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Paul J McKiernan,2 Orla Cunninghamm,1,2 Catherine M Greenem,2 Sally-Ann Cryan1,31School of Pharmacy, Royal College of Surgeons in Ireland, 2Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, 3Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, IrelandAbstract: Cystic fibrosis (CF) is an inherited disorder characterized by chronic airway inflammation. microRNAs (miRNAs) are endogenous small RNAs which act on messenger (m)RNA at a post transcriptional level, and there is a growing understanding that altered expression of miRNA is involved in the CF phenotype. Modulation of miRNA by replacement using miRNA mimics (premiRs) presents a new therapeutic paradigm for CF, but effective and safe methods of delivery to the CF epithelium are limiting clinical translation. Herein, polymeric nanoparticles are investigated for delivery of miRNA mimics into CF airway epithelial cells, using miR-126 as a proof-of-concept premiR cargo to determine efficiency. Two polymers, polyethyleneimine (PEI) and chitosan, were used to prepare miRNA nanomedicines, characterized for their size, surface (zeta) potential, and RNA complexation efficiency, and screened for delivery and cytotoxicity in CFBE41o- (human F508del cystic fibrosis transmembrane conductance regulator bronchial epithelial) cells using a novel high content analysis method. RNA extraction was carried out 24 hours post transfection, and miR-126 and TOM1 (target of Myb1) expression (a validated miR-126 target) was assessed. Manufacture was optimized to produce small nanoparticles that effectively complexed miRNA. Using high content analysis, PEI-based nanoparticles were more effective than chitosan-based nanoparticles in facilitating uptake of miRNA into CFBE41o- cells and this was confirmed in miR-126 assays. PEI-premiR-126 nanoparticles at low nitrogen/phosphate (N/P) ratios resulted in significant knockdown of TOM1 in CFBE41o- cells, with the most significant reduction of 66% in TOM1 expression elicited at an N/P ratio of 1:1 while chitosan-based miR-126 nanomedicines failed to facilitate statistically significant knockdown of TOM1 and both nanoparticles appeared relatively nontoxic. miRNA nanomedicine uptake can be qualitatively and quantitatively assessed rapidly by high content analysis and is highly polymer-dependent but, interestingly, there is not a direct correlation between the levels of miRNA uptake and the downstream gene knockdown. Polymeric nanoparticles can deliver premiRs effectively to CFBEs in order to modulate gene expression but must be tailored specifically for miRNA delivery.Keywords: miR-126, nanotechnology, cystic fibrosis, TOM1, high content analysis, inflammation

Rationale: An unexplained gender gap is observed in cystic fibrosis (CF). Females have poorer lung function, decreased survival, and earlier Pseudomonas colonization.Objectives: To evaluate the effect of 17beta-estradiol (E(2)) on CF bronchial epithelial cells in vitro and in vivo.Methods: On exposure of CFBE41o- cultures to physiological concentrations of E(2), there was a significant dose-dependent inhibition of IL-8 release induced by toll-like receptor agonists, CF bronchoalveolar lavage fluid, or Pseudomonas-conditioned media. Estrogen receptor (ER)-alpha and -beta expression was quantified in cell lines and bronchial brushings from CF and non-CF patients.Measurements and Main Results: Both receptors were expressed in vitro and in vivo, although ERbeta expression was significantly higher in CF. Using ER isoform-specific agonists and antagonists, we established that ERbeta mediates the inhibition of CF bronchoalveolar lavage fluid-induced IL-8 release. We also showed that secretory leucoprotease inhibitor gene expression and protein localization to the nucleus increased in response to E(2). Secretory leucoprotease inhibitor knockdown abrogated the inhibitory effects of E(2).Conclusions: E(2) inhibits IL-8 release by ERbeta in CF bronchial epithelial cells through up-regulation of secretory leucoprotease inhibitor, inhibition of nuclear factor (NF)-kappaB, and IL-8 gene expression. These data implicate a novel anti-inflammatory mechanism for E(2) in females with CF, which predisposes to infection and colonization. This could, in part, account for the observed gender dichotomy in CF. [ABSTRACT FROM AUTHOR]

