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We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32 ± 3 years) and nine older (72 ± 3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water-perfused suit). Gastrointestinal permeability was assessed using a multi-sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I-FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP-2 (TIMP-2 × IGFBP7), neutrophil gelatinase-associated lipocalin and kidney injury molecule-1]. The lactulose-to-rhamnose ratio was increased in both young and older adults (group-wide: Δ0.11 ± 0.11), but the excretion of sucrose was increased only in older adults (Δ1.7 ± 1.5). Young and older adults showed similar increases in plasma LBP (group-wide: Δ0.65 ± 0.89 µg/mL), but no changes were observed for I-FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group-wide: Δ0.08 ± 0.07 mg/dL), cystatin C (group-wide: Δ0.16 ± 0.18 mg/L) and urinary IGFBP7 × TIMP-2 [group-wide: Δ0.64 ± 0.95 (pg/min) 2 ] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Purpose: Surgical patient optimization is a proactive approach to improve postoperative outcomes. This article reviews the development of the Surgical Patient Optimization Collaborative, an initiative supporting preoperative optimization in British Columbia, Canada., Methods: The Collaborative facilitated optimization programs over two cohorts between 2019 and 2024. A "Change Package" offered screening, intervention, and measurement tools for the following 13 surgical risk factors: anemia, anxiety, body mass index (cohort 2 only), cardiac status, frailty, glycemic control, nutrition, sleep apnea, pain management, physical activity, smoking, social support, substance use, and venous thromboembolism (cohort 1 only). Monthly data submissions from participating sites included the number of patients undergoing optimization, National Surgical Quality Improvement Program-defined 30-day outcomes, length of stay, and patient-reported measures. Run charts were used to analyze the progress of optimization implementation across both cohorts., Results: Fourteen sites participated in each cohort. In total, 9,686 patients were screened for optimization, with 7,100/7,505 (95%) patients receiving at least one optimization intervention. Improvement shifts in the number of patients screened were identified in the run charts across both cohorts. Most patients felt that their optimization improved their surgical experience and outcomes. Data for clinical outcomes were inconsistently reported from sites and precluded analyses. Barriers to implementation included project complexity and structural characteristics, and facilitators were knowledge and beliefs about the intervention, reflection, and evaluation., Conclusion: Preoperative optimization programs were successfully implemented across multiple sites in British Columbia. High-quality clinical outcome analyses are still needed to determine the impact of preoperative optimization on postoperative outcomes. The insight gained from the Collaborative's implementation process may help inform future multicentre preoperative optimization efforts., (© 2024. Canadian Anesthesiologists' Society.)

Purpose: Speech-language pathologists provide important services to people recovering from mild traumatic brain injury (mTBI), also called concussion, although they may be underutilized in outpatient care. Because health care providers face challenges in selecting assessments to efficiently describe patient needs, the purpose of this study was to describe factors related to patients receiving speech-language pathology services after mTBI, as well as how assessments predict amount of services received., Method: In this retrospective chart review study, demographic factors, injury characteristics, and assessment scores were extracted from medical records of patients aged 14-65 years receiving services for recent (within 6 months) mTBI at an outpatient specialty clinic. The Post-Concussion Symptom Scale (PCSS), Montreal Cognitive Assessment, Standardized Assessment of Concussion, and a newly developed self-report measure of cognitive-communication function-the Cognitive-Communication Referral Indicator for Concussion (CCoRI-C)-were used as dependent variables to predict speech-language pathology service referral. For those referred, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Behavior Rating Inventory of Executive Function (BRIEF) scores were added as dependent variables predicting speech-language pathology dosage., Results: A total of 132 patient charts met inclusion and exclusion criteria. In addition to CCoRI-C and PCSS symptoms, receiving imaging, being injured in a motor vehicle crash, experiencing loss of consciousness, and being of female sex were related to speech-language pathology referrals. Of the 77 patients referred for speech-language pathology care, higher CCoRI-C, PCSS, BRIEF, RBANS total, and RBANS visuospatial scores were associated with recommended speech-language pathology dosage. Only the CCoRI-C, BRIEF-Adult Version (BRIEF-A) Behavioral Regulation, and BRIEF-A Metacognition were associated with actual number of speech-language pathology sessions attended., Conclusions: Cognitive-communication symptoms and executive function may be important to planning speech-language pathology rehabilitative episodes of care for people with mTBI. Future work should continue to evaluate how assessments augment demographic and injury characteristics in decision making for both referral to and use of speech-language pathology services after mTBI.

