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Health data generated by apps and devices are increasingly popular and expected to affect various aspects of doctor-patient relationships. No longer confined to medically authorised and certified health technologies, a range of biomedical data-from heart rate to blood pressure or oxygen saturation-are captured and processed by consumer health devices. This article outlines different responses of physicians to patients collecting data with popular consumer devices and considers how the data may challenge or reify medical authority. Based on semi-structured interviews with doctors and chronically ill patients in Germany from 2021 to 2023, we compare cases from diabetes, sleep disorders, cardiovascular conditions, obesity and ME/CFS and explore when, how and for what reasons different medical specialists consider patient-generated data (PGD) from consumer devices in outpatient settings. Their response registers vary: whereas some physicians reject PGD that seem to compete with their diagnostic activities, others tolerate the data (collection), whereas still others more readily include them into their diagnostic practices. This suggests nuanced strategies for navigating the demarcation between accepting or rejecting 'uninvited' participation through PGD from consumer apps and devices., (© 2024 The Author(s). Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)

How enteric pathogens adapt their metabolism to a dynamic gut environment is not yet fully understood. To investigate how Salmonella enterica Typhimurium (S.Tm) colonizes the gut, we conducted an in vivo transposon mutagenesis screen in a gnotobiotic mouse model. Our data implicate mixed-acid fermentation in efficient gut-luminal growth and energy conservation throughout infection. During initial growth, the pathogen utilizes acetate fermentation and fumarate respiration. After the onset of gut inflammation, hexoses appear to become limiting, as indicated by carbohydrate analytics and the increased need for gluconeogenesis. In response, S.Tm adapts by ramping up ethanol fermentation for redox balancing and supplying the TCA cycle with α-ketoglutarate for additional energy. Our findings illustrate how S.Tm flexibly adapts mixed fermentation and its use of the TCA cycle to thrive in the changing gut environment. Similar metabolic wiring in other pathogenic Enterobacteriaceae may suggest a broadly conserved mechanism for gut colonization., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Background: Live single-cell metabolomic studies encounter inherent difficulties attributed to the limited sample volume, minimal compound quantity, and insufficient sensitivity in the Mass Spectrometry (MS) method used to obtain single-cell data. However, understanding cellular heterogeneity, functional diversity, and metabolic processes within individual cells is essential. Exploring how individual cells respond to stimuli, including drugs, environmental changes, or signaling molecules, offers insights into biology, oncology, and drug discovery. Efficient release of cell contents (lysis) is vital for accurate metabolite detection at the single-cell level. Despite this, traditional approaches in live single cell metabolomics methods do not emphasize efficient lysis to prevent sample dilution. Instead, current live single cell metabolomics methods use direct infusion to introduce the cell into the mass spectrometry without prior chromatographic separation or a lysis step, which adversely affects sensitivity and metabolic coverage., Results: To address this, we developed an integrated single-cell electrical lysis and nano spray (SCEL-nS) platform coupled to an Orbitrap MS capable of efficiently lysing a single cell after being sampled with specially manufactured micropipettes. Lysis efficiency was validated by comparing live cell stain fluorescent intensities of intact and electrically lysed cells through microscopy imaging. The SCEL-nS platform successfully induced the breakdown of a single cell, significantly reducing the live cell stain's fluorescent intensity indicating cell membrane breakdown. Additionally, SCEL-nS was validated by measuring single cells spiked with the anti-cancer drug tamoxifen by MS. SCEL-nS use resulted in statistically significant increase in the peak measured by the method compared to the traditional non-lysis method., Significance: Overall, our results demonstrate that the newly incorporated SCEL-nS platform achieved higher sensitivities compared to traditional live single cell analysis methods., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Resource competition is a driver of gut microbiota composition. Bacteria can outcompete metabolically similar rivals through the limitation of shared growth-fuelling nutrients. The mechanisms underlying this remain unclear for bacteria with identical sets of metabolic genes. Here we analysed the lactose utilization operon in the murine commensal Escherichia coli 8178. Using in vitro and in vivo approaches, we showed that translation of the lactose utilization repressor gene lacI from its native non-canonical GTG start codon increases the basal expression of the lactose utilization cluster, enhancing adaptation to lactose consumption. Consequently, a strain carrying the wild type lacI GTG start codon outperformed the lacI ATG start codon mutant in the mouse intestine. This advantage was attenuated upon limiting host lactose intake through diet shift or altering the mutant frequency, emphasizing the context-dependent effect of a single nucleotide change on the bacterial fitness of a common member of the gut microbiota. Coupled with a genomic analysis highlighting the selection of non-ATG start codons in sugar utilization regulator genes across the Enterobacteriaceae family, our data exposed an unsuspected function of non-canonical start codons in metabolic competition., (© 2024. The Author(s).)

Introduction: Point-of-care (POC) manufacturing of chimeric antigen receptor (CAR) modified T cell has expanded rapidly over the last decade. In addition to the use of CD19 CAR T cells for hematological diseases, there is a growing interest in targeting a variety of tumor-associated epitopes., Methods: Here, we report the manufacturing and characterization of autologous anti-CD20 CAR T cells from melanoma patients within phase I clinical trial (NCT03893019). Using a second-generation lentiviral vector for the production of the CD20 CAR T cells on the CliniMACS Prodigy®., Results: We demonstrated consistency in cell composition and functionality of the products manufactured at two different production sites. The T cell purity was >98.5%, a CD4/CD8 ratio between 2.5 and 5.5 and transduction rate between 34% and 61% on day 12 (harvest). Median expansion rate was 53-fold (range, 42-65-fold) with 1.7-3.8×10 9 CAR T cells at harvest, a sufficient number for the planned dose escalation steps (1×10 5 /kg, 1×10 6 /kg, 1×10 7 /kg BW). Complementary research of some of the products pointed out that the CAR+ cells expressed mainly central memory T-cell phenotype. All tested CAR T cell products were capable to translate into T cell activation upon engagement of CAR target cells, indicated by the increase in pro-inflammatory cytokine release and by the increase in CAR T cell amplification. Notably, there were some interindividual, cell-intrinsic differences at the level of cytokine release and amplification. CAR-mediated T cell activation depended on the level of CAR cognate antigen., Discussion: In conclusion, the CliniMACS Prodigy® platform is well suited for decentralized POC manufacturing of anti-CD20 CAR T cells and may be likewise applicable for the rapid and automated manufacturing of CAR T cells directed against other targets., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03893019?cond=Melanoma&term=NCT03893019&rank=1, identifier NCT03893019., Competing Interests: UK: Consultant and/or speaker fees: AstraZeneca, Affimed, Glycostem, GammaDelta, Zelluna, Miltenyi Biotec and Novartis Pharma GmbH, Bristol-Myers Squibb GmbH & Co. KGaA; MAk, MAp, MAs, IB, AR, PA und CS are employees of Miltenyi Biotec and Miltenyi Biomedicine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Aleksandrova, Leise, Priesner, Aktas, Apel, Assenmacher, Bürger, Richter, Altefrohne, Schubert, Holzinger, Barden, Bezler, von Bergwelt-Baildon, Borchmann, Goudeva, Glienke, Arseniev, Esser, Abken and Koehl.)

