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Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Hydrochloric acid (HCl) was instilled in the trachea (pH 1.5, 2.5 mL/kg) of anesthetized, intubated supine rats. Animals were randomized ( n = 17 each group) to receive intraperitoneal imatinib or vehicle immediately prior to HCl. All rats then received mechanical ventilation. CT was performed hourly for 4 h. Images were quantitatively analyzed to assess the progression of radiological abnormalities. Injury severity was confirmed via hourly blood gases, serum biomarkers, bronchoalveolar lavage (BAL), and histopathology. Serial blood drug levels were measured in a subset of rats. Imatinib reduced mortality while delaying functional and radiological injury progression: out of 17 rats per condition, 2 control vs. 8 imatinib-treated rats survived until the end of the experiment ( P = 0.02). Imatinib attenuated edema after lung injury ( P < 0.05), and survival time in both groups was negatively correlated with increased lung mass ( R2 = 0.70) as well as other physiological and CT parameters. Capillary leak (BAL protein concentration) was significantly lower in the treated group ( P = 0.04). Peak drug concentration was reached after 70 min, and the drug half-life was 150 min. Imatinib decreased both mortality and lung injury severity in mechanically ventilated rats. Pharmacological inhibition of edema could be used during mechanical ventilation to improve the severity and outcome of lung injury.

Emergency department (ED) crowding poses a severe public health threat, and identifying acceptable means of treating medical conditions in alternative sites of care is imperative. We compared patients' experiences with in-home urgent care via mobile integrated health (MIH) vs urgent care provided in EDs.Survey, completed on paper, online, or by telephone. We surveyed all patients who received MIH care for an urgent health problem (n = 443) and consecutive patients who visited EDs for urgent care (n = 1436).Study participants were members of a managed care plan who were dually eligible for Medicare and Medicaid, 21 years or older, and treated either by MIH or in an ED for nonemergent conditions around Boston, Massachusetts, between February 2017 and June 2018. The survey assessed patients' perceptions of their urgent care experiences.A total of 206 patients treated by community paramedics and 718 patients treated in EDs completed surveys (estimated 66% and 62% response rates, respectively). Patients treated by MIH perceived higher-quality care, more frequently reporting "excellent" (54.7%) or "very good" (32.4%) care compared with ED patients (40.7% and 24.3%, respectively; P .0001), and were significantly more likely to report that decisions made about their care were "definitely right" compared with patients treated in the ED (66.1% vs 55.6%; P = .02).Patients appear satisfied with receiving paramedic-delivered urgent care in their homes rather than EDs, perceiving higher-quality care. This suggests that in-home urgent care via MIH may be acceptable for patients with nonemergent conditions.

A long-standing goal of nanomedicine is to improve a drug’s benefit by loading it into a nanocarrier that homes solely to a specific target cell and organ. Unfortunately, nanocarriers usually end up with only a small percentage of the injected dose (% ID) in the target organ, due largely to clearance by the liver and spleen. Further, cell-type-specific targeting is rarely achieved without reducing target organ accumulation. To solve these problems, we introduce DART (dual affinity to RBCs and target cells), in which nanocarriers are conjugated to two affinity ligands, one binding red blood cells, and one binding a target cell (here, pulmonary endothelial cells). DART nanocarriers first bind red blood cells, then transfer to the target organ’s endothelial cells as the bound red blood cells squeeze through capillaries. We show that within minutes after intravascular injection in mice, nearly 70 % ID of DART nanocarriers accumulate in the target organ (lungs), more than doubling the % ID ceiling achieved by a multitude of prior technologies, finally achieving a majority % ID in a target organ. Humanized DART nanocarriers in ex vivo perfused human lungs recapitulate this phenomenon. Furthermore, DART enhances the selectivity of delivery to target endothelial cells over local phagocytes within the target organ by 6-fold. DART’s marked improvement in both organ- and cell-type targeting may thus be helpful in localizing drugs for a multitude of medical applications.

Measuring the rate of religious non-affiliation is a difficult task in China, one of the least religious countries in the world, and elsewhere. This study evaluates the trend of religious non-affiliation in China using 22 surveys spanning three decades. We found that two surveys asking beliefs in a mix of gods and religions yielded dramatically lower estimates of non-affiliation compared to the others that measured affiliation explicitly. Among the latter, using a filter question (a yes/no question for religious affiliation) increased the reports of non-affiliation but allowing multiple choices and putting “no religion” toward the end of the lists of response options moderately decreased the reports of non-affiliation. After accounting for question design and demographic differences across the surveys, the decline in religious non-affiliation is reduced and becomes not significant during more recent years.

