Search

BackgroundWhen transitioning to adulthood, youth with disabilities and their families face many service gaps. Successful inter-agency collaborations can promote family-centred, inclusive transition support amenable to personal choice and health conditions. This paper reports the 3-year co-design process of an innovative transition service that links a pediatric hospital and adult service agencies and addresses key areas of transition preparedness with joint accountability.MethodsA team of pediatric rehabilitation professionals, adult service providers, young adults with disabilities and their families, and researchers engaged in a co-design process over three years. Following a design thinking (DT) framework, the team went through an iterative process of Empathize. Define, Ideation, Prototyping, and Testing phases. The trial-and-error process allowed for deeper reflection and an opportunity to pivot the design.ResultsThe co-design yielded Transitions Pop-ups, a nimble service model that can “pop up” at critical times and places to meet clients’ urgent and emergent transition-related needs. Two pilot sessions were conducted at the testing phase with adult service agencies. The final model included five key elements: (1) community partnership; (2) targeted information sharing; (3) peer mentoring; (4) action (on-the-spot completion of a key transition task/activity such as submitting an adult funding application); and (5) warm handover.ConclusionThe co-design process highlighted the importance of open communication and iterative prototype testing as a means for trialing new ideas and clarifying the intent of the project. The DT framework optimally facilitated the co-development of a contextually relevant and sustainable service model for pediatric rehabilitation clients and families.

Background Dermal backflow (DBF), which refers to lymphatic reflux due to lymphatic valve insufficiency, is a diagnostic finding in lymphedema. However, the three-dimensional structure of DBF remains unknown. Photoacoustic lymphangiography (PAL) is a new technique that enables the visualization of the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and can provide three-dimensional images of superficial lymphatic vessels and the venous system. This study reports the use of PAL to visualize DBF structures in the extremities of patients with lymphedema after cancer surgery. Methods Patients with a clinical or lymphographic diagnosis of lymphedema who previously underwent surgery for cancer at one of two participating hospitals were included in this study. PAL was performed using the PAI-05 system. ICG was administered subcutaneously in the affected hand or foot, and ICG fluorescence lymphography was performed using a nearinfrared camera system prior to PAL. Results Between April 2018 and January 2019, 21 patients were enrolled and examined using PAL. The DBF was composed of dense, interconnecting, three-dimensional lymphatic vessels. It was classified into three patterns according to the composition of the lymphatic vessels: a linear structure of lymphatic collectors (pattern 1), a network of lymphatic capillaries and lymphatic collectors in an underlying layer (pattern 2), and lymphatic capillaries and precollectors with no lymphatic collectors (pattern 3). Conclusions PAL showed the structure of DBF more precisely than ICG fluorescence lymphography. The use of PAL to visualize DBF assists in understanding the pathophysiology and assessing the severity of cancer-related lymphedema.

AimsThe aim was to describe an innovative initiative that took place in a pediatric rehabilitation hospital. The goal of this organization-wide strategic initiative, called the Transition Strategy, was to improve service delivery to children/youth with disabilities and their families at times of life transition. The research question was: What are the key elements that have contributed to the success of the Strategy, from the perspective of team members? The objectives were to describe: (a) the guiding principles underlying team functioning and team practices, (b) key enablers of positive team functioning, (c) the nature of effective team practices, and (d) lessons learned.MethodsA holistic descriptive case study was conducted, utilizing historical documents, tracked outcome data, and the experiences and insights of multidisciplinary team members (the authors). Reflecting an insiders' perspective, the impressions of team members were key sources of data. The perspectives of team members were used to generate key teamwork principles, enablers of team functioning, team practices, and key learnings.Findings and DiscussionTeam members identified four guiding humanistic principles (respect, support, partnership, and open communication). These principles underpinned three novel practices that contributed to team effectiveness in the eyes of team members: supportive relational practices, human-centered co-design, and solution-focused communication. Key enablers were the relational style of leadership, and a team climate of innovation, autonomy, and trust, supported by the organizational vision. This team climate fostered a sense of psychological safety, thereby encouraging both experimentation and learning from failure.ConclusionsThis article provides information for other healthcare organizations interested in understanding the Strategy's value and its implementation. It provides a practical example of how to adopt a humanistic approach to health care, leading to both innovative service development and thriving among team members.