Psychoneuroimmunology (PNI) is a field of research that deals with the interactions between psyche, nervous, endocrine, and immune systems. Investigating these complex PNI relationships under as ecologically valid as possible conditions ("life as it is lived") necessitates a paradigm change in research. This shift places factors such as "time" and "subjective meaning" of personal experiences at the center of the research methodology. For this purpose, the biosemiotic-systemic research design "Integrative Single-Case Study" was developed. Initial results from healthy individuals as well as patients with systemic lupus erythematosus (SLE), breast cancer, and rheumatoid arthritis (RA) support the validity of the research approach. Specifically, in connection with the occurrence of emotionally meaningful everyday incidents, we repeatedly observed stress system reactions, which were (1) delayed over several days, (2) cyclically patterned, (3) anticipatory, and (4) opposing, depending on a) whether participants experienced emotionally positive or negative everyday incidents, b) whether they were healthy or ill, and c) which stress system parameter was investigated. In this chapter, the Integrative Single-Case Study design is introduced as a holistic research option, presented in detail in its methodology, and critically discussed in terms of its limitations., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Deployment of ultracold atom interferometers (AI) into space will capitalize on quantum advantages and the extended freefall of persistent microgravity to provide high-precision measurement capabilities for gravitational, Earth, and planetary sciences, and to enable searches for subtle forces signifying physics beyond General Relativity and the Standard Model. NASA's Cold Atom Lab (CAL) operates onboard the International Space Station as a multi-user facility for fundamental studies of ultracold atoms and to mature space-based quantum technologies. We report on pathfinding experiments utilizing ultracold 87 Rb atoms in the CAL AI. A three-pulse Mach-Zehnder interferometer was studied to understand the influence of ISS vibrations. Additionally, Ramsey shear-wave interferometry was used to manifest interference patterns in a single run that were observable for over 150 ms free-expansion time. Finally, the CAL AI was used to remotely measure the Bragg laser photon recoil as a demonstration of the first quantum sensor using matter-wave interferometry in space., (© 2024. The Author(s).)

When a technology is seen as the right solution to a recognized problem, the development of alternative technologies comes under threat. To secure much-needed resources, proponents of alternative technologies must, in these conditions, restart societal discussion on the status quo, a process at once technological and discursive known as 'path creation'. In this article, we investigate discussion-restarting strategies employed by supporters of emerging technologies in the field of solar fuels, particularly the advocates of a technology referred to as 'artificial photosynthesis'. For illustrative purposes we explore four such strategies: revisiting weak spots, resizing the problem, redefining the game, and renegotiating labels. We conclude with a methodological reflection on the empirical study of discursive strategies in a socio-technical system. We further suggest a more systematic application of discourse-analytical and argumentation-theoretical insights that can complement current scholarship on path dependence and path creation.

Fatigue is commonly associated with myasthenia gravis (MG), but factors contributing to fatigue development in MG are incompletely understood. This nationwide cross-sectional registry study included 1464 patients diagnosed with autoimmune MG, recruited between February 2019 and April 2023. Frequency and severity of fatigue was assessed at study inclusion using the patient-reported Chalder Fatigue Questionnaire (CFQ). Frequency of fatigue was 59%. Fatigue severity strongly correlated with both patient-reported and physician-assessed MG outcome measures (MG-ADL, MG-QoL15, QMG and MGFA classes) and was associated with a history of myasthenic exacerbation and/or myasthenic crises and a delay in diagnosis of more than 1 year after symptom onset. Fatigue was more prevalent in women and coincided with symptoms of depression, anxiety, and sleep dissatisfaction. Differences in fatigue severity were observed between antibody (ab) subgroups, with highest fatigue severity in LRP4-ab-positive patients and lowest fatigue severity in AChR-ab-positive patients. Fatigue is a frequent and clinically highly relevant symptom of MG. Early diagnosis and prevention of MG crises may limit the long-term burden of fatigue in patients with MG., (© 2024. The Author(s).)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: Exome or genome sequencing (ES or GS) can identify genetic causes of otherwise unexplained congenital anomaly and perinatal death (PND) but is not routine practice. The evidence base for "genomic autopsy" after termination of pregnancy for fetal anomaly (TOPFA) and PND has been synthesized to determine the value of this investigation., Methods: We conducted a systematic review and meta-analysis of studies meeting prespecified inclusion criteria and containing ≥10 cases of TOPFA or PND (with or without major congenital abnormality), in which ES or GS was conducted. We determined test performance, including diagnostic yield, accuracy, and reliability. We also reported outcomes associated with clinical utility and harms, where described., Results: From 2245 potentially eligible studies, 32 publications were eligible and had data extracted, representing 2120 cases that could be meta-analyzed. No diagnostic accuracy or comparative studies were identified, although some analysis of concordance between different ES/GS methodologies could be performed. Studies reporting parent-related outcomes or long-term follow-up did not do so in a systematic or quantifiable manner., Conclusion: Evidence suggests that approximately one-fourth to one-third of fetal losses associated with TOPFA or unexplained PND are associated with a genetic cause identifiable on ES or GS-albeit this estimate varies depending on phenotypic and background risk factors. Despite the large body of evidence on ES and GS, little research has attempted to validate the accuracy of testing, nor measure the clinical or societal outcomes in families that follow the diagnostic investigation in this context., Competing Interests: Conflict of Interest Camille Schubert’s salary was partially funded by the Genomic Autopsy Study (Australian government MRFF grant funded research). All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The cell surface molecule CD40 is a member of the tumor necrosis factor receptor superfamily and is broadly expressed by immune cells including B cells, dendritic cells, and monocytes, as well as other normal cells and some malignant cells. CD40 is constitutively expressed on antigen-presenting cells, and ligation promotes functional maturation, leading to an increase in antigen presentation and cytokine production, and a subsequent increase in the activation of antigen-specific T cells. It is postulated that CD40 agonists can mediate both T cell-dependent and T cell-independent immune mechanisms of tumor regression in mice and patients. In addition, it is believed that CD40 activation also promotes apoptotic death of tumor cells and that the presence of the molecule on the surface of cancer cells is an important factor in the generation of tumor-specific T cell responses that contribute to tumor cell elimination. Notably, CD40 agonistic therapies were evaluated in patients with solid tumors and hematologic malignancies with reported success as a single agent. Preclinical studies have shown that subcutaneous administration of CD40 agonistic antibodies reduces systemic toxicity and elicits a stronger and localized pharmacodynamic response. Two independent studies in cynomolgus macaque (Macaca fascicularis) were performed to further evaluate potentially immunotoxicological effects associated with drug-induced adverse events seen in human subjects. Studies conducted in monkeys showed that when selicrelumab is administered at doses currently used in clinical trial patients, via subcutaneous injection, it is safe and effective at stimulating a systemic immune response., Competing Interests: Conflict of interests: G.B., C.S., A.B.-B., and J.C. are employees and stockholders at Roche., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Histiocytic disorders are pathologic expansions of myeloid cells in multiple organs, including the CNS. They share activation of the MAP kinase pathway due to either BRAF V600E variant or other variants in the RAS-RAF-MEK-ERK pathway. The rarity and heterogeneity of the disease only enable therapy through pathophysiologic considerations., Methods: We present 2 histiocytosis cases without BRAF sequence variants that affect the CNS, one with Erdheim-Chester disease and the other with an unspecified histiocytosis, and their diagnostic and therapeutic challenges., Results: In both cases, comprehensive analysis of the RAS-RAF-MEK-ERK signaling pathway secured the diagnosis. Treatment with the MEK inhibitor cobimetinib brought the disease to a complete halt. However, side effects such as thrombosis and serous macular edema made it necessary to reduce cobimetinib dosage. Low-dose cobimetinib maintenance medication was successful in preventing recurrence of histiocytic disease., Discussion: CNS involvement of histiocytic disorders can lead to detrimental neurologic symptoms. MEK inhibitors are effective treatment options for some of these patients. Since side effects are common, according to our cases we propose a low-dose treatment of 20 mg per day to balance treatment effects with side effects., Classification of Evidence: This case report provides Class IV evidence. This is a single observational study without controls.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1 + sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microbiomes feature recurrent compositional structures under given environmental conditions. However, these patterns may conceal diverse underlying population dynamics that require intrastrain resolution. Here we developed a genomic tagging system, termed wild-type isogenic standardized hybrid (WISH)-tags, that can be combined with quantitative polymerase chain reaction and next-generation sequencing for microbial strain enumeration. We experimentally validated the performance of 62 tags and showed that they can be differentiated with high precision. WISH-tags were introduced into model and non-model bacterial members of the mouse and plant microbiota. Intrastrain priority effects were tested using one species of isogenic barcoded bacteria in the murine gut and the Arabidopsis phyllosphere, both with and without microbiota context. We observed colonization resistance against late-arriving strains of Salmonella Typhimurium in the mouse gut, whereas the phyllosphere accommodated Sphingomonas latecomers in a manner proportional to their presence at the late inoculation timepoint. This demonstrates that WISH-tags are a resource for deciphering population dynamics underlying microbiome assembly across biological systems., (© 2024. The Author(s).)

