Nasal IL-13 production identifies patients with late-phase allergic responses.

BACKGROUND: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the "late allergic response," which occurs in approximately 40% to 50% of patients with allergy. OBJECTIVE: We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response. METHODS: In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days. On days 1 and 3, nasal secretions were collected at selected time points over a 24-hour time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS: Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and the soluble IL-33 receptor serum stimulation 2 (sST2) in nasal secretions within minutes compared with the placebo group. Eight of 20 provoked participants displayed high IL-13 levels 2 to 8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction, which significantly differed from IL-13 nonresponders after 6 hours. CONCLUSIONS: IL-13 response status correlates with clinical responses and type 2 cytokine responses in the late phase after allergen provocation.

Moralistic gods, supernatural punishment and the expansion of human sociality.

Since the origins of agriculture, the scale of human cooperation and societal complexity has dramatically expanded. This fact challenges standard evolutionary explanations of prosociality because well-studied mechanisms of cooperation based on genetic relatedness, reciprocity and partner choice falter as people increasingly engage in fleeting transactions with genetically unrelated strangers in large anonymous groups. To explain this rapid expansion of prosociality, researchers have proposed several mechanisms. Here we focus on one key hypothesis: cognitive representations of gods as increasingly knowledgeable and punitive, and who sanction violators of interpersonal social norms, foster and sustain the expansion of cooperation, trust and fairness towards co-religionist strangers. We tested this hypothesis using extensive ethnographic interviews and two behavioural games designed to measure impartial rule-following among people (n = 591, observations = 35,400) from eight diverse communities from around the world: (1) inland Tanna, Vanuatu; (2) coastal Tanna, Vanuatu; (3) Yasawa, Fiji; (4) Lovu, Fiji; (5) Pesqueiro, Brazil; (6) Pointe aux Piments, Mauritius; (7) the Tyva Republic (Siberia), Russia; and (8) Hadzaland, Tanzania. Participants reported adherence to a wide array of world religious traditions including Christianity, Hinduism and Buddhism, as well as notably diverse local traditions, including animism and ancestor worship. Holding a range of relevant variables constant, the higher participants rated their moralistic gods as punitive and knowledgeable about human thoughts and actions, the more coins they allocated to geographically distant co-religionist strangers relative to both themselves and local co-religionists. Our results support the hypothesis that beliefs in moralistic, punitive and knowing gods increase impartial behaviour towards distant co-religionists, and therefore can contribute to the expansion of prosociality.

Use of a buprenorphine-based pain management protocol is associated with reduced opioid requirements and pain on swallowing in oral mucositis: a retrospective cohort study.

OBJECTIVE: The aim of this study is to ascertain the analgesic efficacy and total oral morphine equivalent daily dose (OMEDD) effect of a buprenorphine-based analgesic protocol in the treatment of severe Oral Mucositis (OM). DESIGN: This is a retrospective cohort study. SETTING: This study was done in a single Quaternary Referral Centre, Haematology Unit. SUBJECTS: Fifty-four stem cell transplant patients suffering at least grade 3 oral mucositis (OM), 24 prior to [Pr-I] and 30 subsequent to [Po-I] a buprenorphine-based OM analgesic protocol. METHODS: We analysed data from the above subjects with the primary outcome measure of difference in total OMEDDs from all opioid types and administration routes, and secondary outcome measures of area under the curve (AUC) of 11-point Numerical Rating Scale (NRS-11) pain assessments, sedation scores and respiratory rate. RESULTS: Post-protocol patients' total OMEDD requirements were significantly reduced [Pr-I: 1961 (1365)mg; Po-I: 928 (625)mg, p = 0.02], as were total NRS-11:hours AUC on swallowing [Pr-I: 54(24) score-hours; Po-I: 41(18) score-hours, p < 0.001]. There were no significant differences in objective measures of OM severity between groups (Number of Grade 3 or 4 OM severity assessments [mean (SD)] Pr-I: 5 (6.2); Po-I: 7 (5.1) or number of days Neutrophil count 0.0 or 0.1 × 109/L; Pr-I: 13 (5.4); Po-I: 15 (4.7)). 5 Pr-I and 4 Po-I patients required ketamine infusions, with 1 Pr-I patient also requiring IV lignocaine. CONCLUSIONS: Use of Buprenorphine via transdermal, sublingual and intravenous Patient Controlled Analgesia (PCA) delivery as part of an analgesic protocol for severe post stem cell transplant oral mucositis in adult patients appears to significantly reduce opioid requirements and pain on swallowing. Further randomised prospective work is required to confirm these associations.

