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Aims: Using a model of isolated and Langendorff-perfused rat heart we analysed whether activation of β3-adrenergic receptors (β3-ARs) influences ventricular lusitropic performance. We also focused on the NOS/NO/cGMP/PKG cascade as the signal transduction mechanism. Methods: Hearts were treated with increasing concentrations (from 10−12 to 10−6 m) of BRL37344, a selective β3-AR agonist, and cardiac performance was evaluated by analysing both lusitropic parameters and coronary motility. Cardiac preparations were also perfused with BRL37344 in the presence of either isoproterenol (ISO) or nadolol, or pertussis toxin (PTx), or selective inhibitors of the NOS/NO/cGMP/PKG pathway. Results: BRL37344 caused a significant concentration-dependent reduction in (LVd P/d t)min, a decrease in half time relaxation significant starting from 10−12 m, and an increase in (LVd P/d t)max/(LVd P/d t)min ratio ( T/− t). BRL37344 abolished the ISO-mediated positive lusitropism. β3-AR-dependent effects on relaxation were insensitive to β1/β2-AR inhibition by nadolol (100 nm), and were abolished by Gi/o protein inhibition by PTx (0.01 nm). NO scavenging by haemoglobin (10 μm), and nitric oxide synthase (NOS) inhibition by NG-monomethyl-l-arginine (10 μm) revealed the involvement of NO signalling in BRL37344 response. Pre-treatment with inhibitors of either soluble guanylate cyclase (ODQ; 10 μm) or PKG (KT5823; 100 nm) abolished β3-AR-dependent negative lusitropism. In contrast, anantin (10 nm), an inhibitor of particulate guanylate cyclase, did not modify the effect of BRL37344 on relaxation. Conclusion: Taken together, our findings provide functional evidence for β3-AR modulation of ventricular relaxation in the rat heart which involves PTx-sensitive inhibitory Gi protein and occurs via an NO-cGMP-PKG cascade. Whether the effects of β3-AR stimulation on lusitropism are beneficial or detrimental remains to be established. [ABSTRACT FROM AUTHOR]

Context: The COVID-19 pandemic has reignited a commitment from the health policy and health services research communities to rebuilding trust in healthcare and created a renewed appetite for measures of trust for system monitoring and evaluation. The aim of the present paper was to develop a multidimensional measure of trust in healthcare that: (1) Is responsive to the conceptual and methodological limitations of existing measures; (2) Can be used to identify systemic explanations for lower levels of trust in equity-deserving populations; (3) Can be used to design and evaluate interventions aiming to (re)build trust., Methods: We conducted a 2021 review of existing measures of trust in healthcare, 72 qualitative interviews (Aug-Dec 2021; oversampling for equity-deserving populations), an expert review consensus process (Oct 2021), and factor analyses and validation testing based on two waves of survey data (Nov 2021, n = 694; Jan-Feb 2022, n = 740 respectively)., Findings: We present the Trust in Multidimensional Healthcare Systems Scale (TIMHSS); a 38-item correlated three-factor measure of trust in doctors, policies, and the system. Measurement of invariance tests suggest that the TIMHSS can also be reliably administered to diverse populations., Conclusions: This global measure of trust in healthcare can be used to measure trust over time at a population level, or used within specific subpopulations, to inform interventions to (re)build trust. It can also be used within a clinical setting to provide a stronger evidence base for associations between trust and therapeutic outcomes., (© 2024. The Author(s).)

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With the aim to identify new factors involved in the processes underlying KD and MIS-C, we analysed the transcriptional levels of HERVs, HERV-related genes, and immune mediators in children during the acute and subacute phases compared with COVID-19 paediatric patients and healthy controls. The results showed higher levels of HERV-W, HERV-K, Syn-1, and ASCT-1/2 in KD, MIS-C, and COV patients, while higher levels of Syn-2 and MFSD2A were found only in MIS-C patients. Moreover, KD and MIS-C shared the dysregulation of several inflammatory and regulatory cytokines. Interestingly, in MIS-C patients, negative correlations have been found between HERV-W and IL-10 and between Syn-2 and IL-10, while positive correlations have been found between HERV-K and IL-10. In addition, HERV-W expression positively correlated with the C-reactive protein. This pilot study supports the role of HERVs in inflammatory diseases, suggesting their interplay with the immune system in this setting. The elevated expression of Syn-2 and MFSD2A seems to be a distinctive trait of MIS-C patients, allowing to distinguish them from KD ones. The understanding of pathological mechanisms can lead to the best available treatment for these two diseases, limiting complications and serious outcomes.