RATIONALE: In patients with chronic inflammatory lung disease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role. OBJECTIVES: To determine whether autoantibodies directed against elastin- and collagen-derived peptides are present in plasma from three groups of patients with chronic inflammatory lung disease compared with a nonsmoking healthy control group and to identify whether autoimmune responses to these peptides may be an important component of the disease process in these patients. METHODS: A total of 124 patients or healthy control subjects were recruited for the study (Z-A1AT deficiency, n = 20; cystic fibrosis, n = 40; chronic obstructive pulmonary disease, n = 31; healthy control, n = 33). C-reactive protein, IL-32, and antinuclear antibodies were quantified. Antielastin and anti-N-acetylated-proline-glycine-proline autoantibodies were measured by reverse ELISA. MEASUREMENTS AND MAIN RESULTS: All patients were deemed stable and noninfective on the basis of the absence of clinical or radiographic evidence of recent infection. There were no significant differences in the levels of autoantibodies or IL-32 in the patients groups compared with the healthy control subjects. CONCLUSIONS: Antielastin or anti-N-acetylated proline-glycine-proline autoantibodies are not evident in chronic inflammatory lung disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Invasive group A streptococcus (GAS) affects approximately 10,500 persons annually; 1 in 5 patients >/=65 years die. In August 2001, CDC investigated a cluster of GAS deaths in a Georgia long-term care facility (LTCF). METHODS: We screened LTCF residents and staff for GAS carriage and conducted a retrospective cohort study among residents. We defined a case as GAS isolation associated with clinical infection. RESULTS: Eight cases were identified (median age: 79 years); 6 (75%) patients died. Carriage was similar in residents (10%) and staff (9%). All isolates among residents and 63% among staff were type emm 77. Risk factors for GAS disease or carriage among residents were receiving skin treatment (relative risk [RR] = 4.0, 95% confidence interval [CI] = 1.9-11.0) and having an infected or colonized roommate (RR = 2.0, 95% CI = 1.10-5.0). No wound care nurse carried GAS. Interventions included education about standardized infection control guidelines and appropriate hand hygiene; carriers were treated with antibiotics. No subsequent GAS cases were identified in the following year. CONCLUSIONS: Transmission of GAS in this outbreak likely occurred during wound care and ended with improved hand hygiene. This investigation highlights additional research and policy needs for control of severe GAS infections among the high-risk LTCF population. [ABSTRACT FROM AUTHOR]

Background: Alpha1-antitrypsin (A1AT) is an abundant protein that is synthesized in the liver and is secreted into the plasma. From the plasma, A1AT diffuses into various body compartments, including the lung where it provides much of the antiprotease protection. The current understanding of the pathogenesis of emphysema in A1AT-deficient individuals focuses on the polymerization of mutant protein within the liver, which results in a deficiency of circulating A1AT and a protease-antiprotease imbalance in the lungs.Methods and Results: In this study, we evaluated BAL fluid samples from five healthy volunteers, five individuals with ZA1AT deficiency, and an individual with the PiZZ phenotype who had received a liver transplant. We show that the lung itself is a source of A1AT. In addition, the Z protein formed in the lung polymerizes, and these polymers are detectable in lung epithelial lining fluid by enzyme-linked immunosorbent assay and Western blot analysis. Finally, we show that polymeric ZA1AT is a potent neutrophil chemoattractant that is similar to polymerized MA1AT.Conclusions: Our findings suggest that the polymerization of locally produced ZA1AT is a contributory factor to the lung inflammation experienced by those with A1AT deficiency and that standard antiprotease therapies may not address this problem. [ABSTRACT FROM AUTHOR]

The struggle to understand research is an ongoing process. Keeping up with the literature and taking from various studies important points that will help dictate the choices made for practice is the essence of a scientifically-based strength and conditioning program. This takes both vigilance and effort in keeping up with the scientific literature and the new findings on topics of importance to your program. [ABSTRACT FROM AUTHOR]

In rich false memory studies, familial informants often provide information to support researchers in planting vivid memories of events that never occurred. The goal of the current study was to assess how effectively we can retract these false memories via debriefing - i.e., to what extent can we put participants back the way we found them? We aimed to establish (1) what proportion of participants would retain a false memory or false belief following debriefing, and (2) whether richer, more detailed memories would be more difficult to retract. Participants (N = 123) completed a false memory implantation protocol as part of a replication of the "Lost in the Mall" study (Loftus & Pickrell, Psychiatric Annals, 25, 720-725, 1995). By the end of the protocol, 14% of participants self-reported a memory for the fabricated event, and a further 52% believed it had happened. Participants were then fully debriefed, and memory and belief for the false event were assessed again. In a follow-up assessment 3 days post-debriefing, the false memory rate had dropped to 6% and false belief rates also fell precipitously to 7%. Moreover, virtually all persistent false memories were found to be nonbelieved memories, where participants no longer accepted that the fabricated event had occurred. Richer, more detailed memories were more resistant to correction, but were still mostly retracted. This study provides evidence that participants can be "dehoaxed", and even very convincing false memories can be retracted., (© 2024. The Author(s).)

Martin Conway's influential theorising about the self-memory system (Conway, M. A., & Pleydell-Pearce, C. W. (2000). The construction of autobiographical memories in the self-memory system. Psychological Review , 107 (2), 261-288) illuminated how the "working self" influences the construction of autobiographical memories. Moreover, his constructive view of self and memory is compatible with the occurrence of various kinds of errors and distortions in remembering. Here we consider one of the "seven sins" of memory (Schacter, D. L. (2021). The seven sins of memory updated edition: How the mind forgets and remembers . Houghton Mifflin Harcourt) that we believe is most closely related to the operation of Conway's self-memory system: bias, which refers to the role of current knowledge, beliefs, and feelings in shaping and sometimes distorting memories for past experiences and attitudes. More specifically, we discuss recent research on three forms of bias - consistency, self-enhancing, and positivity biases - that illuminate their role in influencing how people remember the past and also imagine the future. We consider both theoretical and applied aspects of these biases and, consistent with Conway's perspective, argue that despite sometimes contributing to inaccuracies, bias also serves adaptive functions.

