Epidemiological and clinical burden of Clostridioides difficile infections and recurrences between 2015 - 2019: the RECUR Germany study.

BACKGROUND: This real-world study assessed the epidemiology and clinical complications of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in hospital and community settings in Germany from 2015 - 2019. METHODS: An observational retrospective cohort study was conducted among adult patients diagnosed with CDI in hospital and community settings using statutory health insurance claims data from the BKK database. A cross-sectional approach was used to estimate the annual incidence rate of CDI and rCDI episodes per 100,000 insurants. Patients' demographic and clinical characteristics were described at the time of first CDI episode. Kaplan-Meier method was used to estimate the time to rCDIs and time to complications (colonic perforation, colectomy, loop ileostomy, toxic megacolon, ulcerative colitis, peritonitis, and sepsis). A Cox model was used to assess the risk of developing complications, with the number of rCDIs as a time-dependent covariate. RESULTS: A total of 15,402 CDI episodes were recorded among 11,884 patients. The overall incidence of CDI episodes declined by 38% from 2015 to 2019. Most patients (77%) were aged ≥ 65 years. Around 19% of CDI patients experienced at least one rCDI. The median time between index CDI episode to a rCDI was 20 days. The most frequent complication within 12-months of follow-up after the index CDI episode was sepsis (7.57%), followed by colectomy (3.20%). The rate of complications increased with the number of rCDIs. The risk of any complication increased by 31% with each subsequent rCDI (adjusted hazard ratio [HR]: 1.31, 95% confidence interval: 1.17;1.46). CONCLUSIONS: CDI remains a public health concern in Germany despite a decline in the incidence over recent years. A substantial proportion of CDI patients experience rCDIs, which increase the risk of severe clinical complications. The results highlight an increasing need of improved therapeutic management of CDI, particularly efforts to prevent rCDI.

Linking biodiversity, ecosystem function, and Nature's contributions to people: a macroecological energy flux perspective.

At macroecological scales, the provision of Nature's contributions to people (NCP) is mostly estimated with biophysical information, ignoring the ecological processes underlying them. This hinders our ability to properly quantify the impact of declining biodiversity and the provision of NCP. Here, we propose a framework that combines local-scale food web energy flux approaches and large-scale biodiversity models to evaluate ecosystem functions and flux-related NCP at extensive spatiotemporal scales. Importantly, this approach has the potential to upscale ecosystem functions, assess the vulnerability of flux-related NCP to the climate crisis, and support the development of multiscale mitigation policies.

Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: The RECUR England study.

OBJECTIVES: To generate real-world evidence on all-cause mortality and economic burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: We conducted a cohort study using retrospective data from Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients diagnosed with CDI in hospital and community settings during 2015-2018 were included and followed for ≥1 year. All-cause mortality was described at 6, 12, and 24 months. Healthcare resource usage (HCRU) and associated costs were assessed at 12 months of follow-up. A cohort of non-CDI patients, matched by demographic and clinical characteristics including Charlson Comorbidity Index score, was used to assess excess mortality and incremental costs of HCRU. RESULTS: All-cause mortality among CDI patients at 6, 12, and 24 months was 15.87%, 20.37%, and 27.03%, respectively. A higher proportion of rCDI patients died at any point during follow-up. Compared with matched non-CDI patients, excess mortality was highest at 6 months with 1.81 and 2.53 deaths per 100 patient-months among CDI and ≥1 rCDI patients. Hospitalizations were the main drivers of costs, with an incremental cost of £1209.21 per CDI patient. HCRU and costs increased with rCDIs. CONCLUSION: CDI poses a substantial mortality and economic burden, further amplified by rCDIs.

Quantitative description of six fish species' gut contents and prey abundances in the Baltic Sea (1968-1978).

The dataset presents a compilation of stomach contents from six demersal fish species from two functional groups inhabiting the Baltic Sea. It includes detailed information on prey identities, body masses, and biomasses recovered from both the fish's digestive systems and their surrounding environment. Environmental parameters, such as salinity and temperature levels, have been integrated to enrich this dataset. The juxtaposition of information on prey found in stomachs and in the environment provides an opportunity to quantify trophic interactions across different environmental contexts and investigate how fish foraging behaviour adapts to changes in their environment, such as an increase in temperature. The compilation of body mass and taxonomic information for all species allows approaching these new questions using either a taxonomic (based on species identity) or functional trait (based on body mass) approach.

