Interferon-ε is a tumour suppressor and restricts ovarian cancer.

High-grade serous ovarian cancers have low survival rates because of their late presentation with extensive peritoneal metastases and frequent chemoresistance1, and require new treatments guided by novel insights into pathogenesis. Here we describe the intrinsic tumour-suppressive activities of interferon-ε (IFNε). IFNε is constitutively expressed in epithelial cells of the fallopian tube, the cell of origin of high-grade serous ovarian cancers, and is then lost during development of these tumours. We characterize its anti-tumour activity in several preclinical models: ovarian cancer patient-derived xenografts, orthotopic and disseminated syngeneic models, and tumour cell lines with or without mutations in Trp53 and Brca genes. We use manipulation of the IFNε receptor IFNAR1 in different cell compartments, differential exposure status to IFNε and global measures of IFN signalling to show that the mechanism of the anti-tumour activity of IFNε involves direct action on tumour cells and, crucially, activation of anti-tumour immunity. IFNε activated anti-tumour T and natural killer cells and prevented the accumulation and activation of myeloid-derived suppressor cells and regulatory T cells. Thus, we demonstrate that IFNε is an intrinsic tumour suppressor in the female reproductive tract whose activities in models of established and advanced ovarian cancer, distinct from other type I IFNs, are compelling indications of potential new therapeutic approaches for ovarian cancer.

An assistive listening device improves hearing following aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: Hearing impairment is common following aneurysmal subarachnoid haemorrhage (aSAH). Previous studies have demonstrated that auditory processing disorder (APD) is the primary underlying pathology. Assistive listening devices (ALDs) can be used to manage APD but have not been explored in aSAH. The aim of this study was to assess the benefit of an ALD for patients reporting hearing difficulty after aSAH. METHODS: This was a prospective pilot single-arm intervention study of an ALD for APD following aSAH. Patients who reported subjective hearing difficulty following aSAH were identified from the Wessex Neurological Centre aSAH database. Speech-in-noise was evaluated using the Bamford-Kowal-Bench (BKB) test under 60 and 65 dB noise conditions. BKB performance was compared with and without an ALD. Cognition was assessed using the Addenbrooke's Cognitive Examination-III. RESULTS: Fourteen aSAH patients with self-reported hearing loss were included in the analysis. Under both noise conditions the ALD significantly improved BKB performance (60 dB, Z = -3.30, p < 0.001; 65 dB, Z = -3.33, p < 0.001). There was no relationship between cognition and response to the ALD. CONCLUSIONS: This study demonstrates the marked benefit of ALDs to manage APD following aSAH, regardless of cognitive status. This finding has implications for the management of this common yet disabling deficit which impacts quality of life and employment. A further trial of ALDs in this patient group is needed to test whether these large, short-term benefits can be practically translated to the community for long-term benefit when used at home.

Integrated bimodal fitting and binaural streaming technology outcomes for unilateral cochlear implant users.

OBJECTIVE: Adults typically receive only one cochlear implant (CI) due to cost constraints, with a contralateral hearing aid recommended when there is aidable hearing. Standard hearing aids differ from a CI in terms of processing strategy and function as a separate entity, requiring the user to integrate the disparate signals. Integrated bimodal technology has recently been introduced to address this challenge. The aim of the study was to investigate the performance of unilateral CI users with and without an integrated bimodal fitting and determine whether binaural streaming technology offers additional benefit. STUDY SAMPLE: Twenty-six CI users using integrated bimodal technology. DESIGN: Repeated measures where outcomes and user experience were assessed using a functional test battery more representative of real life listening (speech perception in noise tests, localisation test, tracking test) and the speech, spatial and qualities-of-hearing scale (SSQ). RESULTS: Bimodal outcomes were significantly better than for CI alone. Speech perception in noise improvements ranged from 1.4 dB to 3.5 dB depending on the location of speech and noise. The localisation and tracking tests, and the SSQ also showed significant improvements. Binaural streaming offered additional improvement (1.2 dB to 6.1 dB on the different speech tests). CONCLUSIONS: Integrated bimodal and binaural streaming technology improved the performance of unilateral CI users.

PROPERTIES AND FUNCTIONS OF THE NOVEL TYPE I INTERFERON EPSILON.