Objectives: Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the in vitro effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations., Methods: Preterm infants ( n  = 21) and term control ( n  = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes., Results: Dividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates., Conclusions: This study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses of females mature with advancing gestation, whereas male term and preterm neonates have very similar responses. Female preterm neonates have improved monocyte activation than males, which likely reflects improved innate immune function as reflected clinically by their lower risk of sepsis. Dividing results by sex showed changes in preterm and term infants at baseline and following LPS stimulation, a difference which is reflected clinically by infection susceptibility. The sex difference noted is novel and may be limited to the preterm or early neonatal population as TLR2 expression on monocytes of older children does not differ between males and females. The differences shown in female and male innate immune cells likely reflect a superior innate immune defense system in females with sex differences in immune cell maturation. Existing human studies on sex differences in miRNA expression do not include preterm patients, and most frequently use either adult blood or cord blood. Our findings suggest that miRNA profiles are similar in neonates of opposite sexes at term but require further investigation in the preterm population. Our findings, while novel, provide only very limited insights into sex differences in infection susceptibility in the preterm population leaving many areas that require further study. These represent important areas for ongoing clinical and laboratory study and our findings represent an important contribution to exiting literature.

The fact that memories can be distorted by post-event misinformation has cast considerable doubt over the dependability of eyewitness evidence in legal contexts. However, despite its adverse practical implications, the misinformation effect is likely an unavoidable distortion stemming from the reconstructive nature of episodic memory. Certain cognitive abilities have been reported to offer protection against misinformation, suggesting that mechanisms aside from episodic memory may also be underpinning this type of memory distortion. The purpose of this review was to collate findings of associations between eyewitness misinformation susceptibility and individual differences in cognitive ability in adults aged 18 and over. Nine studies met the eligibility criteria for this review, including 23 distinct associations. Using a narrative synthesis, three categories of cognitive ability were identified as influencing susceptibility to misinformation: general intelligence and reasoning, perceptual abilities, and memory abilities. Across almost all categories, higher levels of ability were associated with reduced susceptibility to misinformation. While there is no indication that any one trait provides total immunity to the misinformation effect, there is a reasonable amount of evidence to suggest that several cognitive abilities create variance in individual levels of susceptibility. Future research should investigate not only if but how these cognitive abilities protect against misinformation distortions, for example, by contributing to more detailed encoding of the memory, enhancing discrepancy detection in the face of post-event misinformation, or improving source-monitoring during an eyewitness memory test., (© 2024. The Author(s).)

Respiratory health has become a prevailing priority amid the diverse global health challenges that the 21st century brings, due to its substantial impact on individuals and communities on a global scale. Due to rapid advances in medicine, emerging knowledge gaps appear along with new challenges and ethical considerations. While breakthroughs in medical science can bring about encouraging possibilities for better treatments and interventions, they also lead to unanswered questions and areas where further research is warranted. A PubMed search on the topic "global respiratory health priorities" between the years 2000 and 2023 was conducted, which returned 236 articles. Of these, 55 were relevant and selected for inclusion in this article. The selection process took into account literature reviews, opinions from expert groups and careful analysis of existing gaps and challenges within the field; our selection encompasses specific infectious and noninfectious respiratory conditions in both adults and children. The global respiratory health priorities identified were selected on the basis that they have been recognised as critical areas of investigation and potential advancement and they span across clinical, translational, epidemiological and population health domains. Implementing these priorities will require a commitment to fostering collaboration and knowledge-sharing among experts in different fields with the ultimate aim to improve respiratory health outcomes for individuals and communities alike., Competing Interests: Conflict of interest: The authors have no conflicts of interest to disclose related to the content of this article., (Copyright ©The authors 2024.)

People are prone to forming false memories for fictitious events described in fake news stories. In this preregistered study, we hypothesized that the formation of false memories may be promoted when the fake news includes stereotypes that reflect positively on one's own nationality or negatively on another nationality. We exposed German and Irish participants ( N = 1,184) to fabricated news stories that were consistent with positive or negative stereotypes about Germany and Ireland. The predicted three-way interaction was not observed. Exploratory follow-up analyses revealed the expected pattern of results for German participants but not for Irish participants, who were more likely to remember positive stories and stories about Ireland. Individual differences in patriotism did not significantly affect false memory rates; however, higher levels of cognitive ability and analytical reasoning decreased false memories and increased participants' ability to distinguish between true and false news stories. These results demonstrate that stereotypical information pertaining to national identity can influence the formation of false memories for fake news, but variations in cultural context may affect how misinformation is received and processed. We conclude by urging researchers to consider the sociopolitical and media landscape when predicting the consequences of fake news exposure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Meta-analyses have found that working memory (WM) can be improved with cognitive training; however, some authors have suggested that these improvements are mostly driven by biases in the measurement of WM, especially the use of similar tasks for assessment and training. In the present meta-analysis, we investigated whether WM, fluid intelligence, executive functions, and short-term memory can be improved by cognitive training and evaluated the impact of possible sources of bias. We performed a risk of bias assessment of the included studies and took special care in controlling for practice effects. Data from 52 independent comparisons were analyzed, including cognitive training aimed at different cognitive functions. Our results show small improvements in WM after training (SMD = 0.18). Much larger effects were observed when the analysis was restricted to assessment tasks similar to those used for training (SMD = 1.15). Fluid intelligence was not found to improve as a result of training, and improvements in WM were not related to changes in fluid intelligence. Our analyses did however indicate that cognitive training can improve specific executive functions. Contrary to expectations, a set of meta-regressions indicated that characteristics of the training programme, such as dosage and type of training, do not have an impact on the effectiveness of training. The risk of bias assessment revealed some concerns in the randomization process and possible selective reporting among studies. Overall, our results identified various potential sources of bias, with the most significant being the choice of assessment tasks., (© 2024. The Author(s).)

