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Hereditary hemochromatosis ( HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p. C282Y substitution. We conducted a study of screening for p. C282Y in high schools where p. C282Y heterozygotes ( CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild-type homozygous ( CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p. C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening. [ABSTRACT FROM AUTHOR]

Iron deficiency anaemia (IDA) remains prevalent in Australia and worldwide, especially among high-risk groups. IDA may be effectively diagnosed in most cases by full blood examination and serum ferritin level. Serum iron levels should not be used to diagnose iron deficiency. Although iron deficiency may be due to physiological demands in growing children, adolescents and pregnant women, the underlying cause(s) should be sought. Patients without a clear physiological explanation for iron deficiency (especially men and postmenopausal women) should be evaluated by gastroscopy/colonoscopy to exclude a source of gastrointestinal bleeding, particularly a malignant lesion. Patients with IDA should be assessed for coeliac disease. Oral iron therapy, in appropriate doses and for a sufficient duration, is an effective first-line strategy for most patients. In selected patients for whom intravenous (IV) iron therapy is indicated, current formulations can be safely administered in outpatient treatment centres and are relatively inexpensive. Red cell transfusion is inappropriate therapy for IDA unless an immediate increase in oxygen delivery is required, such as when the patient is experiencing end-organ compromise (eg, angina pectoris or cardiac failure), or IDA is complicated by serious, acute ongoing bleeding. Consensus methods for administration of available IV iron products are needed to improve the utilisation of these formulations in Australia and reduce inappropriate transfusion. New-generation IV products, supported by high-quality evidence of safety and efficacy, may facilitate rapid administration of higher doses of iron, and may make it easier to integrate IV iron replacement into routine care. [ABSTRACT FROM AUTHOR]

The efficacy of dexamethasone alone or in combination with a serotonergic antagonist to prevent nausea and vomiting in laparoscopic cholecystectomy is well established, but few data exist regarding its effects on perioperative cortisol and glucose levels. Fourteen non-diabetic subjects having elective laparoscopic choleycystectomy and standardised general anaesthesia were randomised to receive 8 mg of intravenous dexamethasone and tropisetron or tropisetron alone. Plasma cortisol and glucose were measured preinduction, at five and 24 hours postoperatively. There was no difference in plasma cortisol at five hours postoperatively in patients who received dexamethasone, but by 24 hours there was marked suppression compared to the control group (P < 0.005) to less than 5% of the preoperative value. There was a small but statistically significant elevation in blood glucose at 24 hours (P < 0.01) in the dexamethasone-treated group. In patients undergoing laparoscopic cholecystectomy, an anti-emetic dose of dexamethasone (8 mg) markedly suppresses plasma cortisol at 24 hours and causes a minor elevation in blood glucose. [ABSTRACT FROM AUTHOR]

Background: Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation. Diseases related to iron overload develop in some C282Y homozygotes, but the extent of the risk is controversial. Methods: We assessed HFE mutations in 31,192 persons of northern European descent between the ages of 40 and 69 years who participated in the Melbourne Collaborative Cohort Study and were followed for an average of 12 years. In a random sample of 1438 subjects stratified according to HFE genotype, including all 203 C282Y homozygotes (of whom 108 were women and 95 were men), we obtained clinical and biochemical data, including two sets of iron measurements performed 12 years apart. Disease related to iron overload was defined as documented iron overload and one or more of the following conditions: cirrhosis, liver fibrosis, hepatocellular carcinoma, elevated aminotransferase levels, physician-diagnosed symptomatic hemochromatosis, and arthropathy of the second and third metacarpophalangeal joints. Results: The proportion of C282Y homozygotes with documented iron-overload-related disease was 28.4% (95% confidence interval [CI], 18.8 to 40.2) for men and 1.2% (95% CI, 0.03 to 6.5) for women. Only one non-C282Y homozygote (a compound heterozygote) had documented iron-overload-related disease. Male C282Y homozygotes with a serum ferritin level of 1000 mug per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who had the wild-type gene. Conclusions: In persons who are homozygous for the C282Y mutation, iron-overload-related disease developed in a substantial proportion of men but in a small proportion of women. [ABSTRACT FROM AUTHOR]