Background: Vaccine hesitancy exists on a continuum ranging between complete adherence and complete refusal due to doubts or concerns within a heterogeneous group of individuals. Despite widespread acknowledgement of the contextual factors influencing attitudes and beliefs shaping COVID-19 vaccine hesitancy, qualitative research with equity-deserving groups, accounting for unique lived experiences, remains a gap in the literature. We aim to identify and begin to understand and document the unique contextual factors shaping hesitancy by equity-deserving groups as it relates to relationships with government and health authorities., Methods: Participants were recruited and interviewed between Aug-Dec 2021. Semi-structured interviews using a convergent interviewing technique were conducted with individuals from the general population, as well as individuals who identify as First Nations, Métis, or Inuit, members of the LGBT2SQ + community, low-income Canadians, Black Canadians, and newcomers. Interviews were audio recorded and transcribed by a team of researchers. Memos were written following interviews and used to complement the thematic analysis of the interview data. Themes are presented in the results section., Results: The rationale for hesitancy among equity-deserving groups is consistent with literature documenting hesitancy in the general population. Contextual factors surrounding equity-deserving groups' attitudes and beliefs, however, are unique and relate to a history of oppression, discrimination, and genocide. We identified factors unique to subgroups; for example, religious or fatalistic beliefs among participant who identify as FNMI, fear associated with lack of testing and speed of vaccines' production among participants who identify as FNMI, Black, and LGBT2SQ + , distrust of the healthcare system for LGBT2SQ + and Black Canadians, and distrust of the government and opposition to vaccine mandates for participating who identify as LGBT2SQ + , low-income, FNMI, or Black Canadian. Newcomers stood out as very trusting of the government and accepting of COVID-19 vaccination., Conclusions: While our data on vaccine hesitancy largely mirror concerns reported in the vast body of literature citing rationale for COVID-19 hesitancy in high-income countries, the contextual factors identified in our work point to the need for wider systemic change. Our results may be used to support efforts, beyond tailored promotion campaigns, to support the confident acceptance of vaccines for COVID-19 and the acceptance of novel vaccines as future infectious diseases emerge., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic., Objectives: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context., Sources: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered., Implications: In the light of the current imbalance between gammaglobulins' demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.

The ability of governments and nations to handle crises and protect the lives of citizens is heavily dependent on the public's trust in their governments and related social institutions. The aim of the present research was to understand public trust in government during a time of crisis, drawing on interview data (N = 56) collected during the COVID-19 pandemic (2021). In addition to the general public (n = 11), participants were sampled to obtain diversity as it relates to identifying as First Nations, Métis, and Inuit (n = 7), LGBT2SQ+ (n = 5), low-income (n = 8), Black Canadians (n = 7), young adult (n = 8), and newcomers to Canada (n = 10). Data were coded in consideration of social theories of trust, and specifically the nature of trust between individuals and institutions working with government in pandemic management. Canadians' trust in government was shaped by perceptions of pandemic communication, as well as decision-making and implementation of countermeasures. Data suggest that although participants did not trust government, they were accepting of measures and messages as presented through government channels, pointing to the importance of (re)building trust in government. Perhaps more importantly however, data indicate that resources should be invested in monitoring and evaluating public perception of individuals and institutions generating the evidence-base used to guide government communication and decision-making to ensure trust is maintained. Theoretically, our work adds to our understanding of the nature of trust as it relates to the association between interpersonal and institutional trust, and also the nature of trust across institutions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Herati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health care providers' recommendations can play an important role in individuals' vaccination decisions. Despite being one of the most popular complementary and alternative medicine (CAM), naturopathy is understudied in relation to vaccination decisions. We sought to address this gap through this study of vaccination perspectives of naturopathy practitioners in the province of Quebec, Canada. We conducted in-depth interviews with 30 naturopaths. Thematic analysis was conducted. Main themes were developed deductively (i.e., based on prior literature) and expanded through inductive coding of the data. Participants noted that they discuss vaccination in their practice, but only when clients asked questions or wanted advice. Naturopaths described refraining from explicitly recommending for or against vaccination. Instead, they focus on empowering their clients to make their own informed decision regarding vaccination. Most participants noted that they direct clients towards sources of information so that clients could decide for themselves, but some mentioned they discussed with clients what they considered to be risks associated with vaccination, as well as its benefits. These discussions were framed through a personalized and individual approach with clients., 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 Elsevier Ltd. All rights reserved.)