Sputum biomarkers during acute severe asthma attacks in children-a case-control study.

AIM: To study sputum mediator profiles pattern in children with acute severe asthma, compared with stable asthma and healthy controls. The mechanisms of acute severe asthma attacks, such as biomarkers cascades and immunological responses, are poorly understood. METHODS: We conducted a prospective observational case-control study of children aged 5 to 17 years, who presented to hospital with an asthma attack. Children with stable asthma were recruited during outpatient asthma clinic visits. Control children without an asthma diagnosis were recruited from surgical wards. Sputum mediator profiles were measured, and sputum leukocyte differential cell counts were generated. RESULTS: Sputum data were available in 48 children (acute asthma; n = 18, stable asthma; n = 17, healthy controls; n = 13). Acute-phase biomarkers and neutrophil attractants such as IL-6 and its receptor, IL-8 and cytokines linked with bacterial signals, including TNF-R1 and TNF-R2, were elevated in asthma attacks versus stable asthma and healthy controls. T-cell attractant cytokines, associated with viral infections, such as CCL-5, CXCL-10 and CXCL-11, and CXCL-9 (secreted from eosinophils after a viral trigger) were also raised. CONCLUSION: Mediator profiles consistent with bacterial and viral respiratory infections, and T2 inflammation markers co-exist in the sputum of children with acute severe asthma attacks.

Sputum microbiomic clustering in asthma and chronic obstructive pulmonary disease reveals a Haemophilus-predominant subgroup.

BACKGROUND: Airway ecology is altered in asthma and chronic obstructive pulmonary disease (COPD). Anti-microbial interventions might have benefit in subgroups of airway disease. Differences in sputum microbial profiles at acute exacerbation of airways disease are reflected by the γProteobacteria:Firmicutes (γP:F) ratio. We hypothesized that sputum microbiomic clusters exist in stable airways disease, which can be differentiated by the sputum γP:F ratio. METHODS: Sputum samples were collected from 63 subjects with severe asthma and 78 subjects with moderate-to-severe COPD in a prospective single centre trial. Microbial profiles were obtained through 16S rRNA gene sequencing. Topological data analysis was used to visualize the data set and cluster analysis performed at genus level. Clinical characteristics and sputum inflammatory mediators were compared across the clusters. RESULTS: Two ecological clusters were identified across the combined airways disease population. The smaller cluster was predominantly COPD and was characterized by dominance of Haemophilus at genus level (n = 20), high γP:F ratio, increased H influenzae, low diversity measures and increased pro-inflammatory mediators when compared to the larger Haemophilus-low cluster (n = 121), in which Streptococcus demonstrated the highest relative abundance at the genus level. Similar clusters were identified within disease groups individually and the γP:F ratio consistently differentiated between clusters. CONCLUSION: Cluster analysis by airway ecology of asthma and COPD in stable state identified two subgroups differentiated according to dominance of Haemophilus. The γP:F ratio was able to distinguish the Haemophilus-high versus Haemophilus-low subgroups, whether the Haemophilus-high group might benefit from treatment strategies to modulate the airway ecology warrants further investigation.

Nurse-initiated pre-prescribed antibiotic orders to facilitate prompt and appropriate antibiotic administration in febrile neutropenia.

