A simple projection method to correlate the principal mechanical direction with the principal microstructural direction of human osteoporotic femoral heads.

The mechanics of the trabecular bone is related to its structure; this work aimed to propose a simple projection method to clarify the correlation between the principal mechanical direction (PMD) and the principal microstructural direction (PMSD) of trabecular bones from osteoporotic femoral heads. A total of 529 trabecular cubes were cropped from five osteoporotic femoral heads. The micro computed tomography (µCT) sequential images of each cube were first projected onto the three Cartesian coordinate planes to have three overlapped images, and the trabecular orientation distribution in the three images was analyzed. The PMSD corresponding to the greatest distribution frequency of the trabecular orientation in the three images was defined. Then, the voxel finite element (FE) models of the cubes were reconstructed and simulated to obtain their compliance matrices, and the matrices were subjected to transversal rotation to find their maximum elastic constants. The PMD corresponding to the maximum elastic constant was defined. Subsequently, the correlation of the defined PMSD and PMD was analyzed. The results showed that PMSD and PMD of the trabecular cubes did not show a significant difference at the xy- and yz-planes except that at the zx-plane. Despite this, the mean PMSD-PMD deviations at the three coordinate planes were close to 0°, and the PMSD-PMD fitting to the line PMSD = PMD demonstrated their high correlation. This study might be helpful to identify the loading direction of anisotropic trabecular bones in experiments by examining the PMSD and also to guide bone scaffold design for bone tissue repair.

Definitive engineering strength and fracture toughness of graphene through on-chip nanomechanics.

Fail-safe design of devices requires robust integrity assessment procedures which are still absent for 2D materials, hence affecting transfer to applications. Here, a combined on-chip tension and cracking method, and associated data reduction scheme have been developed to determine the fracture toughness and strength of monolayer-monodomain-freestanding graphene. Myriads of specimens are generated providing statistical data. The crack arrest tests provide a definitive fracture toughness of 4.4 MPa m . Tension on-chip provides Young's modulus of 950 GPa, fracture strain of 11%, and tensile strength up to 110 GPa, reaching a record of stored elastic energy ~6 GJ m-3 as confirmed by thermodynamics and quantized fracture mechanics. A ~ 1.4 nm crack size is often found responsible for graphene failure, connected to 5-7 pair defects. Micron-sized graphene membranes and smaller can be produced defect-free, and design rules can be based on 110 GPa strength. For larger areas, a fail-safe design should be based on a maximum 57 GPa strength.

Surgery for Craniosynostosis: Developing a Psychosocial Booklet for Families.

Parents of children with craniosynostosis may experience psychological distress, particularly during intensive periods of treatment. Yet, recent research indicates parents may not be accessing the support they need to cope with common challenges. The aim was to develop an evidence-based booklet to promote psychological health in families undergoing surgery and to assess the acceptability of the booklet among the craniosynostosis community. Researchers collaborated with UK charity Headlines Craniofacial Support, 5 parent representatives, and 2 specialist clinical psychologists to develop the booklet based on data obtained from online focus groups, individual interviews, and written accounts. The draft booklet was attached to an online acceptability survey and distributed to a broader group of parents and multidisciplinary craniofacial specialists for feedback. A total of 52 complete responses to the online acceptability survey were received, and acceptability (measured by the number of respondents who would recommend the booklet) was 100%. All respondents supported the UK-wide distribution of the booklet. Evidence for psychological intervention in the craniofacial field remains scarce, and specialist teams may be under-resourced to effectively screen and support families. It is hoped this booklet can begin to address the gap in psychological support for families affected by craniosynostosis.

Melanin-based color variation in response to changing climates in snakes.

