Discontinuous Shear Thickening in Biological Tissue Rheology.

During embryonic morphogenesis, tissues undergo dramatic deformations in order to form functional organs. Similarly, in adult animals, living cells and tissues are continually subjected to forces and deformations. Therefore, the success of embryonic development and the proper maintenance of physiological functions rely on the ability of cells to withstand mechanical stresses as well as their ability to flow in a collective manner. During these events, mechanical perturbations can originate from active processes at the single-cell level, competing with external stresses exerted by surrounding tissues and organs. However, the study of tissue mechanics has been somewhat limited to either the response to external forces or to intrinsic ones. In this work, we use an active vertex model of a 2D confluent tissue to study the interplay of external deformations that are applied globally to a tissue with internal active stresses that arise locally at the cellular level due to cell motility. We elucidate, in particular, the way in which this interplay between globally external and locally internal active driving determines the emergent mechanical properties of the tissue as a whole. For a tissue in the vicinity of a solid-fluid jamming or unjamming transition, we uncover a host of fascinating rheological phenomena, including yielding, shear thinning, continuous shear thickening, and discontinuous shear thickening. These model predictions provide a framework for understanding the recently observed nonlinear rheological behaviors in vivo.

Under pressure: A systematic review of the association between blood pressure variability with depression and anxiety.

Blood pressure variability (BPV) impacts brain health by influencing brain structure and cerebrovascular pathologies, though the mechanisms are poorly understood. Changes in the cerebrovasculature may lead to late-onset depression, cognitive impairment, and dementia, however the relationship between BPV with depression and anxiety remains unclear, due to methodological differences and inconsistencies in past research. This review aims to clarify the association between BPV with depression and anxiety in adults to inform understandings of the mechanisms implicating BPV in cognitive health. A systematic search from inception through to January 2024 was performed on Embase, PubMed, PsycINFO, and Web of Science. Studies that assessed BPV quantified by beat-to-beat, 24-hour, or visit-to-visit were eligible if the standardised assessment of depression and/or anxiety were reported as a linear association, or mean differences across control and affect groups. A total of 14 articles reporting on 13 samples and N = 5055 persons met the inclusion criteria (median female proportion = 61 %, range 0 % - 76 %). A meta-analysis was not possible due to methodological heterogeneity in BPV measurements and metrics across studies. Mixed results were observed across depression studies with inconsistencies and variation in the direction, strength of association, and BPV metric. There was weak evidence from only three studies to support a linear association between systolic coefficient of variation and anxiety. Collectively, the findings contribute to understanding the association between BPV and brain health, suggesting that any relationship between BPV and brain structures critical for cognitive function are independent of depression and only modestly implicate anxiety.

Birth Outcomes Related to Prenatal Zika, Dengue, and Other Flavivirus Infections in the Zika en Embarazadas y Niños Prospective Cohort Study in Colombia.

Zika virus (ZIKV) infection in pregnancy is associated with severe abnormalities of the brain and eye and other adverse outcomes. Zika en Embarazadas y Niños was a prospective cohort study conducted in multiple Colombian cities that enrolled pregnant women in their first trimester. Specimens collected from pregnant women (n = 1,519) during February 2017-September 2018 and their infants (n = 1,080) during June 2017-March 2019 were tested for prenatal ZIKV infection by nucleic acid amplification tests or IgM antibody testing. Zika virus infection in pregnancy was present in 3.2% of pregnant women (incidence rate [IR] per 1,000 person-months = 5.9, 95% CI: 4.3-7.8). Presumptive ZIKV infection was present in 0.8% of infants (IR = 1.6, 95% CI: 0.7-2.9). Five percent of infants with prenatal ZIKV exposure or infection presented with Zika-associated abnormalities; 4.7% were small for gestational age. Understanding the risk of ZIKV infection during pregnancy and associated adverse outcomes can help inform counseling efforts.

Protein and amino acid digestibility: definitions and conventional oro-ileal determination in humans.