Misinformation research can present many ethical challenges to researchers. These challenges are not insurmountable, but recent research suggests that as a field, we should be adopting and reporting stronger ethical practices. In this review, we consider the three D's of ethical misinformation research; the need to balance deception with informed consent, the value of maintaining an open dialogue with research participants to gather their insights and perspectives, and perhaps most importantly, the essential requirement for effective post-experimental debriefing. We make some specific and straightforward recommendations for misinformation researchers to increase the visibility of their ethical practices and outline the benefits for individual researchers and for the field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There is a need for scalable evidence-based psychological interventions for young adolescents experiencing high levels of psychological distress in humanitarian settings and low- and middle-income countries. Poor mental health during adolescence presents a serious public health concern as it is a known predictor of persistent mental disorders in adulthood. This study evaluates the effectiveness of a new group-based intervention developed by the World Health Organization (Early Adolescent Skills for Emotions; EASE), implemented by non-specialists, to reduce young adolescents' psychological distress among mostly Syrian refugees in Lebanon., Methods: We conducted a two-arm, single-blind, individually randomized group treatment trial. Adolescents aged 10 to 14 years who screened positive for psychological distress using the Pediatric Symptom Checklist (PSC) were randomly allocated to EASE or enhanced treatment as usual (ETAU) (1:1.6). ETAU consisted of a single scripted psycho-education home-visit session with the adolescent and their caregivers. EASE consists of seven group sessions with adolescents and three sessions with caregivers. The primary outcome was adolescent-reported psychological distress as measured with the PSC (internalizing, externalizing, and attentional symptoms). Secondary outcomes included depression, posttraumatic stress, well-being, functioning, and caregivers' parenting and distress. All outcomes were assessed at baseline, endline, and 3 months (primary time point) and 12 months follow-up., Results: Due to the COVID-19 pandemic and other adversities in Lebanon at the time of this research, the study was prematurely terminated, resulting in an under-powered trial sample (n = 198 enrolled compared to n = 445 targeted). We screened 604 children for eligibility. The 198 enrolled adolescents were assigned to EASE (n = 80) and ETAU (n = 118), with retention rates between 76.1 and 88.4% across all timepoints. Intent-to-treat analyses demonstrated no between-group differences on any of the outcome measures between the EASE and ETAU. We did observe a significant improvement on the primary outcome equally in the EASE and ETAU groups (-0.90, 95% CI: -3.6, 1.8; p = .52), - a trend that was sustained at three months follow-up. Sub-group analyses, for those with higher depression symptoms at baseline, showed ETAU outperformed EASE on reducing depression symptoms (difference in mean change = 2.7, 95% CI: 0.1, 5.3; p = .04; d = 0.59) and internalizing problems (difference in mean change 1.0, 95% CI: 0.08, 1.9; p = .03; d = 0.56) ., Conclusion: No conclusions can be drawn about the comparative effectiveness of the intervention given that the sample was underpowered as a result of early termination. Both EASE and single session psycho-education home visits resulted in meaningful improvements in reducing psychological distress. We did not identify any indications in the data suggesting that EASE was more effective than a single session family intervention in the context of the COVID-19 pandemic and other crises in Lebanon. Fully powered research is needed to evaluate the effectiveness of EASE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Most family violence research has been conducted in high-income countries, although family violence rates are higher in low- and middle-income countries (LMICs), and outcomes more severe. Given the strong associations of family violence with substance use and mental illness, the aim of this systematic review was to examine interventions that targeted familial violence and at least one other condition of substance use or mental illness to determine effective treatments in LMICs. We conducted a systematic review of interventions that addressed family violence and mental illness or substance use. A committee of three researchers independently screened titles and abstracts and conducted full-text eligibility assessments. Two researchers conducted a risk of bias assessment. Data were extracted using a structured spreadsheet and narratively synthesized. Our search identified 29 articles produced from 19 studies conducted in 13 LMICs. Most ( n  = 15) studies randomized to study condition. Lack of blinding was the most common threat. The external validity of studies was generally poor. Fourteen studies had a primary intervention target of family violence, mental health, substance use, economic improvement, or HIV. None of the studies showed improvements in all intervention areas. Child maltreatment was less likely to be addressed than intimate partner violence (IPV). Targeted interventions for substance and mental health mostly improved primary outcomes, although they were less effective in reducing IPV. Evidence-based treatments must be rigorously evaluated before innovations in implementation can occur. Interventions overwhelmingly addressed IPV victimization and should consider how to work with couples and include men and children., Competing Interests: The authors declare no competing interests exist., (© The Author(s) 2023.)

