Anti-CD45 PBD-based antibody-drug conjugates are effective targeted conditioning agents for gene therapy and stem cell transplant.

Stem cell gene therapy and hematopoietic stem cell transplantation (SCT) require conditioning to ablate the recipient's hematopoietic stem cells (HSCs) and create a niche for gene-corrected/donor HSCs. Conventional conditioning agents are non-specific, leading to off-target toxicities and resulting in significant morbidity and mortality. We developed tissue-specific anti-human CD45 antibody-drug conjugates (ADCs), using rat IgG2b anti-human CD45 antibody clones YTH24.5 and YTH54.12, conjugated to cytotoxic pyrrolobenzodiazepine (PBD) dimer payloads with cleavable (SG3249) or non-cleavable (SG3376) linkers. In vitro, these ADCs internalized to lysosomes for drug release, resulting in potent and specific killing of human CD45+ cells. In humanized NSG mice, the ADCs completely ablated human HSCs without toxicity to non-hematopoietic tissues, enabling successful engraftment of gene-modified autologous and allogeneic human HSCs. The ADCs also delayed leukemia onset and improved survival in CD45+ tumor models. These data provide proof of concept that conditioning with anti-human CD45-PBD ADCs allows engraftment of donor/gene-corrected HSCs with minimal toxicity to non-hematopoietic tissues. Our anti-CD45-PBDs or similar agents could potentially shift the paradigm in transplantation medicine that intensive chemo/radiotherapy is required for HSC engraftment after gene therapy and allogeneic SCT. Targeted conditioning both improve the safety and minimize late effects of these procedures, which would greatly increase their applicability.

Abnormal Activity of Masticatory Muscles in Patients with Diagnosis of Cerebral Palsy. A Systematic Review and Meta-Analysis of Observational Studies.

AIMS: to map and synthesize the results from studies that assessed whether individuals diagnosed with cerebral palsy (CP) have abnormal masseter and temporal muscles activation during the masticatory cycle. METHODS: Six databases were searched for comparative observational studies assessing masticatory muscles activation in individuals with CP through electromyography analysis. Methodological quality was evaluated using the Joanna Briggs Critical Appraisal Checklist. Outcome data were combined in meta-analysis using the Review Manager software. RESULTS: We included five cross-sectional studies with an overall low risk of bias. Meta-analyses showed no difference between CP and healthy individuals regarding maximum voluntary isometric contraction: right masseter (Standard mean difference [SMD] - 0.95; 95% CI -2.03 to 0.13); left masseter (SMD -0.92; 95% CI -1.93 to 0.09); right temporal (SMD -0.72; 95% CI -1.63 to 0.18); and left temporal (SMD -0.68; 95% CI -1.76 to 0.40). Electrical activity amplitude in the inactive period was superior in the CP group, and maximum bite pressure presented higher values in the control group (Mean difference [MD] - 17.38; CI 95% -26.62 to -10.15). CONCLUSIONS: Based on observational studies with a lower level of evidence, individuals with CP seem to present difficulties activating masticatory muscles. Future prospective cohort studies with rigorous methodology are still necessary to support these findings. PROSPERO register CRD42020208444.

Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression.

OBJECTIVE: Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour. DESIGN: We have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs). RESULTS: We demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin+ EVs show a significant increased risk of disease progression. CONCLUSION: PDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.

Impact of Environmental Factors on Post-Stroke Disability: An Analytical Cross-Sectional Study.

OBJECTIVES: Identify how environmental barriers and facilitators are associated with disability in stroke survivors. MATERIALS AND METHODS: An analytical, cross-sectional study was conducted involving individuals in the chronic stage of stroke. The dependent variable was disability, which was assessed using the World Health Organization Disability Assessment Schedule (WHODAS-2.0). Environmental factors (independent variable) were evaluated using the Measure of the Quality of the Environment (MQE). Multiple linear regression analysis was performed to estimate the impact of the environment on disability following a stroke. RESULTS: Seventy-five individuals (mean age: 54.2 + 9.8 years) were analyzed. The most frequent environmental facilitators were related to technology, social networks, and public services. The main barriers were related to the physical environment. Environmental barrier was a predictor of both overall disability [F(1.73) = 4.24; R2=0.06; ß = -0.23; t = -2.06; p=0.04] and participation [F(1.73) = 10.45; R2=0.13; ß = -0.35; t = -3.23; p = 0.01]. Environmental facilitators were not correlated with disability. CONCLUSION: Environmental barriers explained 13% of the variation in restrictions to social participation and were also a significant predictor of overall disability. The main barriers were related to the physical environment. Identifying environmental factors related to disability in stroke victims can assist in the planning of guided therapy.