Recent reports have described several cases of double muscle transfers to restore natural, symmetrical smiles in patients with long-standing facial paralysis. However, these complex procedures sometimes result in cheek bulkiness owing to the double muscle transfer. We present the case of a 67-year-old woman with long-standing facial paralysis, who underwent two-stage facial reanimation using two superficial subslips of the serratus anterior muscle innervated by the masseteric and contralateral facial nerves via a sural nerve graft. Each muscle subslip was transferred to the upper lip and oral commissures, which were oriented in different directions. Furthermore, a horizontal fascia lata graft was added at the lower lip to prevent deformities such as lower lip elongation and deviation. Voluntary contraction was noted at roughly 4 months, and a spontaneous smile without biting was noted 8 months postoperatively. At 18 months after surgery, the patient demonstrated a spontaneous symmetrical smile with adequate excursion of the lower lip, upper lip, and oral commissure, without cheek bulkiness. Dual-innervated muscle transfer using two multivector superficial subslips of the serratus anterior muscle may be a good option for long-standing facial paralysis, as it can achieve a symmetrical smile that can be performed voluntarily and spontaneously.

Background Lymphaticovenular anastomosis (LVA) is a minimally invasive surgical procedure used to treat lymphedema. Volumetric measurements and quality-of-life assessments are often performed to assess the effectiveness of LVA, but there is no method that provides information regarding postoperative morphological changes in lymphatic vessels and veins after LVA. Photoacoustic lymphangiography (PAL) is an optical imaging technique that visualizes the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and provides three-dimensional images of superficial lymphatic vessels and the venous system simultaneously. In this study, we performed PAL in lymphedema patients before and after LVA and compared the images to evaluate the effect of LVA. Methods PAL was performed using the PAI-05 system in three patients (one man, two women) with lymphedema, including one primary case and two secondary cases, before LVA. ICG fluorescence lymphography was performed in all cases before PAL. Follow-up PAL was performed between 5 days and 5 months after LVA. Results PAL enabled the simultaneous visualization of clear lymphatic vessels that could not be accurately seen with ICG fluorescence lymphography and veins. We were also able to observe and analyze morphological changes such as the width and the number of lymphatic vessels and veins during the follow-up PAL after LVA. Conclusions By comparing preoperative and postoperative PAL images, it was possible to analyze the morphological changes in lymphatic vessels and veins that occurred after LVA. Our study suggests that PAL would be useful when assessing the effect of LVA surgery.

Introduction Transition from pediatric to adult care has significant implications for health outcomes in youth with special health care needs. To optimally support the transition, health care and social service providers must work collaboratively with youth and families in service planning, implementation, and evaluation. Based on interviews with 15 youth and their families, we developed an arts-informed interprofessional education activity titled Transitions Theatre using the method of readers’ theater. Methods Three educators with lived experience (one former pediatric rehabilitation client and two parents of youth with special health care needs) and three academic/clinical educators codesigned the transitions. We conducted four online workshops (14–20 participants each). Results A total of 67 people participated: 59 students from 11 health disciplines and seven postlicensure clinicians and one trainee from five disciplines (e.g., occupational therapy, life skills coaching, early childhood education). Twenty-six participants answered both pre- and postworkshop surveys and reported a positive shift in their understanding of client and family perspectives, their roles in transition support, and other providers’ roles in transition support. After the workshop, learners felt more confident with transition support and interprofessional collaboration. The perspectives of the educators with lived experience aligned with the theater scripts and enhanced learners’ empathetic engagement with the topic. Discussion The evidence-based teaching approach of readers’ theater and our coteaching model offered learners a unique opportunity to learn about the challenges clients and their families face at the time of transition to adulthood and identify their role in an interprofessional transition support.

