions. We report decreased performance in both CMJ and anticipation performance under hotter conditions. The results reveal that exposure to hot temperatures had a negative effect on the accuracy of their anticipatory behaviors. We consider the implication of the work for research and training interventions., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Purpose: Hodgkin lymphoma (HL) survivors experience neurocognitive impairment despite receiving no central nervous system-directed therapy, though little is known about the underlying mechanisms., Experimental Design: HL survivors (n = 197) and age-, sex- and race/ethnicity frequency-matched community controls (n = 199) underwent standardized neurocognitive testing, and serum collection. Luminex multiplex or ELISA assays measured markers of inflammation and oxidative stress. Linear regression models compared biomarker concentrations between survivors and controls and with neurocognitive outcomes, adjusting for age, sex, race, body mass index, anti-inflammatory medication, and recent infections., Results: HL survivors [mean (SD) current age 36 (8) years, 22 (8) years after diagnosis] demonstrated higher concentrations of interleukin-6 (IL6), high-sensitivity c-reactive protein (hs-CRP), oxidized low-density lipoprotein, and glutathione peroxidase (GPx), compared with controls (P's < 0.001). Among survivors, higher concentrations of IL6 were associated with worse visuomotor processing speed (P = 0.046). hs-CRP ≥3 mg/L was associated with worse attention, processing speed, memory, and executive function (P's < 0.05). Higher concentrations of malondialdehyde were associated with worse focused attention and visual processing speed (P's < 0.05). Homocysteine was associated with worse short-term recall (P = 0.008). None of these associations were statistically significant among controls. Among survivors, hs-CRP partially mediated associations between cardiovascular or endocrine conditions and visual processing speed, whereas IL6 partially mediated associations between pulmonary conditions and visuomotor processing speed., Conclusions: Neurocognitive function in long-term survivors of HL appears to be associated with inflammation and oxidative stress, both representing potential targets for future intervention trials., (©2024 American Association for Cancer Research.)

Background: The effects of SARS-CoV-2 have varied between significant waves of hospitalization., Research Question: Are cardiovascular complications different among the first, delta and omicron waves of hospitalized COVID-19 pneumonia patients?, Study Design and Methods: This was a multi-centre retrospective study of patients hospitalized with SARS-CoV-2 pneumonia: 632 were hospitalized during the first wave (March-July 2020), 1013 during the delta wave (September 2020-March 2021), and 323 during the omicron wave (January 2022-July 2022). Patients were stratified by wave and occurrence of cardiovascular events., Results: Among all hospitalized patients with cardiovascular events, patients in the omicron wave were younger (62.4 ± 14 years) than patients in the first wave (67.4 ± 7.8 years) and the delta wave (66.9 ± 12.6 years) and had a higher proportion of non-Hispanic White people than in the first wave (78.6% vs. 61.7%). For COVID-19 patients who suffered from cardiovascular events, the omicron wave patients had significantly higher neutrophil/lymphocyte ratio, white blood cell and platelet counts when compared to the first wave. Omicron wave patients had significantly lower albumin and B-type natriuretic peptide levels (only 5.8% of the first wave and 14.6% of the delta wave) when compared to either the first wave or delta wave patients. In COVID-19 patients who suffered cardiovascular events during hospitalization, mortality rate in the omicron wave (26.8%) was significantly lower than the first wave (48.3%), time to mortality for non-survivors of COVID-19 patients who suffered cardiovascular events was significantly longer in the omicron wave (median 16 days) than in the first wave (median 10 days)., Conclusions: Younger and white patients were affected with cardiovascular complications more often by the omicron variant. Despite higher neutrophil/lymphocyte ratio and WBC counts, the omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Roser, Samanapally, Ali, Xu, Han, Salunkhe, Deepti, McGuffin, Huang, Furmanek, Glynn, Ramirez, Jones, Mariyappa, Hogue, Williams, Huang, Arnold, Clifford, Pahwa, Kong and Huang.)