Objective: To investigate accumulation of disability in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) in a changing treatment landscape. We aimed to identify risk factors for the development of disability milestones in relation to disease duration, number of attacks, and age., Methods: We analyzed data from individuals with NMOSD and MOGAD from the German Neuromyelitis Optica Study Group registry. Applying survival analyses, we estimated risk factors and computed time to disability milestones as defined by the Expanded Disability Status Score (EDSS)., Results: We included 483 patients: 298 AQP4-IgG + NMOSD, 52 AQP4-IgG - /MOG-IgG - NMOSD patients, and 133 patients with MOGAD. Despite comparable annualized attack rates, disability milestones occurred earlier and after less attacks in NMOSD patients than MOGAD patients (median time to EDSS 3: AQP4-IgG+ NMOSD 7.7 (95% CI 6.6-9.6) years, AQP4-IgG - /MOG-IgG - NMOSD 8.7) years, MOGAD 14.1 (95% CI 10.4-27.6) years; EDSS 4: 11.9 (95% CI 9.7-14.7), 11.6 (95% lower CI 7.6) and 20.4 (95% lower CI 14.1) years; EDSS 6: 20.1 (95% CI 16.5-32.1), 20.7 (95% lower CI 11.6), and 37.3 (95% lower CI 29.4) years; and EDSS 7: 34.2 (95% lower CI 31.1) for AQP4-IgG + NMOSD). Higher age at onset increased the risk for all disability milestones, while risk of disability decreased over time., Interpretation: AQP4-IgG + NMOSD, AQP4-IgG - /MOG-IgG - NMOSD, and MOGAD patients show distinctive relapse-associated disability progression, with MOGAD having a less severe disease course. Investigator-initiated research has led to increasing awareness and improved treatment strategies appearing to ameliorate disease outcomes for NMOSD and MOGAD. ANN NEUROL 2024;95:720-732., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: C4-dicarboxylates (C4-DC) have emerged as significant growth substrates and signaling molecules for various Enterobacteriaceae during their colonization of mammalian hosts. Particularly noteworthy is the essential role of fumarate respiration during colonization of pathogenic bacteria. To investigate the regulation of aerobic C4-DC metabolism, the study explored the transcriptional control of the main aerobic C4-DC transporter, dctA, under different carbohydrate conditions. In addition, mutants related to carbon catabolite repression (CCR) and C4-DC regulation (DcuS-DcuR) were examined to better understand the regulatory integration of aerobic C4-DC metabolism into CCR. For initial insight into posttranslational regulation, the interaction between the aerobic C4-DC transporter DctA and EIIAGlc from the glucose-specific phosphotransferase system was investigated., Methods: The expression of dctA was characterized in the presence of various carbohydrates and regulatory mutants affecting CCR. This was accomplished by fusing the dctA promoter (PdctA) to the lacZ reporter gene. Additionally, the interaction between DctA and EIIAGlc of the glucose-specific phosphotransferase system was examined in vivo using a bacterial two-hybrid system., Results: The dctA promoter region contains a class I cAMP-CRP-binding site at position -81.5 and a DcuR-binding site at position -105.5. DcuR, the response regulator of the C4-DC-activated DcuS-DcuR two-component system, and cAMP-CRP stimulate dctA expression. The expression of dctA is subject to the influence of various carbohydrates via cAMP-CRP, which differently modulate cAMP levels. Here we show that EIIAGlc of the glucose-specific phosphotransferase system strongly interacts with DctA, potentially resulting in the exclusion of C4-DCs when preferred carbon substrates, such as sugars, are present. In contrast to the classical inducer exclusion known for lactose permease LacY, inhibition of C4-DC uptake into the cytoplasm affects only its role as a substrate, but not as an inducer since DcuS detects C4-DCs in the periplasmic space ("substrate exclusion"). The work shows an interplay between cAMP-CRP and the DcuS-DcuR regulatory system for the regulation of dctA at both transcriptional and posttranslational levels., Conclusion: The study highlights a hierarchical interplay between global (cAMP-CRP) and specific (DcuS-DcuR) regulation of dctA at the transcriptional and posttranslational levels. The integration of global and specific transcriptional regulation of dctA, along with the influence of EIIAGlc on DctA, fine-tunes C4-DC catabolism in response to the availability of other preferred carbon sources. It attributes DctA a central role in the control of aerobic C4-DC catabolism and suggests a new role to EIIAGlc on transporters (control of substrate uptake by substrate exclusion)., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Mental health (MH) disorders are major causes of disability in Guatemala. Unfortunately, limited academic training and funding resources make MH care inaccessible to most people in rural Guatemala. These disparities leave many indigenous populations without care. Project ECHO™ is an educational model used globally to deliver virtual training for providers in rural/ underserved communities. The aim of this project was to implement and evaluate a Project ECHO™ program bridging MH training gaps for providers who serve rural communities in Guatemala., Methods: The Project ECHO™ curriculum was implemented through a partnership between educational and nonprofit institutions in Guatemala City and the United States. Participants were primary care physicians and nurses working in rural Guatemala as well as medical/nursing/psychology students. Evaluation of its implementation was guided by a RE-AIM framework. Reach, effectiveness, adoption, fidelity, sustainability, acceptability, feasibility, and appropriateness were evaluated using a mixed-methods approach, using a pre-post survey and semi-structured focus groups., Results: Forty unique participants attended the five sessions. Attitudes about mental health did not change quantitatively but self-efficacy improved in four of five modules. High quality fidelity scores were noted in two of five sessions. Sustainability scores across multiple domains were highly rated. Scores on instruments measuring acceptability, feasibility, and appropriateness were high. Focus groups showed two main themes: the curriculum filled a gap in education and further adaptation of the model might help improve the experience., Conclusion: Implementation of the Project ECHO™ educational model appeared to have good reach/adoption, showed improvements in self-efficacy, illuminated facilitators and barriers to sustainability, and was felt to be acceptable, feasible, and appropriate. Qualitative analysis supported these conclusions. Future directions would include ongoing evaluation and monitoring of further Project ECHO™ curricular experiences through this partnership and adaptation of this project to other learners and settings in Latin America.