When assessing protein quality, a correction needs to be made to take into consideration the availability of the amino acids. This correction is based on the digestibility of the amino acids. It is recommended to use ileal (end of small intestine) digestibility as opposed to faecal digestibility. A correction needs to be made for endogenous (gut sourced as opposed to diet sourced) amino acids to give true digestibility as opposed to apparent digestibility. Also, this correction should be made by correcting the amino acid composition for individual amino acid digestibilities as opposed to correcting all amino acids for nitrogen digestibility. Determination of true ileal amino acid digestibility requires the collection of ileal digesta. In the human there are two methods that can be used; naso-ileal intubation and using the ileostomy model. Both are discussed in detail and it is concluded that both are appropriate methods to collect ileal digesta.

DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging.

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

Reactions to a Nicotine Reduction Policy Among Adolescents Who Smoke: A Qualitative Study.

INTRODUCTION: The Biden administration is pursuing a nicotine reduction policy in the U.S. to render cigarettes less addictive. In this study, we qualitatively investigated adolescents' subjective responses to very low nicotine content (VLNC) cigarettes, reasons for incomplete adherence to using them, and their expected responses to a nicotine reduction policy. METHODS: Adolescents who smoke cigarettes daily (ages 15-19; N=60) were enrolled in a three-week double-blind randomized clinical trial and assigned to smoke either normal nicotine content (NNC) or VLNC research cigarettes. Following the trial, 52 participants completed qualitative interviews about their reactions to the cigarettes and to the idea of a nicotine reduction policy. We utilized a template style approach to thematic analysis involving immersion in the data, codebook development with both inductive and deductive codes, and iterative refinement of themes. RESULTS: Reasons for incomplete adherence to smoking only research cigarettes focused on dislike for cigarette taste and lower satisfaction compared to usual brand cigarettes. Negative evaluations of research cigarettes were common across both groups. Many participants in both groups reported that they would decrease their smoking or quit entirely if the research cigarettes were the only ones legally available for purchase in the U.S. CONCLUSIONS: Adolescents may respond to a cigarette nicotine reduction policy by decreasing their cigarette smoking and eventually quitting. These findings suggest a need for public health strategies to reduce smoking initiation and progression in young people and to encourage cessation in the context of a nicotine reduction policy. IMPLICATIONS: Participants' negative subjective responses and challenges with research cigarette adherence offer insight into factors that might influence young people's reactions to a real-world nicotine reduction policy. Adolescents who smoke may increase their use of alternative tobacco products, especially e-cigarettes, if this policy were implemented. Specifically, themes identified across participant responses highlight important considerations for how such a policy might be implemented with specific attention to the unique smoking behaviors and needs of this vulnerable population.

A Community Mental Health Integrated Disaster Preparedness Intervention for Bushfire Recovery in Rural Australian Communities: Protocol for a Multimethods Feasibility and Acceptability Pilot Study.

BACKGROUND: Natural hazards are increasing in frequency and intensity due to climate change. Many of these natural disasters cannot be prevented; what may be reduced is the extent of the risk and negative impact on people and property. Research indicates that the 2019-2020 bushfires in Australia (also known as the "Black Summer Bushfires") resulted in significant psychological distress among Australians both directly and indirectly exposed to the fires. Previous intervention research suggests that communities impacted by natural hazards (eg, earthquakes, hurricanes, and floods) can benefit from interventions that integrate mental health and social support components within disaster preparedness frameworks. Research suggests that disaster-affected communities often prefer the support of community leaders, local services, and preexisting relationships over external supports, highlighting that community-based interventions, where knowledge stays within the local community, are highly beneficial. The Community-Based Disaster Mental Health Intervention (CBDMHI) is an evidence-based approach that aims to increase disaster preparedness, resilience, social cohesion, and social support (disaster-related help-seeking), and decrease mental health symptoms, such as depression and anxiety. OBJECTIVE: This research aims to gain insight into rural Australian's recovery needs post natural hazards, and to enhance community resilience in advance of future fires. Specifically, this research aims to adapt the CBDMHI for the rural Australian context and for bushfires and second, to assess the acceptability and feasibility of the adapted CBDMHI in a rural Australian community. METHODS: Phase 1 consists of qualitative interviews (individual or dyads) with members of the target bushfire-affected rural community. Analysis of these data will include identifying themes related to disaster preparedness, social cohesion, and mental health, which will inform the adaptation. An initial consultation phase is a key component of the adaptation process and, therefore, phase 2 will involve additional discussion with key stakeholders and members of the community to further guide adaptation of the CBDMHI to specific community needs, building on phase 1 inputs. Phase 3 includes identifying and training local community leaders in the adapted intervention. Following this, leaders will co-deliver the intervention. The acceptability and feasibility of the adapted CBDMHI within the community will be evaluated by questionnaires and semistructured interviews. Effectiveness will be evaluated by quantifying psychological distress, resilience, community cohesion, psychological preparedness, and help-seeking intentions. RESULTS: This study has received institutional review board approval and commenced phase 1 recruitment in October 2022. CONCLUSIONS: The study will identify if the adapted CBDMHI is viable and acceptable within a village in the Northern Tablelands of New South Wales, Australia. These findings will inform future scale-up in the broader rural Australian context. If this intervention is well received, the CBDMHI may be valuable for future disaster recovery and preparedness efforts in rural Australia. These findings may inform future scale-up in the broader rural Australian context. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53454.