The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunised human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19).

Advanced manufacturing research for sustainable battery life cycles is of utmost importance to reach net zero carbon emissions (European Commission, 2023a) as well as several of the United Nations Sustainable Development Goals (UNSDGs), for example: 30% reduction of CO2 emission, 10 million job opportunities and access to electricity for 600 million people (World Economic Forum, 2019). This editorial paper highlights international motivations for pursuing more sustainable manufacturing practices and discusses key research topics in battery manufacturing. Batteries will be central to our sustainable future as generation and storage become key components to on-demand energy supply. Four underlying themes are identified to address industrial needs in this field: 1. Digitalizing and automating production capabilities: data-driven solutions for production quality, smart maintenance, automation, and human factors, 2. Human-centric production: extended reality for operator support and skills development, 3. Circular battery life cycles: circular battery systems supported by service-based and other novel business models, 4. Future topics for battery value chains: increased industrial resilience and transparency with digital product passports, and next-generation battery chemistries. Challenges and opportunities along these themes are highlighted for transforming battery value chains through circularity and more sustainable production, with a particular emphasis on lithium-ion batteries (LIB). The paper concludes with directions for further research to advance a circular and sustainable battery value chain through utilizing the full potential of digitalization realising a cleaner, more energy-efficient society.

The Late Cretaceous of western North America supported diverse dinosaur assemblages, though understanding patterns of dinosaur diversity, evolution, and extinction has been historically limited by unequal geographic and temporal sampling. In particular, the existence and extent of faunal endemism along the eastern coastal plain of Laramidia continues to generate debate, and finer scale regional patterns remain elusive. Here, we report a new centrosaurine ceratopsid, Lokiceratops rangiformis, from the lower portion of the McClelland Ferry Member of the Judith River Formation in the Kennedy Coulee region along the Canada-USA border. Dinosaurs from the same small geographic region, and from nearby, stratigraphically equivalent horizons of the lower Oldman Formation in Canada, reveal unprecedented ceratopsid richness, with four sympatric centrosaurine taxa and one chasmosaurine taxon. Phylogenetic results show that Lokiceratops, together with Albertaceratops and Medusaceratops, was part of a clade restricted to a small portion of northern Laramidia approximately 78 million years ago. This group, Albertaceratopsini, was one of multiple centrosaurine clades to undergo geographically restricted radiations, with Nasutuceratopsini restricted to the south and Centrosaurini and Pachyrostra restricted to the north. High regional endemism in centrosaurs is associated with, and may have been driven by, high speciation rates and diversity, with competition between dinosaurs limiting their geographic range. High speciation rates may in turn have been driven in part by sexual selection or latitudinally uneven climatic and floral gradients. The high endemism seen in centrosaurines and other dinosaurs implies that dinosaur diversity is underestimated and contrasts with the large geographic ranges seen in most extant mammalian megafauna.

This study explores vocational didactics and embodied knowledge in hairdressing education by studying how perceptive sensoriality is used by teachers and students in creating shared understandings of vocational knowledge. Among multiple actions, touch is distinguished as a central resource in learning the vocation, as it emerges in interaction between teacher and student related to the ongoing teaching and its assignment. The data is based on video-recordings displaying how touch is used in manipulating objects and material, or in assessing qualities and defects. In such instances, touch becomes a diagnostic criterion (Goodwin, 1997) to investigate how the material worked with can be evaluated and handled. To bridge the gap between individual and collective vocational knowledge, metaphors are of use. The results show two approaches to the teaching of perceptive sensoriality. In order to learn the vocational subject content the teaching need to provide for and practice the individual’s embodied sense of touch as well as the vocation’s verbalised collective feel. This is the core of the didactical challenge.

Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants have dominated in the spread of the disease. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently, we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro using protein chemical methods, mass spectrometry, and circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum–hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study the specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in significant quantities as secreted and folded proteins in mammalian cells. The antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, the RBD-specific IgG levels induced with the different vaccines were comparable, but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were seven- and twofold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively, and they were six-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Abstract Background Serum amyloid A (SAA) has been reported to hold promise as diagnostic and prognostic marker in foals. This has not been investigated thoroughly. Objectives Evaluate admission SAA concentrations as predictor of sepsis and outcome. Animals Five hundred and ninety hospitalized foals

Abstract Background The knowledge of how the separate Attention-Deficit/Hyperactivity Disorder (ADHD) subdimensions (impulsivity, hyperactivity, and inattention) are associated with nonsuicidal self-injury (NSSI) and suicidal behavior (SB) is limited. The objective of this study was to investigate the associations of childhood ADHD subdimensions with NSSI and SB in children at risk of neurodevelopmental disorders (NDDs; including ADHD). Methods The sample (N = 391) included twin pairs where at least one twin screened positive for at least one NDD or common comorbidity at age 9 or 12. Data on ADHD subdimensions was collected through a telephone interview with a caregiver/legal guardian at age 9 or 12, and data on NSSI and SB was collected through an in-person clinical assessment at age 15. The associations between the ADHD subdimensions and NSSI or SB were tested in three different models: (1) univariable, (2) together with the other ADHD subdimensions, and (3) in a confounder-adjusted model including other NDD symptoms in addition to ADHD subdimensions, for NSSI and SB separately. Results A total of 32 (8.2%) adolescents reported life-time engagement of NSSI, and 18 (4.6%) SB. Childhood impulsivity was associated with SB and childhood inattention with NSSI, in all models. Hyperactivity was not meaningfully associated with any of the outcomes. Conclusion Impulsivity and inattention, but not hyperactivity, may be of particular importance in understanding SB and NSSI. Brief screening for impulsivity and inattention in childhood could facilitate detection of children vulnerable to NSSI and SB and indicate valuable information for preventive and intervention strategies.

ObjectiveElevated cortisol levels have been frequently reported in Alzheimer’s disease (AD) and linked to brain atrophy, especially of the hippocampus. Besides, high cortisol levels have been shown to impair memory performance and increase the risk of developing AD in healthy individuals. We investigated the associations between serum cortisol levels, hippocampal volume, gray matter volume and memory performance in healthy aging and AD.MethodsIn our cross-sectional study, we analyzed the relationships between morning serum cortisol levels, verbal memory performance, hippocampal volume, and whole-brain voxel-wise gray matter volume in an independent sample of 29 healthy seniors (HS) and 29 patients along the spectrum of biomarker-based AD.ResultsCortisol levels were significantly elevated in patients with AD as compared to HS, and higher cortisol levels were correlated with worse memory performance in AD. Furthermore, higher cortisol levels were significantly associated with smaller left hippocampal volumes in HS and indirectly negatively correlated to memory function through hippocampal volume. Higher cortisol levels were further related to lower gray matter volume in the hippocampus and temporal and parietal areas in the left hemisphere in both groups. The strength of this association was similar in HS and AD.ConclusionIn AD, cortisol levels are elevated and associated with worse memory performance. Furthermore, in healthy seniors, higher cortisol levels show a detrimental relationship with brain regions typically affected by AD. Thus, increased cortisol levels seem to be indirectly linked to worse memory function even in otherwise healthy individuals. Cortisol may therefore not only serve as a biomarker of increased risk for AD, but maybe even more importantly, as an early target for preventive and therapeutic interventions.