Selective drug delivery to injured regions of the brain is an elusive, but biomedically important, goal. It is tempting to co-opt migrating white blood cells (WBC) to carry drugs to the injured brain, using natural WBC tropism. Current approaches to load cargoes to WBC have limited utility, particularly in acute conditions, due to the need for time consuming ex vivo manipulation and loading of cells. Physiological, in vivo loading of WBC may be advantageous in this scenario. Here we devised such a strategy, capitalizing on the unique features of the direct blood exchange between brain and lungs. Mediators emanating from the injured brain directly travel to the pulmonary vasculature via venous flow. In response to these mediators, WBCs, transiently residing in the pulmonary microvascular lumen, disembark and flow with arterial blood to the brain microvasculature, where they adhere and transmigrate to the brain parenchyma via the local chemoattractant gradient. We posited that direct in vivo targeting of cargoes to the pulmonary WBC pool may provide drug transfer to brain via this natural mechanism. To test this, we intravenously injected agents targeted to intercellular adhesion molecule 1 (ICAM) in mice with acute brain inflammation caused by direct injection of tumor necrosis factor alpha (TNF-α). We found that: A) At 2 hours, >20% of ICAM/NP accumulated in lungs, predominantly in WBCs; B) At 6 and 22 hours, ICAM/NP pulmonary uptake markedly decreased; C) In contrast, ICAM/NP uptake in brain increased ~5-fold in this time interval, concomitantly with migration of WBCs to the brain. Cranial window fluorescent microscopy confirmed WBC transport of ICAM/NP to the brain in TNF-α-challenged mice beyond the BBB. Importantly, demonstrating the pharmacologic relevance of this strategy, dexamethasone-loaded ICAM/liposomes abrogated brain edema in this model. In sum, coopting the natural homing of WBC from the lungs via ICAM-targeting to injured brain is an attractive strategy for precise interventions for treatment of acute brain injuries.VISUAL ABSTRACT

Complement opsonization is among the biggest challenges facing nanomedicine. Nearly instantly after injection into blood, nanoparticles are opsonized by the complement protein C3, leading to clearance by phagocytes, fouling of targeting moieties, and release of anaphylatoxins. While surface polymers such as poly(ethylene glycol) (PEG) partially decrease complement opsonization, most nanoparticles still suffer from extensive complement opsonization, especially when linked to targeting moieties. To ameliorate the deleterious effects of complement, two of mammals' natural regulators of complement activation (RCAs), Factors H and I, are here conjugated to the surface of nanoparticles. In vitro, Factor H or I conjugation to PEG-coated nanoparticles decrease their C3 opsonization, and markedly reduce nanoparticle uptake by phagocytes. In an in vivo mouse model of sepsis-induced lung injury, Factor I conjugation abrogates nanoparticle uptake by intravascular phagocytes in the lungs, allowing the blood concentration of the nanoparticle to remain elevated much longer. For nanoparticles targeted to the lung's endothelium by conjugation to anti-ICAM antibodies, Factor I conjugation shifts the cell-type distribution away from phagocytes and toward endothelial cells. Finally, Factor I conjugation abrogates the severe anaphylactoid responses common to many nanoparticles, preventing systemic capillary leak and preserving blood flow to visceral organs and the brain. Thus, conjugation of RCAs, like Factor I, to nanoparticles is likely to help in nanomedicine's long battle against complement, improving several key parameters critical for clinical success.

This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.

Resting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen in rsfMRI. Most of the variance shared between sites lies in the infraslow frequency band (0.01–0.1 Hz) and in the infraslow envelope of higher-frequency bands (e.g. gamma LFP). While gamma LFP and infraslow LFP are both strong correlates of local oxygen, infraslow LFP explains significantly more of the variance shared between correlated oxygen signals than any other electrophysiological signal. Together these findings are consistent with a causal relationship between infraslow LFP and long-range oxygen correlations in the resting state.