Abstract Background and aims: The use of hepatocytes for gene therapy is limited by the difficulty of maintaining and altering primary liver cells in culture. A conditionally immortalized mouse hepatocyte cell line has been developed which can be passaged indefinitely at the permissive temperature (33°C), but fails to proliferate and dies at the non-permissive temperature (39°C) in vitro. Methods: Hepatocytes were harvested from a 6 week-old male transgenic mouse (‘immortomouse’) carrying a thermolabile SV40 Large T gene, using a modified two-step collagenase perfusion method, and serially passaged at 33°C for more than 1 year. To assess the ability of immortohepatocytes to engraft and populate mouse liver, cells were infused into partially hepatectomized congenic mice via the portal vein (n = 10) or the spleen with (n = 2) and without (n = 2) partial hepatectomy. The ability to transfect immortohepatocytes was assessed using the reporter gene enhanced green fluorescent protein (EGFP). Results: All immortohepatocytes in culture stained positive by immunohistochemistry for the hepatocyte markers albumin, AFP, CK8 and CK18. In early cultures a proportion of cells also stained strongly for the biliary epithelial markers CK7 and CK19. Late cell cultures were negative for M2PK and CK7 and stained variably with anti-CK19 antibodies. Cells transferred to the non-permissive temperature of 39°C ceased proliferation and died within 1 week in vitro. Large T DNA was detected in the liver of all postoperative mice up to 2 weeks post-hepatocellular transplantation via PCR and Southern blot analysis. The immortohepatocytes were easily transfected with a reporter gene. Conclusions: Immortohepatocytes can survive in vivo after transfer to liver, and will be useful as a model for hepatic gene therapy. [ABSTRACT FROM AUTHOR]

