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Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes - the main cellular components in BMAC - interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

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OBJECTIVE: Intravenous epinephrine administration is preferred during neonatal resuscitation, but may not always be rapidly administered due to lack of equipment or trained staff. We aimed to compare the time to return of spontaneous circulation (ROSC) and post-ROSC haemodynamics between intravenous, endotracheal (ET) and intranasal (IN) epinephrine in severely asphyxic, bradycardic newborn lambs. METHODS: After instrumentation, severe asphyxia (heart rate <60 bpm, blood pressure ~10 mm Hg) was induced by clamping the cord in near-term lambs. Resuscitation was initiated with ventilation followed by chest compressions. Lambs were randomly assigned to receive intravenous (0.02 mg/kg), ET (0.1 mg/kg) or IN (0.1 mg/kg) epinephrine. If ROSC was not achieved after three allocated treatment doses, rescue intravenous epinephrine was administered. After ROSC, lambs were ventilated for 60 min. RESULTS: ROSC in response to allocated treatment occurred in 8/8 (100%) intravenous lambs, 4/7 (57%) ET lambs and 5/7 (71%) IN lambs. Mean (SD) time to ROSC was 173 (32) seconds in the intravenous group, 360 (211) seconds in the ET group and 401 (175) seconds in the IN group (p<0.05 intravenous vs IN). Blood pressure and cerebral oxygen delivery were highest in the intravenous group immediately post-ROSC (p<0.05), whereas the ET group sustained the highest blood pressure over the 60-min observation (p<0.05). CONCLUSION: Our study supports neonatal resuscitation guidelines, highlighting intravenous administration as the most effective route for epinephrine. ET and IN epinephrine should only be considered when intravenous access is delayed or not feasible.

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Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

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OBJECTIVE: The definition and assessment of remission in anorexia nervosa (AN) needs greater consensus. Particularly in adolescents, the use of patient-reported composite indices (such as the Eating Disorder Examination [EDE] Global Score) as the sole measure of psychological remission has the potential to obscure patients' true clinical status, given developmental factors and the propensity towards symptom minimization in AN. METHOD: End of treatment (EOT) data from a randomized controlled trial comparing two formats of manualized family-based treatment for adolescents with AN (N = 106) were analyzed. Participants completed the EDE, and their parents completed a parent-as-informant version of the EDE (Parent Eating Disorder Examination; PEDE). Rates of remission were compared across indices (i.e., EDE Global Score vs. diagnostic item analysis) and informant (i.e., adolescent vs. parent), both independently and in combination with the achievement of a percent median body mass index (% mBMI) greater than or equal to 95%. RESULTS: For both adolescent and parent reports, there were higher rates of remission when defined by Global Score than when defined by EDE or PEDE diagnostic items. There were no significant differences in remission rates based on informant. DISCUSSION: In the assessment of remission in AN, the EDE Global Score may not detect some adolescents who continue to exhibit clinically significant psychological symptoms. This study supports a detailed, multidimensional approach to assessing remission in adolescent AN to optimize sensitivity to patients' diagnostic profile. Future research should explore whether parent-child concordance on measures of ED psychopathology varies over the course of treatment.

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BACKGROUND AND OBJECTIVES: Eating disorders (EDs) and substance use disorders are prevalent among college students in the United States, with underlying common mechanisms suggesting co-occurrence of these in the student population. As treatment prognosis of EDs improves when they are identified and treated with early intervention, it is essential to understand which substance use behaviors associate with EDs in students. METHODS: Using a sample of 471 college students recruited for a study on high risk drinking (i.e., students needed to pregame regularly to be included), we explored the associations between ED symptomatology and two common substances used in this population: alcohol and cannabis. As most research on EDs focuses on female students only or does not separate out males and females, we examined whether sex assigned at birth moderated the association between ED symptomatology and substance use outcomes. RESULTS: About one-third (32.4%) of the sample screened positive for an ED, with females significantly more likely to screen positive. Males were significantly more likely to screen positive for an alcohol or cannabis use disorder. Screening positive for an ED associated with cannabis use frequency and cannabis use disorder symptoms, but not with alcohol outcomes. Sex moderated the association between ED and cannabis use disorder symptoms, with positive ED screen male students experiencing the highest cannabis use disorder symptoms. DISCUSSION AND CONCLUSIONS: It is necessary to further assess how sex differences in substance use and ED symptomatology inform each other. SCIENTIFIC SIGNIFICANCE: Findings underscore the need to assess and screen for cannabis use disorder among students who screen positive for an ED, and, more specifically, with focused attention on male students with ED symptoms.