It is necessary to accurately capture the growth trajectory of fluorescence where the best fit, precision, and relative efficiency are essential. Having this in mind, a new family of growth functions called TWW (Tabatabai, Wilus, Wallace) was introduced. This model is capable of accurately analyzing quantitative polymerase chain reaction (qPCR). This new family provides a reproducible quantitation of gene copies and is less labor-intensive than current quantitative methods. A new cycle threshold based on TWW that does not need the assumption of equal reaction efficiency was introduced. The performance of TWW was compared with 3 classical models (Gompertz, logistic, and Richard) using qPCR data. TWW models the relationship between the cycle number and fluorescence intensity, outperforming some state-of-the-art models in performance measures. The 3-parameter TWW model had the best model fit in 68.57% of all cases, followed by the Richard model (28.57%) and the logistic (2.86%). Gompertz had the worst fit in 88.57% of all cases. It had the best precision in 85.71% of all cases followed by Richard (14.29%). For all cases, Gompertz had the worst precision. TWW had the best relative efficiency in 54.29% of all cases, while the logistic model was best in 17.14% of all cases. Richard and Gompertz tied for the best relative efficiency in 14.29% of all cases. The results indicate that TWW is a good competitor when considering model fit, precision, and efficiency. The 3-parameter TWW model has fewer parameters when compared to the Richard model in analyzing qPCR data, which makes it less challenging to reach convergence., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs) but emerging variants and waning immunity challenge vaccine effectiveness. This study assesses the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Participants were subset of a longitudinal study of consented NHRs and Healthcare workers (HCWs) who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine post-FDA approval in Fall 2023. NHRs were categorized by whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). After XBB.1.5 vaccination, a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers was observed:17.3 (95% confidence interval [CI] 9.3, 32.4) and NHRs with interval infection and 11.3 (95% CI 5, 25.4) in those without and 13.6 (95% CI 8.4,22) in HCWs. For JN.1-specific titers, GMFRs were 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) in NHRs with and without interval infection, and 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher titers across all analyzed strains analyzed. The XBB.1.5 vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs with more pronounced in those previously infected with SARS-CoV-2 since bivalent vaccination., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The role of computed tomography (CT) before lumbar puncture (LP) is unclear, with limited evidence for a causal link between LP and cerebral herniation or for the ability of CT to identify individuals at risk of herniation. The risks of LP delay or deferral are potentially greater in high-HIV prevalence, resource-limited settings; we analyzed data from such a setting to determine the impact of CT on time to LP and treatment, as well as mortality., Methods: Adults with suspected central nervous system (CNS) infection were enrolled prospectively into the Botswana National Meningitis Survey between 2016 and 2019. Inpatient mortality and clinical data including time of treatment initiation and CT were captured from medical records. Associations between preceding CT and outcomes were assessed using logistic regression., Results: LPs were performed in 711 patients with suspected CNS infection; 27% had a CT before LP, and 73% were HIV positive. Time from admission to LP and time from admission to appropriate treatment were significantly longer in patients who had a CT before LP compared with those who did not (2.8 hours and 13.2 hours, respectively). There was some evidence for treatment delays being associated with increased mortality; however, there was no significant difference in mortality between those who had or did not have CT., Conclusions: Patients who had a CT had delays to diagnostic LP and initiation of appropriate treatment; although treatment delays were associated with increased mortality, our observational study could not demonstrate a causal association between delays in diagnosis and treatment introduced by CT and mortality., Competing Interests: Potential conflicts of interest. J.M., G.M.B., and J.N.J. have received investigator-initiated funding from bioMérieux. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objective: The Yorkshire Kidney Screening Trial (YKST) assessed the feasibility of adding abdominal noncontrast computed tomography (NCCT) to lung cancer screening to screen for kidney cancer and other abdominal pathology., Methods: A prospective diagnostic study offered abdominal NCCT to 55-80-yr-old ever-smokers attending a UK randomised lung cancer screening trial (May 2021 to October 2022). The exclusion criteria were dementia, frailty, previous kidney/lung cancer, and computed tomography (CT) of the abdomen and thorax within previous 6 and 12 mo, respectively. Six-month follow-up was undertaken., Key Findings and Limitations: A total of 4438 people attended lung screening, of whom 4309 (97%) were eligible for and 4019 (93%) accepted abdominal NCCT. Only 3.9% respondents regretted participating. The additional time to conduct the YKST processes was 13.3 min. Of the participants, 2586 (64%) had a normal abdominal NCCT, whilst 787 (20%) required an abdominal NCCT imaging review but no further action and 611 (15%) required further evaluation (investigations and/or clinic). Of the participants, 211 (5.3%) had a new serious finding, including 25 (0.62%) with a renal mass/complex cyst, of whom ten (0.25%) had histologically proven kidney cancer; ten (0.25%) with other cancers; and 60 (1.5%) with abdominal aortic aneurysms (AAAs). Twenty-five (0.62%) participants had treatment with curative intent. Of the participants, 1017 (25%) had nonserious findings, most commonly benign renal cysts (727 [18%]), whereas only 259 (6.4%) had nonserious findings requiring further tests. The number needed to screen to detect one serious abdominal finding was 18; it was 93 to detect one suspicious renal lesion and 402 to detect one histologically confirmed renal cancer. Limitations of the cohort were fixed age range and being prior lung cancer screening attendees., Conclusions and Clinical Implications: In this first prospective risk-stratified screening study of abdominal NCCT offered alongside CT thorax, uptake and participant satisfaction were high. The prevalence of serious findings, cancers, and AAAs, is in the range of established screening programmes such as bowel cancer. Longer-term outcomes and cost effectiveness should now be evaluated., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Surgical ligation and stripping (surgery) and endothermal ablation are both effective treatments for varicose veins, improving quality of life (QoL) up to 5 years. Few data are available on long-term outcomes. The aim of this study was to evaluate the outcomes 10 years after interventions in an RCT. Previously this RCT demonstrated that endothermal ablation is associated with superior postprocedural QoL, more rapid recovery, and lower rates of early clinical recurrence. This analysis reports outcomes at 10 years., Methods: Patients with symptomatic varicose veins owing to unilateral great saphenous vein reflux were randomized to either surgery or endovenous laser ablation (EVLA). Outcomes at 10 years included clinical recurrence and QoL., Results: Data were obtained for 206 of 280 patients (73.6%) at 10 years. Both groups retained significant QoL improvement compared with pretreatment levels (Aberdeen Varicose Vein Questionnaire (AVVQ), Short Form 36 (SF-36®), and EQ-5D™; P < 0.001). Clinical disease progression from baseline was observed in only 10.7% of patients. The clinical recurrence rate was lower in the EVLA group (37 versus 59%; P = 0.005). The number needed to treat with EVLA to avoid one clinical recurrence within 10 years was five. This was associated with significantly higher (better) generic QoL scores with EVLA in several SF-36® domains, including bodily pain (median 84 (i.q.r. 51-100) versus 62 (41-84); P = 0.009) and general health (77 (62-87) versus 67 (52-82); P = 0.017). AVVQ scores in the EVLA group were also lower (better) (3.1 (0-7.7) versus 6.3 (0.7-13.3); P = 0.029)., Conclusion: Both surgery and endothermal ablation are effective treatments for varicose veins at 10 years, with durable improvement in QoL and a very low rate of disease progression. However, endothermal ablation was associated with superior clinical and QoL outcomes. Registration number: NCT00759434 (http://www.clinicaltrials.gov)., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. 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.)

Purpose: College students with concussion experience academic, cognitive and psychosocial challenges, yet frequently lack supports necessary for successful reintegration into school. Success in College after Concussion with Effective Student Supports (SUCCESS) is a virtual peer mentoring program designed to provide education, support and connection through a mobile application. The purpose of this study was to describe use of personas as components of mobile app development and conduct preliminary testing of SUCCESS using personas., Methods: Personas were developed from case studies and portrayed by college students trained as fictitious mentees. Mentors were blinded to use of personas. Eleven mentors completed measures pre and post a 4-week mentoring cycle. Mentors and personas interacted in the app via chat, video calls and sharing of educational materials. Measures included the Post-Concussion Symptom Scale (PCSS); PROMIS Self-Efficacy; Depression, Anxiety and Stress Scale (DASS); and a series of focus groups., Results: Mentors suggested improvements to resolve instability of video calls, expand educational materials to address psychosocial functioning, and add structure to the mentoring relationship. Some preferences around communication, like groups chats and emoji keyboards, were not able to be addressed. As expected, PCSS scores were stable. DASS score ( p  = .04), especially depression ( p  = .03), decreased. PROMIS scores showed a trend towards growth ( p  = .057), although were not statistically significant., Conclusions: Use of personas allowed technical challenges and program refinements to be addressed before including students with subacute concussion in testing. Although continued development will address enhancement of communication modalities preferred by students, future efficacy testing of SUCCESS is warranted.

Objectives: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial., Methods: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability., Results: Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan., Conclusions: Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely., Competing Interests: GDS has received educational grants from Pfizer, AstraZeneca, and Intuitive Surgical; consultancy fees from Pfizer, BMS, Merck, EUSA Pharma, and CMR Surgical; travel expenses from Pfizer; and speaker fees from Pfizer. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Usher-Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tree of Life Groups (a narrative therapy technique) have been used successfully in a number of paediatric populations. The group intervention aims to give children a space to express their difficulties whilst also holding in mind their strengths and hopes, thereby creating a preferred identity incorporating their physical health condition. No studies were identified which described this approach in a paediatric epilepsy population or involving siblings, families and the multidisciplinary team., Methods: The current paper describes a pilot intervention to facilitate a one-day psychoeducational Tree of Life group for children with epilepsy, their siblings and parents. Separate parent and sibling groups were facilitated concurrently. The groups were co-facilitated by Paediatric Psychology and Paediatric Epilepsy team members. Quantitative feedback was completed by the patient group. Patients, siblings, and parents provided qualitative feedback., Results: A total of 6 patients, 14 siblings and 15 parents attended the group. Quantitative feedback indicated some improvement in patients' confidence and knowledge of managing epilepsy, as well as some improvements in psychological adjustment and thoughts about epilepsy. 87.5% of patients and siblings detailed that they would recommend the group to others. Qualitative feedback from patients, siblings and parents indicated the helpfulness of relating to others and safely expressing difficulties., Conclusions: The results indicated that this pilot group intervention was well received by children with epilepsy and their families. Future studies incorporating a larger sample are warranted to explore this further., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Traumatic brain injury (TBI) can result in significant impairments in functioning associated with partial or permanent disabilities. Examining the evidence for domain-specific telehealth interventions is necessary to guide the development of effective clinical and research programs for this population. The present scoping review characterizes the level of evidence across a range of TBI-related disabilities and impairments. A literature search was performed across comprehensive databases using search terms related to TBI, rehabilitation, telehealth, and outcome. A total of 19 publications from 17 studies met inclusion criteria. Articles focused on telehealth interventions to improve global, cognitive, emotional, and physical functioning post-TBI. Levels of evidence ranged from 1 to 4 across domains, with predominantly experimental designs (level 1). Outcomes demonstrating improvement or benefit from telehealth treatments were reported across all functional domains (50-80% of studies). Results highlight the potential of telehealth interventions across the span of comprehensive interdisciplinary rehabilitation care. Expanded research is needed on remote treatment options for physical symptoms, for subgroups within TBI populations (i.e., mild TBI, military populations), as well as on remote and hybrid comprehensive rehabilitation programs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening., Subjects and Methods: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity., Results: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months., Conclusion: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs., Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination., Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection., Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination., Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake., Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