PURPOSE: To assess the impact of a pathway allowing nurse initiation of first dose intravenous (IV) antibiotics on time to antibiotic administration (TTA) in adult inpatients with febrile neutropenia (FN). METHODS: This study evaluated the impact on TTA of a clinical pathway (November 2017 to April 2018) allowing nurse initiation of pre-prescribed antibiotics in adult haematology patients with FN, compared with a prior cohort (November 2016 to April 2017) in which antibiotics were only prescribed and administered after medical review. The primary endpoint for comparison was TTA, calculated as the time between the first recorded fever and IV antibiotic administration. Secondary endpoints included appropriateness of initial antibiotic choice, 30-day all-cause mortality and admission to intensive care unit (ICU). RESULTS: Forty-seven eligible FN episodes in 40 patients and 61 episodes in 52 patients were evaluated in the pre- and post-implementation groups, respectively. Baseline characteristics were comparable between groups. Median (IQR) TTA, in the pre-implementation group [66 min (40-100 min)] was significantly prolonged versus post-implementation group [29 min (20-41 min); p < 0.001]. A significantly higher proportion of episodes were administered appropriate initial antibiotics in the post-versus pre-implementation groups (100% vs. 89%, p = 0.03). There was no significant change in 30-day all-cause mortality (0% vs. 5%, p = 0.3) or ICU admission within 48 h of fever (0% vs. 2%, p > 0.99) between pre- and post-implementation groups, respectively. CONCLUSIONS: A pathway allowing nurse initiation of pre-prescribed antibiotic orders for FN significantly reduced TTA from first recorded fever and increased the proportion of appropriate initial antibiotic choices without significantly impacting on patient outcomes.

Circadian Clock, Time-Restricted Feeding and Reproduction.

The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

Moralizing gods, impartiality and religious parochialism across 15 societies.

The emergence of large-scale cooperation during the Holocene remains a central problem in the evolutionary literature. One hypothesis points to culturally evolved beliefs in punishing, interventionist gods that facilitate the extension of cooperative behaviour toward geographically distant co-religionists. Furthermore, another hypothesis points to such mechanisms being constrained to the religious ingroup, possibly at the expense of religious outgroups. To test these hypotheses, we administered two behavioural experiments and a set of interviews to a sample of 2228 participants from 15 diverse populations. These populations included foragers, pastoralists, horticulturalists, and wage labourers, practicing Buddhism, Christianity, and Hinduism, but also forms of animism and ancestor worship. Using the Random Allocation Game (RAG) and the Dictator Game (DG) in which individuals allocated money between themselves, local and geographically distant co-religionists, and religious outgroups, we found that higher ratings of gods as monitoring and punishing predicted decreased local favouritism (RAGs) and increased resource-sharing with distant co-religionists (DGs). The effects of punishing and monitoring gods on outgroup allocations revealed between-site variability, suggesting that in the absence of intergroup hostility, moralizing gods may be implicated in cooperative behaviour toward outgroups. These results provide support for the hypothesis that beliefs in monitoring and punitive gods help expand the circle of sustainable social interaction, and open questions about the treatment of religious outgroups.

Perceptions of patient participation in symptom management: A qualitative study with cancer patients, doctors, and nurses.

AIM: To explore people with cancer, doctors', and nurses' understanding of and attitudes toward, patient participation in symptom management. BACKGROUND: In health service policies worldwide, patients are recognized as the important members of the treatment care team. The concept of patient participation can be understood from a variety of perspectives, reflecting the limited conceptual clarity and poor congruence between patients' and clinicians' understanding. DESIGN: A qualitative study conducted using individual interviews. METHODS: Forty one people with cancer, five doctors, and seven nurses were recruited from two oncological medical units of a cancer specialized hospital in Shanghai, China between November 2013 - March 2014. Individual interviews were semi-structured. Data were analysed through framework analysis. RESULTS: Patient participation was perceived as a mutual interaction requiring contribution from both patients and clinicians. Three main themes were uncovered: (a) information exchange is the key to patient participation; (b) negotiated decision-making can be achieved in various ways; and (c) patients' self-management can be a form of patient participation. Patient participation was recognized by both patients and clinicians as an important component of cancer care, however concerns relating to patients' limited knowledge and their ability to negotiate treatment decisions existed among most of the patients, doctors, and nurses. CONCLUSION: This study identified the wide range of activities where patient participation can occur in the context of cancer care. Positive recognition of patients' roles in treatment and care should be advocated among both patients and clinicians to facilitate patients' participation in their own care and enhance clinicians' skills in involving patients.