Melanism, the process of heavier melanin deposition, can interact with climate variation at both micro and macro scales, ultimately influencing color evolution in organisms. While the ecological processes regulating melanin production in relation to climate have been extensively studied, intraspecific variations of melanism are seldom considered. Such scientific gap hampers our understanding of how species adapt to rapidly changing climates. For example, dark coloration may lead to higher heat absorption and be advantageous in cool climates, but also in hot environments as a UV or antimicrobial protection mechanism. To disentangle such opposing predictions, here we examined the effect of climate on shaping melanism variation in 150 barred grass snakes (Natrix helvetica) and 383 green whip snakes (Hierophis viridiflavus) across Italy. By utilizing melanistic morphs (charcoal and picturata in N. helvetica, charcoal and abundistic in H. viridiflavus) and compiling observations from 2002 to 2021, we predicted that charcoal morphs in H. viridiflavus would optimize heat absorption in cold environments, while offering protection from excessive UV radiation in N. helvetica within warm habitats; whereas picturata and abundistic morphs would thrive in humid environments, which naturally have a denser vegetation and wetter substrates producing darker ambient light, thus providing concealment advantages. While picturata and abundistic morphs did not align with our initial humidity expectations, the charcoal morph in N. helvetica is associated with UV environments, suggesting protection mechanisms against damaging solar radiation. H. viridiflavus is associated with high precipitations, which might offer antimicrobial protection. Overall, our results provide insights into the correlations between melanin-based color morphs and climate variables in snake populations. While suggestive of potential adaptive responses, future research should delve deeper into the underlying mechanisms regulating this relationship.

Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire.

Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies.

Cracking AlphaFold2: Leveraging the power of artificial intelligence in undergraduate biochemistry curriculums.

AlphaFold2 is an Artificial Intelligence-based program developed to predict the 3D structure of proteins given only their amino acid sequence at atomic resolution. Due to the accuracy and efficiency at which AlphaFold2 can generate 3D structure predictions and its widespread adoption into various aspects of biochemical research, the technique of protein structure prediction should be considered for incorporation into the undergraduate biochemistry curriculum. A module for introducing AlphaFold2 into a senior-level biochemistry laboratory classroom was developed. The module's focus was to have students predict the structures of proteins from the MPOX 22 global outbreak virus isolate genome, which had no structures elucidated at that time. The goal of this study was to both determine the impact the module had on students and to develop a framework for introducing AlphaFold2 into the undergraduate curriculum so that instructors for biochemistry courses, regardless of their background in bioinformatics, could adapt the module into their classrooms.

Methods of Assessment of Zinc Status in Humans: An Updated Review and Meta-analysis.

CONTEXT: The assessment of zinc status is difficult but essential for the identification of zinc deficiency and evaluation of interventions to improve zinc status. OBJECTIVE: The purpose of this systematic review (SR) and meta-analysis was to update the previously published SR of biomarkers of zinc status, conducted by the European Micronutrient Recommendations Aligned (EURRECA) network in 2009, to answer the question: Which putative measures (biomarkers) of zinc status appropriately reflect a change in zinc intake of at least 2 weeks? DATA SOURCES: A structured search strategy was used to identify articles published between January 2007 and September 2022 from MEDLINE (Ovid), Embase (Ovid), Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles were identified using previously defined eligibility criteria. DATA EXTRACTION: Data were extracted and combined with data from the previous SR. DATA ANALYSIS: A random-effects model was used to calculate pooled mean differences using STATA (StataCorp). The risk of bias and the certainty of evidence for all outcomes were assessed. Additional data on 7 of the 32 previously reported biomarkers were identified, along with data on an additional 40 putative biomarkers from studies published since 2007. Pooled data analysis confirmed that, in healthy participants, both plasma/serum zinc concentration and urinary zinc excretion responded to changes in zinc intake (plasma/serum: mean effect [95% CI], controlled studies: 2.17 µmol/L [1.73, 2.61]; P < .005, I2 = 97.8; before-and-after studies: 2.87 µmol/L [2.45, 3.30]; P < .005, I2 = 98.1%; urine zinc: 0.39 mmol/mol creatinine [0.17, 0.62]; P < .005, I2 = 81.2; 3.09 µmol/day [0.16, 6.02]; P = .039, I2 = 94.3). CONCLUSION: The updated analyses support the conclusion that plasma/serum and urinary zinc respond to changes in zinc intake in studies of healthy participants. Several additional putative biomarkers were identified, but more studies are needed to assess the sensitivity and reliability. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42020219843.