Interferon epsilon (IFNε) is a type I IFN with unusual patterns of expression and therefore, function. It is constitutively expressed by reproductive tract epithelium and regulated by hormones during estrus cycle, reproduction, and menopause and by exogenous hormones. The IFNe protein is encoded by a gene in the type I IFN locus, binds to IFNAR1 and 2 which are required for signaling via the JAK STAT pathway. Its affinity for binding receptors and transducing signals is less potent than IFNα or ß subtypes in vitro. Nevertheless, in vivo experiments indicate its efficacy in regulating mucosal immune responses and protecting from bacterial and viral infections. These studies demonstrate a different mechanism of action to type I IFNs. In this organ system with dynamic fluxes in cellularity, requirement to tolerate an implanted fetus, and be protected from disease, there is co-option of a special IFN from a family of effective immunoregulators, with unique controls and modified potency to make it a safe and effective constitutive reproductive tract cytokine.

Ablation of SigH+ pDCs in B6.Nba2 mice prevents lupus-like disease development only if started before disease is fully established.

Systemic lupus erythematosus is characterized by hyper-activation of the immune system, multi-organ inflammation, and end-organ damage. Type I interferons (IFN-I) have been strongly implicated a role in disease etiology as has the main IFN-I-producing cell subset, the plasmacytoid dendritic cell (pDC). The B6.Nba2 mouse model develops a lupus-like disease characterized by elevated IFN-I levels and pDC pathogenicity. We have previously shown that pDC ablation prior to disease development in B6.Nba2 mice effectively prevents disease; however, it remains unclear if a similar protection can be seen if pDC ablation is initiated during later disease stages. This is important as Systemic lupus erythematosus patients are rarely diagnosed until disease is well-established and thus preventative treatment is unlikely to take place. Here we show that ablation of pDCs in the B6.Nba2 mouse model must be initiated early in order to effectively block disease development and that sustained reduction in pDC numbers is necessary for sustained effects. Finally, targeting of pDCs have been hypothesized to affect immunity towards infectious agents, in particular virus and intracellular bacteria. We show here that pDC ablation in B6.Nba2 mice does not affect the anti-viral response to encephalomyocarditic virus or a model T-dependent antigen. In summary, pDC ablation does not affect general immunity, but needs to happen early and be sustained to prevent lupus-like disease development in B6.Nba2 mice.

Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure.

OBJECTIVE: To review the efficacy and safety of vericiguat indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following hospitalization or need for outpatient intravenous diuretics in adult patients with chronic symptomatic HF and ejection fraction (EF) less than 45%. DATA SOURCES: A literature search through MEDLINE with search terms MK1242, BAY 1021189, and vericiguat was conducted. Product labeling and English-language studies assessing pharmacokinetics, pharmacodynamics, efficacy, or safety of vericiguat were included. STUDY SELECTION AND DATA EXTRACTION: Preclinical and clinical studies describing the efficacy and safety of vericiguat were included. DATA SYNTHESIS: The phase 3 VICTORIA clinical trial demonstrated a lower composite primary outcome of death from cardiovascular causes or first hospitalization in the vericiguat group compared to placebo. Total hospitalizations for HF in the vericiguat group were significantly less compared to placebo. The composite secondary outcome of death from any cause or first HF hospitalization was significantly less in the vericiguat group. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The addition of vericiguat offers a new treatment option for those in whom rehospitalization or recurrent outpatient intravenous diuretic treatment is a concern. Given high rates of nonadherence in HF patients, vericiguat represents an additional treatment option, especially for patients who do not tolerate available HF therapies. CONCLUSION: Vericiguat is a novel soluble guanylate cyclase stimulator that is safe and effective for reducing the risk of cardiovascular death and HF hospitalization in adults with symptomatic chronic HF and reduced EF.

The Mediating Role of Family and Cultural Food Beliefs on the Relationship between Family Communication Patterns and Diet and Health Issues across Racial/Ethnic Groups.

Consumption of red meat has been linked to a variety of health issues, yet Americans are resistant to reducing their meat consumption. Family communication environments shape beliefs about food and meat consumption, and therefore are locations for potential interventions to change the way people think about food. Families are embedded in cultures, and both family and cultural norms shape beliefs about what people should eat. This study (N = 773) is interested in understanding how family communication is associated with food beliefs, meat consumption, and health issues across three racial/ethnic groups: Black/African American (n = 256), Hispanic (n = 260), non-Hispanic White (n = 257). Structural equation modeling results showed that conversation orientation was consistently associated with stronger endorsement of family cultural food beliefs across race/ethnicity groups. Family food beliefs were associated with either more health issues or more meat consumption depending on race/ethnicity and mediated the association between conversation orientation and health issues/meat consumption. Conversation orientation moderated the association between conformity orientation and food beliefs for Hispanic and non-Hispanic White participants. Implications for family communication patterns theory and health scholars are discussed along with recommendations for culturally tailored family-focused health interventions.