Restraint upon Embryonic Metatarsal Ex Vivo Growth by Hydrogel Reveals Interaction between Quasi-Static Load and the mTOR Pathway.

Mechanical cues play a vital role in limb skeletal development, yet their influence and underpinning mechanisms in the regulation of endochondral ossification (EO) processes are incompletely defined. Furthermore, interactions between endochondral growth and mechanics and the mTOR/NF-ĸB pathways are yet to be explored. An appreciation of how mechanical cues regulate EO would also clearly be beneficial in the context of fracture healing and bone diseases, where these processes are recapitulated. The study herein addresses the hypothesis that the mTOR/NF-ĸB pathways interact with mechanics to control endochondral growth. To test this, murine embryonic metatarsals were incubated ex vivo in a hydrogel, allowing for the effects of quasi-static loading on longitudinal growth to be assessed. The results showed significant restriction of metatarsal growth under quasi-static loading during a 14-day period and concentration-dependent sensitivity to hydrogel-related restriction. This study also showed that hydrogel-treated metatarsals retain their viability and do not present with increased apoptosis. Metatarsals exhibited reversal of the growth-restriction when co-incubated with mTOR compounds, whilst it was found that these compounds showed no effects under basal culture conditions. Transcriptional changes linked to endochondral growth were assessed and downregulation of Col2 and Acan was observed in hydrogel-treated metatarsi at day 7. Furthermore, cell cycle analyses confirmed the presence of chondrocytes exhibiting S-G2/M arrest. These data indicate that quasi-static load provokes chondrocyte cell cycle arrest, which is partly overcome by mTOR, with a less marked interaction for NF-ĸB regulators.

Exosomes in cancer: Use them or target them?

Exosomes are small extracellular vesicles with a significant role in most processes associated with cancer. On one hand, exosomes role in the different hallmarks of cancer has been widely described, highlighting the urge to understand the potential to target communication mediated by exosomes as a novel therapeutic approach in cancer. On the other hand, exosomes stability in circulation and tumor-targeting capacity shows their applicability in the delivery of anti-cancer molecules. This review will discuss the dual applicability of exosomes in cancer focusing on their usage for therapy improvement, or their targeting to block their supportive role in tumor progression and response to therapy. We highlight the current developments and the strategies used to enhance the potential of exosomes to become clinical partners in the treatment of cancer.

SAPHO syndrome: the value of classic drugs in the era of biologics.

SAPHO syndrome is a rare entity, composed of dermatologic and osteoarticular manifestations. There are no validated diagnostic criteria and treatment is empirical, with a recent focus on biologics. Herein, we present a 50-year-old woman who developed palmoplantar pustulosis and sternoclavicular osteitis, with typical findings on bone scintigraphy. Treatment with bisphosphonate, low-dose systemic corticosteroid, and cyclosporine allowed complete resolution of the articular and dermatologic manifestations with no side effects.

Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant.

A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.

Detection of Leishmania infantum DNA in the non-parasitized lung of dogs with visceral leishmaniasis.

BACKGROUND: Despite the very low or absent parasitism in the lungs, the interstitial pneumonitis is a common lesion found in humans and dogs with visceral leishmaniasis. The lung is a neglected organ in the study of dogs and humans with visceral leishmaniasis, but interstitial pneumonitis represents an important lesion characterized by thickening of the alveolar septum due to fibrosis and inflammatory exudate, and its pathogenesis is still uncertain. In this study, the polymerase chain reaction (PCR) was used to detect Leishmania infantum in paraffin-embedded lung biopsies from naturally infected dogs from an endemic area in Minas Gerais State, Brazil; PCR was compared to histological and immunohistochemical techniques for detecting Leishmania. RESULTS: Eighteen dogs in which leishmaniasis had been diagnosed by serological tests - indirect immunofluorescence assay (IFAT), enzyme-linked immunosorbent assay (ELISA) and complement fixation tests (CFT) - were classified as asymptomatic, oligosymptomatic or symptomatic. Nine of the 18 dogs studied had a positive PCR (50%) but parasites were not detected by histopathological and immunocytochemistry methods. CONCLUSIONS: These data indicate that PCR on DNA extracted from paraffin-embedded tissue is a valuable method for detecting Leishmania infantum parasites in lungs of naturally infected dogs, despite the apparent absence of parasites from standard HE (hematoxylin and eosin) stained slides and of labeled parasites from immunocytochemical preparations.