Background: United States (U.S.) census data from 2017 indicates that the percentage of persons born outside of the U.S. is increasing. However, no studies describe the amount of class time focused on immigrant and refugee health during medical school in the U.S. nor on incoming residents' confidence in providing culturally sensitive care. The objective of this study is to characterize final-year medical students' exposure to immigrant and refugee health and their confidence in caring for these populations., Methods: A voluntary, cross-sectional survey was sent electronically to fourth-year medical students at twelve U.S. medical schools in 2020, with 707 respondents (46% response rate). Questions addressed respondents' curricular exposure to immigrant and refugee health care during medical school and their confidence in providing culturally sensitive care. Chi-square tests were used to assess relationships between categorical variables, and odds ratios were calculated for dichotomized variables., Results: Most students (70.6%) described insufficient class time dedicated to culturally sensitive care, and many (64.5%) reported insufficient clinical exposure in caring for immigrants/refugees. The odds that incoming residents felt 'usually' or 'always' confident in their ability to provide culturally sensitive care to immigrants and refugees were higher in those with more class time on culturally sensitive care (OR 5.2 [3.6-7.4]), those with more clinical opportunities to care for immigrants and refugees (OR 7.2 [5.1-10.2]), and those who participated in a domestic low-resource or international elective (OR 1.4 [1.02-1.9]). More than half (55.3%) of respondents reported feeling 'not at all' or only 'sometimes' confident in their ability to provide culturally sensitive care to immigrants/refugees., Conclusions: Most fourth-year U.S. medical students entering residency feel unprepared to deliver culturally sensitive care to immigrants and refugees. This may be mediated by increased exposure to didactic curricula class time and/or experiential clinical activities, as those factors are associated with improved student confidence.

Introduction: The cyclic nucleotide cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger, which is known to play an important anti-inflammatory role. Astrocytes in the central nervous system (CNS) can modulate inflammation but little is known about the significance of cAMP in their function., Methods: We investigated cAMP dynamics in mouse olfactory bulb astrocytes in brain slices prepared from healthy and experimental autoimmune encephalomyelitis (EAE) mice., Results: The purinergic receptor ligands adenosine and adenosine triphosphate (ATP) both induced transient increases in cAMP in astrocytes expressing the genetically encoded cAMP sensor Flamindo2. The A 2A receptor antagonist ZM241385 inhibited the responses. Similar transient increases in astrocytic cAMP occurred when olfactory receptor neurons were stimulated electrically, resulting in ATP release from the stimulated axons that increased cAMP, again via A 2A receptors. Notably, A 2A -mediated responses to ATP and adenosine were not different in EAE mice as compared to healthy mice., Discussion: Our results indicate that ATP, synaptically released by afferent axons in the olfactory bulb, is degraded to adenosine that acts on A 2A receptors in astrocytes, thereby increasing the cytosolic cAMP concentration. However, this pathway is not altered in the olfactory bulb of EAE mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Wendlandt, Kürten, Beiersdorfer, Schubert, Samad-Yazdtchi, Sauer, Pinto, Schulz, Friese, Gee, Hirnet and Lohr.)

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects cartilage and bone. Psychological stress can both trigger disease exacerbation and result from disease activity. As standard pharmacological interventions alone have limited success in treating RA, a more comprehensive biopsychosocial approach to treatment has been recommended. In this prospective randomized controlled trial (RCT), a psychotherapeutically guided, group-based intervention program will be conducted with RA patients over a period of 9 months. This program combines a dynamic-interactional model with disorder-specific coping-oriented perspectives to improve patients' social, emotional, and problem-solving competencies as well as stress system functional status. The enrolment of 440 patients, randomly allocated to either an intervention (n = 220) or control group (n = 220), is planned. To evaluate the intervention effect, various indicators of RA disease activity, stress system activity, and psychological condition will be assessed through sets of standardized questionnaires and biochemical analyses of blood and saliva samples. Moreover, healthcare-related costs for each patient will be obtained using routine health insurance data. Outcome variables will be measured in all patients at regular intervals prior to intervention (baseline), during the 9-month intervention (five time points), and during a 9-month follow-up phase (three time points), allowing the comprehensive analysis of within- and between-subject effects, i.e. trajectories of the target variables in the intervention and control groups. In addition, to investigate the intervention effects on real-life stress system functioning in RA, 10 integrative single-case studies (n = 5 from the intervention group, n = 5 from the control group) will be conducted. In each study, once before and after the 9-month intervention, urine samples will be collected, and patients will fill out questionnaires for approximately 1 month at 12-h intervals. Moreover, weekly in-depth interviews will be conducted with patients to determine their previous week's emotionally positive and negative incidents. Using time series analysis, it is then possible to investigate whether and how stress system function in these RA patients has improved from the applied intervention. By using both an investigational macro- and microperspective, this project aims to evaluate a psychological intervention in the routine care of individuals with RA.Trial registration German Clinical Trials Register DRKS00028144. Registered on 1 March 2022., (© 2023. The Author(s).)