Characterizing the timing of yolk testosterone metabolism and the effects of etiocholanolone on development in avian eggs.

Maternal transfer of steroids to eggs can elicit permanent effects on offspring phenotype. Although testosterone was thought to be a key mediator of maternal effects in birds, we now know that vertebrate embryos actively regulate their exposure to maternal testosterone through steroid metabolism, suggesting testosterone metabolites, not testosterone, may elicit the observed phenotypic effects. To address the role steroid metabolism plays in mediating yolk testosterone effects, we used European starling (Sturnus vulgaris) eggs to characterize the timing of testosterone metabolism and determine whether etiocholanolone, a prominent metabolite of testosterone in avian embryos, is capable of affecting early embryonic development. Tritiated testosterone was injected into freshly laid eggs to characterize steroid movement and metabolism during early development. Varying levels of etiocholanolone were also injected into eggs, with incubation for either 3 or 5 days, to test whether etiocholanolone influences the early growth of embryonic tissues. The conversion of testosterone to etiocholanolone was initiated within 12 h of injection, but the increase in etiocholanolone was transient, indicating that etiocholanolone is also subject to metabolism, and that exposure to maternal etiocholanolone is limited to a short period during early development. Exogenous etiocholanolone manipulation had no significant effect on the growth rate of the embryos or extra-embryonic membranes early in development. Thus, the conversion of testosterone to etiocholanolone may be an inactivation pathway that buffers the embryo from maternal steroids, with any effects of yolk testosterone resulting from testosterone that escapes metabolism; alternatively, etiocholanolone may influence processes other than growth or take additional time to manifest.

Using online decision trees to support students' self-efficacy in the laboratory.

Failed experiments are a common occurrence in research, yet many undergraduate science laboratories rely on established protocols to ensure students are able to obtain results. While it is logistically challenging to facilitate students' conducting their own experiments in the laboratory, allowing students to "fail" in a safe environment could help with the development of problem-solving skills. To allow students a safe place to fail and encourage them to think through a laboratory protocol, online decision trees were created to lead students through protocols and give them timely feedback. The online decision trees present students with a scenario, then students execute a protocol by selecting options that will lead them down different paths and result in various realistic results from their experiments. They receive feedback and instructional tutorials throughout the simulation that are dependent on their choices. The significance of this new resource for student learning is that it allows students to practice their problem-solving skills and gain theoretical knowledge about the purpose of various experimental steps. The purpose of this research study was to evaluate whether online decision trees affected students' self-efficacy, metacognition, and motivation for completing a wet laboratory. A mixed-methods approach was used; three surveys were administered throughout the academic term. For survey 1, students completed the decision tree and survey before the wet laboratory. For survey 2, students completed the survey before the wet laboratory but completed the decision tree after the wet laboratory. Students' reported self-efficacy and intrinsic motivation were increased with the administration of the online decision trees before the wet laboratory, but their extrinsic motivation and metacognitive scores were unchanged. For survey 3, students provided written feedback about the impact of the online decision trees, and their responses highlighted the importance of the visual components of the approach.

Role of Organic Coatings in Regulating N2O5 Reactive Uptake to Sea Spray Aerosol.

Previous laboratory measurements and field observations have suggested that the reactive uptake of N2O5 to sea spray aerosol particles is a complex function of particle chemical composition and phase, where surface active organics can suppress the reactive uptake by up to a factor of 60. To date, there are no direct studies of the reactive uptake of N2O5 to nascent sea spray aerosol that permit assessment of the role that organic molecules present in sea spray aerosol (SSA) may play in suppressing or enhancing N2O5 uptake kinetics. In this study, SSA was generated from ambient seawater and artificial seawater matrices using a Marine Aerosol Reference Tank (MART), capable of producing nascent SSA representative of ambient conditions. The reactive uptake coefficient of N2O5 (γ(N2O5)) on nascent SSA was determined using an entrained aerosol flow reactor coupled to a chemical ionization mass spectrometer for measurement of surface area dependent heterogeneous loss rates. Population averaged measurements of γ(N2O5) for SSA generated from salt water sequentially doped with representative organic molecular mimics, or from ambient seawater, do not deviate statistically from that observed for sodium chloride (γ(N2O5)NaCl = 0.01-0.03) for relative humidity (RH) ranging between 50 and 65%. The results are consistent with measurements made under clean marine conditions at the Scripps Institution of Oceanography Pier and those conducted on nascent SSA generated in the marine aerosol reference tank. The results presented here suggest that organic films present on nascent SSA (at RH greater than 50%) likely do not significantly limit N2O5 reactive uptake.