Background: Gluteal Compartment Syndrome (GCS) is a rare subtype of acute compartment syndrome (ACS), complex to diagnose and potentially fatal if left untreated. The incidence of ACS is estimated to be 7.3 per 100,000 in males and 0.7 per 100,000 in females [1-3]. Given its rare occurrence, the incidence of GCS is not well reported. In the case of GCS, the most common etiologies are surgical positioning, prolonged immobilization secondary to substance use or loss of consciousness, and traumatic injury. Clinical findings are pulselessness, pallor, parasthesia, paralysis, and most notably pain out of proportion. Swift diagnosis and treatment are imperative to reduce morbidity and mortality, however the ideal management of GCS is difficult to ascertain given the rare occurrence and variable presentation., Methods: Orthopaedic trauma database at a level 1 trauma center was reviewed to identify patients for whom the orthopaedic service was consulted due to suspicion of gluteal compartment syndrome. This yielded 11 patients between 2011 and 2019. Patients with a measured ΔP greater than 30 upon initial consultation and with a concerning exam requiring monitoring were included. Patient demographics, comorbidities, GCS etiology, laboratory values, physical exam findings, pain scores (0-10) and patient outcomes were collected via chart review. Patient demographic and injury characteristics were summarized using descriptive statistics., Results: Prolonged immobilization patients had worse outcomes including longer hospital stays (40.5 days) compared to trauma patients (4.5 days). All adverse medical outcomes recorded including acute renal failure, prolonged neuropathic pain, cardiopulmonary dysfunction were exclusively experienced by prolonged immobilization patients., Conclusions: Our descriptive study demonstrates the bimodal distribution of GCS patients based on etiology. Prolonged immobilization patients have a longer hospital course and more complications. Our study confirms prior reports and provides information that can be used to counsel patients and families appropriately about treatment and recovery following GCS., Level of Evidence: IV., Study Type: Epidemiological., Competing Interests: Dr. Hsu reports consultancy for Globus Medical and personal fees from Smith & Nephew speakers' bureau. For the remaining authors, no conflicts were declared., (© 2024 Published by Elsevier Ltd.)

Prcis: Most glaucoma patients with missed appointments report barriers to care and social risk factors. One third expressed interest in engaging with a patient navigator program. Most expressed interest in rescheduling., Purpose: The purpose of this study was to identify barriers to care among glaucoma patients with missed appointments and to assess their interest in a patient navigator program., Material and Methods: A cross-sectional study involving adult glaucoma patients from an academic eye center who missed their scheduled appointment between April 18 and July 25, 2022. Participants were surveyed about reasons for missed appointments, barriers to care, social risk factors, and interest in consulting with our patient navigator program., Results: Of 172 patients with a missed glaucoma appointment, 73% (126/172) were contacted, and 40% (51/126) of those completed the survey. Participant age averaged 67±14 years, half were female (25/51, 49%), and most identified as Black (27/51, 53%) or White (21/51, 40%). Barriers to seeing a doctor including difficulty scheduling appointments (13/51, 26%), transportation (12/51, 24%), and cost or insurance barriers (8/51, 16%). Twenty-eight (55%) respondents reported at least one social risk factor. A positive association was found between having at least one risk factor and expressing interest in consulting our patient navigator (odds ratio=6.7, P =0.009). Overall, a third of respondents expressed interest in engaging with our patient navigator program (17/51, 33%). Two thirds of participants reported awareness of missed appointments (34/51, 67%), of whom 35% (12/34) reported having already rescheduled, 41% (14/34) expressed interest in rescheduling, and 24% (8/34) did not wish to return., Conclusions: Glaucoma patients with missed appointments report barriers to care and face social risk factors. Telephone outreach may help to re-engage them with care, and patients expressed interest in a patient navigator program to address social needs., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This prospective randomized study evaluates surgical outcomes of head and neck free tissue transfer surgery performed by a single head and neck reconstructive surgeon comparing the use of surgical loupes and the operating microscope., Methods: Cases using surgical loupes were performed under ×3.5 magnification, whereas cases using the microscope were done using the standard operating microscope. Patient demographics, comorbidities, operative details, surgical outcomes, and flap failure were assessed., Results: Eighty-five free tissue transfer surgeries were included. Of these, 51.8% (n = 44) free tissue transfers were performed using loupe magnification and 48.2% (n = 41) were performed using the operating microscope. Total cases requiring intraoperative microvascular anastomosis revision was 12 (15.4%)-of these, 41.7% (n = 5) were originally performed with surgical loupes and 58.3% (n = 7) were with microscope (p = 0.24)., Conclusion: The current study provides novel, prospective data regarding a single head and neck reconstructive surgeon's experience at a single academic institution. From this, surgical loupes or the operating microscope can be used to perform head and neck microvascular reconstruction with no significant difference in rates of free tissue transfer failure or perioperative complications or outcomes., (© 2024 Wiley Periodicals LLC.)