Background: Avian influenza (AI) virus detections occurred frequently in 2022 and continue to pose a health, economic, and food security risk. The most recent global analysis of official reports of animal outbreaks and human infections with all reportable AI viruses was published almost a decade ago. Increased or renewed reports of AI viruses, especially high pathogenicity H5N8 and H5N1 in birds and H5N1, H5N8, and H5N6 in humans globally, have established the need for a comprehensive review of current global AI virus surveillance data to assess the pandemic risk of AI viruses., Objective: This study aims to provide an analysis of global AI animal outbreak and human case surveillance information from the last decade by describing the circulating virus subtypes, regions and temporal trends in reporting, and country characteristics associated with AI virus outbreak reporting in animals; surveillance and reporting gaps for animals and humans are identified., Methods: We analyzed AI virus infection reports among animals and humans submitted to animal and public health authorities from January 2013 to June 2022 and compared them with reports from January 2005 to December 2012. A multivariable regression analysis was used to evaluate associations between variables of interest and reported AI virus animal outbreaks., Results: From 2013 to 2022, 52.2% (95/182) of World Organisation for Animal Health (WOAH) Member Countries identified 34 AI virus subtypes during 21,249 outbreaks. The most frequently reported subtypes were high pathogenicity AI H5N1 (10,079/21,249, 47.43%) and H5N8 (6722/21,249, 31.63%). A total of 10 high pathogenicity AI and 6 low pathogenicity AI virus subtypes were reported to the WOAH for the first time during 2013-2022. AI outbreaks in animals occurred in 26 more Member Countries than reported in the previous 8 years. Decreasing World Bank income classification was significantly associated with decreases in reported AI outbreaks (P<.001-.02). Between January 2013 and June 2022, 17/194 (8.8%) World Health Organization (WHO) Member States reported 2000 human AI virus infections of 10 virus subtypes. H7N9 (1568/2000, 78.40%) and H5N1 (254/2000, 12.70%) viruses accounted for the most human infections. As many as 8 of these 17 Member States did not report a human case prior to 2013. Of 1953 human cases with available information, 74.81% (n=1461) had a known animal exposure before onset of illness. The median time from illness onset to the notification posted on the WHO event information site was 15 days (IQR 9-30 days; mean 24 days). Seasonality patterns of animal outbreaks and human infections with AI viruses were very similar, occurred year-round, and peaked during November through May., Conclusions: Our analysis suggests that AI outbreaks are more frequently reported and geographically widespread than in the past. Global surveillance gaps include inconsistent reporting from all regions and human infection reporting delays. Continued monitoring for AI virus outbreaks in animals and human infections with AI viruses is crucial for pandemic preparedness., (©Christine M Szablewski, Chelsea Iwamoto, Sonja J Olsen, Carolyn M Greene, Lindsey M Duca, C Todd Davis, Kira C Coggeshall, William W Davis, Gideon O Emukule, Philip L Gould, Alicia M Fry, David E Wentworth, Vivien G Dugan, James C Kile, Eduardo Azziz-Baumgartner. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.08.2023.)

The seminal Lost in the Mall study has been enormously influential in psychology and is still cited in legal cases. The current study directly replicated this paper, addressing methodological weaknesses including increasing the sample size fivefold and preregistering detailed analysis plans. Participants ( N  = 123) completed a survey and two interviews where they discussed real and fabricated childhood events, based on information provided by an older relative. We replicated the findings of the original study, coding 35% of participants as reporting a false memory for getting lost in a mall in childhood (compared to 25% in the original study). In an extension, we found that participants self-reported high rates of memories and beliefs for the fabricated event. Mock jurors were also highly likely to believe the fabricated event had occurred and that the participant was truly remembering the event, supporting the conclusions of the original study.

Bronchiectasis is a common progressive respiratory disease with recognisable radiological abnormalities and a clinical syndrome of cough, sputum production and recurrent respiratory infections. Inflammatory cell infiltration into the lung, in particular neutrophils, is central to the pathophysiology of bronchiectasis. Herein we explore the roles and relationships between infection, inflammation and mucociliary clearance dysfunction in the establishment and progression of bronchiectasis. Microbial and host-mediated damage are important processes underpinning bronchiectasis and the relative contribution of proteases, cytokines and inflammatory mediators to the propagation of inflammation is presented. We also discuss the emerging concept of inflammatory endotypes, defined by the presence of neutrophilic and eosinophilic inflammation, and explore the role of inflammation as a treatable trait. Current treatment for bronchiectasis focuses on treatment of underlying causes, enhancing mucociliary clearance, controlling infection and preventing and treating complications. Data on airway clearance approaches via exercise and mucoactive drugs, pharmacotherapy with macrolides to decrease exacerbations and the usefulness of inhaled antibiotics and bronchodilators are discussed, finishing with a look to the future where new therapies targeting host-mediated immune dysfunction hold promise., Competing Interests: Conflict of interest: J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed, outside the submitted work; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer and Zambon, outside the submitted work. Conflict of interest: S. Elborn holds a joint public–private grant from the European commission in the innovative medicines initiative with Novartis AG and Spexsis; he worked as a paid consultant for Vertex Pharmaceuticals and Viatris Inc.; and has been a paid speaker for many pharmaceutical companies over 30 years in respiratory medicine. Conflict of interest: C.M. Greene reports grants or contracts from NIH and Vertex, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Vertex, outside the submitted work; support for attending meetings and/or travel from European Respiratory Society, outside the submitted work; and was Head of ERS Assembly 3 2019–2022, outside the submitted work., (Copyright ©The authors 2023.)