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The objective of this study was to determine prevalence and perform genomic analysis of Salmonella spp. and Campylobacter spp. isolated from different stages of an integrated NAE broiler complex. Environmental samples were screened with 3M-Molecular Detection System (MDS) and MDS positive samples were further processed for confirmation of results and identification. Core genome-based phylogenies were built for both bacteria isolated from this study along with selected NCBI genomes. The odds ratios and 95% confidence limits were compared among stages and sample types (α < 0.05) using multivariable model. Based on MDS results, 4% and 18% of total samples were positive for Salmonella spp. and Campylobacter spp. respectively. The odds of Salmonella detection in hatchery samples were 2.58 times as likely as compared to its detection in production farms' samples (P = 0.151) while the odds of Campylobacter detection in production farms' samples were 32.19 times as likely as its detection in hatchery (P = 0.0015). Similarly, the odds of Campylobacter detection in boot swabs, soil, water, and miscellaneous samples were statistically significant (P < 0.05) as compared with fly paper as reference group. The serovars identified for Salmonella were Typhimurium, Barranquilla, Liverpool, Kentucky, Enteritidis, Luciana, and Rough_O:r:1,5. For Campylobacter, the species identified were Campylobacter jejuni and Campylobacter coli. Phylogeny results show close genetic relatedness among bacterial strains isolated from different locations within the same stage and between different stages. The results show possibility of multiple entry points of such bacteria entering broiler complex and can potentially contaminate the final raw product in the processing plant. It suggests the need for a comprehensive control strategy with strict biosecurity measures and best management practices to minimize or eliminate such pathogens from the poultry food chain.

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AIM: Cardiorespiratory events in preterm infants pose a major challenge in the Neonatal Intensive Care Unit as they require a prompt response. We aimed to describe caregivers' responses to these events. METHODS: We performed a prospective observational study in 19 preterm infants (28 ± 2 weeks) on non-invasive respiratory support using video recordings of the inside of the incubator for 72 (55-72) h. Caregivers' responses to these events were then identified from the videos. RESULTS: We recorded and assessed 1851 cardiorespiratory events with a median duration of 11.0 (5.0-23.0) s. No response was observed in the majority of the events (91.5%). In the remaining 8.5% events, caregivers responded by pausing the alarm, adjusting devices and/or providing tactile stimulation with an average response time of 25.4 (13.8-35.9) s. Stimulation was the most observed response and was applied in 38 different ways. On average, stimulation lasted 18.7 (11.6-44.6) s and the cardiorespiratory events were resolved 30.6 (19.5-47.6) s after stimulation started. CONCLUSION: Our study showed that cardiorespiratory events are common in preterm infants in the NICU, but often not followed by intervention of the caregiver. The indication, timing and execution of responses to cardiorespiratory events is highly variable.

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BACKGROUND: The timing of cord clamping has become a focal point for neonatal caregivers due to the promising outcomes associated with delayed cord clamping, which is a simple and cost-effective method to enhance the survival and well-being of preterm infants. While initially the rationale behind delaying clamping was to facilitate increased placental transfusion, research has unveiled additional hemodynamic benefits. SUMMARY: Experimental studies have demonstrated improved circulatory transition when clamping is postponed until the lungs are adequately aerated. This suggests that infants requiring assistance during the transition phase may benefit from stabilization while still attached to the cord. The Aeration, Breathing, and then Clamping (ABC) project aimed to translate these experimental findings into clinical practice. KEY MESSAGE: In this review, we will discuss the insights gained and lessons learned from the project's implementation.

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Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.