Background: Concerns for youth sports in the United States often focus on early sport specialization, overemphasis on competition, injuries, and burnout. Little research has addressed relationships among the preceding and other concerns, including time away from organized sport, sleep, and perceptions of physical and psychological well-being. Hypothesis: There is an association between reported competitive gameplay volume and specialization, injury, and fatigue among elite youth basketball players. Study Design: Cross-sectional study; convenience sample. Level of Evidence: Level 4. Methods: An anonymous questionnaire was administered to a convenience sample of youth basketball players between 13 and 18 years of age from across the United States. Participants were queried about multiple factors, including the extent of their participation in organized basketball and other sports, time away from organized basketball, injury, sleep, and feelings of exhaustion related to basketball participation. Results: A total of 772 participants (145 girls, 627 boys) completed a survey. All participants played for a select or elite club basketball team and/or a high school basketball team. Overall, 49% played more than 50 games within the past year. A total of 73% were specialized in basketball, 58% prior to age 14 years, and 35% prior to age 11 years. In all, 70% reported less than 1 month away from organized basketball within the past year, and 28% reported no time away. A total of 54% reported sleeping less than the recommended 8 hours each night during the school year. Within the prior year, 55% reported feeling physically exhausted and 45% reported feeling mentally exhausted from basketball. Regression analysis did not find any significant relationships between early specialization prior to age 14 years and basketball-related injury or feelings of mental or physical exhaustion. Conclusion: In this select group of youth basketball players, the majority specialized in basketball prior to age 14 years and reported a large number of competitive events with little time away from organized basketball. Clinical Relevance: The results from a sample of highly competitive youth basketball players indicate issues that warrant further attention and research regarding the potential impact of specialization, frequent competitions, lack of time away from organized sport, and perceptions of well-being in young athletes.

Introduction Wearable biosensors have the potential to monitor physiological change associated with opioid overdose among people who use drugs. Methods We enrolled 16 individuals who reported ≥4 daily opioid use events within the previous 30 day. Each was assigned a wearable biosensor that measured respiratory rate (RR) and actigraphy every 15 seconds for 5 days and also completed a daily interview assessing drug use. We describe the volume of RR data collected, how it varied by participant characteristics and drug use over time using repeated measures one-way ANOVA, episodes of acute respiratory depression (≤5 breaths/minute), and self-reported overdose experiences. Results We captured 1626.4 hours of RR data, an average of 21.7 daily hours/participant over follow-up. Individuals with longer injection careers and those engaging in polydrug use captured significantly fewer total hours of respiratory data over follow-up compared to those with shorter injections careers (94.7 vs. 119.9 hours, p = 0.04) and injecting fentanyl exclusively (98.7 vs. 119.5 hours, p = 0.008), respectively. There were 385 drug use events reported over follow-up. There were no episodes of acute respiratory depression which corresponded with participant reports of overdose experiences. Discussion Our preliminary findings suggest that using a wearable biosensor to monitor physiological changes associated with opioid use was feasible. However, more sensitive biosensors that facilitate triangulation of multiple physiological data points and larger studies of longer duration are needed.

Drug delivery research pursues many types of carriers including proteins and other macromolecules, natural and synthetic polymeric structures, nanocarriers of diverse compositions and cells. In particular, liposomes and lipid nanoparticles represent arguably the most advanced and popular human-made nanocarriers, already in multiple clinical applications. On the other hand, red blood cells (RBCs) represent attractive natural carriers for the vascular route, featuring at least two distinct compartments for loading pharmacological cargoes, namely inner space enclosed by the plasma membrane and the outer surface of this membrane. Historically, studies of liposomal drug delivery systems (DDS) astronomically outnumbered and surpassed the RBC-based DDS. Nevertheless, these two types of carriers have different profile of advantages and disadvantages. Recent studies showed that RBC-based drug carriers indeed may feature unique pharmacokinetic and biodistribution characteristics favorably changing benefit/risk ratio of some cargo agents. Furthermore, RBC carriage cardinally alters behavior and effect of nanocarriers in the bloodstream, so called RBC hitchhiking (RBC-HH). This article represents an attempt for the comparative analysis of liposomal vs RBC drug delivery, culminating with design of hybrid DDSs enabling mutual collaborative advantages such as RBC-HH and camouflaging nanoparticles by RBC membrane. Finally, we discuss the key current challenges faced by these and other RBC-based DDSs including the issue of potential unintended and adverse effect and contingency measures to ameliorate this and other concerns.