Background: The relationship between Thoroughbred yearling laryngeal function (YLF) grade and race performance is unclear., Objectives: To determine the effect of YLF on future race performance., Study Design: Retrospective cohort study., Methods: Post-sale endoscopic recordings were reviewed from Australian yearling sales in 2018-2019. Race performance was evaluated for career and as 2-, 3- and ≥4-year-olds. Multivariable generalised linear modelling examined the association between YLF and performance, with risk estimates presented as coefficients (95% CI)., Results: The YLF in 5175 examinations was graded I in 29.8% (n = 1542); II.1 in 49.0% (n = 2537), II.2 in 16.5% (n = 855), III.1 in 3.9% (n = 200), III.2 in 0.8% (n = 39) and III.3 in <0.04% (n = 2). Additional endoscopic abnormalities included ventroaxial luxation of the corniculate process (VLAC, n = 77, 1.5%); arytenoid mucosal lesions (n = 392, 7.6%) and intermittent dorsal displacement of the soft palate (iDDSP, n = 1264, 24.4%). Median (IQR) career earnings were: grade I $45 095 ($15 565, $113 220); grade II.1 $45 315 ($15 915, $107 490), grade II.2 $38 610 ($14 326, $95 218), grade III.1 $32 765 ($8565, $86 030) and grade III.2 $35 810 ($3700, $65 770). There was no difference in career earnings for YLF grades II.2 and III.1, compared with referent grade I/II.1, whereas grade III.2 earned less overall (-$46 015 (95% CI: -$89 994, -$2036), p = 0.04). Earnings in ≥4-year-olds were less for grades III.1 (-$35 076 (-$56 129, -$14 024), p = 0.001) and III.2 (-$53 219, (-$76 062, -$30 375) p < 0.001)., Main Limitations: Lack of follow-up data due to retrospective nature of study. Exclusion of unraced horses and those with no prize money from analysis., Conclusions: Ninety-five percent of the yearling population had grades I, II.1 or II.2 YLF and minimal difference in race performance was identified between them. Horses with grade III.1 YLF performed similarly to grades I/II.1 in their early careers but had reduced race performance at ≥4-year-old., (© 2025 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Delivery of safe maternity care requires not only individual competence but collective team work, influenced by knowledge, team culture and physical working spaces. The ideal layout for a birthing unit is not known, but deliberate changes to the built environment can influence patient care., Aims: To explore the impact of creation of an open 'hub' on maternity team culture in a tertiary birthing unit and how physical changes to the environment shape values and practice., Materials and Methods: Semi-structured interviews of members of the interprofessional team in a tertiary birth suite were performed and analysed using thematic analysis., Results: Seventeen healthcare workers participated in interviews. Themes included: (i) enhanced psychological safety; (ii) impacts on teamwork; (iii) unintended consequences; and (iv) future directions for team cohesion and collaboration., Conclusions: Changes to the built environment can impact team work. This qualitative study identified benefits and unintended consequences to removing a wall, creating a maternity hub. Individuals, departmental leadership, and hospital executives should consider how changes to the built environment can be an effective and efficient way to shape teamwork and organisational culture., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Infant feeding guidelines in Australia changed in 2016 to recommend introducing common allergy-causing foods by age 1 year to prevent food allergy. Although most Australian infants now eat peanut and egg by age 6 months, some still develop food allergy despite the early introduction of allergens., Objectives: To describe the prevalence of food allergy in a cohort recruited after introducing the nationwide allergy prevention recommendations; identify characteristics of infants who developed allergy despite early introduction of allergens; and estimate the causal effect of modifiable exposures on food allergy prevalence and whether this differed between infants who were introduced to allergens before or after age 6 months., Methods: We recruited a population-based sample of 12-month-old infants in Melbourne, Australia. Infants had skin prick tests to four foods and parents completed questionnaires. Infants with evidence of sensitization were offered oral food challenges. Prevalence estimates were adjusted using inverse probability weighting., Results: In a cohort of infants (n = 1,420) in which nearly all infants had been introduced to common allergens such as egg, milk, and peanut by age 1 year, the prevalence of food allergy remained high at 11.3% (95% CI, 9.6-13.4). Infants who developed food allergy despite introduction of the allergen by age 6 months were more likely to have Asian-born parents. Early-onset moderate or severe eczema was associated with an increased odds of food allergy irrespective of whether allergens were introduced before or after age 6 months. Among infants who were introduced to peanut at age 6 months or earlier, antibiotic use by age 6 months was associated with an increased odds of peanut allergy (adjusted odds ratio = 6.03; 95% CI, 1.15-31.60)., Conclusions: In a cohort in which early allergen introduction was common, the prevalence of food allergy remained high. Infants who developed food allergy despite introduction of the respective allergen by age 6 months were more likely to have had Asian parents and early-onset eczema. New interventions are needed for infants with a phenotype of food allergy that is not amenable to early allergen introduction., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, protein expression, and cytokine secretion over time. MDMs exposed to shear stress exhibited a rounder morphology compared to statically-cultured controls. RT-qPCR results showed significant upregulation of TNF-α, and analysis of cytokine release revealed increased secretion of IL-8, IL-18, fractalkine, and other chemokines. The upregulation of pro-inflammatory factors was evident with both increasing magnitudes of shear and time. Taken together, these results indicate that prolonged shear exposure induced a pro-inflammatory phenotype in human MDMs. These findings have implications for medical technology development, such as in situ vascular graft design wherein macrophages are exposed to shear and have been shown to affect graft resorption, and in delineating disease pathophysiology, for example to further illuminate the role of macrophages in atherosclerosis where shear is directly related to disease outcome., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy., Objective: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants., Methods: In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression., Clinicaltrials: gov (NCT01906853)., Results: Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration)., Conclusions and Clinical Relevance: Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life., (© 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen tolerance, such as nano-aerobe Bacteroides thetaiotaomicron and strict anaerobe Blautia sp., we demonstrate that IOPC can successfully support 24-48 hours HIO-microbe coculture. The IOPC recapitulates the contrasting oxygen conditions across the intestinal epithelium seen in vivo. The IOPC cultured HIOs showed increased barrier integrity, and induced expression of immunomodulatory genes. A transcriptomic analysis suggests that HIOs from different donors show differences in the magnitude of their response to coculture with anaerobic bacteria. Thus, the IOPC system provides a robust coculture setup for investigating host-microbe interactions in complex, patient-derived intestinal tissues, that can facilitate the study of mechanisms underlying the role of the microbiome in health and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fofanova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Human Genome Project, completed in 2003, heralded a new era in precision medicine. Somewhat tempering the excitement of the elucidation of the human genome is the emerging recognition that there are fewer single gene disorders than first anticipated, with most diseases predicted to be polygenic or at least gene-environment modified. Hereditary haemochromatosis (HH) is an inherited iron overload disorder, for which the vast majority of affected individuals (>90%) have homozygosity for a single pathogenic variant in the HFE gene, resulting in p.Cys282Tyr. Further, there is significant benefit to an individual in identifying the genetic risk of HH, since the condition evolves over decades, and the opportunity to intervene and prevent disease is both simple and highly effective through regular venesection. Add to that the immediate benefit to society of an increased pool of ready blood donors (blood obtained from HH venesections can generally be used for donation), and the case for population screening to identify those genetically at risk for HH becomes more cogent. Concerns about genetic discrimination, creating a cohort of "worried well", antipathy to acting on medical advice to undertake preventive venesection or simply not understanding the genetic risk of the condition adequately have all been allayed by a number of investigations. So why then has HH population genetic screening not been routinely implemented anywhere in the world? The answer is complex, but in this article we explore the pros and cons of screening for HH and the different views regarding whether it should be phenotypic (screening for iron overload by serum ferritin and/or transferrin saturation) or genotypic (testing for HFE p.Cys282Tyr). We argue that now is the time to give this poster child for population genetic screening the due consideration required to benefit the millions of individuals at risk of HFE -related iron overload.