The relationship between emotional states and immune system activity is characterized by bidirectional influences; however, limited information is available regarding the temporal dynamics of these effects. The goal of this investigation was to examine how these psychoimmunological interdependencies unfold over time under conditions of "life as it is lived". For this purpose, three healthy women collected their entire urine over a period of approximately two months at 12-h intervals (8 am-8 pm, 8 pm-8 am), resulting in a total of 112 to 126 consecutive measurements per subject. In addition, among other regular psychological assessments, the subjects completed the EWL-60-S, an emotional state questionnaire, each morning and evening. To assess the extent of T-helper type 1 immune activation, the neopterin per creatinine concentration was measured in the urine samples using high-pressure liquid chromatography. The dynamic relationships between the time series of the six emotional states (performance-related activity, general inactivity, extraversion/introversion, general feeling of comfort, emotional irritation, anxiety/depressiveness) and urinary neopterin levels were estimated in vector-autoregressive models and evaluated using Granger-causality tests, impulse-response functions and forecast error variance decompositions. The findings showed that emotional states explained up to 20% of the variance of urinary neopterin per creatinine levels, whereby most of the effects occurred within a period of approximately three days. Across all subjects, increases in anxiety/depressiveness and extraversion led to increases in neopterin levels, while a general feeling of comfort led to decreases in neopterin. These results emphasize the importance of the interdependencies between emotional states and immune system activity and showcase the potential that intensive longitudinal study designs offer for psychoneuroimmunology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Seizer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fermentation processes can only succeed if intact and active starter cultures are present. Bacteriophages, which can lyse bacteria and thus bring entire fermentation processes to a standstill, therefore pose a major threat. Cheese production, for example, is often affected. The by-product whey can be highly contaminated with bacteriophages (≤10 9 plaque-forming units/mL) and in this state, further utilization is a quality and processing risk. Therefore, an orthogonal process consisting of membrane filtration followed by UV-C irradiation could be applied to eliminate bacteriophages and to generate "phage-free" whey. In order to define suitable process parameters, 11 lactococcal bacteriophages belonging to different families and genera and differing in their morphology, genome size, heat resistance, and other attributes, were screened for their UV-C resistance in whey. P369 was found to be the most resistant and could thus be well-suited as a biomarker. Starting from a 4 log unit bacteriophage reduction by membrane filtration, another 5 log unit decrease should be realized when applying a UV-C dose of 5 J/cm 2 . A clear correlation of UV-C sensitivity to the chosen attributes studied such as bacteriophage morphology and genome size was difficult and ambiguous, presumably because other yet unidentified parameters are important. Mutation experiments were performed with the representative bacteriophage P008 by multiple cycles of UV-C irradiation and propagation. A few mutational events were found, but could not be linked to an artificially generated UV-C resistance, indicating that the process used would probably not lose its effectiveness over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

More than a decade ago, two faculty met at a conference. Each talked about how they were charged with leading global health education efforts at their institutions and longed to have an opportunity to share resources and learn from each other. After reaching out to a few other Midwestern colleagues and finding a date, the first Midwest Consortium of Global Child Health Educators meeting was held in Madison, WI. Now, after a dozen annual meetings, more than 30 articles, chapters, abstracts, and workshops, as well as the creating, piloting, and sharing of several widely used curricula in global health education, the founding consortium members share the practical steps for faculty looking to form similar regional consortia around shared interests. In this article, the authors provide a recipe for the successful formation of an academic consortium based on the lessons learned from their experience. [ Pediatr Ann . 2023;52(9):e351-e356.] .

The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine whether women with MS experience increased relapse rates after delivery. A systematic literature search was conducted in the databases MEDLINE and Epistemonikos on the topic 'motherhood choice in MS' in March 2022. We included cohort studies assessing the association between pregnancy and MS relapse activity defined by the annualised relapse rate after 3, 6, 9 and 12 months post partum. Furthermore, information about disease-modifying therapies (DMT) and breast feeding was considered, if available. 5369 publications were identified. Of these, 93 full-text articles on MS relapse activity during the postpartum period were screened. 11 studies including 2739 pregnancies were eligible. Women with MS showed a significantly increased relapse rate in the first 6 months post partum, compared with preconception with the incidence rate ratio (IRR) almost doubled in the first 3 months post partum (1.87, 95% CI 1.40 to 2.50). However, at 10-12 months post partum, the IRR decreased significantly (0.81, 95% CI 0.67 to 0.98). Subanalysis on influencing parameters suggested that preconceptional DMTs (IRR for highly-effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. Increased postpartum annualised relapse rate and possible modifiers should be considered in counselling women with MS who are considering pregnancy., Competing Interests: Competing interests: AG, ACR, CR, JP and LS have nothing to declare. KH reports research support and speaker honoraria from Biogen, Bayer Healthcare, Novartis Pharma, Teva, Sanofi Genzyme, Merck Serono and Roche. SMG reports honoraria from Mylan GmbH, Almirall S.A. and Celgene and research grants from Biogen, outside the submitted work. He receives research funding from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Bundesministerium für Gesundheit, the National MS Society and the European Commission. TF reports personal fees from Novartis, Bayer, Janssen, Roche, Vifor, BiosenseWebster, CSL Behring, Fresenius Kabi, Coherex Medical, LivaNova, Minoryx, Immunic, Bristol Myers Squibb, Enanta, IQVIA; all outside the submitted work. AS reports grants from the Fondazione Italiana Sclerosi Multipla and the European Academy of Neurology, during the conduct of the study; personal fees from Almirall and Merck Serono. CH received research grants or speaker honoraries from Biogen, Bristol Myers Squibb, Merck, Novartis and Roche., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Large-momentum-transfer (LMT) atom interferometers using elastic Bragg scattering on light waves are among the most precise quantum sensors to date. To advance their accuracy from the mrad to the μrad regime, it is necessary to understand the rich phenomenology of the Bragg interferometer, which differs significantly from that of a standard two-mode interferometer. We develop an analytic model for the interferometer signal and demonstrate its accuracy using comprehensive numerical simulations. Our analytic treatment allows the determination of the atomic projection noise limit of a LMT Bragg interferometer and provides the means to saturate this limit. It affords accurate knowledge of the systematic phase errors as well as their suppression by 2 orders of magnitude down to a few μrad using appropriate light-pulse parameters.

The workflow in modern hospitals entails that the medical treatment of a patient is distributed between several physicians and nurses. This leads to intensive cooperation, which takes place under particular time pressure and requires efficient conveyance of relevant patient-related medical data to colleagues. This requirement is difficult to achieve with traditional data representation approaches. In this paper, we introduce a novel concept of anatomically integrated in-place visualization designed to engage with cooperative tasks on a neurosurgical ward by using a virtual patient's body as spatial representation of visually encoded abstract medical data. Based on the findings of our field studies, we provide a set of formal requirements and procedures for this kind of visual encoding. Moreover, we implemented a prototype on a mobile device that supports the diagnosis of spinal disc herniation and has been evaluated by 10 neurosurgeons. The physicians have assessed the proposed concept as beneficial, especially emphasizing the advantages of the anatomical integration such as intuitiveness and a better data availability due to providing all information at a glance. Particularly, four of nine respondents have stressed solely benefits of the concept, other four have mentioned benefits with some limitations and only one person has seen no benefits.