IFNε, IFNω and IFNλ: interferons defending the mucosa.

The unconventional type I interferons IFNε and IFNω and type III interferon IFNλ are gradually emerging as tissue-specific cytokines in defence of mucosal tissues. This review provides an overview of the distinct features and functions that define these IFNs as protective factors in the respiratory, gastrointestinal and reproductive tracts, highlighting their immunoregulatory roles against pathogens while maintaining tolerance against commensal microbes. In particular, we discuss recent advances in our understanding of the constitutively expressed IFNε and its role in protecting against mucosal infections, inflammation and cancers. We identify an emerging theme for this unique cytokine as a key contributor to the 'first line of defence' against pathogens and maintenance of mucosal tissue homeostasis, primarily through its regulation of immune cell populations.

Internet-Delivered Psychological Pain Management: A Prospective Cohort Study Examining Routine Care Delivery by a Specialist Regional Multidisciplinary Pain Service.

Several clinical trials have demonstrated the effectiveness of internet-delivered psychological-based pain management programs (PMPs). However, to date, no large studies have reported the outcomes of PMPs when delivered by specialist multidisciplinary pain services in routine care. The present study reports (n = 653) the outcomes of an internet-delivered PMP provided as routine care by a specialist Australian regional pain service over a 6-year period. High levels of treatment commencement (85%) and completion (72%) were observed, with more than 80% of patients reporting they were satisfied with the intervention. Clinical improvements were observed from pretreatment to post-treatment (% change, 95% confidence intervals (CI)) in pain-related disability (8.8%; 4.5, 12.8), depression (28.4%; 23.0, 33.4), anxiety (21.9%; 14.6, 28.5), and pain intensity (7%; 3.5, 10.5), which were maintained to 3-month follow-up. At 3-month follow-up, 27% (23, 31), 46% (41, 51), 44% (39, 49), and 22% (19, 26) reported clinically meaningful (defined as ≥ 30%) improvements in pain-related disability, depression, anxiety, and pain intensity, respectively. These results were obtained with relatively little therapist time per patient (M = 30.0, (standard deviation) SD = 18.8) to deliver the intervention. The current findings highlight the potential of internet-delivered PMPs as part of the services provided by specialist pain services, particularly those servicing large geographical regions and for patients unable to travel to clinics for face-to-face care. PERSPECTIVE: This study reports the outcomes of the routine delivery of an internet-delivered psychological PMP by a specialist pain service. The findings highlight the potential of this model of care when provided by specialist pain services, particularly for patients not unable to attend and not requiring intensive face-to-face care.

Evolving concepts of developmental auditory processing disorder (APD): a British Society of Audiology APD special interest group 'white paper'.

Children with listening difficulties, but normal audiometry, may be diagnosed with APD. The diagnosis is typically based on poor performance on tests of perception of both non-speech and speech stimuli. However, non-speech test results correlate only weakly with evaluations of speech-in-noise processing, cognitive skills, and caregiver evaluations of listening ability. The interpretation of speech test results is confounded by the involvement of language processing mechanisms. Overall, listening ability is associated more with higher-level, cognitive and analytic processing than with lower-level sensory processing. Current diagnosis of a child with APD, rather than another problem (e.g. language impairment, LI), is determined more by the referral route than by the symptoms. Co-occurrence with other learning problems suggests that APD may be a symptom of a more varied neurodevelopmental disorder. Alternately, APD has been proposed as a cause of language-based disorders, but there is no one-to-one mapping between listening and language among individuals. Screening for APD may be most appropriately based on a well-validated, caregiver questionnaire that captures the fundamental problem of listening difficulties and identifies areas for further assessment and management. This approach has proved successful for LI, and may in future serve as a metric to help assess other, objective testing methods.

Multifactorial influences on successful health outcomes for an adolescent with Prader-Willi syndrome: a qualitative case study.