Objective: Masculinities have been explored in men with testicular cancer (TC), though limited contemporary research is available on traditional masculine norms important to masculine self-perception. The purpose of this research was to explore the discourse of TC experience in relation to masculine self-perception., Methods: A qualitative descriptive study was conducted consisting of semi-structured interviews with 21 men. Men were aged between 31 and 47 (M age  = 35.7). Most men were diagnosed with Stage 1 cancer (66.6%), all men had finished active treatment and time since diagnosis ranged from 17.3 to 71.8 months (M = 47.2). Independent coding was conducted by two researchers and was refined in coding meetings with authors. Themes were developed in a predominantly deductive manner, and analysis of themes was undertaken using a reflexive analysis approach., Results: Traditional masculine norms showed differing relationships to masculine self-perception. Two main themes were identified [1] Maintained or enhanced masculine self-perception and [2] threats to masculine self-perception. Subthemes demonstrated that maintaining emotional control, strength and 'winning' was important to men, and reduced physical competencies (i.e., strength, sexual dysfunction, virility) challenged self-perception. Strict adherence to traditional norms in response to threatened self-perception related to psychological distress., Conclusion: Leveraging traditionally masculine norms such as physical strength and control and developing flexible adaptations of masculinities should be encouraged with men with TC to retain self-perception and potentially enable better coping. Masculine self-perception of gay/bisexual men may centre around sexual functioning, though further research is required., (© 2024 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.)

Exposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycaemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. Thus, a vmPFC-RVLM connection could represent a circuit mechanism linking stress appraisal and physiological reactivity. The current study investigated a direct vmPFC-RVLM circuit utilizing genetically encoded anterograde and retrograde tract tracers. Together, these studies found that stress-activated vmPFC neurons project to catecholaminergic neurons throughout the ventrolateral medulla in male and female rats. Next, we utilized optogenetic terminal stimulation to evoke vmPFC synaptic glutamate release in the RVLM. Photostimulating the vmPFC-RVLM circuit during restraint stress suppressed glycaemic stress responses in males, without altering the female response. However, circuit stimulation decreased corticosterone responses to stress in both sexes. Circuit stimulation did not modulate affective behaviour in either sex. Further analysis indicated that circuit stimulation preferentially activated non-catecholaminergic medullary neurons in both sexes. Additionally, vmPFC terminals targeted medullary inhibitory neurons. Thus, both male and female rats have a direct vmPFC projection to the RVLM that reduces endocrine stress responses, likely by recruiting local RVLM inhibitory neurons. Ultimately, the excitatory/inhibitory balance of vmPFC synapses in the RVLM may regulate stress reactivity and stress-related health outcomes. KEY POINTS: Glutamatergic efferents from the ventromedial prefrontal cortex target catecholaminergic neurons throughout the ventrolateral medulla. Partially segregated, stress-activated ventromedial prefrontal cortex populations innervate the rostral and caudal ventrolateral medulla. Stimulating ventromedial prefrontal cortex synapses in the rostral ventrolateral medulla decreases stress-induced glucocorticoid release in males and females. Stimulating ventromedial prefrontal cortex terminals in the rostral ventrolateral medulla preferentially activates non-catecholaminergic neurons. Ventromedial prefrontal cortex terminals target medullary inhibitory neurons., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Genome editing technologies have the potential to transform our understanding of how genetic variation gives rise to complex traits through the systematic engineering and phenotypic characterization of genetic variants. However, there has yet to be a system with sufficient efficiency, fidelity, and throughput to comprehensively identify causal variants at the genome scale. Here we explored the ability of templated CRISPR editing systems to install natural variants genome-wide in budding yeast. We optimized several approaches to enhance homology-directed repair (HDR) with donor DNA templates, including donor recruitment to target sites, single-stranded donor production by bacterial retrons, and in vivo plasmid assembly. We uncovered unique advantages of each system that we integrated into a single superior system named MAGESTIC 3.0. We used MAGESTIC 3.0 to dissect causal variants residing in 112 quantitative trait loci across 32 environmental conditions, revealing an enrichment for missense variants and loci with multiple causal variants. MAGESTIC 3.0 will facilitate the functional analysis of the genome at single-nucleotide resolution and provides a roadmap for improving template-based genome editing systems in other organisms., Competing Interests: Competing Interests K.R.R., J.D.S., J.E.H., R.P.S, and L.M.S. have filed a patent application based on the MAGESTIC multiplexed editing system and the donor recruitment approach (U.S. provisional application No. 62/559,493, Publication US20200270632A1). K.R.R., J.D.S., R.P.S, and L.M.S. have filed patent applications on the ribozyme-based methods to enhance retron production (U.S. provisional application No. 63/214,197, WIPO Publication WO2022272293A1) and the retron donor recruitment approach (U.S. provisional application No. 63/214,196, WIPO Publication WO2022272294A1). K.R.R. and L.M.S have filed a patent application based on the MAGESTIC 3.0 system and the integrated plasmid removal system (U.S. provisional application No. 63/401,083).