C4-dicarboxylates (C4-DCs) such as fumarate, l-malate and l-aspartate are key substrates for Enterobacteria such as Escherichia coli or Salmonella typhimurium during anaerobic growth. In general, C4-DCs are oxidants during biosynthesis, e.g., of pyrimidine or heme, acceptors for redox balancing, a high-quality nitrogen source (l-aspartate) and electron acceptor for fumarate respiration. Fumarate reduction is required for efficient colonization of the murine intestine, even though the colon contains only small amounts of C4-DCs. However, fumarate can be produced endogenously by central metabolism, allowing autonomous production of an electron acceptor for biosynthesis and redox balancing. Bacteria possess a complex set of transporters for the uptake (DctA), antiport (DcuA, DcuB, TtdT) and excretion (DcuC) of C4-DCs. DctA and DcuB exert regulatory functions and link transport to metabolic control through interaction with regulatory proteins. The sensor kinase DcuS of the C4-DC two-component system DcuS-DcuR forms complexes with DctA (aerobic) or DcuB (anaerobic), representing the functional state of the sensor. Moreover, EIIA Glc from the glucose phospho-transferase system binds to DctA and presumably inhibits C4-DC uptake. Overall, the function of fumarate as an oxidant in biosynthesis and redox balancing explains the pivotal role of fumarate reductase for intestinal colonization, while the role of fumarate in energy conservation (fumarate respiration) is of minor importance., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Psychoneuroimmunology (PNI) is an area of interdisciplinary research exploring the complex interactions within the immuno-neuro-endocrine system in response to psychosocial influences. Such influences can trigger neurological changes, leading to immunological effects related to the emergence and course of various diseases. This concise clinical review explores the role of PNI in oral medicine in three exemplary models of oral disease: periodontitis, herpes labialis, and oral lichen planus. Previous literature has shown that psychosocial stress is related to exacerbations in these three oral diseases and to poorer overall oral health. The presumed biological mechanisms affect the activity of stress axes, i.e. the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), and subsequent immune system dysregulation. Although these PNI mechanisms remain poorly understood, several stress reduction interventions in clinical oral medicine have already yielded promising results. In future work, the elucidation of pathways within PNI networks will require carefully designed studies with sensitive methodology, e.g. the integrative single-case design. A biopsychosocial approach has the potential to move disease models in oral medicine from simple connections rooted in empirical dualism and reductionism to the establishment of network-based models. Further research on these complex connections should lead to novel clinical approaches and preventive strategies in oral medicine., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Recently studies based on limited sample sizes procured from minor hop growing regions have speculated that the elemental profile of hops can possibly be used to authenticate the origin of a hop because changes in hop elemental profiles were realted to growing region and that these changes might also be related to beer quality. To explore this further, 205 hop samples (i.e. 203 whole cone hops and 2 pelletized samples) compromised of 19 varieties were procured from the major hop growing regions (i.e. the U.S. and Germany). These hops were digested with microwave digestion and analyzed for 25 elements using ICP-MS. Hops from most of the U.S. regions (mainly WA) had vastly different elemental profiles than hops from Germany. German hops had significantly lower concentrations for most of the elements except for Cu and K. Interestingly, high alpha varieties had significantly different elemental profiles than varieties bred for aroma purposes. Dry-hopping trials were then performed in an ale and a lager with the hops that had significantly different elemental profiles. Although heavy metals were extracted from hops into beer, at the 5 g/L dry-hopping load used in this study, beer concentrations of these elements remained below regulated water quality standards set by Germany, the U.S., and Canada. Based on electron paramagnetic resonance, dry-hopping had an antioxidant impact on beer regardless of the original elemental profile of the hops which was correlated to hop polyphenol and α/ β - acid concentrations. Overall these results highlight that many factors including location have the potential to influence the elemental profile of hops and that changes in the elemental profiles of hops can be related to beer quality., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Understanding the factors which lead to the (in)stability of the chemistry and sensory of hoppy beer styles such as India Pale Ales (IPAs) has become a major concern for many brewers. Therefore, the evolution of several volatiles under different storage conditions (room temperature, cold storage, forced aging) was investigated in eleven hoppy ales and one lager which were commercially produced in Germany. Compared to the lager, the fresh ales contained higher initial aldehyde levels. Furthermore, the distribution of lipid oxidation and Maillard reaction products differed from those typically found in lager beer. Upon storage, significant increases of some staling aldehydes were observed. Interestingly, the concentrations of some hop aroma volatiles like terpenoids (i.e. linalool and geraniol) were relatively stable throughout storage and counteracted "oxidized" impressions in ales high in these compounds. In comparison, hop aroma in some ales was driven by less stable volatiles such as esters., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Metabolons represent the structural organization of proteins for metabolic or regulatory pathways. Here, the interaction of fumarase FumB, aspartase AspA, and L-tartrate dehydratase TtdAB with the C4-dicarboxylate (C4-DC) transporters DcuA, DcuB, DcuC, and the L-tartrate transporter TtdT of Escherichia coli was tested by a bacterial two-hybrid (BACTH) assay in situ, or by co-chromatography using mSPINE (membrane Streptavidin protein interaction experiment). From the general C4-DC transporters, DcuB interacted with FumB and AspA, DcuA with AspA, whereas DcuC interacted with neither FumB nor AspA. Moreover, TtdT did not interact with TtdAB. The fumB-dcuB, the dcuA-aspA, and the ttdAB-ttdT genes encoding the respective proteins colocalize on the genome and each pair of genes forms cotranscripts, whereas the dcuC gene lies alone. The data suggest the formation of DcuB/FumB and DcuB/AspA metabolons for the uptake of L-malate, or L-aspartate, and their conversion to fumarate for fumarate respiration and excretion of the product succinate. The DcuA/AspA metabolon catalyzes uptake and conversion of L-aspartate to fumarate coupled to succinate excretion. The DcuA/AspA metabolon provides ammonia at the same time for nitrogen assimilation (ammonia shuttle). On the other hand, TtdT and TtdAB are not organized in a metabolon. Reasons for the formation (DcuA/AspA, DcuB/FumB, and DcuB/AspA) or nonformation (DcuC, TtdT, and TtdAB) of metabolons are discussed based on their metabolic roles., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Centralization of clinical nurse educators (CNEs) from medical-surgical and critical care in a rural Midwestern hospital created role confusion and poor role outcomes. An evidence-based quality improvement project was developed to integrate the Association of Nursing Professional Development's transition to practice fellowship and practice model. Outcomes were focused on CNE self-assessed competency and three nurse-sensitive quality outcomes. Results were mixed but support that CNEs influenced patient quality outcomes and improved their self-assessed competency., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To gain a better understanding about which aspects of the treatment work for obsessive-compulsive disorders (OCD), the investigation of possible change factors is essential. Psychological flexibility (PsyF) has been of interest in research on successful OCD therapy for some time. Exposure interventions and cognitive strategies in cognitive behavioural therapy (CBT) for OCD may enhance PsyF. To date, however, no process studies have been published that clarify the role of PsyF as a possible change factor for the reduction of OCD symptoms., Aims: This study investigates whether PsyF works as a mediator in successful CBT treatment of OCD., Method: The study recruited 112 adults diagnosed with OCD in a multi-modal in-patient treatment with specific CBT including exposure and response prevention (ERP). The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to measure OCD symptoms and three self-constructed items to assess PsyF. PsyF was conceptualised as the capability of patients to accept stressful feelings and thoughts. Data were collected weekly. For statistical analysis at the process level, longitudinal multi-level models (MLMs) with random intercepts and linear growth curves were estimated to test for mediation of PsyF on Y-BOCS., Results: OCD symptoms decreased significantly and PsyF increased in patients throughout the course of therapy. MLM revealed that higher average values in PsyF were associated with lower Y-BOCS sum values, but only values between subjects significantly predicted the degree of obsessions and compulsions., Conclusions: Although research shows that PsyF is enhanced by CBT and also shows a connection with Y-BOCS values, its role as a mediator could not be confirmed.