Newcomers to Canada have been disproportionally affected by COVID-19, with higher rates of infection and severity of illness. Determinants of higher rates may relate to social and structural inequities that impact newcomers' capacity to follow countermeasures. Our aim was to describe and document factors shaping newcomers' acceptance of COVID-19 countermeasures. Semi-structured qualitative interviews were conducted with individuals living in Canada for <5 years. Participants were asked to discuss their pandemic experiences, and perceptions and acceptance of measures. Five themes were identified: (i) belief in the necessity and efficacy of countermeasures; (ii) negative impact of measures on health/wellbeing; (iii) existing barriers to newcomer settlement exacerbated by pandemic measures; (iv) countermeasure adherence related to immigration status and (v) past experiences shaping countermeasure acceptance. Government should continue to provide messaging regarding the importance of measures for individual and population heath and continue to demonstrate a commitment to the interests of citizens. Importantly, newcomer trust in government should not be taken for granted, as this trust is critical for the acceptance of government interventions now and moving forward. It will be important to ensure that newcomers are given support to overcome challenges to settlement that were intensified during the pandemic., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The COVID-19 pandemic highlighted and exacerbated inequities in health for structurally marginalised Canadians. Their location on society's hierarchies constrained their ability to access healthcare and follow recommended health behaviours. The aim of this article is to identify, from the perspective of marginalised populations, factors influencing the acceptance or rejection of COVID-19 countermeasures by structurally marginalised Canadians. Interviews were conducted with Canadians 18 + who identified as Black (n = 8), First Nations, Métis, or Inuit (n = 7) and low-income (<40,000 annual household income) (n = 8) between August and December 2021. Measures were said to impact well-being and interfere with revenue generating activities. Longstanding unfavourable living and environmental conditions as they relate to structural marginalisation was said to fuel anger toward the government and lead to a greater reluctance to accept countermeasures. Participants described concerns about government decisions being made without considering their unique contexts, or knowledge of the experiences of the population for whom these decisions were being made. Effective proactive action from government is important to foster trust with marginalised populations to support acceptance of health information and address growing inequities. Action that demonstrates government competence and commitment to the interests of marginalised populations is critical.

Chronotype is the attitude of subjects to carry out their daily activities mainly in the morning ("lark") or in the evening ("owl"). The intermediate chronotype is located between these two categories. It has been demonstrated that chronotype can influence the incidence, course and response to treatments of tumors. In particular patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and evening chronotype are characterized by unhealthy lifestyle, obesity, metabolic syndrome, a worsen cardiometabolic profile, a poor prognosis with a progressive disease and the development of metastasis. In addition, evening chronotype has been associated with sleep disturbances, which in turn have been related to tumor development and progression of tumors. There is a strict connection between sleep disturbances and NENs because of the hyperactivation of proangiogenic factors that caused aberrant neoangiogenesis. A nutritional tailored approach could represent a tool to align subjects with evening chronotype to physiological biological rhythms based on the properties of some macro and micronutrients of being substrate for melatonin synthesis. Thus, we aimed to provide an overview on the association of chronotype categories and sleep disturbances with NENs and to provide nutritional advices to manage subjects with NENs and these disturbances of circadian rhythm.

In recent years, location-based real-time dating apps like Grindr and Tinder have assumed an increasingly pivotal role in brokering socio-sexual relations between men seeking men and have proven to be fertile ground for the study of identity negotiation and impression management. However, current research has given insufficient consideration to how various contextual elements of technology use interact with one another to shape self-presentation behaviour. Through analysis of interview data, we found impression construction on these apps reflects tensions between authentic depiction of the self-concept and self-enhancement via deception. Whether and the extent to which one engages in deception depends on how a number of technological affordances, platform-specific community norms and userbase characteristics interact with each other. Self-presentational choices were a result of a combination of deception facilitators, for example, belief in the normalcy of lying, and constraining determinants, for example, the expectation of brokering physical connection. Impression construction determinants also interact in ways where the influence of any one element is dependent on others. This was most plainly evidenced in the interactions between stigma management concerns, the affordances of audience visibility/control and locatability and common ground reinforcing social hierarchy., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2022.)