Depression and cardiovascular disease are both augmented by daily life stress. Yet, the biological mechanisms that translate psychological stress into affective and physiological outcomes are unknown. Previously, we demonstrated that stimulation of the ventromedial prefrontal cortex (vmPFC) has sexually divergent outcomes on behavior and physiology. Importantly, the vmPFC does not innervate the brain regions that initiate autonomic or neuroendocrine stress responses; thus, we hypothesized that intermediate synapses integrate cortical information to regulate stress responding. The posterior hypothalamus (PH) directly innervates stress-effector regions and receives substantial innervation from the vmPFC. In the current studies, circuit-specific approaches examined whether vmPFC synapses in the PH coordinate stress responding. Here we tested the effects of optogenetic vmPFC-PH circuit stimulation in male and female rats on social and motivational behaviors as well as physiological stress responses. Additionally, an intersectional genetic approach was used to knock down synaptobrevin in PH-projecting vmPFC neurons. Our collective results indicate that male vmPFC-PH circuitry promotes positive motivational valence and is both sufficient and necessary to reduce sympathetic-mediated stress responses. In females, the vmPFC-PH circuit does not affect social or preference behaviors but is sufficient and necessary to elevate neuroendocrine stress responses. Altogether, these data suggest cortical regulation of stress reactivity and behavior is mediated, in part, by projections to the hypothalamus that function in a sex-specific manner., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: A preoperative supervised exercise program (SEP) improves cardiorespiratory fitness and perioperative outcomes for patients undergoing elective abdominal aortic aneurysm (AAA) repair. The aim of this study was to assess the effect of a preoperative SEP on long-term survival of these patients. A secondary aim was to consider long-term changes in cardiorespiratory fitness and quality of life., Methods: Patients scheduled for open or endovascular AAA repair were previously randomized to either a 6-week preoperative SEP or standard management, and a significant improvement in a composite outcome of cardiac, pulmonary, and renal complications was seen following SEP. For the current analysis, patients were followed up to 5 years post-surgery. The primary outcome for this analysis was all-cause mortality. Data were analyzed on an intention to treat (ITT) and per protocol (PP) basis, with the latter meaning that patients randomized to SEP who did not attend any sessions were excluded. The PP analysis was further interrogated using a complier average causal effect (CACE) analysis on an all or nothing scale, which adjusts for compliance. Additionally, patients who agreed to follow-up attended the research center for cardiopulmonary exercise testing and/or provided quality of life measures., Results: ITT analysis demonstrated that the primary endpoint occurred in 24 of the 124 participants at 5 years, with eight in the SEP group and 16 in the control group (P = .08). The PP analysis demonstrated a significant survival benefit associated with SEP attendance (4 vs 16 deaths; P = .01). CACE analysis confirmed a significant intervention effect (hazard ratio, 0.36; 95% confidence interval, 0.16-0.90; P = .02). There was no difference between groups for cardiorespiratory fitness measures and most quality of life measures., Conclusions: These novel findings suggest a long-term mortality benefit for patients attending a SEP prior to elective AAA repair. The underlying mechanism remains unknown, and this merits further investigation., Competing Interests: Disclosures None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The objective of the following retrospective review was to perform a cost-effectiveness analysis of the use of molecular testing of indeterminate thyroid nodules compared to current management practices in Nova Scotia, Canada., Methods: All cases of cytologically indeterminate thyroid nodules from January 1st, 2014 to December 31st, 2018 were reviewed. All interventions related to an indeterminate thyroid nodule were recorded. Patients were excluded if less than 18 years old if no further information regarding medical management was electronically available beyond the diagnosis of an indeterminate thyroid nodule, history of radiation, or previous thyroid surgery prior to diagnosis of an indeterminate thyroid nodule in the remaining lobe. Microcosting was performed to determine the cost of all relevant interventions including repeat fine needle aspiration biopsy, ultrasound, thyroid surgery(s), and molecular testing. Institution-specific transition state probabilities were calculated and used to build a cost-effectiveness analysis model. Model output was an incremental cost-effectiveness ratio, defined as the ratio of cost difference to effectiveness difference between routine molecular testing and the current management strategy, yielding cost per surgery avoided., Results: The mean effectiveness of the current management of indeterminate thyroid nodules in Nova Scotia based on the American Thyroid Association guidelines is 64% at a mean cost of $6431, while the simulated mean effectiveness of routine molecular testing is 89% at a mean cost of $8414. Differences in management strategies generated an incremental cost-effectiveness ratio of $7876 per surgery avoided., Conclusion: Routine molecular testing is the more effective strategy for the appropriate management of indeterminate thyroid nodules; however, it comes at a higher mean cost compared to the current management strategy. As the cost of molecular testing continues to decrease, and the cost of OR resources continues to rise, molecular testing is likely to become the optimal strategy in Nova Scotia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale: Sarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis., Methods: In this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3 + Treg biology, including suppressive function, epigenetic features and stability., Results: We identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases., Conclusion: Tregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity., 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., (Copyright © 2023 Patterson, Miller, Hancock and Akimova.)

The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8 + T cells play a vital role. Nonetheless, the characterization of the specificity and TCR composition of CD8 + T cells targeting non-spike protein of SARS-CoV-2 before and after infection remains incomplete. Here, we analyzed CD8 + T cells recognizing six epitopes from the SARS-CoV-2 nucleocapsid (N) protein and found that SARS-CoV-2 infection slightly increased the frequencies of N-recognizing CD8 + T cells but significantly enhanced activation-induced proliferation compared to that of the uninfected donors. The frequencies of N-specific CD8 + T cells and their proliferative response to stimulation did not decrease over one year. We identified the N 222-230 peptide (LLLDRLNQL, referred to as LLL thereafter) as a dominant epitope that elicited the greatest proliferative response from both convalescent and uninfected donors. Single-cell sequencing of T cell receptors (TCR) from LLL-specific CD8 + T cells revealed highly restricted Vα gene usage (TRAV12-2) with limited CDR3α motifs, supported by structural characterization of the TCR-LLL-HLA-A2 complex. Lastly, transcriptome analysis of LLL-specific CD8 + T cells from donors who had expansion (expanders) or no expansion (non-expanders) after in vitro stimulation identified increased chromatin modification and innate immune functions of CD8 + T cells in non-expanders. These results suggests that SARS-CoV-2 infection induces LLL-specific CD8 + T cell responses with a restricted TCR repertoire., (© 2023. Springer Nature Limited.)

Nogo-A, B, and C are well described members of the reticulon family of proteins, most well known for their negative regulatory effects on central nervous system (CNS) neurite outgrowth and repair following injury. Recent research indicates a relationship between Nogo-proteins and inflammation. Microglia, the brain's immune cells and inflammation-competent compartment, express Nogo protein, although specific roles of the Nogo in these cells is understudied. To examine inflammation-related effects of Nogo, we generated a microglial-specific inducible Nogo KO (MinoKO) mouse and challenged the mouse with a controlled cortical impact (CCI) traumatic brain injury (TBI). Histological analysis shows no difference in brain lesion sizes between MinoKO-CCI and Control-CCI mice, although MinoKO-CCI mice do not exhibit the levels of ipsilateral lateral ventricle enlargement as injury matched controls. Microglial Nogo-KO results in decreased lateral ventricle enlargement, microglial and astrocyte immunoreactivity, and increased microglial morphological complexity compared to injury matched controls, suggesting decreased tissue inflammation. Behaviorally, healthy MinoKO mice do not differ from control mice, but automated tracking of movement around the home cage and stereotypic behavior, such as grooming and eating (termed cage "activation"), following CCI is significantly elevated. Asymmetrical motor function, a deficit typical of unilaterally brain lesioned rodents, was not detected in CCI injured MinoKO mice, while the phenomenon was present in CCI injured controls 1-week post-injury. Overall, our studies show microglial Nogo as a negative regulator of recovery following brain injury. To date, this is the first evaluation of the roles microglial specific Nogo in a rodent injury model., (© 2023 The Authors. GLIA published by 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.)

Exposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. Thus, a vmPFC-RVLM connection could represent a circuit mechanism linking stress appraisal and physiological reactivity. The current study investigated a direct vmPFC-RVLM circuit utilizing genetically-encoded anterograde and retrograde tract tracers. Together, these studies found that stress-reactive vmPFC neurons project to catecholaminergic neurons throughout the ventrolateral medulla in male and female rats. Next, we utilized optogenetic terminal stimulation to evoke vmPFC synaptic glutamate release in the RVLM. Photostimulating the vmPFC-RVLM circuit during restraint stress suppressed glycemic stress responses in males, without altering the female response. However, circuit stimulation decreased corticosterone responses to stress in both sexes. Circuit stimulation did not modulate affective behavior in either sex. Further analysis indicated that circuit stimulation preferentially activated non-catecholaminergic medullary neurons in both sexes. Additionally, vmPFC terminals targeted medullary inhibitory neurons. Thus, both male and female rats have a direct vmPFC projection to the RVLM that reduces endocrine stress responses, likely through the recruitment of local RVLM inhibitory neurons. Ultimately, the excitatory/inhibitory balance of vmPFC synapses in the RVLM may regulate stress reactivity as well as stress-related health outcomes., Competing Interests: The authors have no conflicts of interest to declare

Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood-borne immune cell types (naive B, naive CD4 + and CD8 + T cells, granulocytes, monocytes, and NK cells) collected from healthy individuals interspersed over a wide age range. Of the thousands of age-associated sites, only 350 sites were differentially methylated in the same direction in all cell types and validated in an independent longitudinal cohort. Genes close to age-associated hypomethylated sites were enriched for collagen biosynthesis and complement cascade pathways, while genes close to hypermethylated sites mapped to neuronal pathways. In silico analyses showed that in most cell types, the age-associated hypo- and hypermethylated sites were enriched for ARNT (HIF1β) and REST transcription factor (TF) motifs, respectively, which are both master regulators of hypoxia response. To conclude, despite spatial heterogeneity, there is a commonality in the putative regulatory role with respect to TF motifs and histone modifications at and around these sites. These features suggest that DNA methylation changes in healthy aging may be adaptive responses to fluctuations of oxygen availability., Competing Interests: RR, PK, JC, DS, CU, DH, MK, SA, AS, AB, JK, AM, TT, JM, LZ, CN, TW, CD, WW, YP, CC, SD, JS, NW, RS, LF No competing interests declared