Background: There are no studies of longitudinal immunoglobulin measurements in a population-based cohort alongside challenge-confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood., Objectives: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG 4 in the first 10 years of life, in a population cohort of children with challenge-confirmed peanut allergy, and to determine whether peanut-specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age., Methods: One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total-IgE, sIgE and sIgG 4 to peanut and Ara h 2., Results: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p = .01) and increasing peanut sIgG 4 (p < .001), Ara h 2 sIgG 4 (p = .01), peanut sIgG 4 /sIgE (p < .001) and Ara h 2 sIgG 4 /sIgE (p < .001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity., Conclusion: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG 4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Returning to work after maternity leave poses significant challenges, with potential long-term implications including decreased engagement or attrition of clinicians. Many quantitative studies have identified challenges and supports for women during pregnancy, maternity leave and re-entry to clinical practice. This qualitative study explored the experiences of anaesthetists returning to clinical work after maternity leave, to identify influential factors with the aim of providing a framework to assist planning re-entry. We conducted semi-structured interviews with 15 anaesthetists. Attendees of a re-entry programme were invited to participate, with purposive sampling and snowball recruitment to provide diversity of location and training stage, until data saturation was reached at 13 interviews. Five themes were identified: leave duration; planning re-entry; workplace culture; career impact and emotional impact. Leave duration was influenced by concerns about deskilling, but shorter periods of leave had logistical challenges, including fatigue. Most participants started planning to return to work with few or no formal processes in the workplace. Workplace culture, including support for breastfeeding, was identified as valuable, but variable. Participants also experienced negative attitudes on re-entry, including difficulty accessing permanent work, with potential career impacts. Many participants identified changes to professional and personal identity influencing the experience with emotional sequelae. This research describes factors which may be considered to assist clinicians returning to work after maternity leave and identifies challenges, including negative attitudes, which may pose significant barriers to women practising in anaesthesia and may contribute to lack of female leadership in some workplaces., (© 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Gender inequity remains an issue in anaesthesia despite increasing numbers of women training and achieving fellowship in the speciality. Women are under-represented in all areas of anaesthetic research, academia and leadership. The Gender Equity Subcommittee of the Australian and New Zealand College of Anaesthetists recently conducted a survey asking "Does gender still matter in the pursuit of a career in anaesthesia in 2022?". The survey was distributed to a randomly selected sample of 1225 anaesthetic consultants and completed by 470 respondents (38% response rate) with 793 free-text comments provided. Three overarching themes were identified: gender effects on the career and family interface; women do not fit the mould; and gender equity changes the status quo. Women respondents described a need to make a choice between career and family, which was not described by men, as well as stigmatisation of part-time work, a lack of access to challenging work and negative impacts of parental leave. Women respondents also described a sense of marginalisation within anaesthesia due to a 'boys' club' mentality, a lack of professional respect and insufficient structural supports for women in leadership. This was compounded for women from ethnically and culturally diverse backgrounds. A need for specific strategies to support anaesthetic careers for women was described as well as normalisation of flexibility in workplaces, combined with a broadening of our definition of success to allow people of all genders to experience fulfilment both at home and at work. This study is the first published qualitative data on factors affecting gender equity for anaesthetists in Australia and Aotearoa New Zealand. It highlights the need for further exploration, as well providing a foundation for changes in attitude and structural changes towards advancing gender equity., (© 2024 Association of Anaesthetists.)