Graphical abstract Targeted drug delivery and nanomedicine hold the potential promise of delivering drugs solely to target organs or cell types, thus decreasing off-target side effects and improving efficacy. However, nano-scale drug carriers face several barriers to this goal, with one of the most formidable being the complement cascade. Complement proteins, especially C3, opsonize not just the microbes they evolved to contain, but also nanocarriers. This results in multiple problems, including marking the nanocarriers for clearance by leukocytes, likely fouling of the targeting moieties on nanocarriers, and release of toxins which produce deleterious local and systemic effects. Here, we review how complement achieves its blockade of nanomedicine, which nanocarrier materials properties best avoid complement, and current and future strategies to control complement to unleash nanomedicine’s potential.

Data on the psychosocial implications of sport specialization in pediatric athletes are lacking. Sport specialization often requires increased training hours and may predispose young athletes to social isolation, poor academic performance, increased anxiety, greater stress, inadequate sleep, decreased family time, and burnout. Sport specialization frequently introduces multiple stressors that could be expected to adversely affect mental health and function in young athletes and may increase the risk for burnout. This may be confounded by altered sleep duration and quality, increased drive for elite status, and perfectionistic personality types. The signs and symptoms of burnout in young athletes can be difficult to detect. It is important to be aware of the possible diagnosis of burnout in young athletes who display vague symptoms and a decrease in academic performance. The purpose of this review was to survey the available literature on sport specialization in young athletes and its association with mental health, sleep, the drive for success in sport, and burnout.

A strong relationship between creativity and major depression has been attested to in many past studies. These suggest a correlation between high creative propensity and the prevalence of depressio...

New advances in intra-arterial (IA) catheters offer clinically proven local interventions in the brain. Here we tested the effect of combining local IA delivery and vascular immunotargeting. Microinjection of tumor necrosis factor alpha (TNFα) in the brain parenchyma causes cerebral overexpression of Inter-Cellular Adhesion Molecule-1 (ICAM-1) in mice. Systemic intravenous injection of ICAM-1 antibody (anti-ICAM-1) and anti-ICAM-1/liposomes provided nearly an order of magnitude higher uptake in the inflamed vs normal brain (from ~0.1 to 0.8%ID/g for liposomes). Local injection of anti-ICAM-1 and anti-ICAM-1/liposomes via carotid artery catheter provided an additional respective 2-fold and 5-fold elevation of uptake in the inflamed brain vs levels attained by IV injection. The uptake in the inflamed brain of respective untargeted IgG counterparts was markedly lower (e.g., uptake of anti-ICAM-1/liposomes was 100-fold higher vs IgG/liposomes). These data affirm the specificity of the combined effect of the first pass and immunotargeting. Intravital real-time microscopy via cranial window revealed that anti-ICAM-1/liposomes, but not IgG/liposomes bind to the lumen of blood vessels in the inflamed brain within minutes after injection. This straightforward framework provides the basis for translational efforts towards local vascular drug targeting to the brain.

Background The incidence of opioid-related overdose deaths has been rising for 30 years and has been further exacerbated amidst the COVID-19 pandemic. Naloxone can reverse opioid overdose, lower death rates, and enable a transition to medication for opioid use disorder. Though current formulations for community use of naloxone have been shown to be safe and effective public health interventions, they rely on bystander presence. We sought to understand the preferences and minimum necessary conditions for wearing a device capable of sensing and reversing opioid overdose among people who regularly use opioids. Methods We conducted a combined cross-sectional survey and semi-structured interview at a respite center, shelter, and syringe exchange drop-in program in Philadelphia, Pennsylvania, USA, during the COVID-19 pandemic in August and September 2020. The primary aim was to explore the proportion of participants who would use a wearable device to detect and reverse overdose. Preferences regarding designs and functionalities were collected via a questionnaire with items having Likert-based response options and a semi-structured interview intended to elicit feedback on prototype designs. Independent variables included demographics, opioid use habits, and previous experience with overdose. Results A total of 97 adults with an opioid use history of at least 3 months were interviewed. A majority of survey participants (76%) reported a willingness to use a device capable of detecting an overdose and automatically administering a reversal agent upon initial survey. When reflecting on the prototype, most respondents (75.5%) reported that they would wear the device always or most of the time. Respondents indicated discreetness and comfort as important factors that increased their chance of uptake. Respondents suggested that people experiencing homelessness and those with low tolerance for opioids would be in greatest need of the device. Conclusions The majority of people sampled with a history of opioid use in an urban setting were interested in having access to a device capable of detecting and reversing an opioid overdose. Participants emphasized privacy and comfort as the most important factors influencing their willingness to use such a device. Trial registration NCT04530591.