Psoriasis is a skin disorder which mostly affects adults, beginning in childhood in almost one-third of patients. In adults it is associated with increased risk for cardiovascular diseases (CVD), while this association is still debated at younger age. Our aim was to evaluate the association between psoriasis and metabolic markers and cardiovascular findings in this age group. Twenty consecutive patients previously diagnosed with psoriasis (group A) were enrolled and compared with healthy non- psoriatic age- and sex-matched subjects (group B). The severity of the disease, CV risk factors, including anthropometric data with adiposity and its distribution, blood pressure (BP), laboratory metabolic tests, echocardiography and vascular ultrasound (transcranial echo-Doppler and carotid artery echo-Doppler with carotid intima-media thickness, cIMT) were performed for each subject. Personal history for CV risk, BP, anthropometric data were similar between the two groups, while familiar history for psoriasis was more frequent in group A (p < 0.02). C-IMT was significantly higher in group A compared to B (right, p = 0.001; left, p = 0.002). In addition, c-IMT was positively correlated with disease duration, triglycerides and triglycerides/glucose. Cerebral flow velocities, cardiac measurements, systo-diastolic function, ventricle geometry and mass were normal and comparable between the two groups, and did not correlate with CV risk factors. In childhood psoriasis c-IMT could represent a marker of pre-clinical cardiovascular involvement and contribute to start a personalized management, while cardiac findings seem to be normal in the early stage of disease. Longitudinal studies can clarify the progression of CV involvement in paediatric-onset psoriasis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are pediatric diseases characterized by systemic inflammation and vascular injury, potentially leading to coronary artery lesions (CALs). Data on vascular injury occurring during acute COVID-19 (AC19) in children are still lacking. The aim of our study was to investigate endothelial injury in KD-, MIS-C- and AC19-dosing circulating endothelial cells (CECs)., Methods: We conducted a multicenter prospective study. CECs were enumerated by CellSearch technology through the immunomagnetic capture of CD146-positive cells from whole blood., Results: We enrolled 9 KD, 20 MIS-C and 10 AC19. During the acute stage, the AC19 and KD patients had higher CECs levels than the MIS-C patients. From the acute to subacute phase, a significant CEC increase was observed in the KD patients, while a mild decrease was detected in the MIS-C patients. Cellular clusters/syncytia were more common in the KD patients. No correlation between CECs and CALs were found in the MIS-C patients. The incidence of CALs in the KD group was too low to investigate this correlation., Conclusions: Our study suggests a possible role of CECs as biomarkers of systemic inflammation and endothelial dysfunction in KD and MIS-C and different mechanisms of vascular injury in these diseases. Further larger studies are needed.

Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the most frequent vasculitis in childhood. For both, a multifactorial mechanism has been hypothesised, with an abnormal immune response in genetically predisposed children. Gut microbiota (GM) alterations might trigger the hyperimmune reaction. Our aim was to explore the GM in KD and compare it with the GM of HSP and febrile children. Children diagnosed with KD, HSP and non-KD febrile illness (F) were enrolled. GM was profiled by 16S rRNA gene sequencing and compared with the profiles of healthy children from previous studies. We enrolled 13 KD, 10 HSP and 12 F children. Their GM significantly differed from controls, with an overall reduction in the relative abundance of beneficial taxa belonging to the Ruminococcaceae and Lachnospiraceae families. Potential KD and HSP signatures were identified, including smaller amounts of Dialister in the former, and Clostridium and Akkermansia in the latter. Notably, the GM structures of KD, HSP and F patients stratified by abdominal involvement, with more severe dysbiosis in those suffering from intestinal symptoms. This is the first study analysing GM in a mostly Caucasian cohort of KD and HSP children. Our data could open up new opportunities for childhood vasculitis treatment.

Kawasaki Disease (KD) is systemic vasculitis involving medium-sized vessels in children. The aim of our study is to determine if fecal calprotectin (FC) could be useful in predicting the development or persistence of coronary artery lesions (CALs) in KD. We conducted a prospective monocentric study including all consecutive diagnoses of. Clinical, laboratory, echocardiographic data were recorded during the acute and subacute phase, including FC. Correlations among laboratory values, FC, clinical manifestations, IVIG-responsiveness and CALs development were investigated. We enrolled 26 children (76.9% boys; median age 34.5 months). The combination of FC > 250 microg/g and z-score > 2 during the acute phase was associated with the persistence of CALs (p = 0.022). A z-score > 2 alone during the acute phase was not related to CALs during the subacute stage (p > 0.05). A neutrophil percentage > 70% and WBC > 15,000/mmc during the acute phase significantly correlated with the presence of CALs during the subacute phase (p = 0.008). C-reactive protein (CRP) > 13 mg/dL at KD onset was significantly associated with the presence of CALs during the acute (p = 0.017) and subacute phase (p = 0.001). The combination of FC > 250 microg/g and a z-score > 2 during the acute phase of KD may be used as a predictor of CALs persistence. It can be useful especially in children with an initial CRP < 13 mg/dl., (© 2022. The Author(s).)

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.