Interpersonal movement synchrony facilitates pro-social behavior in children's peer-play.

The emergence of pro-social behaviors and social interaction skills is a major focus of research on children's development. Here, we consider one important feature of human social interactions, interpersonal movement synchrony, and explore its effects on pro-sociality among young children. Coordinated movements are a crucial part of mother-infant interactions, with important social effects extending well into childhood. Musical interactions are also known to facilitate bonding between infants and caretakers and pro-sociality among peers. We specifically examine the pro-social effects of interpersonal movement synchrony in a naturalistic peer-play context among 4- to 6-year-old children. We assessed the amount of helping behavior between pairs of children following an activity that they performed synchronously or non-synchronously. Children who engaged in synchronous play, as compared with non-synchronous play, showed significantly more subsequent spontaneous helping behavior. Further, more mutual smiling and eye contact were observed in the synchronous condition and amounts of mutual smiling and eye contact during the movement task correlated with amount of helping behavior observed. Neither measure mediated the condition-wise effects on helping, however. These results are discussed in terms of their contribution to existing literature and their broader implications for the development of pro-sociality and coordinated movements in early childhood.

Gendered styles of student-faculty interaction among college students.

Scholars have examined gender differences in many areas of college life, but we know little about how men and women may interact differently with faculty-an activity with strong links to student outcomes. Using data from the National Survey of Student Engagement, I investigate whether men and women demonstrate different styles of interaction with faculty. I find that women are more likely than men to engage frequently in instrumental interactions, such as emailing and discussing course logistics with faculty. In contrast, men are more likely than women to have frequent higher order interactions, such as discussing ideas and participating in research. These findings introduce a new typology of student-faculty interaction and contribute to our understanding of gendered pathways through higher education.

Synchrony and exertion during dance independently raise pain threshold and encourage social bonding.

Group dancing is a ubiquitous human activity that involves exertive synchronized movement to music. It is hypothesized to play a role in social bonding, potentially via the release of endorphins, which are analgesic and reward-inducing, and have been implicated in primate social bonding. We used a 2 × 2 experimental design to examine effects of exertion and synchrony on bonding. Both demonstrated significant independent positive effects on pain threshold (a proxy for endorphin activation) and in-group bonding. This suggests that dance which involves both exertive and synchronized movement may be an effective group bonding activity.

Rock with me: the role of movement synchrony in infants' social and nonsocial choices.

Matching the timing of one's movements to the movements of others has been proposed to increase affiliation and prosociality. Although coordinated movements facilitate early social interactions, not much is known about the mechanisms and effects of movement synchrony throughout development. Two studies investigated 12-month-olds' (Study 1, N = 40) and 9-month-olds' (Study 2, N = 41) preferences for synchronous others in a social as opposed to a nonsocial context. It was found that movement synchrony exclusively guides infants' social choices at 12 months. In contrast, 9-month-olds did not show any preferences for synchronous movements in social or nonsocial contexts. Results suggest that movement synchrony is important in guiding infants' social preferences and its effects emerge toward the end of the 1st year of life.

Interdependence, bonding and support are associated with improved mental wellbeing following an outdoor team challenge.

Social relationships and mental health are functionally integrated throughout the lifespan. Although recent laboratory-based research has begun to reveal psychological pathways linking social interaction, interdependence, bonding and wellbeing, more evidence is needed to integrate and understand the potential significance of these accounts for real-world events and interventions. In a questionnaire-based, repeated measures design, we measured the wellbeing of 13- to 19-year-old participants (n = 226) in the Ten Tors Challenge (United Kingdom) 7-10 days before (T1) and after (T4) the event. Immediately before (T2) and after (T3) the event, we administered measures of team bonding, perceived and experienced interdependence, perceived and received support, physical pain and fatigue, and performance satisfaction. There was a significant increase in participants' wellbeing (pre-to-post event). Post-event social bonding and performance satisfaction positively predicted the wellbeing increase. Bonding was, in turn, positively predicted by experienced interdependence, received support, pain and fatigue, and the sense of having done better as a team than expected. Results provide novel field-based evidence on the associations between meaningful bonds of mutual reliance in a challenging team event and adolescent wellbeing. Team challenge events potentially offer effective contexts for forging social interactions, interdependencies, and bonds that can support mental and physical health.