Sex Differences in Morphine Sensitivity of Neuroligin-3 Knockout Mice.

Sex has a strong influence on the prevalence and course of brain conditions, including autism spectrum disorders. The mechanistic basis for these sex differences remains poorly understood, due in part to historical bias in biomedical research favoring analysis of male subjects, and the exclusion of female subjects. For example, studies of male mice carrying autism-associated mutations in neuroligin-3 are over-represented in the literature, including our own prior work showing diminished responses to chronic morphine exposure in male neuroligin-3 knockout mice. We therefore studied how constitutive and conditional genetic knockout of neuroligin-3 affects morphine sensitivity of female mice. In contrast to male mice, female neuroligin-3 knockout mice showed normal psychomotor sensitization after chronic morphine exposure. However, in the absence of neuroligin-3 expression, both female and male mice show a similar change in the topography of locomotor stimulation produced by morphine. Conditional genetic deletion of neuroligin-3 from dopamine neurons increased the locomotor response of female mice to high doses of morphine, contrasting with the decrease in psychomotor sensitization caused by the same manipulation in male mice. Together, our data reveal that knockout of neuroligin-3 has both common and distinct effects on morphine sensitivity in female and male mice. These results also support the notion that female sex can confer resilience against the impact of autism-associated gene variants.

Conservative management versus invasive management of significant traumatic pneumothoraces in the emergency department (the CoMiTED trial): a study protocol for a randomised non-inferiority trial.

INTRODUCTION: Traumatic pneumothoraces are present in one of five victims of severe trauma. Current guidelines advise chest drain insertion for most traumatic pneumothoraces, although very small pneumothoraces can be managed with observation at the treating clinician's discretion. There remains a large proportion of patients in whom there is clinical uncertainty as to whether an immediate chest drain is required, with no robust evidence to inform practice. Chest drains carry a high risk of complications such as bleeding and infection. The default to invasive treatment may be causing potentially avoidable pain, distress and complications. We are evaluating the clinical and cost-effectiveness of an initial conservative approach to the management of patients with traumatic pneumothoraces. METHODS AND ANALYSIS: The CoMiTED (Conservative Management in Traumatic Pneumothoraces in the Emergency Department) trial is a multicentre, pragmatic parallel group, individually randomised controlled non-inferiority trial to establish whether initial conservative management of significant traumatic pneumothoraces is non-inferior to invasive management in terms of subsequent emergency pleural interventions, complications, pain, breathlessness and quality of life. We aim to recruit 750 patients from at least 40 UK National Health Service hospitals. Patients allocated to the control (invasive management) group will have a chest drain inserted in the emergency department. For those in the intervention (initial conservative management) group, the treating clinician will be advised to manage the participant without chest drain insertion and undertake observation. The primary outcome is a binary measure of the need for one or more subsequent emergency pleural interventions within 30 days of randomisation. Secondary outcomes include complications, cost-effectiveness, patient-reported quality of life and patient and clinician views of the two treatment options; participants are followed up for 6 months. ETHICS AND DISSEMINATION: This trial received approval from the Wales Research Ethics Committee 4 (reference: 22/WA/0118) and the Health Research Authority. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN35574247.

Exploring Medical Student Experiences With Direct Observation During the Pediatric Clerkship.