Key Clinical Message: Iliac artery-enteric fistula is a rare cause of lower GI bleeding and can cause life-threatening consequences. A high degree of clinical suspicion is needed in patients with previous aortic surgery to allow early multidisciplinary intervention., Abstract: This case study discusses the staged management of a 78-year-old patient presenting with life-threatening lower gastrointestinal (GI) bleeding secondary to an aortoiliac graft-enteric fistula (GEF) into the sigmoid colon on the background of an adenocarcinoma and diverticular disease. The patient had an aorto bi-iliac synthetic dacron graft repair of an abdominal aortic aneurysm (AAA) some 20 years ago. Here, we present a case of successful endovascular treatment of massive hemorrhage as a bridge to definitive second-stage dacron graft explant and autologous vein reconstruction with a simultaneous anterior resection., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective: A significant proportion of patients with abdominal and thoracic aortic aneurysms (AA) do not proceed to intervention after reaching treatment threshold diameter due to a combination of poor cardiovascular reserve, frailty, and aortic morphology. This patient cohort has a high mortality; however, until this study, there exist no studies on the end-of-life care conservatively managed patients receive., Methods: This is a retrospective multicenter cohort study of 220 conservatively managed patients with AA referred to Leeds Vascular Institute (UK) and Maastricht University Medical Centre (the Netherlands) for intervention between 2017 and 2021. Demographic details, mortality, cause of death, advance care planning and palliative care outcomes were analysed to examine predictors of palliative care referral and efficacy of palliative care consultation., Results: A total of 1506 patients with AA were seen over this time period, giving a nonintervention rate of 15%. There was a 3-year mortality rate of 55%, a median survival of 364 days, and rupture was the reported cause of death in 18% of the decedents. Median follow-up was 34 months. Only 8% of all patients and 16% of decedents received a palliative care consultation, which took place a median of 3.5 days before death. Patients >81 years of age were more likely to have advance care planning. Only 5% and 23% of conservatively managed patients had documentation of preferred place of death and care priorities respectively. Patients with a palliative care consultation were more likely to have these services in place., Conclusions: Only a small proportion of conservatively treated patients had advance care planning and this was far below international guidelines on end-of-life care for adults, which recommends it for each of these patients. Pathways and guidance should be implemented to ensure patients not offered AA intervention receive end-of-life care and advance care planning., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Depression and cardiovascular disease are both augmented by daily life stress. Yet, the biological mechanisms that translate psychological stress into affective and physiological outcomes are unknown. Previously, we demonstrated that stimulation of the ventromedial prefrontal cortex (vmPFC) has sexually divergent outcomes on behavior and physiology. Importantly, the vmPFC does not innervate the brain regions that initiate autonomic or neuroendocrine stress responses; thus, we hypothesized that intermediate synapses integrate cortical information to regulate stress responding. The posterior hypothalamus (PH) directly innervates stress-effector regions and receives substantial innervation from the vmPFC. In the current studies, circuit-specific approaches examined whether vmPFC synapses in the PH coordinate stress responding. Here we tested the effects of optogenetic vmPFC-PH circuit stimulation in male and female rats on social and motivational behaviors as well as physiological stress responses. Additionally, an intersectional genetic approach was used to knock down synaptobrevin in PH-projecting vmPFC neurons. Our collective results indicate that male vmPFC-PH circuitry promotes positive motivational valence and is both sufficient and necessary to reduce sympathetic-mediated stress responses. In females, the vmPFC-PH circuit does not affect social or preference behaviors but is sufficient and necessary to elevate neuroendocrine stress responses. Altogether, these data suggest cortical regulation of stress reactivity and behavior is mediated, in part, by projections to the hypothalamus that function in a sex-specific manner., Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Stress-related disorders such as depression and anxiety exhibit sex differences in prevalence and negatively impact both mental and physical health. Affective illness is also frequently accompanied by changes in ventromedial prefrontal cortical (vmPFC) function. However, the neurobiology that underlies sex-specific cortical processing of affective stimuli is poorly understood. Although rodent studies have investigated the prefrontal impact of chronic stress, postmortem studies have focused largely on males and yielded mixed results. Therefore, genetically defined population recordings in behaving animals of both sexes were used to test the hypothesis that chronic variable stress (CVS) impairs the neural processing of affective stimuli in the rodent infralimbic region. Here, we targeted expression of a calcium indicator, GCaMP6s, to infralimbic pyramidal cells. In males, CVS reduced infralimbic responses to social interaction and restraint stress but increased responses to novel objects and food reward. In contrast, females did not have CVS-induced changes in infralimbic activity, which was partially dependent on the ovarian status. These results indicate that both male and female vmPFC cells encode social, stress, and reward stimuli. However, chronic stress effects are sex-dependent and behavior-specific. Ultimately, these findings extend the understanding of chronic stress-induced prefrontal dysfunction and indicate that sex is a critical factor for cortical processing of affective stimuli., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Concussions are caused by a hit or blow to the head that alters normal brain functioning. The Success in College after Concussion with Effective Student Supports (SUCCESS) program was developed to provide students with psychosocial support and resources-both key components of concussion management-to assist in recovery and return-to-learn following concussion. In this preliminary evaluation of intervention efficacy, SUCCESS was delivered through a mobile application connecting mentors (students who have recovered from concussion and successfully returned to school) with mentees who were currently recovering. Mentor-mentee pairs met virtually through the app, using chat and videoconferencing features to share support, resources, and program-specific educational materials. Results from 16 mentoring pairs showed that mentee symptoms (V = 119, p = 0.009) and academic problems decreased (V = 114.5, p = 0.002), while academic self-efficacy increased (V = 13.5, p = 0.009) following mentoring. As expected, mentor measures were stable, indicating that providing mentoring did not exacerbate previously resolved concussion complaints. Virtual peer mentoring provided through a mobile application may be a feasible intervention to support academic success and psychosocial processing during recovery for college students with concussion.

Purpose: Typical measures of recovery from concussion-such as symptom scales, neurocognitive testing, or exertion measures-may not capture individualized experiences of concussion. This report examines how college students with concussion interact with and consider their recovery., Method: Sixteen college students who sustained concussions while in college completed 40- to 75-min semistructured interviews. All were enrolling to become mentors in a peer mentoring program for students with concussion. Questions addressed experiences as a college student with concussion, life changes following concussion, and role of peers in recovery. Using phenomenological reduction, analysis focused on the phenomenon of recovery and motivation for participation in a mentoring program., Results: Two main themes were found: (a) What Recovery Looks Like and (b) Gaining Perspective, Learning to Cope and Adapting to Change . Thirteen participants denied the label of "recovered" even though all had been deemed recovered and discharged from medical care. Instead, two subthemes emerged within What Recovery Looks Like : Ongoing Recovery and Reconceptualizing Recovery . Perceptions of recovery were influenced by effort, capacity, and resilience. In the second theme, students described strategies, resources, and supports used to cope with their injuries; most commonly used was emotion-focused coping., Conclusions: College students with concussion consider recovery as an ongoing process rather than a dichotomized condition. Student experiences may not be reflected in commonly used symptom scales or objective assessments., Supplemental Material: https://doi.org/10.23641/asha.21084925.