Coping strategies and social support in nursing students during clinical practice: A scoping review.

AIM: To identify the coping strategies and social support received by nursing students during clinical practice. DESIGN: Scoping review. METHODS: Primary studies on coping strategies and social support, in full text, in English, French, Spanish or Portuguese and published in 2018 or later were included. Search was carried out in January 2023 on EBSCOhost, PubMed, SciELO, ScienceDirect, OpenAIRE, MedNar Search, WorldWideScience and the references of previously selected articles. RESULTS: A total of 24 studies were identified. Seven studies mentioned social support as a useful strategy and several instruments were identified that allow measurement. CONCLUSIONS: Few studies establish a direct relationship between the effectiveness of coping strategies with stressful situations. Positive coping strategies are associated with effective stress management. The relationship between social support and stress reduction is scarcely addressed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Stressful situations can have an impact on students' health and on the quality of care. Nursing schools and healthcare institutions must work together in programmes to improve students coping abilities. IMPACT: This review addressed coping strategies used by nursing students during clinical practice. A set of relevant coping strategies were identified that can be used by teachers to improve students' outcomes. REPORTING METHOD: The review was performed according to Preferred Reporting Items for Scoping Reviews (PRISMA-ScR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Clostridioides difficile infections, recurrences, and clinical outcomes in real-world settings from 2015 to 2019: The RECUR England study.

OBJECTIVE: To estimate the epidemiological and clinical burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: This retrospective study included adult patients diagnosed with CDI (community or hospital settings) over 2015-2019 from Clinical Practice Research Datalink and Hospital Episode Statistics databases. Incidences of CDI and rCDI were determined annually. Time to subsequent rCDI was estimated by Kaplan-Meier method. Rates of complications were assessed within 12 months from index episode. Association of risk factors with complications was evaluated using a Cox regression model. RESULTS: A total of 52,443 CDI episodes were recorded among 36,913 patients. Of these, 75% were aged ≥65 years, 59% were women; 73% were treated in community settings. CDI incidence remained stable (111 episodes per 100,000 patients in 2019). Around 21% of patients had ≥1 rCDI. Sepsis (12%) was the most common complication, followed by colectomy and ulcerative colitis. Age, gender, comorbidities, rCDI, preindex medical procedures, hospitalizations and consultations, and CDI treatment in hospital, were found to increase the risk of complication. CONCLUSIONS: CDI remains a concern in England. The study highlights the importance of managing primary and rCDI episodes via effective and improved therapies to prevent fatal complications.

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.

In vitro production of cat-restricted Toxoplasma pre-sexual stages.

Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described1,2. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. 1), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.

Preclinical Evaluation of a Radiotheranostic Single-Domain Antibody Against Fibroblast Activation Protein α.