A Case of Hepatic Tuberculosis in a Patient on Adalimumab for Ankylosing Spondylitis.

Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on immunosuppressive medications or those with a human immunodeficiency virus (HIV) infection. Primary hepatic TB is rare, and liver involvement is often secondary to spreading from the lymphatics, portal vein, or hepatic artery. We report a case of hepatic TB in a patient on adalimumab for ankylosing spondylitis (AS).

National survey of patient perspectives on cost discussions among recipients of copay assistance.

BACKGROUND: Individuals with cancer and other medical conditions often experience financial concerns from high costs-of-care and may utilize copay assistance programs (CAP). We sought to describe CAP recipients' experiences/preferences for cost discussions with clinicians. METHODS: We conducted a national, cross-sectional electronic-survey from 10/2022 to 11/2022 of CAP recipients with cancer or autoimmune conditions to assess patient perspectives on cost discussions. We used multivariable logistic regression models to explore associations of patient perspectives on cost discussions with patient characteristics and patient-reported outcomes (eg, financial toxicity, depression/anxiety, and health literacy). RESULTS: Among 1,566 participants, 71% had cancer and 29% had autoimmune conditions. Although 62% of respondents desired cost discussions, only 32% reported discussions took place. Additionally, 52% of respondents wanted their doctor to consider out-of-pocket costs when deciding the best treatment, and 61% of respondents felt doctors should ensure patients can afford treatment prescribed. Participants with depression symptoms were more likely to want doctors to consider out-of-pocket costs (OR = 1.54, P = .005) and to believe doctors should ensure patients can afford treatment (OR = 1.60, P = .005). Those with severe financial toxicity were more likely to desire cost discussions (OR = 1.65, P < .001) and want doctors to consider out-of-pocket costs (OR = 1.52, P = .001). Participants with marginal/inadequate health literacy were more likely to desire cost discussions (OR = 1.37, P = .01) and believe doctors should ensure patients can afford treatment (OR = 1.30, P = .036). CONCLUSIONS: In this large sample of CAP recipients with cancer and autoimmune conditions, most reported a desire for cost discussions, but under one-third reported such discussions took place.

Tropoelastin modulates systemic and local tissue responses to enhance wound healing.

Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair process. Tropoelastin (TE) based materials are known to shorten the period for wound repair but the mechanism of anti-inflammatory performance is not known. To explore this, we compared the performance of the gold standard Integra Dermal Regeneration Template (Integra), polyglycerol sebacate (PGS), and TE blended with PGS, in a murine full-thickness cutaneous wound healing study. Systemically, blending with TE favorably increased the F4/80+ macrophage population by day 7 in the spleen and contemporaneously induced elevated plasma levels of anti-inflammatory IL-10. In contrast, the PGS graft without TE prompted prolonged inflammation, as evidenced by splenomegaly and greater splenic granulocyte and monocyte fractions at day 14. Locally, the inclusion of TE in the graft led to increased anti-inflammatory M2 macrophages and CD4+T cells at the wound site, and a rise in Foxp3+ regulatory T cells in the wound bed by day 7. We conclude that the TE-incorporated skin graft delivers a pro-healing environment by modulating systemic and local tissue responses. STATEMENT OF SIGNIFICANCE: Tropoelastin (TE) has shown significant benefits in promoting the repair and regeneration of damaged human tissues. In this study, we show that TE promotes an anti-inflammatory environment that facilitates cutaneous wound healing. In a mouse model, we find that inserting a TE-containing material into a full-thickness wound results in defined, pro-healing local and systemic tissue responses. These findings advance our understanding of TE's restorative value in tissue engineering and regenerative medicine, and pave the way for clinical applications.