Objective: Iliocaval thrombotic obstruction is a challenging condition, especially because thrombus age and corresponding pathological remodeling at presentation are unknown, which directly impacts management. Our aim was to assess the ability of magnetic resonance imaging (MRI) in determining age thresholds of experimentally created inferior vena cava (IVC) thrombosis in pigs., Methods: We used a previously described swine model of IVC thrombosis. The animals underwent MRI at baseline, immediately after thrombosis creation, and after a follow-up period extending from 2 to 28 days. Thirteen pigs were divided into three groups according to disease chronicity: acute group (AG; n = 5), subacute group (SAG; n = 4), and chronic group (CG; n = 4), with a mean thrombosis age of 6.4 ± 2.5 days, 15.7 ± 2.8 days, and 28 ± 5.7 days, respectively. A T 1 -weighted volumetric interpolated breath-hold examination sequence was used to anatomically delineate IVC thrombus as a region of interest. Three other MRI sequences were used to assess the thrombus signal., Results: The Kruskal-Wallis test showed a statistically significant difference in T 1 relaxation times after contrast injection (P = .026) between the three groups of chronicity. The AG (360.2 ± 102.5 ms) was significantly different from the CG (336.7 ± 55.2 ms; P = .003), and the SAG (354.1 ± 89.7 ms) was significantly different from the AG (P = .027). There was a statistically significant difference in native T 2 relaxation times (P = .038) between the three groups. The AG (160 ± 86.7 ms) was significantly different from the SAG (142.3 ± 55.4 ms; P = .027), and the SAG was significantly different from the CG (178.4 ± 11.7 ms; P = .004)., Conclusions: This study highlighted MRI characteristics in a swine model that might have the potential to significantly differentiate subacute and chronic stages from an acute stage of deep vein thrombosis in humans. Further clinical studies in humans are warranted., Clinical Relevance: In addition to providing a better understanding of venous thrombosis remodeling over time, magnetic resonance imaging has the potential to be a tool that could allow us to characterize the composition of venous thrombus over an interval, allowing for a refined analysis of the local evolution of venous thrombosis. We propose a noninvasive and innovative method to characterize different thresholds of chronicity with magnetic resonance imaging features of central deep vein thrombosis of the inferior vena cava experimentally obtained using a totally endovascular in vivo swine model, mimicking human pathophysiology. Being able to determine these features noninvasively is critical for vascular specialists when it comes to choosing between fibrinolytic therapy, percutaneous thrombectomy, or surgical management., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There are limited longitudinal data on the population prevalence of allergic conditions during childhood, and few studies have incorporated the reference standard oral food challenge to confirm food allergy., Objective: To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia., Methods: The HealthNuts study recruited 5,276 1-year-old infants in Melbourne, Australia, with repeat assessments at ages 6 and 10 years. At ages 6 and 10 years, carers completed a questionnaire on symptoms and doctor diagnosis of allergic conditions (International Study of Asthma and Allergies in Children). Children were invited to attend a clinic assessment including skin prick test, lung function tests, and oral food challenges when indicated. To minimize the impact of attrition bias, prevalence estimates among participants at ages 6 and 10 years were weighted to reflect characteristics of the whole cohort at recruitment., Results: In total, 4,455 and 4,065 families participated at ages 6 and 10 years, respectively (84% and 77% of the original cohort). Of those, 73% and 55% of participants ages 6 and 10 years, respectively, completed clinical assessments. Overall, 36.5% (95% CI, 34.8-38.2) and 38.2% (95% CI, 36.5-40.1%) of 6- and 10-year-olds had at least one current allergic disease, and around one third of those had two or more allergic diseases. Food allergy occurred in 6.4% (95% CI, 5.6-7.2) of 6-year olds and 6.3% (95% CI, 5.5-7.2) of 10-year-olds. Among infants with challenge-confirmed food allergy in infancy, 45% had persistent disease at age 10 years. The prevalence of current diagnosed asthma at ages 6 and 10 years were 12.1% (95% CI, 10.9-13.3) and 13.1% (95% CI, 11.9-14.4), respectively, current eczema decreased slightly from 15.3% (95% CI, 14.1-19.7) at age 6 years to 12.9% (95% CI, 11.7-14.2) at age 10 years, and current rhinitis increased from 15.1% (95% CI, 13.9-16.5) at age 6 years to 25.0% (95% CI, 23.4-26.7) at age 10 years., Conclusions: Allergic diseases affect 40% of primary school-age children; one third have multiple allergic diagnoses. Challenge-confirmed food allergy prevalence remains high, and 45% of infants with food allergy have persistent disease to age 10 years., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Yearling laryngeal function (YLF) is frequently assessed at the time of sale and the outcomes of these assessments can have significant economic implications. The YLF of horses that subsequently underwent a prosthetic laryngoplasty (PL) is unknown., Objectives: We hypothesised horses with YLF ≥grade II.2 would be at increased risk of requiring PL, compared with YLF