In this review, the Basic and Translational Science Assembly of the European Respiratory Society provides an overview of the 2022 International Congress highlights. We discuss the consequences of respiratory events from birth until old age regarding climate change related alterations in air quality due to pollution caused by increased ozone, pollen, wildfires and fuel combustion as well as the increasing presence of microplastic and microfibres. Early life events such as the effect of hyperoxia in the context of bronchopulmonary dysplasia and crucial effects of the intrauterine environment in the context of pre-eclampsia were discussed. The Human Lung Cell Atlas (HLCA) was put forward as a new point of reference for healthy human lungs. The combination of single-cell RNA sequencing and spatial data in the HLCA has enabled the discovery of new cell types/states and niches, and served as a platform that facilitates further investigation of mechanistic perturbations. The role of cell death modalities in regulating the onset and progression of chronic lung diseases and its potential as a therapeutic target was also discussed. Translational studies identified novel therapeutic targets and immunoregulatory mechanisms in asthma. Lastly, it was highlighted that the choice of regenerative therapy depends on disease severity, ranging from transplantation to cell therapies and regenerative pharmacology., Competing Interests: Conflict of interest: S. Cuevas Ocaña was supported by an Action for Pulmonary Fibrosis award to support attendance at the European Respiratory Society International Congress 2022. S. Rolandsson Enes declares personal consulting fees from Swedish StromaBio AB outside the submitted work. C. Voss declares research funding and salary from the European Union's Horizon 2020 research and innovation programme under grant agreement number 953183 (HARMLESS) and number 686098 (SmartNanoTox); and nonfinancial interests in spin-off company Infinite from H2020 SmartNanoTox. L.S.N. Dean reports being a postdoctoral research associate on a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/V004573/1) and an NIHR Southampton Biomedical Research Centre (BRC) Senior Research Fellowship, and that they received a British Association for Lung Research Travel Award to the European Respiratory Society International Congress 2022. M. Loxham reports a BBSRC David Phillips Fellowship (BB/V004573/1) and an NIHR Southampton BRC Senior Research Fellowship to fund research and salary for a fellow; as well as research and equipment grants (total ∼GBP 13 000) from Asthma, Allergy, and Inflammation Research Charity (UK), in the 36 months prior to manuscript submission. C.M. Greene declares research funding paid to their institution by the National Institutes of Health, Vertex and the Alpha-1 Foundation; and an honorarium from Insmed, all in the 36 months prior to manuscript submission; as well as support for travel and accommodation at the European Respiratory Society International Congress 2022. I.H. Heijink declares research funding from Boehringer Ingelheim and Roche, outside the submitted work. A. Joannes declares research funding to their institution, and support for attending meetings and/or travel from AIR de Bretagne, in the 36 months prior to manuscript submission. A.M. van der Does declares an unpaid role as Secretary of European Respiratory Society Group 03.02 (Airway cell biology and immunopathology). D.E. Wagner declares research grants from the Swedish Research Council, the European Research Council, Vinnova, the Alternatives Research and Development Foundation and the Knut and Alice Wallenberg Foundation; and support from AstraZeneca for attendance at the company's Science Day 2022 in Gothenburg; and receipt of electrospun membranes to their lab from Cellevate AB, all in the 36 months prior to manuscript submission; as well as patents relating to “De- and recellularization of whole organs” and “Microwave processing for calcium phosphate nanowhiskers”; personal stock investments in Merck, Pfizer, Thermofisher and Viatris; and an unpaid role as Secretary of European Respiratory Society Group 03.03 (Mechanisms of lung injury and repair). All other authors declare no competing interests., (Copyright ©The authors 2023.)

ABSTRACT Deception is often a necessity in rich false memory studies, but is this deception acceptable to participants? In the current study, we followed up with 175 participants who had taken part in a replication of the Lost in the Mall childhood false memory study (Loftus & Pickrell, 1995), as either a research subject or a familial informant. We found that both participants and informants were generally very positive about their experience, did not regret taking part and found the deceptive methods acceptable. Importantly, the vast majority reported that they would still have taken part had they known the true objectives from the beginning. Participants also reported learning something interesting about memory and enjoying the nostalgia and family discussions that were prompted by the study. We would encourage other researchers to assess the ethical implications of false memory research paradigms and to incorporate the valuable feedback from participants and informants.

In recent years there has been an explosion of research on misinformation, often involving experiments where participants are presented with fake news stories and subsequently debriefed. In order to avoid potential harm to participants or society, it is imperative that we establish whether debriefing procedures remove any lasting influence of misinformation. In the current study, we followed up with 1547 participants one week after they had been exposed to fake news stories about COVID-19 and then provided with a detailed debriefing. False memories and beliefs for previously-seen fake stories declined from the original study, suggesting that the debrief was effective. Moreover, the debriefing resulted in reduced false memories and beliefs for novel fake stories, suggesting a broader impact on participants' willingness to accept misinformation. Small effects of misinformation on planned health behaviours observed in the original study were also eliminated at follow-up. Our findings suggest that when a careful and thorough debriefing procedure is followed, researchers can safely and ethically conduct misinformation research on sensitive topics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Greene, Murphy. 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.)