PURPOSE: Prader-Willi syndrome (PWS) is the most common syndromic cause of childhood obesity. This qualitative case study aimed to identify and describe lifestyle themes of an adolescent with PWS that resulted in maintenance of a healthy body mass index (BMI). CASE DESCRIPTION: The 16-year-old female demonstrated failure to thrive upon birth and underwent 9 months supplemented tube feeding, achieving 50th percentile weight for height. Throughout childhood she received treatment of physical, occupational, and speech therapies, and has maintained a healthy BMI ranging from 25-50th percentile weight for height. METHODS AND RESULTS: Two video interviews were completed separately. Qualitative analysis of the transcribed data identified two overarching themes for maintaining a healthy BMI in this adolescent: 1) adolescent and parent individual characteristics; and 2) family dynamics and lifestyle. Adolescent and parental characteristics included: high level of cognitive function for diagnosis, mild hyperphagia, desire for a regimented schedule, parental type A personalities, intentionality in parental decisions/actions. Family lifestyle characteristics included strong parental involvement and well-defined expectations for their daughter, purposeful integration of physical activity into lifestyle, and presence of a strong family support system. CONCLUSION: The convergence of multiple optimal influences provided an ideal health outcome in the adolescent.

Immunoregulation by type I interferons in the peritoneal cavity.

The peritoneal cavity, a fluid-containing potential space surrounding the abdominal and pelvic organs, is home to a rich network of immune cells that maintain tissue homeostasis and provide protection against infection. However, under pathological conditions such as peritonitis, endometriosis, and peritoneal carcinomatosis, the peritoneal immune system can become dysregulated, resulting in nonresolving inflammation and disease progression. An enhanced understanding of the factors that regulate peritoneal immune cells under both homeostatic conditions and in disease contexts is therefore required to identify new treatment strategies for these often life-limiting peritoneal pathologies. Type I interferons (T1IFNs) are a family of cytokines with broad immunoregulatory functions, which provide defense against viruses, bacteria, and cancer. There have been numerous reports of immunoregulation by T1IFNs within the peritoneal cavity, which can contribute to both the resolution or propagation of peritoneal disease states, depending on the specifics of the disease setting and local environment. In this review, we provide an overview of the major immune cell populations that reside in the peritoneal cavity (or infiltrate it under inflammatory conditions) and highlight their contribution to the initiation, progression, or resolution of peritoneal diseases. Additionally, we will discuss the role of T1IFNs in the regulation of peritoneal immune cells, and summarize the results of laboratory studies and clinical trials which have investigated T1IFNs in peritonitis/sepsis, endometriosis, and peritoneal carcinomatosis.

Can We Identify Predictors of Success in Contouring Education for Radiation Oncology Trainees? An Analysis of the Anatomy and Radiology Contouring Bootcamp.

PURPOSE: Although several different contouring instructional programs are available to radiation oncologists and trainees, very little is known about which methods and resources benefit learners most, and whether some learners may need alternate forms of instruction. This study aimed to determine the factors that were predictors of learners' success in anatomy, radiology, and contouring education. METHODS AND MATERIALS: Participants in the online and face-to-face Anatomy and Radiology Contouring (ARC) Bootcamp completed pre- and postintervention evaluations that assessed anatomy/radiology knowledge, contouring skills, self-confidence, and spatial ability. Baseline factors were assessed as predictors of outcomes across multiple educational domains. RESULTS: One hundred and eighty (face-to-face: n = 40; online: n = 140) participants enrolled in the ARC Bootcamp, and 57 (face-to-face: n = 30; online: n = 27) participants completed both evaluations. Of the participants enrolled, 37% were female, and most were radiation oncology residents (62%). In the anatomy/radiology knowledge testing, all quartiles (based on baseline performance) improved numerically; however, the largest improvements occurred in learners with the lowest baseline scores (P < .001). At the end of the Bootcamp, learners with lower-performing scores did not reach the level of learners with the highest baseline scores (Bonferroni-corrected P < .001). Regarding the contouring assessment, improvements were only evident for the participants with lower-performing baseline scores (P < .05). Spatial anatomy skills, as measured by the spatial anatomy task, were correlated to contouring ability. Overall, the greatest improvements were seen for learners in postgraduate year 1 to 3, those with no previous rotation experience in a given discipline, and those who attended from other programs (ie, medical physics residents and medical students). CONCLUSIONS: The ARC Bootcamp improved all levels of performers' anatomy and radiology knowledge but only lower-performers' contouring ability. The course alone does not help lower-performing learners reach the abilities of higher-performers. The ARC Bootcamp tends to be most beneficial for participants with less radiation oncology experience. Curriculum modifications can be made to help support ARC Bootcamp participants with lower performing scores.