Fibroblast activation protein α (FAP) is highly expressed on cancer-associated fibroblasts of epithelial-derived cancers. Breast, colon, and pancreatic tumors often show strong desmoplastic reactions, which result in a dominant presence of stromal cells. FAP has gained interest as a target for molecular imaging and targeted therapies. Single-domain antibodies (sdAbs) are the smallest antibody-derived fragments with beneficial pharmacokinetic properties for molecular imaging and targeted therapy. Methods: We describe the generation, selection, and characterization of a sdAb against FAP. In mice, we assessed its imaging and therapeutic potential after radiolabeling with tracer-dose 131I and 68Ga for SPECT and PET imaging, respectively, and with 131I and 225Ac for targeted radionuclide therapy. Results: The lead sdAb, 4AH29, exhibiting picomolar affinity for a distinct FAP epitope, recognized both purified and membrane-bound FAP protein. Radiolabeled versions, including [68Ga]Ga-DOTA-4AH29, [225Ac]Ac-DOTA-4AH29, and [131I]I-guanidinomethyl iodobenzoate (GMIB)-4AH29, displayed radiochemical purities exceeding 95% and effectively bound to recombinant human FAP protein and FAP-positive GM05389 human fibroblasts. These radiolabeled compounds exhibited rapid and specific accumulation in human FAP-positive U87-MG glioblastoma tumors, with low but specific uptake in lymph nodes, uterus, bone, and skin (∼2-3 percentage injected activity per gram of tissue [%IA/g]). Kidney clearance of unbound [131I]I-GMIB-4AH29 was fast (<1 %IA/g after 24 h), whereas [225Ac]Ac-DOTA-4AH29 exhibited slower clearance (8.07 ± 1.39 %IA/g after 24 h and 2.47 ± 0.18 %IA/g after 96 h). Mice treated with [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 demonstrated prolonged survival compared with those receiving vehicle solution. Conclusion: [68Ga]Ga-DOTA-4AH29 and [131I]I-GMIB-4AH29 enable precise FAP-positive tumor detection in mice. Therapeutic [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 exhibit strong and sustained tumor targeting, resulting in dose-dependent therapeutic effects in FAP-positive tumor-bearing mice, albeit with kidney toxicity observed later for [225Ac]Ac-DOTA-4AH29. This study confirms the potential of radiolabeled sdAb 4AH29 as a radiotheranostic agent for FAP-positive cancers, warranting clinical evaluation.

Factors Associated with Parenting Adaptability in Facing the First COVID-19 Lockdown: A Study on Portuguese Parents.

Parenting was drastically challenged during the COVID-19 pandemic as families complied with the consequent containment for sanitary and social reasons. The purpose of this study is to explore the relationships among self-report measures (co-parenting, emotional experience and parental support network) and the employment condition (teleworking parents and at-home parents with governmental leave aid) that might be associated with the everyday life change, and their contribution towards family's daily routines during the first COVID-19 lockdown. A sample of 878 parents (90.2% mothers), aged from 21 to 61 years (39.58 ± 6.08), and mainly of Portuguese nationality (97.2%), was gathered through an online survey. Participants completed sociodemographic data and answered questions related to four positive parenting dimensions (Daily routines, Co-parenting, Emotional experience, and Support network) rating on a five-point Likert scale how much their behavior changed during the lockdown. Descriptive statistics and multilinear regression models were tested as well as a mediation model. The results showed that Emotional experience, Co-parenting, and Support network played an important role in family Daily routines, reinforcing that the first COVID-19 lockdown was lived differently by parents according to their employment conditions. Furthermore, the pathways model of factors associated with parental adaptability is suggestive that the direct effect of Emotional experience on Daily routines is partially mediated by Co-parenting and Support network. In line with previous studies on the complexity and dynamic ecology of parenting, the reported indicators showcase the interrelated facets of parenting and its corresponding support needs. Further, clear indicators for the design of family support interventions and family resilience enhancement to stressor events are discussed.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

Economic impact of reducing treatment gaps in depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent across Europe. While evidence-based treatments exist, many people with MDD have their condition undetected and/or untreated. This study aimed to assess the cost-effectiveness of reducing treatment gaps using a modeling approach. METHODS: A decision-tree model covering a 27-month time horizon was used. This followed a care pathway where MDD could be detected or not, and where different forms of treatment could be provided. Expected costs pertaining to Germany, Hungary, Italy, Portugal, Sweden, and the UK were calculated and quality-adjusted life years (QALYs) were estimated. The incremental costs per QALY of reducing detection and treatment gaps were estimated. RESULTS: The expected costs with a detection gap of 69% and treatment gap of 50% were €1236 in Germany, €476 in Hungary, €1413 in Italy, €938 in Portugal, €2093 in Sweden, and €1496 in the UK. The incremental costs per QALY of reducing the detection gap to 50% ranged from €2429 in Hungary to €10,686 in Sweden. The figures for reducing the treatment gap to 25% ranged from €3146 in Hungary to €13,843 in Sweden. CONCLUSIONS: Reducing detection and treatment gaps, and maintaining current patterns of care, is likely to increase healthcare costs in the short term. However, outcomes are improved, and reducing these gaps to 50 and 25%, respectively, appears to be a cost-effective use of resources.