The Synchrony-Prosociality Link Cannot Be Explained Away as Expectancy Effect: Response to Atwood et al. ().

Moving in time to others, as is often observed in dance, music, sports and much of children's play cross-culturally, is thought to make people feel and act more prosocially towards each other. In a recent paper, Atwood et al. (2022) argued that the inferential validity of this link found between synchronous behaviour and prosociality might be mainly due to "expectancy effects generated by a combination of (1) experimenter expectancy, leading to experimenter bias; and (2) participant expectancy (i.e., placebo effects)". Here, we counter these arguments with (1) examples of studies devoid of experimenter expectancy effects that nevertheless demonstrate a positive link between synchrony and prosociality, and (2) insights from the developmental literature that address participant expectancy by showing how expectations formed through lived experiences of synchronous interactions do not necessarily threaten inferential validity. In conclusion, there is already sufficient good-quality evidence showing the positive effects of synchronous behaviours on prosociality beyond what can be explained by experimenter or participant expectation effects.

Gods are watching and so what? Moralistic supernatural punishment across 15 cultures.

Psychological and cultural evolutionary accounts of human sociality propose that beliefs in punitive and monitoring gods that care about moral norms facilitate cooperation. While there is some evidence to suggest that belief in supernatural punishment and monitoring generally induce cooperative behaviour, the effect of a deity's explicitly postulated moral concerns on cooperation remains unclear. Here, we report a pre-registered set of analyses to assess whether perceiving a locally relevant deity as moralistic predicts cooperative play in two permutations of two economic games using data from up to 15 diverse field sites. Across games, results suggest that gods' moral concerns do not play a direct, cross-culturally reliable role in motivating cooperative behaviour. The study contributes substantially to the current literature by testing a central hypothesis in the evolutionary and cognitive science of religion with a large and culturally diverse dataset using behavioural and ethnographically rich methods.

Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine.

Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.

Joining up action to address social determinants of health and health inequities in Canada.

Efforts are underway at the international, national, provincial/territorial, and local levels to address factors like income, education, and environment that influence the health of Canadians. Also known as the social determinants of health, these factors are closely linked to health equity. There are important Canadian innovations in research, practice, and policy that reflect our growing understanding of social determinants. However, concerted efforts are still required by health professionals to address social determinants of health through their work settings.

Finding the facts in an infodemic: framing effective COVID-19 messages to connect people to authoritative content.

The public's need for timely and trusted COVID-19 information remains high. Governments and global health agencies such as the WHO have sought to disseminate accurate and timely information to counteract misinformation and disinformation that has arisen as part of an 'infodemic'-the overabundance of information on COVID-19-some accurate and some not. In early 2020, WHO began a collaboration with Google to run online public service announcements on COVID-19, in the form of search ads displayed above results of Google Search queries. Web-based text ads can drive online searchers of COVID-19 information to authoritative COVID-19 content but determining what message is most effective is a challenge. WHO wanted to understand which message framing, that is, the way in which ad information is worded for the public, leads searchers to click through to WHO content. WHO tested 71 text ads in English across four COVID-19 topics using a mix of message frames: descriptive, collective, gain, loss, appeals to values and emphasising reasons. Between 11 September 2020 and 23 November 2020, there were 13 million views of the experimental WHO text ads leading to 1.4 million click-throughs to the WHO website. Within the set of 71 ads, there was a large spread between the most effective and least effective messages; for messages on COVID-19, the best performing framings were more than twice as effective as the worst performing framings (18.7% vs 8.5% engagement rate). Health practitioners can apply the messaging tactics WHO found to be successful to rapidly optimise messages for their own public health campaigns and better reach the public with authoritative information. Similar collaboration between big technology companies and governments and global health agencies has the potential to advance public health.