Purpose: Individuals who experience brain injury and are uninsured often do not have access to health care services following their injury. The Georgia Rehabilitation Services Volunteer Partnership (GA RSVP) Clinic is a free outpatient rehabilitation program for uninsured individuals with acquired brain injury (ABI) and/or spinal cord injury (SCI) for all racial and ethnic backgrounds. While the clinic serves people with ABI and SCI, this clinical focus article will focus on people with ABI by describing the clinic, lessons learned from operations, an ABI patient case study, and future directions., Method: Our mission is to provide free outpatient rehabilitation care that maximizes independence, wellness, and community participation. The clinic has been in operation since September 2020, staffed by volunteers who provide services once a month in donated space at a rehabilitation hospital. We currently have 69 active volunteers, seven founding Board of Directors, and 17 founding Advisory Board members. We provide education to clients and their families and run peer and family support groups. For clients who cannot attend due to medical or transportation challenges, we have added telehealth services. We have 11 partner organizations as well as individual donor's financial support. The Chair of the clinic volunteers 50% of time managing clinic operations., Results: From September 2020 to December 2021, we provided care for 40 clients: 23 clinic admissions and 17 were provided information/referral services to access necessary health care services., Conclusions: A volunteer, free outpatient rehabilitation clinic is feasible and can contribute to improved outcomes for uninsured individuals with ABI. Further research to understand impact on patient outcomes is needed.

Background: Patients with abdominal aortic aneurysm (AAA) are at a significant risk of cardiovascular events, similar to that of patients who have already experienced a major cardiac event. The European Society for Vascular Society AAA guidelines suggest that antiplatelet therapy and lipid-lowering therapy (LLT) should be considered in all patients with AAA. This study explores the overall prevalence and intensity of antithrombotic therapy and LLT, and lipid profile monitoring in a single center AAA surveillance cohort alongside any sex differences., Methods: This was a retrospective, single center, cross-sectional study of 614 patients enrolled in the AAA surveillance program of a tertiary vascular surgery unit. All patients undergoing at least 1 surveillance scan from January 1, 2018, to December 31, 2020, were assessed. Electronic hospital records linked to real-time primary care records were interrogated for data on demographics, comorbidities, antiplatelet and LLT prescriptions, and serum cholesterol laboratory results. An analysis of covariance test was used to account for the effects of confounding comorbidities., Results: Twenty-one percent of patients were not on antithrombotic therapy, and 20% of patients were not on LLT which reflects a group of patients receiving sub-optimal clinical care. In total, 47% of the cohort were on low/moderate intensity statin therapy which reflects a group of patients where care can be improved upon. Female sex was independently associated with a reduced likelihood of being prescribed LLT (P = 0.008, eta squared (η p 2 ) = 0.012, small effect size) but not antithrombotic therapy (P = 0.202). Fewer women underwent low-density lipoprotein cholesterol (LDL-C) monitoring (mean difference 9%, P = 0.040) and achieved the European Society of Cardiology-European Atherosclerosis Society- LDL-C target of <1.4 mmol/L (mean difference 9%, P = 0.040)., Conclusions: Overall, there is room for improvement in these aspects of cardiovascular risk prevention for both sexes. Sex differences in the prescription of LLT, the prevalence of lipid profile monitoring, and likelihood of achieving LDL-C targets exist among patients with AAA, with a lower prevalence in women., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Soil organic matter (SOM) constitutes roughly 60% organic carbon (OC) and therefore plays a crucial role in regulating global climate. However, our understanding of the long-term dynamics of the soil carbon pool remains constrained by limitations in analytical approaches capable of providing high resolution molecular-level information from arguably the most complex biomaterial on the planet. In this contribution, we combine hydrofluoric acid (HF) treatment with a spectroscopic approach as a strategy to provide refined molecular-level information on the interactions between soil minerals and SOM. Critically, we have not seen the use of this combined approach anywhere in the literature and strongly believe that it could allow us to improve our overall understanding to the mechanisms and pathways that regulate SOM transformation. Results clearly illustrates which organic structures are preferentially adsorbed to soil minerals and are likely to be protected from degradation, as well as spatial co-variations of SOM with specific mineral components such as Al 3+ , Si 4+ and dibasic cations such as Mg 2+ as a function of their importance in the interaction process.•Soil samples were collected from different land-use types in rural farming communities of the Upper Rio Grande Valley.•Samples were oven dried, disaggregated, sieved, treated with 10% HF, rinsed and oven dried.•Oven dried samples were subjected to Mid-infrared (4000-400 cm -1 ), XRD and ED-XRF analyses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Aim: To gain a better understanding of how the FreeStyle Libre (FSL) flash glucose monitor influences the eating habits and relationship with food of adults with type 1 diabetes (T1D)., Methods: Reflexive thematic analysis was conducted on fifteen semi-structured interviews conducted with adults with T1D, exploring their experiences of at least one year of FSL use., Results: Four themes were constructed from the qualitative data: (1) Personal Food Story (what food represented before and after diabetes diagnosis), (2) New Opportunities (the FSL offered novel discoveries and increased self-confidence regarding food choices), (3) Body as a Machine (participants viewed their bodies as a collection of complex processes requiring continuous maintenance), and (4) re-evaluating Diabetes (participants expressed a shift in their expectations of themselves and their diabetes management). Although the FSL offered participants more freedom and flexibility with their eating, this was constrained by feeling forever under scrutiny from the data., Conclusions: Findings suggest the FSL influences users' eating habits, including when, why, what and how much they eat. Participants described both the positive and negative impact of these changes on their emotional wellbeing and relationship with diabetes, arguing for a need to address patients' relationship with food in routine clinic care., Competing Interests: Declaration of Competing Interest The authors 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This pilot study assessed the feasibility of using SwapMyMood, a smartphone application supporting evidence-based strategies for emotion regulation and problem-solving as a supplement to conventional care for military service members and veterans (SM/Vs) experiencing chronic symptoms of mild traumatic brain injury (mTBI) and co-occurring psychological conditions. Eight military SM/Vs were recruited from an intensive outpatient program. Participants were block randomized to an experimental group (conventional care plus use of the SwapMyMood app) or a conventional care only group for six weeks. Conventional care included instruction on problem-solving and emotion regulation strategies using traditional paper manuals and protocols. Effects on the knowledge and use of strategies and related goal attainment were measured. Patient-reported outcomes were measured via several validated problem-solving and emotion regulation scales. No differences were found between groups in goal attainment, global executive function, problem-solving, emotion regulation, and knowledge of how to use the problem-solving and emotion regulation strategies targeted. Experimental group participants rated the application positively, demonstrating feasibility of integration of the app into clinical care. The implementation of SwapMyMood is feasible in a clinical setting. SwapMyMood may be a clinically effective supplemental tool for supporting executive function in SM/Vs with mTBI and co-occurring psychological conditions.

Background: The COVID-19 pandemic necessitated the implementation of telehealth and hybrid service delivery models and provided an opportunity to study the impact of this care model in military populations with history of traumatic brain injury (TBI)., Objective: To present telehealth service utilization rates across rehabilitation specialties, treatment outcome indicators, and patient satisfaction outcomes from a retrospective clinical sample., Methods: The study sample consists of 34 patients who underwent telehealth/hybrid Intensive Outpatient Programming (IOP) at a major rehabilitation hospital. Retrospective chart review and clinical data extraction were performed. A historical cohort receiving in-person care was used as a comparison group. Statistical analyses included partial correlations, mixed method analysis of variance (ANOVA), and independent sample t-tests., Results: Medical, behavioral health, physical, occupational, and speech-language therapy providers exhibited similar rates of telehealth service delivery (35 to 41% of all sessions). No significant association was found between percent telehealth sessions and the global treatment outcome indicator. Comparison of treatment effects across cohorts revealed similar benefits of IOP. No between-group differences were noted in satisfaction ratings., Conclusion: The comparable treatment-related gains and reports of positive patient experience support the use of a telehealth and hybrid delivery model for military service members and veterans with TBI.