Adenine nucleotides, such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), as well as the nucleoside adenosine are important modulators of neuronal function by engaging P1 and P2 purinergic receptors. In mitral cells, signaling of the G protein-coupled P1 receptor adenosine 1 receptor (A 1 R) affects the olfactory sensory pathway by regulating high voltage-activated calcium channels and two-pore domain potassium (K2P) channels. The inflammation of the central nervous system (CNS) impairs the olfactory function and gives rise to large amounts of extracellular ATP and adenosine, which act as pro-inflammatory and anti-inflammatory mediators, respectively. However, it is unclear whether neuronal A 1 R in the olfactory bulb modulates the sensory function and how this is impacted by inflammation. Here, we show that signaling via neuronal A 1 R is important for the physiological olfactory function, while it cannot counteract inflammation-induced hyperexcitability and olfactory deficit. Using neuron-specific A 1 R-deficient mice in patch-clamp recordings, we found that adenosine modulates spontaneous dendro-dendritic signaling in mitral and granule cells via A 1 R. Furthermore, neuronal A 1 R deficiency resulted in olfactory dysfunction in two separate olfactory tests. In mice with experimental autoimmune encephalomyelitis (EAE), we detected immune cell infiltration and microglia activation in the olfactory bulb as well as hyperexcitability of mitral cells and olfactory dysfunction. However, neuron-specific A 1 R activity was unable to attenuate glutamate excitotoxicity in the primary olfactory bulb neurons in vitro or EAE-induced olfactory dysfunction and disease severity in vivo . Together, we demonstrate that A 1 R modulates the dendro-dendritic inhibition (DDI) at the site of mitral and granule cells and impacts the processing of the olfactory sensory information, while A 1 R activity was unable to counteract inflammation-induced hyperexcitability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schubert, Schulz, Träger, Plath, Omriouate, Rosenkranz, Morellini, Friese and Hirnet.)

In a previous integrative single-case study, we collected biological, psychological and social time-series data on a 25-year-old healthy woman over the course of 126 12-h intervals (63 days) and used urinary neopterin as an indicator of cellular immune activity [Schubert et al. 2012 (1)]. The present re-evaluation introduced Dynamic Complexity (DC) as an additional non-linear and non-stationary measure to further investigate the subject's biopsychosocial dynamics during the study. The new time series dealing with urinary neopterin complexity revealed a cyclic, circaseptan (about-weekly) repeating pattern (6.59 days). The only weekly reoccurring events over the course of the study that were associated with this immunological pattern were the in-depth interviews with the subject (mean distance between interviews: 6.5 days). Superposed epoch analysis (SEA) revealed a U-shaped relation between neopterin complexity and interviews, with a decrease in neopterin complexity before and during interviews and an increase after interviews. Furthermore, the complexity scores for irritation, anxiousness/depressiveness and mental activity were positively correlated with neopterin complexity. The results suggest that the interviews, which had been found to be related to the subject's need for educational and/or social accomplishment, were marked by stress (decrease in psycho-immunological flexibility and adaptability), which was then relieved after the interviews (increase in psycho-immunological flexibility and adaptability). It appears that the subject's cellular immune activity, as indicated by neopterin complexity, functionally mirrored the emotional meaning she ascribed to the in-depth interviews. This re-evaluation is in line with the view that biopsychosocial research requires multimodal analysis of single cases based on qualitative (e.g., in-depth interviews) and quantitative (e.g., time series analysis) data under conditions of "life as it is lived"., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seizer, Cornélissen-Guillaume, Schiepek, Chamson, Bliem and Schubert.)

A novel interprofessional clinical informatics curriculum was developed, piloted, and implemented, using an academic medical record. Targeted learners included undergraduate, graduate, and professional students across five health science colleges. A team of educators and practitioners representing those five health science colleges was formed in 2016, to design, develop, and refine educational modules covering the essentials of clinical informatics. This innovative curriculum consists of 10 online learning modules and 18 unique imbedded exercises that use standardized patient charts and tailored user views. The exercises allow learners to adopt the role of various providers who document in EMRs. Students are exposed to the unique perspectives of an attending physician, nurse, radiological technician, and health information manager, with the goal of developing knowledge and skills necessary for efficient and effective interprofessional communication within the EMR. The campus-wide clinical informatics curriculum is online, flexible, asynchronous, and well-established within each college, allowing faculty to select and schedule content based on discipline-specific learner and course needs. Program modifications over the past 4 years have correlated with a positive impact on the students' experience., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

The C 4 -dicarboxylates (C4-DC) l-aspartate and l-malate have been identified as playing an important role in the colonization of mammalian intestine by enteric bacteria, such as Escherichia coli and Salmonella enterica serovar Typhimurium, and succinate as a signaling molecule for host-enteric bacterium interaction. Thus, endogenous and exogenous fumarate respiration and related functions are required for efficient initial growth of the bacteria. l-Aspartate represents a major substrate for fumarate respiration in the intestine and a high-quality substrate for nitrogen assimilation. During nitrogen assimilation, DcuA catalyzes an l-aspartate/fumarate antiport and serves as a nitrogen shuttle for the net uptake of ammonium only, whereas DcuB acts as a redox shuttle that catalyzes the l-malate/succinate antiport during fumarate respiration. The C4-DC two-component system DcuS-DcuR is active in the intestine and responds to intestinal C4-DC levels. Moreover, in macrophages and in mice, succinate is a signal that promotes virulence and survival of S . Typhimurium and pathogenic E. coli. On the other hand, intestinal succinate is an important signaling molecule for the host and activates response and protective programs. Therefore, C4-DCs play a major role in supporting colonization of enteric bacteria and as signaling molecules for the adaptation of host physiology.