PD-1 expression on mouse intratumoral NK cells and its effects on NK cell phenotype.

Although PD-1 was shown to be a hallmark of T cells exhaustion, controversial studies have been reported on the role of PD-1 on NK cells. Here, we found by flow cytometry and single cell RNA sequencing analysis that PD-1 can be expressed on MHC class I-deficient tumor-infiltrating NK cells in vivo. We also demonstrate distinct alterations in the phenotype of PD-1-deficient NK cells and a more mature phenotype which might reduce their capacity to migrate and kill in vivo. Tumor-infiltrating NK cells that express PD-1 were highly associated with the expression of CXCR6. Furthermore, our results demonstrate that PD-L1 molecules in membranes of PD-1-deficient NK cells migrate faster than in NK cells from wild-type mice, suggesting that PD-1 and PD-L1 form cis interactions with each other on NK cells. These data demonstrate that there may be a role for the PD-1/PD-L1 axis in tumor-infiltrating NK cells in vivo.

Is Remote Learning as Effective as In-Person Learning for Contouring Education? A Prospective Comparison of Face-to-Face versus Online Delivery of the Anatomy and Radiology Contouring Bootcamp.

PURPOSE: The Anatomy and Radiology Contouring (ARC) Bootcamp was a face-to-face (F2F) intervention providing integrated education for radiation oncology (RO) residents and medical physicists. To increase access, we launched an online offering in 2019. We evaluated the effect of the online course on participants' knowledge acquisition, contouring skills, and self-confidence by comparing it with the F2F course. METHODS AND MATERIALS: Using modules, the online course offers content similar to that of the F2F comparator. Participants from the 2019 F2F and the 2019-2020 online course completed pre- and postevaluations assessing anatomy and radiology knowledge, contouring skills, self-confidence, and course satisfaction. RESULTS: There were 180 individuals enrolled (F2F: n = 40; online: n = 140); 57 participants (F2F: n = 30; online: n = 27) completed both evaluations. The online course had a wider geographic participation (19 countries) than F2F (4 countries). F2F had primarily RO resident participation (80%), compared with online (41%). Both cohorts demonstrated similar improvements in self-confidence pertaining to anatomy and radiology knowledge, contouring skills, and interpreting radiology images (all P < .001). Both the online (mean ± SD improvement: 6.6 ± 6.7 on a 40-point scale; P < .001) and F2F (3.7 ± 5.7; P = .002) groups showed anatomy and radiology knowledge improvement. Only the F2F group demonstrated improvement with the contouring assessment (F2F: 0.10 ± 0.17 on a 1-point Dice scale; P = .004; online: 0.07 ± 0.16; P = .076). Both cohorts perceived the course as a positive experience (F2F: 4.8 ± 0.4 on a 5-point scale; online: 4.5 ± 0.6), stated it would improve their professional practice (F2F: 4.6 ± 0.5; online: 4.2 ± 0.8), and said they would recommend it to others (F2F: 4.8 ± 0.4; online: 4.4 ± 0.6). CONCLUSIONS: The online ARC Bootcamp demonstrated improved self-confidence, knowledge scores, and high satisfaction levels among participants. The offering had lower completion rates but was more accessible to geographic regions, provided a flexible learning experience, and allowed for ongoing education during the COVID-19 pandemic.

Regulation of inflammation by the antioxidant haem oxygenase 1.

Haem oxygenase 1 (HO-1), an inducible enzyme responsible for the breakdown of haem, is primarily considered an antioxidant, and has long been overlooked by immunologists. However, research over the past two decades in particular has demonstrated that HO-1 also exhibits numerous anti-inflammatory properties. These emerging immunomodulatory functions have made HO-1 an appealing target for treatment of diseases characterized by high levels of chronic inflammation. In this Review, we present an introduction to HO-1 for immunologists, including an overview of its roles in iron metabolism and antioxidant defence, and the factors which regulate its expression. We discuss the impact of HO-1 induction in specific immune cell populations and provide new insights into the immunomodulation that accompanies haem catabolism, including its relationship to immunometabolism. Furthermore, we highlight the therapeutic potential of HO-1 induction to treat chronic inflammatory and autoimmune diseases, and the issues faced when trying to translate such therapies to the clinic. Finally, we examine a number of alternative, safer strategies that are under investigation to harness the therapeutic potential of HO-1, including the use of phytochemicals, novel HO-1 inducers and carbon monoxide-based therapies.