Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. METHODS: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score ≥3 and fecal calprotectin >150 µg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 µg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events. RESULTS: In total, 62 patients were randomized to continue (n = 20) or withdraw (n = 42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 µg/mL, interquartile rate [IQR], 12.3-18.5 µg/mL versus 15.9 µg/mL, IQR, 10.1-22.7 µg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal. CONCLUSIONS: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Frailty on the island of Ireland: evidence from the NICOLA and TILDA studies.

BACKGROUND: Aimed to compare the prevalence, characteristics, and associated mortality risk of frailty in Northern Ireland (NI) and the Republic of Ireland (ROI). METHODS: Secondary analysis of the first wave of two nationally representative cohorts, the Northern Ireland Cohort for the Longitudinal Study of Ageing or NICOLA study (N = 8504) and the Irish Longitudinal Study on Ageing or TILDA study (N = 8504). Frailty was assessed using a harmonized accumulation deficits frailty index (FI) containing 30 items. FI scores classified individuals as non-frail (<0.10), pre-frail (0.10-0.24) and frail (≥0.25). Linkage to respective administrative data sources provided mortality information with a follow-up time of 8 years. RESULTS: The prevalence of frailty was considerably higher in NI compared with the ROI (29.0% compared with 15.0%), though pre-frailty was slightly lower (35.8% and 37.3%, respectively). Age, female sex, and lower socio-economic status were consistently associated with a higher likelihood of both pre-frailty and frailty. In the pooled analysis, both frailty and pre-frailty were higher in NI (RR = 2.68, 95% CIs 2.45, 2.94 and RR = 1.30, 95% CIs 1.21, 1.40, respectively). Frailty was associated with an increased mortality risk in both cohorts, even after full adjustment for all other characteristics, being marginally higher in TILDA than in NICOLA (HR = 2.43, 95% CIs 2.03, 2.91 vs. HR = 2.31, 95% CIs 1.90, 2.79). CONCLUSIONS: Frailty is a major public health concern for both jurisdictions. Further research and monitoring are required to elucidate why there is a higher prevalence in NI and to identify factors in early life that may be driving these differences.

Plasminogen activator inhibitor 1 is associated with high-grade serous ovarian cancer metastasis and is reduced in patients who have received neoadjuvant chemotherapy.

Introduction: High-grade serous ovarian cancer (HGSOC) is the most prevalent and deadliest subtype of epithelial ovarian cancer (EOC), killing over 140,000 people annually. Morbidity and mortality are compounded by a lack of screening methods, and recurrence is common. Plasminogen-activator-inhibitor 1 (PAI-1, the protein product of SERPIN E1) is involved in hemostasis, extracellular matrix (ECM) remodeling, and tumor cell migration and invasion. Overexpression is associated with poor prognosis in EOC. Platelets significantly increase PAI-1 in cancer cells in vitro, and may contribute to the hematogenous metastasis of circulating tumor cells (CTCs). CTCs are viable tumor cells that intravasate and travel through the circulation-often aided by platelets - with the potential to form secondary metastases. Here, we provide evidence that PAI-1 is central to the platelet-cancer cell interactome, and plays a role in the metastatic cascade. Methods: SK-OV-3 cells where PAI-1 had been silenced, treated with healthy donor platelets, and treated with platelet-conditioned medium were used as an in vitro model of metastatic EOC. Gene expression analysis was performed using RNA-Seq data from untreated cells and cells treated with PAI-1 siRNA or negative control, each with and without platelets. Four cohorts of banked patient plasma samples (n = 239) were assayed for PAI-1 by ELISA. Treatment-naïve (TN) whole blood (WB) samples were evaluated for CTCs in conjunction with PAI-1 evaluation in matched plasma. Results and discussion: Significant phenotypic changes occurring when PAI-1 was silenced and when platelets were added to cells were reflected by RNA-seq data, with PAI-1 observed to be central to molecular mechanisms of EOC metastasis. Increased proliferation was observed in cells treated with platelets. Plasma PAI-1 significantly correlated with advanced disease in a TN cohort, and was significantly reduced in a neoadjuvant chemotherapy (NACT) cohort. PAI-1 demonstrated a trend towards significance in overall survival (OS) in the late-stage TN cohort, and correlation between PAI-1 and neutrophils in this cohort was significant. 72.7% (16/22) of TN patients with plasma PAI-1 levels higher than OS cutoff were CTC-positive. These data support a central role for PAI-1 in EOC metastasis, and highlight PAI-1's potential as a biomarker, prognostic indicator, or gauge of treatment response in HGSOC.

Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study.

BACKGROUND: The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. METHODS: We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated. RESULTS: A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. CONCLUSIONS: Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

Literature supporting therapeutic drug monitoring at secondary loss of response and post dose-intensification of adalimumab is limited. Adalimumab drug levels following dose-intensification rather than at the time of secondary loss of response are associated with subsequent Crohn's disease remission.

You & Me: Test and Treat study protocol for promoting COVID-19 test and treatment access to underserved populations.

BACKGROUND: Infections and deaths from the COVID-19 pandemic have disproportionately affected underserved populations. A community-engaged approach that supports decision making around safe COVID-19 practices is needed to promote equitable access to testing and treatment. You & Me: Test and Treat (YMTT) will evaluate a systematic and scalable community-engaged protocol that provides rapid access to COVID-19 at-home tests, education, guidance on next steps, and information on local resources to facilitate treatment in underserved populations. METHODS: This direct-to-participant observational study will distribute at-home, self-administered, COVID-19 testing kits to people in designated communities. YMTT features a Public Health 3.0 framework and Toolkit prescribing a tiered approach to community engagement. We will partner with two large community organizations, Merced County United Way (Merced County, CA) and Pitt County Health Department (Pitt County, NC), who will coordinate up to 20 local partners to distribute 40,000 COVID tests and support enrollment, consenting, and data collection over a 15-month period. Participants will complete baseline questions about their demographics, experience with COVID-19 infection, and satisfaction with the distribution event. Community partners will also complete engagement surveys. In addition, participants will receive guidance on COVID-19 mitigation and health-promoting resources, and accessible and affordable therapeutics if they test positive for COVID-19. Data collection will be completed using a web-based platform that enables creation and management of electronic data capture forms. Implementation measures include evaluating 1) the Toolkit as a method to form community-academic partnerships for COVID-19 test access, 2) testing results, and 3) the efficacy of a YMTT protocol coupled with local resourcing to provide information on testing, guidance, treatment, and links to resources. Findings will be used to inform innovative methods to address community needs in public health research that foster cultural relevance, improve research quality, and promote health equity. DISCUSSION: This work will promote access to COVID-19 testing and treatment for underserved populations by leveraging a community-engaged research toolkit. Future dissemination of the toolkit can support effective community-academic partnerships for health interventions in underserved settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05455190 . Registered 13 July 2022.

Formal health care costs among older people in Ireland: methods and estimates using The Irish Longitudinal Study on Ageing (TILDA).

Background: Reliable data on health care costs in Ireland are essential to support planning and evaluation of services. New unit costs and high-quality utilisation data offer the opportunity to estimate individual-level costs for research and policy. Methods: Our main dataset was The Irish Longitudinal Study on Ageing (TILDA). We used participant interviews with those aged 55+ years in Wave 5 (2018) and all end-of-life interviews (EOLI) to February 2020. We weighted observations by age, sex and last year of life at the population level. We estimated total formal health care costs by combining reported usage in TILDA with unit costs (non-acute care) and public payer reimbursement data (acute hospital admissions, medications). All costs were adjusted for inflation to 2022, the year of analysis. We examined distribution of estimates across the population, and the composition of costs across categories of care, using descriptive statistics. We identified factors associated with total costs using generalised linear models. Results: There were 5,105 Wave 5 observations, equivalent at the population level to 1,207,660 people aged 55+ years and not in the last year of life, and 763 EOLI observations, equivalent to 28,466 people aged 55+ years in the last year of life. Mean formal health care costs in the weighted sample were EUR 8,053; EUR 6,624 not in the last year of life and EUR 68,654 in the last year of life. Overall, 90% of health care costs were accounted for by 20% of users. Multiple functional limitations and proximity to death were the largest predictors of costs. Other factors that were associated with outcome included educational attainment, entitlements to subsidised care and serious chronic diseases. Conclusions: Understanding the patterns of costs, and the factors associated with very high costs for some individuals, can inform efforts to improve patient experiences and optimise resource allocation.

Hospital-presenting self-harm among older adults living in Ireland: a 13-year trend analysis from the National Self-Harm Registry Ireland.