Background: We estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication., Methods: We collected residue sera from multiple antenatal-care blood draws during October 2016-April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance., Results: Among all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness., Conclusions: The incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Long non-coding RNAs (lncRNAs) regulate gene expression. Their expression in alpha-1 antitrypsin (AAT) deficiency has not been investigated. Treatment of AAT deficiency involves infusion of plasma-purified AAT and this augmentation therapy has previously been shown to alter microRNA expression in monocytes of AAT-deficient (ZZ) individuals. Here, we assess the effect of AAT augmentation therapy on the lncRNA expression profile in ZZ monocytes. Peripheral blood monocytes were isolated from ZZ individuals pre (Day 0)- and post (Day 2)-AAT augmentation therapy. Arraystar lncRNA microarray profiling was performed; a total of 17,761 lncRNAs were detectable across all samples. The array identified 7509 lncRNAs with differential expression post-augmentation therapy, 3084 were increased and 4425 were decreased (fold change ≥ 2). Expression of many of these lncRNAs were similarly altered in ZZ monocytes treated ex vivo with 27.5 μM AAT for 4 h. These properties may contribute to the manifold effects of AAT augmentation therapy.

We conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017-2018 and 2018-2019, we collected environmental samples from 14 LPMs, 4 poultry farms, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% - 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology., Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin (Ang)-converting enzyme 2 (ACE2). Altering ACE2 levels may affect entry of SARS-CoV-2 and recovery from COVID-19. Decreased cell surface density of ACE2 leads to increased local levels of Ang II and may contribute to mortality resulting from acute lung injury and fibrosis during COVID-19. Studies published early during the COVID-19 pandemic reported that people with cystic fibrosis (PwCF) had milder symptoms, compared to people without CF. This finding was attributed to elevated ACE2 levels and/or treatment with the high efficiency CFTR modulators. Subsequent studies did not confirm these findings reporting variable effects of CFTR gene mutations on ACE2 levels. Transforming growth factor (TGF)-β signaling is essential during SARS-CoV-2 infection and dominates the chronic immune response in severe COVID-19, leading to pulmonary fibrosis. TGF-β1 is a gene modifier associated with more severe lung disease in PwCF but its effects on the COVID-19 course in PwCF is unknown. To understand whether TGF-β1 affects ACE2 levels in the airway, we examined miRNAs and their gene targets affecting SARS-CoV-2 pathogenesis in response to TGF-β1. Small RNAseq and micro(mi)RNA profiling identified pathways uniquely affected by TGF-β1, including those associated with SARS-CoV-2 invasion, replication, and the host immune responses. TGF-β1 inhibited ACE2 expression by miR-136-3p and miR-369-5p mediated mechanism in CF and non-CF bronchial epithelial cells. ACE2 levels were higher in two bronchial epithelial cell models expressing the most common CF-causing mutation in CFTR gene F508del, compared to controls without the mutation. After TGF-β1 treatment, ACE2 protein levels were still higher in CF, compared to non-CF cells. TGF-β1 prevented the modulator-mediated rescue of F508del-CFTR function while the modulators did not prevent the TGF-β1 inhibition of ACE2 levels. Finally, TGF-β1 reduced the interaction between ACE2 and the recombinant spike RBD by lowering ACE2 levels and its binding to RBD. Our data demonstrate novel mechanism whereby TGF-β1 inhibition of ACE2 in CF and non-CF bronchial epithelial cells may modulate SARS-CoV-2 pathogenicity and COVID-19 severity. By reducing ACE2 levels, TGF-β1 may decrease entry of SARS-CoV-2 into the host cells while hindering the recovery from COVID-19 due to loss of the anti-inflammatory and regenerative effects of ACE2. The above outcomes may be modulated by other, miRNA-mediated effects exerted by TGF-β1 on the host immune responses, leading to a complex and yet incompletely understood circuitry., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Studies of eyewitness memory commonly employ variations on a standard misinformation paradigm. Participants are (a) exposed to an event (e.g., a simulated crime), (b) misled about certain details of the event and (c) questioned about their memory of the original event. Misinformation may be provided in the second step via a range of methods. Here, we directly compared the effectiveness of six misinformation delivery methods-leading questions, elaborate leading questions, doctored photographs, simple narratives, scrambled narratives, and missing word narratives. We presented 1182 participants with a video of a simulated robbery and randomly assigned them to receive misinformation about two out of four critical details via one of these methods. In line with the levels of processing account of memory, we report that methods that encourage deeper processing of misinformation result in more memory distortions. Contrary to previous reports, doctored photographs were not a successful method of implanting misinformation. The six delivery methods resulted in minimal differences in confidence and metamemory estimates, but participants were more likely to notice the presence of misinformation in the simple narrative condition. We conclude with suggestions for the selection of an appropriate method of misinformation delivery in future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Interstitial lung diseases (ILD) are a group of heterogeneous progressive pulmonary disorders, characterised by tissue remodelling and/or fibrotic scarring of the lung parenchyma. ILD patients experience lung function decline with progressive symptoms, poor response to treatment, reduced quality of life and high mortality. ILD can be idiopathic or associated with systemic or connective tissue diseases (CTD) but idiopathic pulmonary fibrosis (IPF) is the most common form. While IPF has a male predominance, women are affected more greatly by CTD and therefore associated ILDs. The mechanisms behind biological sex differences in these progressive lung diseases remain unclear. However, differences in environmental exposures, variable expression of X-chromosome related inflammatory genes and sex hormones play a role. Here, we will outline sex-related differences in the incidence, progression and mechanisms of action of these diseases and discuss existing and novel cellular and pre-clinical studies. Furthermore, we will highlight how sex-differences are not adequately considered in pre-clinical disease models, how gender bias exists in clinical diagnosis and how women are underrepresented in clinical trials. Future action on these observations will hopefully shed light on the role of biological sex in disease development, identify potential targets for intervention and increase female participant numbers in clinical trials.