Lower galactosylation levels of the Lipophosphoglycan from Leishmania (Leishmania) major-like strains affect interaction with Phlebotomus papatasi and Lutzomyia longipalpis.

BACKGROUND Leishmania major is an Old World species causing cutaneous leishmaniasis and is transmitted by Phlebotomus papatasi and Phlebotomus duboscqi. In Brazil, two isolates from patients who never left the country were characterised as L. major-like (BH49 and BH121). Using molecular techniques, these isolates were indistinguishable from the L. major reference strain (FV1). OBJECTIVES We evaluated the lipophosphoglycans (LPGs) of the strains and their behaviour in Old and New World sand fly vectors. METHODS LPGs were purified, and repeat units were qualitatively evaluated by immunoblotting. Experimental in vivo infection with L. major-like strains was performed in Lutzomyia longipalpis (New World, permissive vector) and Ph. papatasi (Old World, restrictive or specific vector). FINDINGS The LPGs of both strains were devoid of arabinosylated side chains, whereas the LPG of strain BH49 was more galactosylated than that of strain BH121. All strains with different levels of galactosylation in their LPGs were able to infect both vectors, exhibiting colonisation of the stomodeal valve and metacyclogenesis. The BH121 strain (less galactosylated) exhibited lower infection intensity compared to BH49 and FV1 in both vectors. MAIN CONCLUSIONS Intraspecific variation in the LPG of L. major-like strains occur, and the different galactosylation levels affected interactions with the invertebrate host.

Experimental mixed infection of Leishmania (Leishmania) amazonensis and Leishmania (L.) infantum in hamsters (Mesocricetus auratus).

In South America, visceral leishmaniasis is frequently caused by Leishmania infantum and, at an unknown frequency, by Leishmania amazonensis. Therefore, mixed infections with these organisms are possible. Mixed infections might affect the clinical course, immune response, diagnosis, treatment and epidemiology of the disease. Here we describe the clinical course of mixed infections with L. amazonensis and L. infantum in a hamster model. We show that mixed infections are associated with more severe clinical disease than infection with L. amazonensis or L. infantum alone. In spleens with mixed infections, L. infantum outcompeted L. amazonensis in the tissue, but not in culture from tissue. We found increased levels of IgG in animals infected with L. infantum. Although more than 30 bands were revealed in a Western blot, the highest immunogenicity was observed with proteins having molecular masses of 95 and 90 kDa, whereas proteins with molecular masses of lower than 50 kDa were reactive frequently with serum from hamsters infected with L. amazonensis, and proteins with molecular masses of 80 and 70 kDa were reactive only with serum from hamsters infected with L. infantum. This finding has important implications regarding the biology of Leishmania and humoral immune responses to infections with these organisms.

Immediate effect of transcranial direct current stimulation combined with functional electrical stimulation on activity of the tibialis anterior muscle and balance of individuals with hemiparesis stemming from a stroke.

[Purpose] The aim of the present study was to evaluate the immediate effects of transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) on activity of the tibialis anterior muscle (TA) and static balance of individuals with hemiparesis stemming from stroke. [Subjects and Methods] A randomized, double-blind, crossover, clinical trial conducted with 30 individuals with chronic post-stroke hemiparesis. Median frequency of electrical activity of the TA were determined using electromyography in five contractions concentrics and Static balance (body sway velocity and frequency), both before and immediately after the intervention. The participants were submitted to four 20-minute intervention protocols with 48-hour interval: anodal tDCS + sham FES; sham tDCS + active FES; anodal tDCS + active FES and sham tDCS + sham FES. Anodal tDCS was administered over C3 or C4, the cathode was positioned in the supraorbital region on the contralateral side and FES was administered to the affected TA. [Results] No significant differences among the protocols were found regarding electrical activity of the TA and static balance. [Conclusion] The results demonstrate that tDCS alone or in combination with FES had no immediate effect on electrical activity of the TA and static balance of the 30 individuals analyzed.

Psychometric properties of the stroke specific quality of life scale for the assessment of participation in stroke survivors using the rasch model: a preliminary study.