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BACKGROUND: Hospitals use Press Ganey surveys to evaluate patient satisfaction. The goal of our study was to evaluate whether surgeon-driven gifting to patients postoperatively affects Press Ganey Survey responses. METHODS: There were 1,468 patients undergoing arthroplasty at our institution who were randomized to receive a thank-you gift, a small bouquet of flowers, and a note from their provider after surgery, or nothing for completing their preoperative arthroplasty registry questionnaire. Press Ganey surveys were sent to patients who received and did not receive flowers immediately after their hospital stay and after the patients' first postoperative visit. Scores were reported as the mean score and the fraction of responses with a top-box rating. One-sided student t-tests and Fisher's exact tests were used to assess statistical significance. RESULTS: Hospital Discharge: Patients who received flowers had higher Press Ganey survey scores than patients who did not receive flowers. For example, for "physician's concerns for questions," they had higher scores (mean difference: 3.7 ± 1.6 points, P = .012) and a 9% higher top-box rating (P = .032). For "staff attitude toward visitors," they also had higher scores (mean difference: 2.8 ± 1.3 points, P = .019) and a 7% higher top-box rating (P = .049). First Follow-up: Patients who received flowers had a higher top-box rating for "concern provider showed for questions" and "amount of time provider spent with you" by 6% (P = .046) and 11% (P = .009), respectively. They also had higher scores for "information provider gave about medications" (mean difference: 4.0 ± 1.6 points, P = .009) and 11% higher top-box rating (P = .006). CONCLUSIONS: Press Ganey Surveys were higher in orthopaedic patients who received bouquets of flowers from their arthroplasty surgeons compared to patients who did not. At follow-up, improved Press Ganey scores persisted if the patient received flowers. The gift of flowers generates patient loyalty to their surgeon.

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BACKGROUND: Assessment of eating disorders (ED) in youth relies heavily on self-report, yet persistent lack of recognition of the presence and/or seriousness of symptoms can be intrinsic to ED. This study examines the psychometric properties of a semi-structured interview, the parent version of the Eating Disorder Examination (PEDE), developed to systematically assess caregiver report of symptoms. METHODS: A multi-site, clinical sample of youth (N = 522; age range: 12 to 18 years) seeking treatment for anorexia nervosa (AN) and subsyndromal AN were assessed using the Eating Disorder Examination (EDE) for youth and the PEDE for collateral caregiver report. RESULTS: Internal consistencies of the four PEDE subscales were on par with established ranges for the EDE. Significant medium-sized correlations and poor to moderate levels of agreement were found between the corresponding subscales on each measure. For the PEDE, confirmatory factor analysis of the EDE four-factor model provided a poor fit; an exploratory factor analysis indicated that a 3-factor model better fits the PEDE. CONCLUSIONS: Findings suggest that the PEDE has psychometric properties on par with the original EDE. The addition of the caregiver perspective may provide incremental information that can aid in the assessment of AN in youth. Future research is warranted to establish psychometric properties of the PEDE in broader transdiagnostic ED samples.

Assessments for eating disorders rely primarily on self-report; yet, the denial of symptoms or symptom severity among adolescents with anorexia nervosa can complicate assessment and delay treatment in this population. The Parent Eating Disorder Examination (PEDE) is the first semi-structured interview formally developed to improve childhood eating disorder assessment by including caregiver perspectives. In this study, a large sample of adolescents with anorexia nervosa completed a self-report interview (the Eating Disorder Examination or EDE) and their parents completed the PEDE. The PEDE appeared to measure parents' report of their child's eating disorder symptoms consistently. Results from both interviews were related to one another but did not completely agree. This suggests that in an eating disorder assessment, the PEDE can provide additional information from caregivers that might reduce diagnostic confusion and lead to earlier intervention for youth with anorexia nervosa.

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BACKGROUND: As very preterm infants have surfactant-deficient and highly incompliant lungs, slowing lung deflation during expiration might help preserve functional residual capacity(FRC) during lung aeration. In this study, we investigated the effect of expiratory resistance(Re) on lung aeration during positive pressure ventilation in preterm rabbits immediately after birth. METHODS: Preterm rabbit pups were delivered at 29 days gestation, mechanically ventilated from birth and simultaneously imaged to measure lung aeration using phase-contrast X-ray. Re was varied by altering the length (0, 60 or 1000 mm) of the expiratory circuit. RESULTS: Increasing Re led to a decrease in lung deflation rates and both peak expiratory flows and flow rates at mid-deflation. As a result, the rate of de-acceleration(slowing) in lung deflation when approaching FRC was markedly reduced with increasing resistance. During lung aeration, FRC was significantly different between resistance groups and was significantly higher over time in the high compared to the low resistance group. While FRC values tended to be higher with higher Re, they were not significantly different at end-ventilation (t = 7 min). CONCLUSION: Increasing Re of the ventilation circuit during lung aeration in preterm rabbits immediately after birth decreased lung deflation rates and increased the accumulation of FRC over time. IMPACT: The expiratory phase of the ventilatory cycle has been largely overlooked as an opportunity to improve ventilation in preterm infants after birth. Increasing the expiratory resistance of the ventilator circuit during lung aeration in preterm rabbits immediately after birth markedly decreased lung deflation rates and increased FRC accumulation, compared to a low expiratory resistance. This indicates that ventilation devices that reduce the "work of breathing" by reducing the expiratory resistance, may have the unintended effect of reducing FRC, particularly in extremely preterm infants that have surfactant deficient highly incompliant lungs.