Guideline recommendation for a plant bioactive such as flavan-3-ols is a departure from previous recommendations because it is not based on deficiencies but rather improvement in health outcomes. Nevertheless, there is a rapidly growing body of clinical data reflecting benefits of flavan-3-ol intake that outweigh potential harms. Thus, the objective of the Expert Panel was to develop an intake recommendation for flavan-3-ols and cardiometabolic outcomes to inform multiple stakeholders including clinicians, policymakers, public health entities, and consumers. Guideline development followed the process set forth by the Academy of Nutrition and Dietetics, which includes use of the Evidence to Decision Framework. Studies informing this guideline (157 randomized controlled trials and 15 cohort studies) were previously reviewed in a recently published systematic review and meta-analysis. Quality and strength-of-evidence along with risk-of-bias in reporting was reviewed. In drafting the guideline, data assessments and opinions by authoritative scientific bodies providing guidance on the safety of flavan-3-ols were considered. Moderate evidence supporting cardiometabolic protection resulting from flavan-3-ol intake in the range of 400-600 mg/d was supported in the literature. Further, increasing consumption of dietary flavan-3-ols can help improve blood pressure, cholesterol concentrations, and blood sugar. Strength of evidence was strongest for some biomarkers (i.e., systolic blood pressure, total cholesterol, HDL cholesterol, and insulin/glucose dynamics). It should be noted that this is a food-based guideline and not a recommendation for flavan-3-ol supplements. This guideline was based on beneficial effects observed across a range of disease biomarkers and endpoints. Although a comprehensive assessment of available data has been reviewed, evidence gaps identified herein can inform scientists in guiding future randomized clinical trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Cytomegalovirus (CMV) infection leads to effector memory CD8 + T cell expansion and is associated with immune dysfunction in older adults. However, the molecular alterations of CMV-specific CD8 + T cells in CMV infected healthy young and middle-aged adults has not been fully characterized., Results: We compared CD8 + T cells specific for a CMV epitope (pp65 495-503 , NLV) and an influenza A virus (IAV) epitope (M1 58-66 , GIL) from the same young and middle-aged healthy adults with serum positive for anti-CMV IgG. Compared to the IAV-specific CD8 + T cells, CMV-specific CD8 + T cells contained more differentiated effector memory (T EM and T EMRA ) cells. Isolated CMV-specific central memory (T CM ) but not naïve (T N ) cells had a significant reduced activation-induced expansion in vitro compared to their IAV-specific counterparts. Furthermore, we found that CD70 expression was reduced in CMV-specific CD28 + CD8 + T CM and that CD70 + T CM had better expansion in vitro than did CD70 - T CM . Mechanistically, we showed that CD70 directly enhanced MAPK phosphorylation and CMV-specific CD8 + T CM cells had a reduced MAPK signaling upon activation. Lastly, we showed that age did not exacerbate reduced CD70 expression in CMV- specific CD8 + T CM cells., Conclusion: Our findings showed that CMV infection causes mild expansion of CMV-NLV-specific CD8 + T cells, reduced CD70 expression and signaling, and proliferation of CMV-NLV-specific CD8 + T CM cells in young and middle-aged healthy adults and revealed an age-independent and CMV infection-specific impact on CD8 + memory T cells., (© 2022. The Author(s).)

Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing toward distinct subpopulations. The subpopulations of macrophages that reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis with unsupervised clustering, we found 11 distinct macrophage clusters in male mouse SKM with enriched gene expression programs linked to reparative, proinflammatory, phagocytic, proliferative, and senescence-associated functions. Using a complementary classification, membrane markers LYVE1 and MHCII identified four macrophage subgroups: LYVE1-/MHCII hi (M1-like, classically activated), LYVE1+/MHCII lo (M2-like, alternatively activated), and two new subgroups, LYVE1+/MHCII hi and LYVE1-/MHCII lo . Notably, one new subgroup, LYVE1+/MHCII hi , had traits of both M2 and M1 macrophages, while the other new subgroup, LYVE1-/MHCII lo , displayed strong phagocytic capacity. Flow cytometric analysis validated the presence of the four macrophage subgroups in SKM and found that LYVE1- macrophages were more abundant than LYVE1+ macrophages in old SKM. A striking increase in proinflammatory markers ( S100a8 and S100a9 mRNAs) and senescence-related markers ( Gpnmb and Spp1 mRNAs) was evident in macrophage clusters from older mice. In sum, we have identified dynamically polarized SKM macrophages and propose that specific macrophage subpopulations contribute to the proinflammatory and senescent traits of old SKM., Competing Interests: LK, PC, CC, KM, CD, YP, JF, CS, TW, CN, IR, RM, DT, SD, PS, LF, MG No competing interests declared

Motivation: AlphaFold has been a major advance in predicting protein structure, but still leaves the problem of determining which sub-molecular components of a protein are essential for it to carry out its function within the cell. Direct coupling analysis predicts two- and three-amino acid contacts, but there may be essential interdependencies that are not proximal within the 3D structure. The problem to be addressed is to design a computational method that locates and ranks essential non-proximal interdependencies within a protein involving five or more amino acids, using large, multiple sequence alignments (MSAs) for both globular and intrinsically unstructured proteins., Results: We developed PSICalc (Protein Subdomain Interdependency Calculator), a laptop-friendly, pattern-discovery, bioinformatics software tool that analyzes large MSAs for both structured and unstructured proteins, locates both proximal and non-proximal inter-dependent sites, and clusters them into pairwise (second order), third-order and higher-order clusters using a k-modes approach, and provides ranked results within minutes. To aid in visualizing these interdependencies, we developed a graphical user interface that displays these subdomain relationships as a polytree graph. To demonstrate, we provide examples of both proximal and non-proximal interdependencies documented for eukaryotic topoisomerase II including between the unstructured C-terminal domain and the N-terminal domain., Availability and Implementation: https://github.com/jdeweeselab/psicalc-package., Supplementary Information: Supplementary data are available at Bioinformatics Advances online., (© The Author(s) 2022. Published by Oxford University Press.)

Background/objective: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF., Methods: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models., Results: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome., Conclusion: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors., Competing Interests: M.D.G. is supported by the National Institutes of Health Grant K23 AR073931-01 and has received consulting fees from AbbVie and research support from Bristol-Myers Squibb and GlaxoSmithKline for unrelated work. M.F.B. is supported by National Institutes of Health grant U01 HL152970, by The Robert L Mayock and David A Cooper Endowed Professorship, and via unrestricted funds from the Perelman School of Medicine Department of Medicine Research Fund. M.K.P. is supported by The William “Dutch” Dyson Fund. The other authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: In the Northern Territory, people who commit drink driving offences are required to undertake an approved course or treatment to be eligible for a driver's licence, however, course uptake is low. We investigated barriers to program uptake., Methods: We conducted semi-structured interviews with 24 program attendees, course providers and government stakeholders. We used a framework analysis., Results: Program coverage in remote areas was limited, leading to inequitable access. The course cost affected uptake and exacerbated existing financial hardship. There were mixed views among government stakeholders on the program. While some held a view that offenders should 'pay the price', some also saw the user-pays model and high program cost as a clear barrier to accessibility., Conclusions: The data from this study demonstrate how the current delivery model for drink and drug driving education increases inequities for those in regional and remote areas, and Aboriginal and Torres Strait Islander people., Implications for Public Health: Moving away from the current user-pays model to a subsidised or free model may facilitate greater access. Online delivery may increase accessibility; however, consultation is required to ensure the program is delivered equitably with consideration of language, literacy, cultural factors and access to technology., (© 2022 The Authors.)