In addition to vaccines, there is an urgent need for supplemental antiviral therapeutics to dampen the persistent COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The transmembrane protease serine 2 (TMPRSS2), that is responsible for proteolytic priming of the SARS-CoV-2 spike protein, appears as a rational therapeutic target. Accordingly, selective inhibitors of TMPRSS2 represent potential tools for prevention and treatment of COVID-19. Previously, we identified the human milk glycoprotein lactoferrin as a natural inhibitor of plasminogen conversion to plasmin, a serine protease homologous to TMPRSS2. Here, we tested whether lactoferrin and lactoferricin, a biologically active natural peptide produced by pepsin-mediated digestion of lactoferrin, together with synthetic peptides derived from lactoferrin, were able to block TMPRSS2 and SARS-CoV-2 infection. Particularly, we revealed that both lactoferricin and the N-terminal synthetic peptide pLF1 significantly inhibited: i) proteolytic activity of TMPRSS2 and plasmin, ii) proteolytic processing of the SARS-CoV-2 spike protein, and iii) SARS-CoV-2 infection of SARS-CoV-2-permissive cells. Thus, natural and synthetic peptides derived from lactoferrin represent feasible candidates for supporting prevention and treatment of COVID-19.

Abstract Objective In order to assess the applicability of a direct-to-consumer (DTC) genetic testing to translational research for obtaining new knowledge on relationships between drug target genes and diseases, we examined possibility of these data by associating SNPs and disease related phenotype information collected from healthy individuals. Results A total of 12,598 saliva samples were collected from the customers of commercial service for SNPs analysis and web survey were conducted to collect phenotype information. The collected dataset revealed similarity to the Japanese data but distinguished differences to other populations of all dataset of the 1000 Genomes Project. After confirmation of a well-known relationship between ALDH2 and alcohol-sensitivity, Phenome-Wide Association Study (PheWAS) was performed to find association between pre-selected drug target genes and all the phenotypes. Association was found between GRIN2B and multiple phenotypes related to depression, which is considered reliable based on previous reports on the biological function of GRIN2B protein and its relationship with depression. These results suggest possibility of using SNPs and phenotype information collected from healthy individuals as a translational research tool for drug discovery to find relationship between a gene and a disease if it is possible to extract individuals in pre-disease states by properly designed questionnaire.

Abstract Background The risk of heart failure is disproportionately high among the socioeconomically disadvantaged. Furthermore, socioeconomically deprived patients are at risk of inequitable access to heart failure treatment and poor outcomes. Non-employment as a risk factor in this respect has not previously been studied at the level of the individual. The aim of this register-based cohort study was to analyse equity in access to renin-angiotensin system blockers and mortality, by employment status and educational level. Methods The study population consisted of Swedish patients aged 20–64 years hospitalised for heart failure in July 2006–December 2010, without a heart failure hospitalisation within one year or more before index hospitalisation and without renin-angiotensin system blocker dispensation in the 6 months preceding index hospitalisation. Non-access to renin-angiotensin system blockers, measured as drug dispensations, was investigated by employment status and educational level through logistic regression. Cox regression models were used to obtain hazard ratios for all-cause death by educational level and employment status. Interaction analysis was used to test whether associations between access to treatment and mortality differed by employment status. Results Among the 3874 patients, 1239 (32%) were women. The median age was 57 years. Fifty-three percent were employed. The non-employed patients had more comorbidity and lower access (68%) to renin-angiotensin system blockers compared with the employed (82%). The adjusted odds ratio for non-access to renin-angiotensin system blockers among the non-employed was 1.76. Non-employment was associated with an adjusted hazard ratio of 1.76 for death. Low educational level was associated with a higher death risk. Mortality was highest among the non-employed without access to renin-angiotensin system blockers and the association between access to renin-angiotensin system blockers and survival was slightly weaker in this group. Conclusions Non-employment and low educational level were associated with elevated mortality in heart failure. Non-employment was a risk factor for lower access to evidence-based treatment, and among the non-employed access to treatment was associated with a slightly smaller risk reduction than among the employed. The results underscore that clinicians need to be aware of the importance of socioeconomic factors in heart failure care.

Iliac branch endograft devices offer an elegant solution to preserve perfusion to the internal iliac artery when treating aortoiliac aneurysms; however, they are difficult to perform when bilateral access is not available owing to aortoiliac anatomy or previous endovascular aortic aneurysm repair. We present a technique to perform iliac branch endograft deployment from ipsilateral access in a patient with a prior EVAR endovascular aortic aneurysm repair, obviating the need for a difficult up-and-over access.

BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11

Lactoferrin is an iron-binding glycoprotein present in most human exocrine fluids, particularly breast milk. Lactoferrin is also released from neutrophil granules, and its concentration increases rapidly at the site of inflammation. Immune cells of both the innate and the adaptive immune system express receptors for lactoferrin to modulate their functions in response to it. On the basis of these interactions, lactoferrin plays many roles in host defense, ranging from augmenting or calming inflammatory pathways to direct killing of pathogens. Complex biological activities of lactoferrin are determined by its ability to sequester iron and by its highly basic N-terminus, via which lactoferrin binds to a plethora of negatively charged surfaces of microorganisms and viruses, as well as to mammalian cells, both normal and cancerous. Proteolytic cleavage of lactoferrin in the digestive tract generates smaller peptides, such as N-terminally derived lactoferricin. Lactoferricin shares some of the properties of lactoferrin, but also exhibits unique characteristics and functions. In this review, we discuss the structure, functions, and potential therapeutic uses of lactoferrin, lactoferricin, and other lactoferrin-derived bioactive peptides in treating various infections and inflammatory conditions. Furthermore, we summarize clinical trials examining the effect of lactoferrin supplementation in disease treatment, with a special focus on its potential use in treating COVID-19.

Influenza D virus (IDV) has been detected in bovine respiratory disease (BRD) outbreaks, and experimental studies demonstrated this virus’s capacity to cause lesions in the respiratory tract. In addition, IDV-specific antibodies were detected in human sera, which indicated that this virus plays a potential zoonotic role. The present study aimed to extend our knowledge about the epidemiologic situation of IDV in Swedish dairy farms, using bulk tank milk (BTM) samples for the detection of IDV antibodies. A total of 461 and 338 BTM samples collected during 2019 and 2020, respectively, were analyzed with an in-house indirect ELISA. In total, 147 (32%) and 135 (40%) samples were IDV-antibody-positive in 2019 and 2020, respectively. Overall, 2/125 (2%), 11/157 (7%) and 269/517 (52%) of the samples were IDV-antibody-positive in the northern, middle and southern regions of Sweden. The highest proportion of positive samples was repeatedly detected in the south, in the county of Halland, which is one of the counties with the highest cattle density in the country. In order to understand the epidemiology of IDV, further research in different cattle populations and in humans is required.

More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused the unforeseen COVID-19 pandemic with millions of deaths. In the meantime, SARS-CoV-2 has become endemic and is now part of the repertoire of viruses causing seasonal severe respiratory infections. Due to several factors, among them the development of SARS-CoV-2 immunity through natural infection, vaccination and the current dominance of seemingly less pathogenic strains belonging to the omicron lineage, the COVID-19 situation has stabilized. However, several challenges remain and the possible new occurrence of highly pathogenic variants remains a threat. Here we review the development, features and importance of assays measuring SARS-CoV-2 neutralizing antibodies (NAbs). In particular we focus on in vitro infection assays and molecular interaction assays studying the binding of the receptor binding domain (RBD) with its cognate cellular receptor ACE2. These assays, but not the measurement of SARS-CoV-2-specific antibodies per se, can inform us of whether antibodies produced by convalescent or vaccinated subjects may protect against the infection and thus have the potential to predict the risk of becoming newly infected. This information is extremely important given the fact that a considerable number of subjects, in particular vulnerable persons, respond poorly to the vaccination with the production of neutralizing antibodies. Furthermore, these assays allow to determine and evaluate the virus-neutralizing capacity of antibodies induced by vaccines and administration of plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 variants or synthetic compounds to be used for therapy of COVID-19 and assist in the preclinical evaluation of vaccines. Both types of assays can be relatively quickly adapted to newly emerging virus variants to inform us about the magnitude of cross-neutralization, which may even allow us to estimate the risk of becoming infected by newly appearing virus variants. Given the paramount importance of the infection and interaction assays we discuss their specific features, possible advantages and disadvantages, technical aspects and not yet fully resolved issues, such as cut-off levels predicting the degree of in vivo protection.