Application of thermography to estimate respiratory rate in the emergency room: The journal Temperature toolbox.

Among the vital signs collected during hospital triage, respiratory rate is an important parameter associated with physiological, pathophysiological, and emotional changes. In recent years, the importance of its verification in emergency centers due to the severe acute respiratory syndrome 2 (SARS2) pandemic has become very clear, although it is still one of the least evaluated and collected vital signs. In this context, infrared imaging has been shown to be a reliable estimator of respiratory rate, with the advantage of not requiring physical contact with patients. The objective of this study was to evaluate the potential of analyzing a sequence of thermal images as an estimator of respiratory rate in the clinical routine of an emergency room. We used an infrared thermal camera (T540, Flir Systems) to obtain the respiratory rate data of 136 patients, based on nostrils' temperature fluctuation, during the peak of the COVID-19 pandemic in Brazil and compared it with the chest incursion count method, commonly employed in the emergency screening procedures. We found a good agreement between both methods, with Bland-Altman limits of agreement ranging from -4 to 4 min-1, no proportional bias (R2 = 0.021, p = 0.095), and a strong correlation between them (r = 0.95, p < 0.001). Our results suggest that infrared thermography has potential to be a good estimator of respiratory rate in the routine of an emergency room.

10th antibody industrial symposium: new developments in antibody and adoptive cell therapies.

The annual "Antibody Industrial Symposium", co-organized by LabEx MAbImprove and MabDesign, held its 10th anniversary edition in Montpellier, France, on June 28-29, 2022. The meeting focused on new results and concepts in antibody engineering (naked, mono- or multi-specific, conjugated to drugs or radioelements) and also on new cell-based therapies, such as chimeric antigenic receptor (CAR)-T cells. The symposium, which brought together scientists from academia and industry, also addressed issues concerning the production of these molecules and cells, and the necessary steps to ensure a strong intellectual property protection of these new molecules and approaches. These two days of exchanges allowed a rich discussion among the various actors in the field of therapeutic antibodies.

Potential of using facial thermal imaging in patient triage of flu-like syndrome during the COVID-19 pandemic crisis.

The screening of flu-like syndrome is difficult due to nonspecific symptoms or even oligosymptomatic presentation and became even more complex during the Covid-19 pandemic. However, an efficient screening tool plays an important role in the control of highly contagious diseases, allowing more efficient medical-epidemiological approaches and rational management of global health resources. Infrared thermography is a technique sensitive to small alterations in the skin temperature which may be related to early signs of inflammation and thus being relevant in the detection of infectious diseases. Thus, the objective of this study was to evaluate the potential of facial thermal profiles as a risk evaluator of symptoms and signs of SARs diseases, using COVID-19 as background disease. A total of 136 patients were inquired about the most common symptoms of COVID-19 infection and were submitted to an infrared image scanning, where the temperatures of 10 parameters from different regions of the face were captured. We used RT-qPCR as the ground truth to compare with the thermal parameters, in order to evaluate the performance of infrared imaging in COVID-19 screening. Only 16% of infected patients had fever at the hospital admission, and most infrared thermal variables presented values of temperature significantly higher in infected patients. The maximum eye temperature (MaxE) showed the highest predictive value at a cut-off of >35.9°C (sn = 71.87%, sp = 86.11%, LR+ = 5.18, LR- = 0.33, AUC = 0.850, p < 0.001). Our predictive model reached an accuracy of 86% for disease detection, indicating that facial infrared thermal scanning, based on the combination of different facial regions and the thermal profile of the face, has potential to act as a more accurate diagnostic support method for early COVID-19 screening, when compared to classical infrared methods, based on a single spot with the maximum skin temperature of the face.

Height benefit of GnRH agonists after age 8 in a Portuguese cohort of central precocious puberty.