OBJECTIVES: To examine trends in rates of self-harm among emergency department (ED) presenting older adults in Ireland over a 13-year period. DESIGN: Population-based study using data from the National Self-Harm Registry Ireland. SETTING: National hospital EDs. PARTICIPANTS: Older adults aged 60 years and over presenting with self-harm to hospital EDs in Ireland between January 1, 2007 and December 31, 2019. MEASUREMENTS: ED self-harm presentations. RESULTS: Between 2007 and 2019, there were 6931 presentations of self-harm in older adults. The average annual self-harm rate was 57.8 per 100,000 among older adults aged 60 years and over. Female rates were 1.1 times higher compared to their male counterparts (61.4 vs 53.9 per 100,000). Throughout the study time frame, females aged 60-69 years had the highest rates (88.1 per 100,000), while females aged 80 years and over had the lowest rates (18.7 per 100,000). Intentional drug overdose was the most commonly used method (75.5%), and alcohol was involved in 30.3% of presentations. Between the austerity and recession years (2007-2012), self-harm presentations were 7% higher compared to 2013-2019 (incidence rate ratio (IRR): 1.07 95% CI 1.02-1.13, p = 0.01). CONCLUSIONS: Findings indicate that self-harm in older adults remains a concern with approximately 533 presentations per year in Ireland. While in younger age groups, females report higher rates of self-harm, this gender difference was reversed in the oldest age group (80 years and over), with higher rates of self-harm among males. Austerity/recession years (2007-2012) had significantly higher rates of self-harm compared to subsequent years.

Evaluation of a 3-Item Health Index in Predicting Mortality Risk: A 12-Year Follow-Up Study.

This study was carried out using a large cohort (N = 4265; 416 deceased) of older, community-dwelling adults from The Irish Longitudinal Study on Ageing (TILDA). The study compared the performance of a new 3-item health index (HI) with two existing measures, the 32-item frailty index (FI) and the frailty phenotype (FP), in predicting mortality risk. The HI was based on the objective measurement of resting-state systolic blood pressure sample entropy, sustained attention reaction time performance, and usual gait speed. Mortality data from a 12-year follow up period were analyzed using Cox proportional regression. All data processing was performed using MATLAB and statistical analysis using STATA 15.1. The HI showed good discriminatory power (AUC = 0.68) for all-cause mortality, similar to FI (AUC = 0.68) and superior to FP (AUC = 0.60). The HI classified participants into Low-Risk (84%), Medium-Risk (15%), and High-Risk (1%) groups, with the High-Risk group showing a significant hazard ratio (HR) of 5.91 in the unadjusted model and 2.06 in the fully adjusted model. The HI also exhibited superior predictive performance for cardiovascular and respiratory deaths (AUC = 0.74), compared with FI (AUC = 0.70) and FP (AUC = 0.64). The HI High-Risk group had the highest HR (15.10 in the unadjusted and 5.61 in the fully adjusted models) for cardiovascular and respiratory mortality. The HI remained a significant predictor of mortality even after comprehensively adjusting for confounding variables. These findings demonstrate the effectiveness of the 3-item HI in predicting 12-year mortality risk across different causes of death. The HI performed similarly to FI and FP for all-cause mortality but outperformed them in predicting cardiovascular and respiratory deaths. Its ability to classify individuals into risk groups offers a practical approach for clinicians and researchers. Additionally, the development of a user-friendly MATLAB App facilitates its implementation in clinical settings. Subject to external validation in clinical research settings, the HI can be more useful than existing frailty measures in the prediction of cardio-respiratory risk.

An investigation of what protective individual- and community-level factors are associated with life satisfaction in middle-aged and older family carers in Ireland.

Background: Family care plays an essential role in providing care in society. However, caring can cause stress, and mental and physical responses to caring vary widely. Different outcomes for carers may reflect different approaches or adaptability to caring and their ability to maintain or recover their mental health and wellbeing following an adverse event (psychosocial resilience). We aim to identify factors that may promote psychosocial resilience, conceptualized as maintaining or recovering subjective wellbeing and operationalized as satisfaction with life, among carers. Methods: Data were from 6 Waves (2009-2021) of The Irish Longitudinal Study on Aging (TILDA), a prospective biennial nationally representative longitudinal study of older adults aged ≥50 in Ireland. Family caregiving was assessed in Waves 3-6. Participants were asked if they cared for someone, their relationship to the recipient, and the number of hours per week that they provided care. We used growth mixture modeling to identify latent trajectories of satisfaction with life (SWL) before and after caring was initiated. Regression modeling was then used to identify protective factors (at the individual, family, and community levels) associated with resilient trajectories. Results: Overall, 731 (12.2%) participants became carers during follow-up. We identified three trajectories in SWL in carers following initiation of caring, namely, Resilient-Stable (81%), Resilient-Recovery (12%), and Non-recovery (6%). Membership in Resilient-Stable and Resilient-Recovery trajectories was associated with fewer depressive symptoms (OR = 0.86, 95% CI 0.78, 0.94) and chronic conditions (OR = 0.21, 95% CI 0.06, 0.74), larger social networks (OR = 2.03, 95% CI 1.06, 3.86), more close friends and relatives (OR = 1.15, 95% CI 1.01, 1.32), and caring for someone other than a child (OR = 0.19, 95% CI 0.07, 0.51) compared to the Non-recovery group. Conclusion: Becoming a family carer was associated with a decline in SWL over time in some carers. However, most carers either did not experience a decline in SWL or recovered their SWL over time. We found that both individual and community-level supports may be protective for carers' wellbeing. These results will inform the priorities for social and community-level services and support for older carers and contribute to the design of new projects and programs to meet these needs.

Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.

Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with ß3 integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly ß3 integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa.

Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1.

Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.

Ex vivo expansion of circulating tumour cells (CTCs).

Circulating tumour cells (CTCs) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/purification has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha (HIF-1α). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than 8 weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.

Aortic Injury From High-Speed Deceleration Against a Lap Belt in a 10-year-Old.

Traumatic aortic injuries in children and adolescents are rare, and even more rare are blunt traumatic injury to the abdominal aorta in this population. Therefore, there are few reports discussing the presentation and repair of such injuries, especially within the pediatric population. We report the successful repair of traumatic abdominal aortic transection in a 10-year-old female after a high speed MVC. She arrived in extremis with a seatbelt sign and was taken emergently for damage control laparotomy with subsequent postoperative CT findings of aortic transection/dissection at L3 with active extravasation. She immediately underwent open thrombectomy of the bilateral iliac arteries, and repair of her aortic injury with a 12 × 7 mm Hemashield interposition graft extending just distal to the IMA and 1 cm proximal to the aortic bifurcation. There are little data regarding long-term outcomes of pediatric patients undergoing different aortic repair techniques, and further research is needed.

Circulating tumour cells: The Good, the Bad and the Ugly.

This review is an overview of the current knowledge regarding circulating tumour cells (CTCs), which are potentially the most lethal type of cancer cell, and may be a key component of the metastatic cascade. The clinical utility of CTCs (the "Good"), includes their diagnostic, prognostic, and therapeutic potential. Conversely, their complex biology (the "Bad"), including the existence of CD45+/EpCAM+ CTCs, adds insult to injury regarding their isolation and identification, which in turn hampers their clinical translation. CTCs are capable of forming microemboli composed of both non-discrete phenotypic populations such as mesenchymal CTCs and homotypic and heterotypic clusters which are poised to interact with other cells in the circulation, including immune cells and platelets, which may increase their malignant potential. These microemboli (the "Ugly") represent a prognostically important CTC subset, however, phenotypic EMT/MET gradients bring additional complexities to an already challenging situation.

Biomass carbon stocks and stock changes in managed hedgerows.

Landscape features, such as hedgerows, can play a role in enhancing terrestrial carbon (C) sinks, especially in North-western Europe, where they form a large part of the agricultural landscape. To date, there are few studies relating aerial imagery to ground-truthed biomass measurements and relating changes in biomass to hedgerow management. This study sought to develop relationships between measured biomass of hedgerows and digital elevation model (DEM) data from drones and aircraft. Furthermore, changes in hedgerow above-ground and below-ground biomass stocks were assessed using a systematic grid sample, DEM data and developed volume-biomass regression models. The developed inventory framework was then applied to a pilot study area of 419,701 ha in Ireland. Robust relationships were developed relating DEM data to volume and above-ground biomass. Model equations were also developed linking above-ground and below-ground biomass. However, these were less robust due to the confounding impacts of hedgerow management intensity, hedgerow type and dominant species. Above-ground biomass density was linearly correlated with hedge volume. Wider, less intensively managed, irregular hedges exhibit a higher biomass stocks per km, when compared to regular, more intensively managed hedgerows. When the models were extrapolated to the county level, hedgerow biomass C pools for Co Wexford and Waterford are suggested to be a net emission of -0.3 tC ha-1 year-1 due to hedgerow removals and management. Flailing or coppicing of hedgerows, in particular irregular profile hedgerows, had the largest impact on the biomass C balance in the pilot study area. Re-introduction of traditional management practices such as layering and increasing the allowable hedgerow width in areas qualifying for farm payments could be considered with the aim of increasing the maximum sink potential of established hedgerows.