The coronavirus disease (COVID-19) pandemic has created significant stressors for the academic and scientific community, with unique challenges for early-career physician-scientists. The pandemic-related disruptions have significantly affected research productivity, access to mentoring, professional development and networking opportunities, funding, and personal wellness. This is especially true for pulmonary and critical care medicine faculty because of the burden of specialized clinical care responsibilities that the COVID-19 pandemic has demanded. Departmental, institutional, and national leadership should foster open dialogue to identify and mitigate these challenges to promote ongoing career development of early-career physician-scientists. Implementation of thoughtful interventions to address these challenges will provide essential support for junior faculty and help retain a generation of physician-scientists.

After acute ischemic stroke, the cerebral vasculature is known to become more permeable to circulating leukocytes (WBC). Several laboratories attempted to use this for co-opting WBC do deliver into the central nervous system drugs and nanoparticle (NP) loaded into WBC ex vivo or in the peritoneal cavity. In theory, intravascular loading WBC may provide an interesting alternative. We hypothesize: i) direct in vivo targeting of WBC accessible to NP in the bloodstream (mainly pulmonary intravascular monocytes and marginated neutrophils in lungs), followed by carrier WBC migration to the brain will allow NP delivery to the brain and, ii) that targeted NP against WBC would be a relevant in treatment of acute brain inflammation. In fact, intravenous injection of ICAM-targeted NP 2h after the injection of tumor necrosis factor (TNF) in the brain initially showed a low uptake of the carrier in the brain that increased with time, as shown by radiotracing (5 times increase) and intravital microscopy of the brain. However, ICAM targeted NP were rapidly accumulated in the lungs and declined with time. Complete blood counts and flow cytometry revealed: i) an increase in circulating WBC counts following injury, ii) >60% of the ICAM-targeted NP were uptaken by WBC in the lungs, iii) ICAM targeted NP were almost exclusively in WBC in the brain (>98%; panel A shows the cellular distribution). Finally, we observed that the anti-inflammatory drug dexamethasone reduces brain edema only when encapsulated in ICAM-targeted nanoparticles (panel B). In conclusion, ICAM targeted NP: i) can be taken up by WBC, ii) migrate to the inflamed brain and iii) can reduce brain edema when encapsulating dexamethasone.

Targeted drug delivery is an attractive strategy for treatment of life-threatening inflammatory brain pathologies such as ischemic stroke. In these conditions, adhesion molecule expression (e.g. vascular cellular adhesion molecule-1, VCAM) is upregulated on endothelium. Hence, VCAM represents a relevant target for selective drug delivery. We have utilized αVCAM monoclonal antibodies to target therapeutic proteins and nanocarriers (liposomes and lipid nanoparticles, LNPs) to the pathologically-altered vasculature.To assess tissue biodistribution and therapeutic effects of VCAM-targeted agents, we used 2 mouse models: 1) acute inflammation induced by intra-striatal injection of tumor necrosis factor-α (TNF), and 2) ischemic stroke induced by transient middle cerebral artery occlusion (tMCAO). Biodistribution was assayed by measuring radioactivity in blood and organs 30 minutes after injection. Efficacy was determined by tracing radiolabeled albumin extravasation to assess edema.The results showed that VCAM targeting was increased by TNF injection, and that targeting to VCAM enhanced the cerebral accumulation of αVCAM conjugated thrombomodulin (TM) and nanocarriers by orders of magnitude (Fig A). It is noteworthy that αVCAM-TM and free αVCAM antibody had similar levels of brain uptake. Our data also demonstrated the protective effect of αVCAM-liposome loaded with dexamethasone on brain edema (Fig B), indicating the therapeutic potential of VCAM-targeting drug delivery strategies. Further, the results in tMCAO model recapitulated our findings in the TNF model that targeting to VCAM significantly improves delivery to the ischemic brain (Fig C). In summary, we have shown that targeting VCAM permits delivery of a diverse array of therapeutics to the inflamed vasculature in conditions such as ischemic stroke. Future work will focus on evaluating the therapeutic properties of VCAM-targeted drug delivery strategies.