PURPOSE: Direct observation (DO) enables assessment of vital competencies, such as clinical skills. Despite national requirement that medical students experience DOs during each clerkship, the frequency, length, quality, and context of these DOs are not well established. This study examines the quality, quantity, and characteristics of DOs obtained during pediatrics clerkships across multiple institutions. METHOD: This multimethod study was performed at 6 U.S.-based institutions from March through October 2022. In the qualitative phase, focus groups and/or semistructured interviews were conducted with third-year medical students at the conclusion of pediatrics clerkships. In the quantitative phase, the authors administered an internally developed instrument after focus group discussions or interviews. Qualitative data were analyzed using thematic analysis, and quantitative data were analyzed using anonymous survey responses. RESULTS: Seventy-three medical students participated in 20 focus groups, and 71 (97.3%) completed the survey. The authors identified 7 themes that were organized into key principles: before, during, and after DO. Most students reported their DOs were conducted primarily by residents (62 [87.3%]) rather than attendings (6 [8.4%]) in inpatient settings. Participants reported daily attending observation of clinical reasoning (38 [53.5%]), communication (39 [54.9%]), and presentation skills (58 [81.7%]). One-third reported they were never observed taking a history by an inpatient attending (23 [32.4%]), and one-quarter reported they were never observed performing a physical exam (18 [25.4%]). CONCLUSIONS: This study revealed that students are not being assessed for performing vital clinical skills in the inpatient setting by attendings as frequently as previously believed. When observers set expectations, create a safe learning environment, and follow up with actionable feedback, medical students perceive the experience as valuable; however, the DO experience is currently suboptimal. Therefore, a high-quality, competency-based clinical education for medical students is necessary to directly drive future patient care by way of a competent physician workforce.

Psychosocial Experiences of Spanish-Speaking Parents of Children With Craniofacial Microsomia.

Craniofacial microsomia (CFM) and microtia psychosocial research in the US is primarily with English-speaking participants. Given that 19% of the US is Latino, and there is a higher prevalence of CFM in Latino populations, this study aims to describe psychosocial experiences related to CFM among Spanish-speaking Latino caregivers to better inform health care. Narrative interviews (mean 73±17 min) were completed in Spanish with parents of children with CFM aged 3 to 17 (mean age 10.8±4.8 years). Transcripts were analyzed using quantitative linguistic analyses and reflexive thematic analysis. Participants (N=12) were mostly mothers (83%) who had immigrated to the US and had low socioeconomic status. Based upon analysis of grouped word counts, participants spent approximately half of their narratives discussing the first two years of their child's life. Themes selected based on US Latino sociodemographics and cultural values included the Impact of Language, Healthcare Challenges, Supportive Healthcare Experiences, Caregiver Coping with CFM, Family Roles, and Addressing Social Implications of CFM. Results highlighted that the first years of care are of critical importance to parents and suggest this is an optimal time to focus on education and support services for families. Additional treatment suggestions include providing interpretation and informational materials in Spanish, addressing care barriers, supporting familial and child coping, accounting for the role of extended family, and helping address social concerns. Ongoing research with Latino families can further assist in guiding culturally sensitive CFM health care.

In Silico Evaluation of In Vivo Degradation Kinetics of Poly(Lactic Acid) Vascular Stent Devices.

Biodegradable vascular stents (BVS) are deemed as great potential alternatives for overcoming the inherent limitations of permanent metallic stents in the treatment of coronary artery diseases. The current study aimed to comprehensively compare the mechanical behaviors of four poly(lactic acid) (PLA) BVS designs with varying geometries via numerical methods and to clarify the optimal BVS selection. Four PLA BVS (i.e., Absorb, DESolve, Igaki-Tamai, and Fantom) were first constructed. A degradation model was refined by simply including the fatigue effect induced by pulsatile blood pressures, and an explicit solver was employed to simulate the crimping and degradation behaviors of the four PLA BVS. The degradation dynamics here were characterized by four indices. The results indicated that the stent designs affected crimping and degradation behaviors. Compared to the other three stents, the DESolve stent had the greatest radial stiffness in the crimping simulation and the best diameter maintenance ability despite its faster degradation; moreover, the stent was considered to perform better according to a pilot scoring system. The current work provides a theoretical method for studying and understanding the degradation dynamics of the PLA BVS, and it could be helpful for the design of next-generation BVS.

Homologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over.

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.

Dissecting aortitis in a goat associated with Pasteurella multocida and Staphylococcus spp infection.