Elevated Lipid Metabolites in Stored Clinical OCA Media Correlate With Chondrocyte Death.

BACKGROUND: A major limitation of osteochondral allografts (OCA) is the deterioration of cartilage health associated with cell death during prolonged storage. However, little is known about the mechanisms that contribute to chondrocyte death during storage. PURPOSE/HYPOTHESIS: This study aimed to determine whether bioactive lipid metabolites accumulate in the storage media of OCA and whether they are associated with a loss of chondrocyte viability during prolonged storage. It was hypothesized that free fatty acids (FFAs) would accumulate over time in the storage media of OCA and adversely affect cartilage health during storage. STUDY DESIGN: Controlled laboratory study. METHODS: A group of 21 (n = 6-8 OCA/treatment group) fresh human hemicondylar OCA tissues and media were analyzed after 7, 28, and 68 days of prolonged cold (4°C) storage. Targeted mass spectrometry analysis was used to quantify bioactive FFAs, as well as primary (lipid hydroperoxide [ROOH]) and secondary (malondialdehyde) lipid oxidation products. Chondrocyte viability was measured using a fluorescence-based live/dead assay and confocal microscopy. RESULTS: The concentration of all targeted fatty acid metabolites in storage media was significantly increased with increased cold storage time (P < .05). ROOH was significantly higher on day 28 of cold storage. No difference in secondary ROOH products in storage media was observed. Chondrocyte viability significantly declined in both the en face and the vertical cross-sectional analysis with increased cold storage time and inversely correlated with fatty acid metabolites (P < .05). CONCLUSION: It is well established that elevated levels of certain FFAs and lipid oxidation products can alter cell function and cause cell death via lipotoxicity and other mechanisms. This work is the first to identify elevated levels of FFA metabolites and primary oxidation lipid products in the storage media from clinical OCA. The concentrations of FFA metabolites were measured at levels (>100 µM) known to induce cell death and were directly correlated with chondrocyte viability. CLINICAL RELEVANCE: These findings provide important targets for understanding why cartilage health declines during cold storage, which can be used to optimize media formulations and improve graft health.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Vaginal anaerobes are associated with cervicitis: A case-control study.

OBJECTIVES: Cervicitis is associated with important reproductive sequelae. Primary causes include chlamydia and gonorrhoea, but a known sexually transmitted infection (STI) is not identified in >50% of cases (i.e. STI-negative cervicitis). Bacterial vaginosis (BV) and specific BV-associated bacteria have also been associated with cervicitis, but data are limited. We investigated the association between STI-negative cervicitis and vaginal microbiota composition. METHODS: This was a case-control sub-study of the OhMG study conducted at the Melbourne Sexual Health Centre. Cases were women with cervicitis who tested negative for STIs (STI-negative cervicitis, n = 64). Controls were STI-negative asymptomatic women attending for STI-screening (n = 128). The vaginal microbiota was characterised using 16S rRNA gene sequencing. Vaginal community state types were compared between cases and controls using logistic regression. Differential abundance analysis was performed to identify taxa associated with STI-negative cervicitis. RESULTS: STI-negative cervicitis cases were more likely than controls to have a Lactobacillus-deficient non-optimal microbiota (adjusted-odds-ratio 2.55, 95% CI 1.18-5.50). Compared to controls, cases had increased abundance of four BV-associated bacteria (Gardnerella, Fannyhessea vaginae, Prevotella bivia, Dialister micraerophilus) and decreased abundance of optimal lactobacilli. CONCLUSIONS: We report a positive association between non-optimal vaginal microbiota composition and STI-negative cervicitis. Specific anaerobic BV-associated bacteria may represent infectious causes of cervicitis.

Subducting plate structure and megathrust morphology from deep seismic imaging linked to earthquake rupture segmentation at Cascadia.