Background and Objectives: Muscle blood flow is impeded during resistance exercise contractions, but immediately increases during recovery. The purpose of this study was to determine the impact of brief bouts of rest (2 s) between repetitions of resistance exercise on muscle blood flow and exercise tolerance. Materials and Methods: Ten healthy young adults performed single-leg knee extension resistance exercises with no rest between repetitions (i.e., continuous) and with 2 s of rest between each repetition (i.e., intermittent). Exercise tolerance was measured as the maximal power that could be sustained for 3 min (PSUS) and as the maximum number of repetitions (Reps80%) that could be performed at 80% one-repetition maximum (1RM). The leg blood flow, muscle oxygenation of the vastus lateralis and mean arterial pressure (MAP) were measured during various exercise trials. Alpha was set to p ≤ 0.05. Results: Leg blood flow was significantly greater, while vascular resistance and MAP were significantly less during intermittent compared with continuous resistance exercise at the same power outputs (p < 0.01). PSUS was significantly greater during intermittent than continuous resistance exercise (29.5 ± 2.1 vs. 21.7 ± 1.2 W, p = 0.01). Reps80% was also significantly greater during intermittent compared with continuous resistance exercise (26.5 ± 5.3 vs. 16.8 ± 2.1 repetitions, respectively; p = 0.02), potentially due to increased leg blood flow and muscle oxygen saturation during intermittent resistance exercise (p < 0.05). Conclusions: In conclusion, a brief rest between repetitions of resistance exercise effectively decreased vascular resistance, increased blood flow to the exercising muscle, and increased exercise tolerance to resistance exercise.

Background: Diaphragmatic breathing is an evidence-based intervention for managing stress and anxiety; however, some military veterans with mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) report challenges to learning and practicing the technique. BreatheWell Wear assists performance of breathing exercises through reminders, biofeedback, and visual, tactile, and auditory guidance., Objective: To evaluate feasibility of implementing BreatheWell Wear, a mobile smartwatch application with companion smartphone app, as an intervention for stress management in military veterans with mTBI and PTSD., Methods: Thirty veterans with chronic symptoms of mTBI and PTSD recruited from an interdisciplinary, intensive outpatient program participated in this pilot pragmatic clinical trial. Participants were randomly assigned to the experimental (BreatheWell Wear and conventional care) and control (conventional care) groups for 4 weeks. Conventional care included instruction on relaxation breathing and participation in behavioral health therapy. Effects on goal attainment, treatment adherence, diaphragmatic breathing technique knowledge, and stress were measured through surveys and diaries. Changes in symptoms, mood, and well-being were measured pre/postintervention via the Posttraumatic Checklist for DSM-5, Beck Anxiety Inventory, Beck Depression Inventory, and Flourishing Scale., Results: Person-centered goal attainment (t = 4.009, P < .001), treatment adherence (t = 2.742, P = .001), diaphragmatic breathing technique knowledge (t = 1.637, P < .001), and reported ease of remembering to practice (t = -3.075, P = .005) were significantly greater in the experimental group. As expected, measures of PTSD, anxiety, depression, and psychological well-being showed clinically meaningful change in both groups, and both groups demonstrated reduced stress following diaphragmatic breathing., Conclusion: These preliminary findings indicate that BreatheWell Wear may be a clinically feasible tool for supporting diaphragmatic breathing as an intervention in veterans with mTBI and PTSD, and a future effectiveness trial is warranted., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Speech-language pathologists are increasingly being recognized as key members of concussion management teams. This study investigates whether self-report of communication problems postconcussion may be useful in identifying clients who could benefit from speech-language pathology services., Method: Participants included 41 adolescents and adults from an outpatient specialty concussion clinic. All completed the La Trobe Communication Questionnaire (LCQ) at admission, and 23 repeated this measure at discharge. Participants were prospectively enrolled, with chart reviews providing demographic, injury, and medical factors. The analysis considered (a) communication complaints and resolution over time, including comparison to two previously published LCQ studies of typical adults and adults with and without traumatic brain injury (TBI); (b) the relationship between communication complaints, participant factors, and common concussion assessments; and (c) factors related to speech-language pathology service referral for rehabilitation., Results: At first visit, 12 of 41 participants (29%) reported communication problems, although 19 (46%) reported difficulty with greater than half of LCQ items. At a group level, compared to published reference data of both people with chronic mixed severity TBI and controls, participants in this study reported more problems at first visit with communication overall, as well as greater difficulty with the LCQ Initiation/Conversation Flow subscale. Partner Sensitivity subscale scores at first visit were also greater than published control data. LCQ subscale scores of Initiation/Conversation Flow and Partner Sensitivity decreased from first visit to last visit, demonstrating resolution over time. Only concussion symptom scales and not demographic, injury, or cognitive screenings were related to LCQ scores. The same two LCQ subscales, Initiation/Conversation Flow and Partner Sensitivity, predicted referral for speech-language pathology services, along with symptom scales and being injured due to motor vehicle crash., Discussion: A subset of people recovering from concussion report experiencing communication problems. Reporting of particular communication problems was related to referral for speech-language pathology rehabilitation services and may be useful in directing care after concussion.

Following the identification of the Omicron variant of the SARS-CoV-2 virus in late November 2021, governments worldwide took actions intended to minimise the impact of the new variant within their borders. Despite guidance from the WHO advising a risk-based approach, many rapidly implemented stringent policies focused on travel restrictions. In this paper, we capture 221 national-level travel policies issued during the 3 weeks following publicisation of the Omicron variant. We characterise policies based on whether they target travellers from specific countries or focus more broadly on enhanced screening, and explore differences in approaches at the regional level. We find that initial reactions almost universally focused on entry bans and flight suspensions from Southern Africa, and that policies continued to target travel from these countries even after community transmission of the Omicron variant was detected elsewhere in the world. While layered testing and quarantine requirements were implemented by some countries later in this 3-week period, these enhanced screening policies were rarely the first response. The timing and conditionality of quarantine and testing requirements were not coordinated between countries or regions, creating logistical complications and burdening travellers with costs. Overall, response measures were rarely tied to specific criteria or adapted to match the unique epidemiology of the new variant., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Peripheral artery disease (PAD) encompasses conditions with poor outcome and severe suffering, both mentally and physically, yet utilization and research into palliative care interventions remain sparse. Objective: The purpose of this study is to identify existing evidence on palliative care intervention for chronic limb threatening ischaemia (CLTI) and abdominal aortic aneurysm (AAA). Design: We conducted a PROSPERO-registered systematic review of studies published between 1991 and 2020 in which people with PAD received palliative care interventions and at least one patient outcome was recorded. For the purpose of this study, a palliative care intervention was defined as one which aims primarily to reduce negative impact of PAD on patients' and/or caregivers' physical, emotional, psychological, social, or spiritual condition. Results: A total of 8 studies involving 87,024 patients met the inclusion criteria (4 cohort studies and 4 cross-sectional studies). Methodological quality ranged from low to moderate. The small number of studies and study heterogeneity precluded meta-analysis. Regarding our primary outcomes, only two articles recorded patient-reported outcomes. Five articles found an association between palliative care and reduction in health care utilization, a secondary outcome of the study. Most of the studies reported that palliative care was likely underused. Only two of the studies included non-hospital patients. Conclusion: Despite high mortality and morbidity associated with PAD, evidence of the effectiveness of palliative care in this group of patients is lacking. There are only a handful of articles on palliative care for people with PAD, and the majority are small, methodologically flawed and lack meaningful patient-reported outcomes. High-quality research of palliative care interventions in patients with PAD is urgently needed to better understand the impact of palliative care on quality of end of life and to develop and evaluate service-level interventions.