Reports of primary cardiovascular disease in goats are rare and most commonly include ventricular septal defect, valvular endocarditis, traumatic pericarditis, ionophore poisoning and nutritional cardiomyopathies. We now report the pathological findings in a 67 kg, 6-year-old, adult female Boer goat that presented with neurological signs (ie, head pressing, unsteadiness and paddling) and hyperthermia 2 days prior to death. Lack of therapeutic response to meloxicam and penicillin‒streptomycin and poor prognosis led to euthanasia of the animal. At necropsy, the main findings included severe aortic dissection with luminal thrombosis and stenosis, and pulmonary congestion and oedema. Histological examination of the aorta revealed severe chronic granulomatous and fibrosing dissecting aortitis with mineralization. Bacterial culture of the affected aortic segment resulted in isolation of a profuse growth of Pasteurella multocida and a moderate growth of Staphylococcus spp. Histopathological findings in the central nervous system were consistent with neurolisteriosis.

Autoantibodies Targeting Nephrin in Podocytopathies.

BACKGROUND: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear. METHODS: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin. RESULTS: The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice. CONCLUSIONS: In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).

"I can't provide what my child needs": Early feeding experiences of caregivers of children with craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) is a congenital condition that can be associated with feeding challenges in infants. As part of the larger 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program, this study described caregivers' early feeding experiences. DESIGN AND MATERIALS: US-based caregivers of 34 children with CFM participated in remote narrative interviews. Two authors completed inductive thematic analysis in an iterative process until consensus was reached. RESULTS: Caregivers' narratives outlined the inherent challenges of feeding an infant with special healthcare needs. The first theme 'Navigating Challenges and Managing Expectations' describes the distress participants experienced when they were unable to breastfeed and the negative emotional effect of switching to formula. The second theme 'Making Adaptations' outlines the methods participants tried, including breast pumps and feeding tubes. The third theme 'Accessing Support' describes participants' interactions with healthcare providers and challenges accessing feeding support. The final theme 'Growing from Adversity' recounts participants' relief once their child established a feeding pattern and the personal growth gained from their experiences. CONCLUSIONS: Caregivers reported several feeding related challenges associated with CFM, many of which negatively affected their wellbeing. Negative consequences were particularly pronounced in cases where caregivers' feeding experiences differed from their expectations. Participants identified challenges in accessing reliable feeding information and support. Despite difficult experiences, caregivers cited some positive outcomes, including increased confidence and resilience. PRACTICE IMPLICATIONS: Holistic feeding information and support for families affected by CFM should be inclusive of several feeding methods to improve care delivery, child health, and the caregiver experience.

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) project.

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).

A Conceptual Thematic Framework of Psychological Adjustment in Caregivers of Children with Craniofacial Microsomia.

OBJECTIVE: Children with craniofacial microsomia (CFM) have complex healthcare needs, resulting in evaluations and interventions from infancy onward. Yet, little is understood about families' treatment experiences or the impact of CFM on caregivers' well-being. To address this gap, the NIH-funded 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program sought to develop a conceptual thematic framework of caregiver adjustment to CFM. DESIGN: Caregivers reported on their child's medical and surgical history. Narrative interviews were conducted with US caregivers (n = 62) of children aged 3-17 years with CFM. Transcripts were inductively coded and final themes and subthemes were identified. RESULTS: Components of the framework included: 1) Diagnostic Experiences, including pregnancy and birth, initial emotional responses, communication about the diagnosis by healthcare providers, and information-seeking behaviors; 2) Child Health and Healthcare Experiences, including feeding, the child's physical health, burden of care, medical decision-making, surgical experiences, and the perceived quality of care; 3) Child Development, including cognition and behavior, educational provision, social experiences, and emotional well-being; and 4) Family Functioning, including parental well-being, relationships, coping strategies, and personal growth. Participants also identified a series of "high" and "low" points throughout their journey and shared their priorities for future research. CONCLUSIONS: Narrative interviews provided rich insight into caregivers' experiences of having a child with CFM and enabled the development of a conceptual thematic framework to guide clinical care and future research. Information gathered from this study demonstrates the need to incorporate evidence-based psychological support for families into the CFM pathway from birth onward.