Objective: Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors., Design: Cross-sectional study using retrospective cohort., Methods: In total, 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, and global cognition) and self-reported emotional distress were included in our study. Participants were stratified by sex and gonadal status. Outcomes were compared between hypogonadal and eugonadal groups by multivariable analysis, adjusting for established predictors, and mediation analyses to determine the direct/indirect effects of hypogonadism on outcomes., Results: The hypogonadal group exhibited a higher prevalence of neurocognitive impairment across domains, but no difference in emotional distress. Hypogonadal females exhibited higher relative risk (1.7, 95% CI, 1.2-2.5) for impaired visual processing speed, compared to eugonadal females after adjusting for cancer-related variables. In mediation models, hypogonadism had a significant direct (P < .01) and indirect (from P < .01) impact on impairment in visual processing speed among females. Males demonstrated direct (P = .03) and indirect (P = .04) impact of hypogonadism on motor processing speed., Conclusion: Processing speed may be the most vulnerable neurocognitive domain associated with hypogonadism in survivors, while other domains were mainly impacted by cancer-related variables. Our findings support the need for further evaluation of the impact of sex hormone replacement therapy on neurocognitive function., Competing Interests: Conflict of interest: None of the authors have any conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Migrating epithelial cells globally align their migration machinery to achieve tissue-level movement. Biochemical signaling across leading-trailing cell-cell interfaces can promote this alignment by partitioning migratory behaviors like protrusion and retraction to opposite sides of the interface. However, how signaling proteins become organized at interfaces to accomplish this is poorly understood. The follicular epithelial cells of Drosophila melanogaster have two signaling modules at their leading-trailing interfaces - one composed of the atypical cadherin Fat2 (also known as Kugelei) and the receptor tyrosine phosphatase Lar, and one composed of Semaphorin5c and its receptor Plexin A. Here, we show that these modules form one interface signaling system with Fat2 at its core. Trailing edge-enriched Fat2 concentrates both Lar and Semaphorin5c at leading edges of cells, but Lar and Semaphorin5c play little role in the localization of Fat2. Fat2 is also more stable at interfaces than Lar or Semaphorin5c. Once localized, Lar and Semaphorin5c act in parallel to promote collective migration. We propose that Fat2 serves as the organizer of this interface signaling system by coupling and polarizing the distributions of multiple effectors that work together to align the migration machinery of neighboring cells., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background: Maternal folate and vitamin B 12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B 12 status among women of reproductive age (WRA) in Malawi., Objective: We assessed folate and vitamin B 12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant., Methods: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B 12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design., Results: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B 12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education., Conclusions: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B 12 nutrition among Malawian WRA., (© 2024 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Tumor necrosis factor (TNF)α is a major regulator of inflammation. However, the epigenetic regulation of TNFα in the context of an exercise intervention among older adults with cancer is understudied. In this exploratory analysis, we used data from a single-arm mobile health (mHealth) exercise intervention among older adults with myeloid malignancies to 1) assess changes in TNFα promoter methylation, TNFα mRNA expression, serum TNFα and other related-cytokine levels after intervention; and 2) assess correlations between blood markers and exercise levels. Twenty patients were included. From baseline to post-intervention, there was no statistical changes in TNFα promoter methylation status at seven CpG sites, TNFα mRNA expression, and serum TNFα levels. Effect sizes, however, were moderate to large for several CpG sites (-120, -147, -162, and -164; Cohen's d = 0.44-0.75). Median serum TNFα sR1 levels increased (83.63, IQR 130.58, p = 0.06; Cohen's d = 0.18) but not the other cytokines. Increases in average daily steps were correlated with increases in TNFα promoter methylation at CpG sites -147 (r = 0.48; p = 0.06) and -164 (r = 0.51; p = 0.04). Resistance training minutes were negatively correlated with TNFα promoter methylation at CpG site -120 (r = -0.62; p = 0.02). All effect sizes were moderate to large. In conclusion, after a mHealth exercise intervention, we demonstrated changes with moderate to large effect sizes in several CpG sites in the TNFα promoter region. Exercise levels were correlated with increases in TNFα promoter methylation. Larger exercise trials are needed to better evaluate TNFα regulation to inform interventions to augment TNFα regulation in order to improve outcomes in older adults with cancer., Competing Interests: Declaration of competing interest Dr. Loh has served as a consultant to Pfizer and Seagen and has received honoraria from Pfizer. All other authors have no relevant conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Estimating the return on investment for public health services, tailored to the state level, is critical for demonstrating their value and making resource allocation decisions. However, many health departments have limited staff capacity and expertise to conduct economic analyses in-house., Program: We developed a user-friendly, interactive Excel-based spreadsheet model that health departments can use to estimate the impact of increases or decreases in sexually transmitted infection (STI) prevention funding on the incidence and direct medical costs of chlamydia, gonorrhea, syphilis, and STI-attributable HIV infections. Users tailor results to their jurisdictions by entering the size of their population served; the number of annual STI diagnoses; their prior annual funding amount; and their anticipated new funding amount. The interface was developed using human-centered design principles, including focus groups with 15 model users to collect feedback on an earlier model version and a usability study on the prototype with 6 model users to finalize the interface., Implementation: The STI Prevention Allocation Consequences Estimator ("SPACE Monkey 2.0") model will be publicly available as a free downloadable tool., Evaluation: In the usability testing of the prototype, participants provided overall positive feedback. They appreciated the clear interpretations, outcomes expressed as direct medical costs, functionalities to interact with the output and copy charts into external applications, visualization designs, and accessible information about the model's assumptions and limitations. Participants provided positive responses to a 10-item usability evaluation survey regarding their experiences with the prototype., Discussion: Modeling tools that synthesize literature-based estimates and are developed with human-centered design principles have the potential to make evidence-based estimates of budget changes widely accessible to health departments., Competing Interests: The authors declare they have no conflicts of interest.

Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, ∼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg; P = 0.021) and isocapnic hypoxia (placebo, 22 ± 5; pentoxifylline, 20 ± 4 mmHg; P = 0.029), but not in males. Acute pentoxifylline administration in lowlanders at 3,800 m had no impact on arterial blood gases, hemorheology, inflammation, gCBF, or ventilation. Unexpectedly, however, pentoxifylline reduced PASP in female participants, indicating a potential effect of sex on the pulmonary vascular responses to pentoxifylline. NEW & NOTEWORTHY We conducted a double-blind, placebo-controlled study on the rheological, cardiorespiratory and cerebrovascular effects of acute pentoxifylline in healthy lowlanders after 11-14 days at 3,800 m. Although red blood cell deformability was reduced and blood viscosity increased compared with low altitude, acute pentoxifylline administration had no impact on arterial blood gases, hemorheology, inflammation, cerebral blood flow, or ventilation. Pentoxifylline decreased pulmonary artery systolic pressure in female, but not male, participants.

The diagnosis of cancer during adolescent and young adulthood (AYA) may alter the development and psychological trajectory of survivors across their lifespan. The current review focuses broadly on emotional health, social functioning, health behaviors, and cancer-related cognitive impairment (CRCI) among AYA survivors. Overall, AYA survivors appear to be at elevated risk of emotional distress symptoms, mood and anxiety disorders, suicide, and mental health care service utilization compared with individuals without a cancer history. Difficulties with social relationships and reduced achievement of expected social outcomes including educational attainment and employment have been reported. Despite risk for health-related morbidities, including subsequent neoplasms, many AYA survivors do not engage in health behaviors at the recommended levels for physical activity, diet, or tobacco and alcohol use. Although CRCI has not been comprehensively characterized in this population, subgroups of AYA survivors appear to be at risk for experiencing CRCI, including survivors of central nervous system tumors, Hodgkin lymphoma, testicular, and breast cancer. Across each considered domain of psychological functioning, intervention efforts have largely focused on acceptability and feasibility with an increasing focus on e/mHealth approaches. Future research should include multiphase studies, including randomized controlled trials designed to evaluate intervention efficacy and effectiveness. It is imperative that psychological interventions consider the unique needs of AYA survivors by developmental stage and across multiple levels of influence (patient, support system, institution, and health care system).

Retinol binding protein (RBP) is used as a proxy for retinol in population-based assessments of vitamin A deficiency (VAD) for cost-effectiveness and feasibility. When the cut-off of < 0·7 μmol/l for retinol is applied to RBP to define VAD, an equivalence of the two biomarkers is assumed. Evidence suggests that the relationship between retinol and RBP is not 1:1, particularly in populations with a high burden of infection or inflammation. The goal of this analysis was to longitudinally evaluate the retinol:RBP ratio over 1 month of follow-up among fifty-two individuals exposed to norovirus ( n 26 infected, n 26 uninfected), test whether inflammation (measured as α -1-acid glycoprotein (AGP) and C-reactive protein (CRP)) affects retinol, RBP and the ratio between the two and assess whether adjusting vitamin A biomarkers for AGP or CRP improves the equivalence of retinol and RBP. We found that the median molar ratio between retinol and RBP was the same among infected (0·68) and uninfected (0·68) individuals. AGP was associated with the ratio and RBP individually, controlling for CRP, and CRP was associated with both retinol and RBP individually, controlling for AGP over 1 month of follow-up. Adjusting for inflammation led to a slight increase in the ratio among infected individuals (0·71) but remained significantly different from the expected value of one. These findings highlight the need for updated recommendations from the WHO on a cut-off value for RBP and an appropriate method for measuring and adjusting for inflammation when using RBP in population assessments of VAD.