Many legal cases hinge on evaluating the veracity of two versions of events ("he said, she said"). Expert witnesses are often called upon to testify on the malleability of memory, most often testifying for the defence. This may lead to the theoretically unfounded assumption that it is only victims who are vulnerable to distorted memories of a crime. Inspired by this question, we conducted a series of five experiments in which 2010 participants played a novel version of the Prisoner's Dilemma. Participants could either betray their partner in the game ("winners") or be betrayed by their partner ("losers"). We exposed participants to misinformation concerning the other player's statements to assess whether winners and losers may be differentially susceptible to false memories of the event in question. Across our experiments, including where real financial rewards were at stake, we found that winners were just as susceptible as losers to memory distortion. We highlight the need to consider the possibility of faulty memory affecting all parties to in legal cases, though further research is needed beyond this highly artificial paradigm.

Misinformation continually threatens efforts to control the COVID-19 pandemic, with vaccine misinformation now a key concern. False memories for misinformation can influence behavioural intentions, yet little is known about the factors affecting (false) memories for vaccine-related news items. Across two experiments (total n  = 1481), this paper explores the effects of pre-existing vaccine opinions on reported memories for true and false news items. In Study 1, participants ( n  = 817) were exposed to fabricated pro- or anti-vaccine news items, and then asked if they have a memory of this news event having occurred. In Study 2, participants ( n  = 646) viewed true pro- or anti-vaccine news items. News items were more likely to be remembered when they aligned with participants' pre-existing vaccine beliefs, with stronger effects for pro-vaccine information. We conclude by encouraging researchers to consider the role of attitudinal bias when developing interventions to reduce susceptibility to misinformation., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Applied Cognitive Psychology published by John Wiley & Sons Ltd.)

Misinformation has been a pressing issue since the beginning of the COVID-19 pandemic, threatening our ability to effectively act on the crisis. Nevertheless, little is known about the actual effects of fake news on behavioural intentions. Does exposure to or belief in misinformation about COVID-19 vaccines affect people's intentions to receive such a vaccine? This paper attempts to address this question via three preregistered experiments (N = 3463). In Study 1, participants (n = 1269) were exposed to fabricated pro- or anti-vaccine information or to neutral true information, and then asked about their intentions to get vaccinated. In Study 2, participants (n = 646) were exposed to true pro- and anti-vaccine information, while Study 3 (n = 1548) experimentally manipulated beliefs in novel misinformation about COVID-19 vaccines by increasing exposure to the information. The results of these three studies showed that exposure to false information about the vaccines had little effect on participants' intentions to get vaccinated, even when multiple exposures led them to believe the headlines to be more accurate. An exploratory meta-analysis of studies 1 and 3, with a combined sample size of 2683, showed that exposure to false information both supporting and opposing COVID-19 vaccines actually increased vaccination intentions, though the effect size was very small. We conclude by cautioning researchers against equating exposure to misinformation or perceived accuracy of false news with actual behaviours., (© 2022. The Author(s).)

Introduction: The airway epithelium is a key system within the lung. It acts as a physical barrier to inhaled factors, and can actively remove unwanted microbes and particles from the lung via the mucociliary escalator. On a physiological level, it senses the presence of pathogens and initiates innate immune responses to combat their effects. Hydration of the airways is also controlled by the epithelium. Within the cystic fibrosis (CF) lung, these properties are suboptimal and contribute to the pulmonary manifestations of CF., Areas Covered: In this review, we discuss how various host and microbial factors can contribute to airway epithelium dysfunction in the CF lung focusing on mechanisms relating to the mucociliary escalator and protease expression and function. We also explore how alterations in microRNA expression can impact the behavior of the airway epithelium., Expert Opinion: Notwithstanding the unprecedented benefits that CFTR modulator drugs now provide to the health of CF sufferers, it will be important to delve more deeply into additional mechanisms underpinning CF lung disease such as those illustrated here in an attempt to counteract these aberrant processes and further enhance quality of life for people with CF.