The origin of rupture segmentation along subduction zone megathrusts and linkages to the structural evolution of the subduction zone are poorly understood. Here, regional-scale seismic imaging of the Cascadia margin is used to characterize the megathrust spanning ~900 km from Vancouver Island to the California border, across the seismogenic zone to a few tens of kilometers from the coast. Discrete domains in lower plate geometry and sediment underthrusting are identified, not evident in prior regional plate models, which align with changes in lithology and structure of the upper plate and interpreted paleo-rupture patches. Strike-slip faults in the lower plate associated with oblique subduction mark boundaries between regions of distinct lower plate geometry. Their formation may be linked to changes in upper plate structure across long-lived upper plate faults. The Juan de Fuca plate is fragmenting within the seismogenic zone at Cascadia as the young plate bends beneath the heterogeneous upper plate resulting in structural domains that coincide with paleo-rupture segmentation.

Urinary Oxalate Excretion During Pregnancy in Primary Hyperoxaluria Type 1: A Report of 4 Cases.

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by excessive oxalate production because of specific gene defects. PH1 is the most prevalent type, causing recurrent kidney stone disease and often leading to chronic kidney disease and kidney failure. Our previous study suggested that pregnancy did not adversely affect kidney function in female patients with PH. In this study, we identified 4 PH1 cases with urinary oxalate (UOx) measurements during pregnancy from the Rare Kidney Stone Consortium and Oxalosis and Hyperoxaluria Foundation PH registry to investigate UOx levels during pregnancy in patients with PH1. The PH Registry is approved by the Institutional Review Board of Mayo Clinic (Rochester, MN). All 4 showed a decrease in UOx during pregnancy when compared with before pregnancy and after delivery. These findings contrast with those of the general population, in which the UOx tends to increase during pregnancy because of a simultaneous physiological increase in the glomerular filtration rate. Elucidating the mechanism underlying reduced UOx during pregnancy in PH1 could suggest novel PH therapies. These findings could also affect the clinical management and have implications regarding the safety of withholding novel PH1-directed molecular therapies that currently have uncertain safety profiles during pregnancy. We highlight the need for additional data on urinary changes in patients with PH and other populations while pregnant to clarify changes in UOx throughout pregnancy.

Isolated Optic Nerve Relapse in a Pediatric Patient With T-Cell Lymphoblastic Leukemia: A Brief Report.

Isolated optic nerve (ON) relapse is a rare occurrence in lymphoblastic leukemia (LBL). A 10-year-old boy with T-LBL presented 8 months after diagnosis with blurred vision and thickening of right ON on magnetic resonance imaging consistent with relapse. Cerebrospinal fluid and bone marrow were negative for leukemia. He received reinduction chemotherapy (including nelarabine and craniospinal radiation) followed by a myeloablative matched sibling donor bone marrow transplant. He remains in remission 2 years post-transplant with normal vision. We also review the literature for reports of isolated ON relapse in patients with LBL. Our patient's clinical course demonstrates that disease control can be achieved with early detection of ON relapse before disease progression.

Psychosocial experiences of clinicians providing care for children with severe neurological impairment.

AIM: To investigate clinicians' psychosocial experiences navigating interdisciplinary care for children with severe neurological impairment (SNI), for example children with a developmental epileptic encephalopathy; secondarily, to identify preferences for future interventions to support clinicians caring for children with SNI. METHOD: We conducted a qualitative descriptive study with interdisciplinary clinicians by using a purposeful sampling recruitment strategy. Twenty-four participants with expertise caring for children with SNI completed in-depth, semi-structured interviews. We transcribed the interviews, de-identified them, and performed inductive thematic analysis. RESULTS: Thematic analysis elicited interrelated themes. Clinicians experienced immense professional barriers providing patient-centred care across fragmented healthcare contexts. Physical, emotional, and psychological impacts were attributed to inadequate reflective practice training and a paucity of integrated resources to support clinicians over time. Multipronged strategies were prioritized by clinicians, incorporating psychoeducation, interdisciplinary peer mentorship, and psychological resources to build reflective practice skills for clinicians providing complex care in an advancing era of medicine. INTERPRETATION: This study provides novel and in-depth insight into clinicians' experiences navigating care for children with SNI. The results will be used to inform future integrated and multipronged co-developed resources tailored for clinicians, on the basis of their recommendations.