There is limited research on the experiences of people in working to embed, integrate and sustain simulation programmes. This interview-based study explored leaders' experiences of normalising a simulation-based education programme in a teaching hospital. Fourteen known simulation leaders across Australia and North America were interviewed. Semi-structured interviews were analysed using reflexive thematic analysis sensitised by normalisation process theory, an implementation science theory which defines 'normal' as something being embedded, integrated and sustained. We used a combined social and experiential constructivist approach. Four themes were generated from the data: (1) Leadership, (2) business startup mindset, (3) poor understanding of simulation undermines normalisation and (4) tension of competing objectives. These themes were interlinked and represented how leaders experienced the process of normalising simulation. There was a focus on the relationships that influence decision-making of simulation leaders and organisational buy-in, such that what started as a discrete programme becomes part of normal hospital operations. The discourse of 'survival' was strong, and this indicated that simulation being normal or embedded and sustained was still more a goal than a reality. The concept of being like a 'business startup' was regarded as significant as was the feature of leadership and how simulation leaders influenced organisational change. Participants spoke of trying to normalise simulation for patient safety, but there was also a strong sense that they needed to be agile and innovative and that this status is implied when simulation is not yet 'normal'. Leadership, change management and entrepreneurship in addition to implementation science may all contribute towards understanding how to embed, integrate and sustain simulation in teaching hospitals without losing responsiveness. Further research on how all stakeholders view simulation as a normal part of a teaching hospital is warranted, including simulation participants, quality and safety teams and hospital executives. This study has highlighted that a shared understanding of the purpose and breadth of simulation is a prerequisite for embedding and sustaining simulation. An approach of marketing simulation beyond simulation-based education as a patient safety and systems improvement mindset, not just a technique nor technology, may assist towards simulation being sustainably embedded within teaching hospitals., (© 2024. The Author(s).)

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.

Modeling organ-blood barriers through the inclusion of microvessel networks within in vitro tissue models could lead to more physiologically accurate results, especially since organ-blood barriers are crucial to the normal function, drug transport, and disease states of vascularized organs. Microvessel networks are difficult to form, since they push the practical limits of most fabrication methods, and it is difficult to coax vascular cells to self-assemble into structures larger than capillaries. Here, we present a method for rapidly forming networks of microvessel-like structures using sacrificial alginate structures. Specifically, we encapsulated endothelial cells within short alginate threads, and then embedded them in collagen gel. Following enzymatic degradation of the alginate, the collagen gel contained a network of hollow channels seeded with cells, all surrounding a perfusable central channel. This method uses a 3D-printed coaxial extruder and syringe pumps to generate short threads in a way that is repeatable and easily transferrable to other labs. The cell-laden, sacrificial alginate threads can be frozen after fabrication and thawed before embedding without significant loss of cell viability. The ability to freeze the threads enables future scale-up and ease of use. Within millifluidic devices that restrict access to media, the threads enhance cell survival under static conditions. These results indicate the potential for use of this method in a range of tissue engineering applications.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating "avatars" (herein defined as an extension of "digital twins") of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells., (© 2023 The Authors.)

Background: Metagenome-assembled genomes have greatly expanded the reference genomes for skin microbiome. However, the current reference genomes are largely based on samples from adults in North America and lack representation from infants and individuals from other continents., Results: Here we use deep shotgun metagenomic sequencing to profile the skin microbiota of 215 infants at age 2-3 months and 12 months who are part of the VITALITY trial in Australia as well as 67 maternally matched samples. Based on the infant samples, we present the Early-Life Skin Genomes (ELSG) catalog, comprising 9483 prokaryotic genomes from 1056 species, 206 fungal genomes from 13 species, and 39 eukaryotic viral sequences. This genome catalog substantially expands the diversity of species previously known to comprise human skin microbiome and improves the classification rate of sequenced data by 21%. The protein catalog derived from these genomes provides insights into the functional elements such as defense mechanisms that distinguish early-life skin microbiome. We also find evidence for microbial sharing at the community, bacterial species, and strain levels between mothers and infants., Conclusions: Overall, the ELSG catalog uncovers the skin microbiome of a previously underrepresented age group and population and provides a comprehensive view of human skin microbiome diversity, function, and development in early life., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young's modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis., (© 2023. Springer Nature Limited.)