A mixed-methods approach to understand university students' perceived impact of returning to class during COVID-19 on their mental and general health.

PURPOSE: This study investigated the prevalence and risk factors of mental and general health symptoms among university students attending in-person and online classes during COVID-19. We also explored their experiences returning to in-person classes and their views on the university's COVID-19-related policies. METHODS: In this sequential explanatory mixed-methods study (2020-2021), U.S. university student respondents (N = 1030; 603 women [58.5%], 907 [88.1%] aged 18-24 years) completed a quantitative, cross-sectional survey assessing their mental and general health symptoms experienced while taking classes during the COVID-19 pandemic. The survey link was distributed through social media and email invitations. Three separate follow-up focus groups (n = 27), consisting of an average of nine focus group respondents who had completed the quantitative survey per group, were conducted using a semi-structured interview guide. Focus group respondents provided qualitative responses on their experiences returning to class during COVID-19 and adhering to COVID-19-related policies. RESULTS: The prevalence of mental health symptoms among survey respondents were 57.6% (n = 593) for depression, 41.5% (n = 427) for anxiety, and 40.8% (n = 420) for stress. Over 90% of respondents reported perceptions of good general health. Female respondents and respondents identified as non-binary gender had an increased risk for mental health symptoms compared to male respondents. Respondents with preexisting medical conditions had an increased risk for worse general health. Themes identified through qualitative analysis included (1) attending class during COVID-19 is associated with unhealthy behaviors, and poor health, (2) perceived challenges of online learning and increased feelings of isolation, (3) demand for COVID-19 policy reform and greater transparency of COVID-19 statistics; (4) difficulties in adhering to COVID-19 policies; and (5) concerns about acquiring and transmitting COVID-19. CONCLUSIONS: Our findings indicate that university students attending classes during the pandemic are experiencing negative mental health impacts. Although students were aware of COVID-19-related policies, many found it challenging to comply. Broad acceptance of COVID-19 policies will require greater transparency and information sharing.

Core Muscle Injury: Evaluation and Treatment in the Athlete.

BACKGROUND: Pain in the groin region, where the abdominal musculature attaches to the pubis, is referred to as a "sports hernia,""athletic pubalgia," or "core muscle injury" and has become a topic of increased interest due to its challenging diagnosis. Identifying the cause of chronic groin pain is complicated because significant symptom overlap exists between disorders of the proximal thigh musculature, intra-articular hip pathology, and disorders of the abdominal musculature. PURPOSE: To present a comprehensive review of the pathoanatomic features, history and physical examination, and imaging modalities used to make the diagnosis of core muscle injury. STUDY DESIGN: Narrative and literature review; Level of evidence, 4. METHODS: A comprehensive literature search was performed. Studies involving the diagnosis, treatment, and rehabilitation of athletes with core muscle injury were identified. In addition, the senior author's extensive experience with the care of professional, collegiate, and elite athletes was analyzed and compared with established treatment algorithms. RESULTS: The differential diagnosis of groin pain in the athlete should include core muscle injury with or without adductor longus tendinopathy. Current scientific evidence is lacking in this field; however, consensus regarding terms and treatment algorithms was facilitated with the publication of the Doha agreement in 2015. Pain localized proximal to the inguinal ligament, especially in conjunction with tenderness at the rectus abdominis insertion, is highly suggestive of core muscle injury. Concomitant adductor longus tendinopathy is not uncommon in these athletes and should be investigated. The diagnosis of core muscle injury is a clinical one, although dynamic ultrasonography is becoming increasingly used as a diagnostic modality. Magnetic resonance imaging is not always diagnostic and may underestimate the true extent of a core muscle injury. Functional rehabilitation programs can often return athletes to the same level of play. If an athlete has been diagnosed with athletic pubalgia and has persistent symptoms despite 12 weeks of nonoperative treatment, a surgical repair using mesh and a relaxing myotomy of the conjoined tendon should be considered. The most common intraoperative finding is a deficient posterior wall of the inguinal canal with injury to the distal rectus abdominis. Return to play after surgery for an isolated sports hernia is typically allowed at 4 weeks; however, if an adductor release is performed as well, return to play occurs at 12 weeks. CONCLUSION: Core muscle injury is a diagnosis that requires a high level of clinical suspicion and should be considered in any athlete with pain in the inguinal region. Concurrent adductor pathology is not uncommon.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.