The reconstruction of Armenian-Jewish relations in the seventeenth to eighteenth centuries is not an easy task due to the scarcity of historical material. Both peoples underwent resettlement, segregation, coercive conversions under Muslim rule (fighting the side-effects of religious policies for social disciplining), political agendas, the influx of Catholic missionaries, and interstate wars throughout the Safavid to Qajar periods. The current article attempts to revisit the perceptions about Jews and Armenians within inter-confessional debates by examining the early modern polemical literature from the Iranian Armenian context and by employing textual material from the Ottoman Armenian milieu that complements the Iranian case. It further aims to reveal the specifics of the Armenian-Jewish connections in the Persianate Muslim environment and detect the reasons for the ambiguous silence in the Armenian literature from the period in question.

In a SARS-CoV-2 seroprevalence study conducted with 1,655 working adults in spring of 2020, 12 of the subjects presented with positive neutralization test (NT) titers (>1:10). They were here followed up for 1 year to assess their Ab persistence. We report that 7/12 individuals (58%) had NT_50 titers ≥1:50 and S1-specific IgG ≥50 BAU/ml 1 year after mild COVID-19 infection. S1-specific IgG were retained until a year when these levels were at least >60 BAU/ml at 3 months post-infection. For both the initial fast and subsequent slow decline phase of Abs, we observed a significant correlation between NT_50 titers and S1-specific IgG and thus propose S1-IgG of 60 BAU/ml 3 months post-infection as a potential threshold to predict neutralizing Ab persistence for 1 year. NT_50 titers and S1-specific IgG also correlated with circulating S1-specific memory B-cells. SARS-CoV-2-specific Ab levels after primary mRNA vaccination in healthy controls were higher (Geometric Mean Concentration [GMC] 3158 BAU/ml [CI 2592 to 3848]) than after mild COVID-19 infection (GMC 82 BAU/ml [CI 48 to 139]), but showed a stronger fold-decline within 5–6 months (0.20–fold, to GMC 619 BAU/ml [CI 479 to 801] vs. 0.56–fold, to GMC 46 BAU/ml [CI 26 to 82]). Of particular interest, the decline of both infection- and vaccine-induced Abs correlated with body mass index. Our data contribute to describe decline and persistence of SARS-CoV-2-specific Abs after infection and vaccination, yet the relevance of the maintained Ab levels for protection against infection and/or disease depends on the so far undefined correlate of protection.

Despite tremendous progress in the understanding of COVID-19, mechanistic insight into immunological, disease-driving factors remains limited. We generated maVie16, a mouse-adapted SARS-CoV-2, by serial passaging of a human isolate. In silico modeling revealed how only three Spike mutations of maVie16 enhanced interaction with murine ACE2. maVie16 induced profound pathology in BALB/c and C57BL/6 mice, and the resulting mouse COVID-19 (mCOVID-19) replicated critical aspects of human disease, including early lymphopenia, pulmonary immune cell infiltration, pneumonia, and specific adaptive immunity. Inhibition of the proinflammatory cytokines IFNγ and TNF substantially reduced immunopathology. Importantly, genetic ACE2-deficiency completely prevented mCOVID-19 development. Finally, inhalation therapy with recombinant ACE2 fully protected mice from mCOVID-19, revealing a novel and efficient treatment. Thus, we here present maVie16 as a new tool to model COVID-19 for the discovery of new therapies and show that disease severity is determined by cytokine-driven immunopathology and critically dependent on ACE2 in vivo.

Abstract Background It is highly desirable to assess the probability of survival in sick neonatal foals upon admission. The foal survival score (FSS) is a published scoring system used to estimate the probability of survival in hospitalized neonatal foals