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Chronic cough is a frequent disorder that is defined by cough of more than 8 weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (RFC1) gene corresponding mostly to an intronic AAGGG repeat expansion. Chronic cough in patients with CANVAS shares similar characteristics with cough hypersensitivity syndrome. The high prevalence of chronic cough in CANVAS gives the opportunity to better understand the neurogenic mechanism of chronic cough. In this review, we will describe the characteristics and mechanisms of CANVAS. We will also address the potential mechanisms responsible for chronic cough in CANVAS. Finally, we will address chronic cough management in the context of CANVAS.

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In an influential article, Jones et al. (1995) provide evidence that auditory distraction by changing relative to repetitive auditory distracters (the changing-state effect) did not differ between a visual-verbal and visual-spatial serial recall task, providing evidence for an amodal mechanism for the representation of serial order in short-term memory that transcends modalities. This finding has been highly influential for theories of short-term memory and auditory distraction. However, evidence vis-à-vis the robustness of this result is sorely lacking. Here, two high-powered replications of Jones et al.'s (1995) crucial Experiment 4 were undertaken. In the first partial replication (n = 64), a fully within-participants design was adopted, wherein participants undertook both the visual-verbal and visual-spatial serial recall tasks under different irrelevant sound conditions, without a retention period. The second near-identical replication (n = 128), incorporated a retention period and implemented the task-modality manipulation as a between-participants factor, as per the original Jones et al. (1995; Experiment 4) study. In both experiments, the changing-state effect was observed for visual-verbal serial recall but not for visual-spatial serial recall. The results are consistent with modular and interference-based accounts of distraction and challenge some aspects of functional equivalence accounts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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BACKGROUND: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. METHODS: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks. RESULTS: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer's disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. CONCLUSION: Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences.

We sought to understand why females have higher rates of Alzheimer's disease, and males have higher rates of autism. One idea was that the female brain at baseline may be more similar to an Alzheimer's brain, so it is easier for them to shift into that state (likewise, males may be more similar to autism). To test this, we examined gene expression differences between brains of biological males and biological females. While all people have the same ~ 25,000 genes, each gene can be on or off ('expressed') to different extents. Overall, we found that there were differences in gene expression between males and females in all brain regions tested but more differences in some brain regions than others. By looking at the role of these genes we estimate that female immune system processes might be more active in the brain. We also found female brain gene expression looked slightly more like people with Alzheimer's compared to people without Alzheimer's, which may explain why females get Alzheimer's disease more easily. However, the male brain gene expression did not look more like autism, suggesting that the reason males have higher rates of autism is complex and needs further investigation.

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INTRODUCTION: Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin-sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin-a by-product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward-related processes, may provide critical insights into reward circuit function in AN. METHODS: This study will incorporate neuromelanin-sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight-restored AN (N = 30), and age-matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin-sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. CONCLUSION: This study will be among the first to interrogate midbrain neuromelanin in AN-a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.

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Refractory chronic cough is a disabling disease with very limited therapeutic options. A better understanding of cough pathophysiology has led to the development of emerging drugs targeting cough receptors. Recent strides have illuminated novel therapeutic avenues, notably centred on modulating transient receptor potential (TRP) channels, purinergic receptors, and neurokinin receptors. By modulating these receptors, the goal is to intervene in the sensory pathways that trigger cough reflexes, thereby providing relief without compromising vital protective mechanisms. These innovative pharmacotherapies hold promise for improvement of refractory chronic cough by offering improved efficacy and potentially mitigating adverse effects associated with current recommended treatments. A deeper comprehension of their precise mechanisms of action and clinical viability is imperative for optimising therapeutic interventions and elevating patient care standards in respiratory health. This review delineates the evolving landscape of drug development in this domain, emphasising the significance of these advancements in reshaping the paradigm of cough management.

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