Objective: To assess the effectiveness of a pharmacist-led intervention using validated tools to reduce medicine-induced deterioration and adverse reactions., Design and Setting: Multicenter, open-label parallel randomised controlled trial involving 39 Australian aged-care facilities., Participants: Residents on ≥4 medicines or ≥1 anticholinergic or sedative medicine., Intervention: Pharmacist-led intervention using validated tools to detect signs and symptoms of medicine-induced deterioration which occurred every 8 weeks over 12 months., Comparator: Usual care (Residential Medication Management Review) provided by accredited pharmacists., Outcomes: Primary outcome was change in Frailty Index at 12 months. Secondary outcomes included changes in cognition, 24-hour movement behaviour by accelerometry, grip strength, weight, adverse events and quality of life., Results: 248 persons (median age 87 years) completed the study; 120 in the interventionand, 128 in control arms. In total 575 pharmacist, sessions were undertaken in the intervention arm. There was no statistically significant difference for change in frailty between groups (mean difference: 0.009, 95% CI: -0.028, 0.009, P = 0.320). A significant difference for cognition was observed, with a mean difference of 1.36 point change at 12 months (95% CI: 0.01, 2.72, P = 0.048). Changes in 24-hour movement behaviour, grip strength, adverse events and quality of life were not significantly different between groups. Point estimates favoured the intervention arm at 12 months for frailty, 24-hour movement behaviour and grip strength., Conclusions: The use of validated tools by pharmacists to detect signs of medicine-induced deterioration is a model of practice that requires further research, with promising results from this trial, particularly with regards to improved cognition., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Matricaria aurea (Loefl.) Schultz Bip. (Asteraceae), known as golden chamomile, has been traditionally used for the treatment of various diseases. In this study, total phenolic, flavonoid, and tannin contents of total extract and different fractions of this plant were determined. The antioxidant, cytotoxic, and antimicrobial activities were also evaluated. Moreover, the phenolic profiles of selected fractions were determined by HPLC and LC-MS/MS analysis. Results demonstrated total phenolic contents of 37.8-57.2 mg GAE/g and total flavonoid contents of 3.0-111.2 mg QE/g. The ethyl acetate and methanol fractions (EF and MF) had the highest concentrations of phenolic, tannin, and flavonoid compounds. In both DPPH radical scavenging assay and phosphomolybdenum reduction assay, EF showed the best antioxidant activity, followed by MF. EF and MF indicated also the best antibacterial activities against Bacillus subtilis (MIC 1.56 and 12.5 mg ml -1 ) and Staphylococcus aureus (MIC 0.78 and 12.5 mg ml -1 ). Hexane fraction (HF) had no antibacterial effect. None of the samples had antifungal effect. MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed for EF and HF the highest antiproliferative activities (IC 50 values ranged from 111.8 to 294.6 μg ml -1 ). The presence of chlorogenic acid, ferulic acid, and luteolin-7-O-glucoside in MF, and p-coumaric acid in EF was confirmed and quantified., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Abstract: Resource restraints and the movement toward competency-based education encourage exploration of innovative simulation experiences in advanced practice registered nurse education. Building upon existing best practices in simulation development, this pilot project explores opportunities and challenges translating these practices to the advanced practice registered nurse context. Innovations focused on using a competency-based framework, developing a competency-based evaluation tool, and providing feedback from faculty and standardized patients. Lessons learned from this experience inform recommendations for how to design instructional experiences and provide formative methods of feedback for nurse practitioner student assessment., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2021 National League for Nursing.)

Background: Students who value peer feedback processes are more likely to provide supportive feedback to peers., Purpose: The purpose of this study was to explore the factors that motivate and demotivate students to provide supportive feedback to peers., Method: A secondary analysis of qualitative data collected from 148 graduate nursing students in 7 master's-level courses was conducted to identify the themes related to motivating and demotivating factors in peer review and how they related to students' sense of value for providing supportive peer feedback., Results: Common themes included perceived potential for supportive peer feedback to improve self, peer, and team performance, and quality of patient care. Themes related to demotivation included lack of time and fear of negative impact on peers., Conclusion: Faculty should emphasize to students the positive impact of supportive peer feedback on nursing care. Assignments can be structured to promote a fair exchange of supportive feedback between peers., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pediatric residents participating in global health electives (GHEs) report an improved knowledge of medicine and health disparities. However, GHEs may pose challenges that include cost, personal safety, or individual mental health issues. The objective of this study was to describe the use of guided reflections to understand resident resilience during GHEs. Forty-five residents enrolled in two pediatric training programs were asked to respond in writing to weekly prompts during a GHE and to complete a post-trip essay. Analysis of the reflections and essays, including an inductive thematic analysis, was completed. Two coders performed a second analysis to support classification of themes within the Flinders Student Resilience (FSR) framework. Four themes emerged from the initial analysis: 1) benefits, 2) stresses and challenges, 3) career development, and 4) high-value care. Analysis using the FSR framework revealed the following themes: acknowledgment of personal limitations, importance of relationships in coping throughout the GHE, and discernment of career focus. Reflective writing provided insight into how residents mitigate GHE challenges and develop resilience. Despite statements of initial distress, residents focused on their personal benefits and growth during the GHE. The FSR framework revealed the residents' robust self-awareness of limitations and that strong relationships on the ground and at home were associated with perceived benefits and growth. Programs should consider helping residents to identify healthy coping practices that can promote personal resilience during GHEs as part of pre-departure preparation and debriefing, as well as providing for supportive communities during the GHE.

Transcranial alternating current stimulation (tACS) modulates oscillations in a frequency- and location-specific manner and affects cognitive and motor functions. This effect appears during stimulation as well as "offline," following stimulation, presumably reflecting neuroplasticity. Whether tACS produces long-lasting aftereffects that are physiologically meaningful, is still of current debate. Thus, for tACS to serve as a reliable method for modulating activity within neural networks, it is important to first establish whether "offline" aftereffects are robust and reliable. In this study, we employed a novel machine-learning approach to detect signatures of neuroplasticity following 10-Hz tACS to two critical nodes of the motor network: left motor cortex (lMC) and right cerebellum (rCB). To this end, we trained a classifier to distinguish between signals following lMC-tACS, rCB-tACS, and sham. Our results demonstrate better classification of electroencephalography (EEG) signals in both theta (θ, 4-8 Hz) and alpha (α, 8-13 Hz) frequency bands to lMC-tACS compared with rCB-tACS/sham, at lMC-tACS stimulation location. Source reconstruction allocated these effects to premotor cortex. Stronger correlation between classification accuracies in θ and α in lMC-tACS suggested an association between θ and α efffects. Together these results suggest that EEG signals over premotor cortex contains unique signatures of neuroplasticity following 10-Hz motor cortex tACS., (© The Author(s) 2022. Published by Oxford University Press.)

Background: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care., Methods: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm., Results: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04)., Conclusion: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The National Aeronautics and Space Administration's Deep Space Quantum Link mission concept enables a unique set of science experiments by establishing robust quantum optical links across extremely long baselines. Potential mission configurations include establishing a quantum link between the Lunar Gateway moon-orbiting space station and nodes on or near the Earth. This publication summarizes the principal experimental goals of the Deep Space Quantum Link. These goals, identified through a multi-year design study conducted by the authors, include long-range teleportation, tests of gravitational coupling to quantum states, and advanced tests of quantum nonlocality., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)