OBJECTIVE: Idiopathic central precocious puberty (iCPP) is common in paediatric endocrinology. Gonadotropin-releasing hormone agonists (GnRHa) are safe, but the effect on final height and the ideal timing for treatment remains controversial. This study aims to assess the effectiveness of GnRHa on growth outcomes in girls with iCPP treated before and after the age of 8 years old. DESIGN AND PATIENTS: This retrospective longitudinal study evaluated data from Portuguese girls with iCPP who completed treatment between 2010 and 2021. MEASUREMENTS: Auxological and clinical characteristics were compared according to age at treatment onset. RESULTS: A cohort of 134 girls with iCPP, was divided into early treatment (ET) (<8 years, n = 48) and later treatment (LT) groups (≥8 years, n = 86). In both groups, most children presented with Tanner II and III. Tanner IV was more frequent in LT group (p = .003). At the end of treatment, predicted adult height increased in both groups (ET p = .032; LT p = .04) and bone age significantly slowed down in all participants (p = .008, p = .034). The height gain was greater in the ET group, but without significant differences (p = .065). CONCLUSIONS: Treatment with GnRHa improved final height in all girls with iCPP, even when initiated after 8 years. To achieve better outcomes, treatment should be provided promptly after diagnosis.

In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming.

Sexual reproduction of Toxoplasma gondii , which is restricted to the small intestine of felids, is sparsely documented, due to ethical concerns surrounding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described 1 . In this study, we found that transcription factors AP2XII-1 and AP2XI-2, expressed in tachyzoite stage that causes acute toxoplasmosis, can silence genes necessary for merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites. Pre-gametes produced in vitro under these conditions are characterized by specific protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit the epigenitors MORC and HDAC3 1 , which in turn restrict the accessibility of chromatin to the transcriptional machinery. Thus, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. This effective in vitro culture of merozoites paves the way to explore Toxoplasma sexual reproduction without the need to infect kittens and has potential for the development of therapeutics to block parasite transmission.

Measuring subjective aspects of participation in adults with disabilities: A systematic review of the coverage, content validity and internal structure of standardised instruments.

OBJECTIVE: To systematically review evidence on the coverage, content validity and internal structure of self-report measures capturing subjective aspects of participation for adults with disabilities. DATA SOURCES: EMBASE, MEDLINE and reference lists were searched until July 10th, 2022 for articles on measurement properties of instruments measuring participation as defined in the International Classification of Functioning, Disability and Health, from a subjective perspective. METHOD: Each instrument was assessed for its coverage of subjective aspects of participation. The Consensus-based Standards for the Selection of Health Measurement Instruments were used to assess the quality of each study. Content validity and internal structure (structural validity, internal consistency and cross-cultural validity) were rated against published standards and qualified by the adapted Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Thirty-eight studies regarding 10 instruments were analysed. Most instruments mix activity and participation items. Only the Measure of Experiential Aspects of Participation (with high-quality evidence of sufficient structural validity and generally sufficient internal consistency), the Participation Enfranchisement and the Community Integration Measure showed adequate coverage. For all instruments, evidence of content validity is of low- to very low quality. There is high-quality evidence that the Participation Scale is not unidimensional. CONCLUSION: In general, the coverage and the evidence for content validity and internal structure of measures capturing experiential aspects of participation are limited. The Measure of Experiential Aspects of Participation has the best level of evidence in support of its use. The score of the Participation Scale cannot be considered an adequate reflection of participation.

Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation.

Microglia and border-associated macrophages (BAMs) are brain-resident self-renewing cells. Here, we examined the fate of microglia, BAMs, and recruited macrophages upon neuroinflammation and through resolution. Upon infection, Trypanosoma brucei parasites invaded the brain via its border regions, triggering brain barrier disruption and monocyte infiltration. Fate mapping combined with single-cell sequencing revealed microglia accumulation around the ventricles and expansion of epiplexus cells. Depletion experiments using genetic targeting revealed that resident macrophages promoted initial parasite defense and subsequently facilitated monocyte infiltration across brain barriers. These recruited monocyte-derived macrophages outnumbered resident macrophages and exhibited more transcriptional plasticity, adopting antimicrobial gene expression profiles. Recruited macrophages were rapidly removed upon disease resolution, leaving no engrafted monocyte-derived cells in the parenchyma, while resident macrophages progressively reverted toward a homeostatic state. Long-term transcriptional alterations were limited for microglia but more pronounced in BAMs. Thus, brain-resident and recruited macrophages exhibit diverging responses and dynamics during infection and resolution.