How do parents pass on who they are—their beliefs and values, norms and habits, and the social groups with which they identify—to their children? This complex process, called socialization, is a route by which parents, family members, friends, and others in the family’s community influence children’s identity development, including the development of their religious identities. This research novelly integrates socialization processes into identity theory, illustrating intergenerational transmission of identity, using the religious identity as an example. The study uses a clustered sample of resident mothers, fathers, and their adolescent children to investigate the connections between parents’ and children’s religious identities. Models estimate the influence of mothers’ and fathers’ religious identity prominence (the affective value parents place on their religious identities) and salience (the likelihood of enacting the religious identity across situations, religious and otherwise) and their behavior in the religious identity on those of their children. Reverse paths from children’s religious identities to those of their parents are also estimated. Findings suggest that mothers’ religious identities have a strong influence on those of their children but the influence of fathers’ religious identities are more limited. Finally, children’s religious identities have limited influence on those of their parents.

Identity theory is concerned with how the self is shaped by social forces. This research examines how the ability to traverse the physical environment shapes the prominence and salience of the religious identity. We propose that relational positioning in terms of the distance between locations where identities are enacted, is a form of intermediate social structure which facilitates and constrains contact with identity-related others. The physical environment impacts the identity process by shaping the composition of one’s daily contacts, for example, someone who has to travel a long way to church will have a less religiously homogenous social circle, which shapes the subsequent identity process. This proposition is examined using data collected from individuals residing in communities which vary in the difficulty of traveling through the physical environment. The results support the inclusion of relational positioning as a form of intermediate social structure in identity theory, opening a potential pathway for connecting research on social inequalities and identity theory.

In chronic infection, inflammation and cancer, the tissue microenvironment controls how local immune cells behave, with tissue-resident fibroblasts emerging as a key cell type in regulating activation or suppression of an immune response. Fibroblasts are heterogeneous cells, encompassing functionally distinct populations, the phenotypes of which differ according to their tissue of origin and type of inciting disease. Their immunological properties are also diverse, ranging from the maintenance of a potent inflammatory environment in chronic inflammation to promoting immunosuppression in malignancy, and encapsulating and incarcerating infectious agents within tissues. In this Review, we compare the mechanisms by which fibroblasts control local immune responses, as well as the factors regulating their inflammatory and suppressive profiles, in different tissues and pathological settings. This cross-disease perspective highlights the importance of tissue context in determining fibroblast–immune cell interactions, as well as potential therapeutic avenues to exploit this knowledge for the benefit of patients with chronic infection, inflammation and cancer. © 2021, Springer Nature Limited.

Asynchronous video interviews (AVIs) are increasingly used to preselect applicants. Previous research found that interviewees in AVIs receive better interview ratings compared to other forms of interviews. It has been suggested that this difference could be due to the preparation time given for each AVI question. A pilot study confirmed that preparation time in AVIs is indeed beneficial for interview performance. Furthermore, our main study replicated the significant effect of preparation time on interview performance and revealed that it was mediated by active response preparation, whereas no mediation effects were found for strain and for the use of impression management. Finally, preparation time had no direct effect on fairness perceptions but a positive indirect effect via honest impression management., Practitioner points It was previously suggested that applicants receive better interview ratings in asynchronous video interviews (AVIs) than in synchronous interviews because of the preparation time that is provided for each question in an AVI. Our results confirmed that preparation time in AVIs indeed leads to better interview performance ratings. The positive effects of preparation time were due to active response preparation (i.e., interviewees made notes and structured their answers). Longer preparation time did not affect dishonest impression management or fairness perceptions but might affect the validity of AVIs., publishedVersion

Sport specialisation is becoming increasingly common among youth and adolescent athletes in the USA and many have raised concern about this trend. Although research on sport specialisation has grown significantly, numerous pressing questions remain pertaining to short-term and long-term effects of specialisation on the health and well-being of youth, including the increased risk of overuse injury and burnout. Many current elite athletes did not specialise at an early age. Methodological and study design limitations impact the quality of current literature, and researchers need to prioritise pressing research questions to promote safe and healthy youth sport participation. The American Medical Society for Sports Medicine hosted a Youth Early Sport Specialization Summit in April 2019 with the goal of synthesising and reviewing current scientific knowledge and developing a research agenda to guide future research in the field based on the identified gaps in knowledge. This statement provides a broad summary of the existing literature, gaps and limitations in current evidence and identifies key research priorities to help guide researchers conducting research on youth sport specialisation. Our goals are to help improve the quality and relevance of research on youth sport specialisation and to ultimately assure that opportunities for healthy and safe sport participation continue for all youth.