[Purpose] The aim of the present study was to analyze the psychometric properties of the Stroke Specific Quality of Life (SS-QOL) scale for the assessment of social participation following a stroke. [Methods] A preliminary analysis was performed of the SS-QOL items that address the participation category. For this, the scoring patterns of the answers of individuals and internal consistence were determined using the Rasch model. Reliability was assessed by intraclass correlation coefficients (ICC). [Results] The reliability coefficients analyzed by the Rasch model were 0.91 for the items and 0.87 for the patients. The separation index was 3.19 for the items and 2.58 for the patients. The findings indicate that the items separated the patients into three levels of participation: low, medium, and high. Among the 26 items addressing participation, three did not fit the model. All items showed adequate reliability (ICC ≥ 0.60). [Conclusion] The Rasch analysis detected three items with erratic behavior; however, the erratic patterns of these items may be explained by individual peculiarities among the patients. These items should be monitored to determine if the problems found in the present study persist. If so, the items should also be revised or possibly even eliminated.

Impact in oral health and the prevalence of temporomandibular disorder in individuals with Parkinson's disease.

The aims of the present study were to investigate the prevalence of temporomandibular disorder (TMD) in a group of patients with Parkinson's disease (PD), and to analyze oral health according to the severity of the disease. [Methods] Signs and symptoms of TMD were evaluated using the Research Diagnostic Criteria for Temporomandibular Disorders, and oral health impact was measured using the Oral Health Impact Profile. The unpaired Student's t-test was used to compare groups with and without TMD. Pearson's correlation coefficients were calculated to determine correlations between the level of functional independence and oral health impact. Fisher's exact test was used to test the association between TMD and the severity of symptoms of PD. [Results] Fifty-nine individuals with PD were analyzed. The prevalence of TMD was 20.33%. No statistically significant associations were found between TMD and the severity of PD. Oral health impact was considered weak, but a statistically significant difference between groups with and without TMD was found for psychological disability (p = 0.003). No significant correlation was found between the level of functional independence and oral health impact. [Conclusion] The prevalence of TMD among patients with Parkinson's disease was 20.33%. A statistically significant difference between groups with and without TMD was found regarding the psychological disability domain.

Evaluation of post-stroke functionality based on the International Classification of Functioning, Disability, and Health: a proposal for use of assessment tools.

This study aimed to identify the International Classification of Functioning, Disability, and Health categories addressed by the assessment tools commonly used in post-stroke rehabilitation and characterize patients based on its evaluation model. [Subjects and Methods] An exploratory, descriptive, cross-sectional study was conducted involving 35 individuals with chronic post-stroke hemiparesis. Handgrip strength was assessed to evaluate body functions and structures. The 10-meter gait speed test and Timed Up and Go test were administered to evaluate activity. The Stroke Specific Quality of Life scale was used to evaluate participation. Moreover, a systematic review of the literature was performed to identify studies that have associated these assessment tools with the International Classification of Functioning, Disability, and Health categories. [Results] The tools employed in this study for evaluating function addressed 63 International Classification of Functioning, Disability, and Health categories: 24 related to body functions and structures; 36 related to activity and participation; and 3 related to environmental factors. [Conclusion] The assessment tools employed in this study addressed 63 International Classification of Functioning, Disability, and Health categories and allowed a more complete evaluation of stroke survivors with hemiparesis. Use of this classification can therefore be more easily incorporated into clinical practice.

Identification of virulence factors in Leishmania infantum strains by a proteomic approach.

Knowledge of Leishmania virulence is essential for understanding how the contact between the pathogen and host cells can lead to pathogenesis. Virulence in two L. infantum strains was characterized using macrophages and hamsters. Next, we used difference gel electrophoresis (DIGE) and mass spectrometry to identify the differentially expressed proteins. A total of 63 spots were identified corresponding to 36 proteins; 20 were up-regulated, in which 16 had been previously associated with Leishmania virulence. Considering our results and what has been reported before, we suggest the hypothesis that L. infatum virulence could be a result of the increased expression of KMP-11 and metallopeptidase, associated with an improved parasite-host interacting efficiency and degradation of the protective host proteins and peptides, respectively. Other factors are tryparedoxin peroxidase and peroxidoxin, which protect the parasite against the stress response, and 14-3-3 protein-like, which can prolong infected host cell lifetime. Proteins as chaperones and endoribonuclease L-PSP can increase parasite survival. Enolase is able to perform versatile functions in the cell, acting as a chaperone or in the transcription process, or as a plasminogen receptor or in cell migration events. As expected in more invasive cells with high replication rates, energy consumption and protein synthesis are higher, with up-regulation of Rieske iron-sulfur protein precursor, EF-2, S-adenosylhomocysteine, and phosphomannomutase.

Intranasal administration of sertraline ensures sustained brain delivery and antidepressant effect in a mouse model of depression.

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/toxicity study to explore the therapeutic effect in mice subjected to the unpredictable chronic mild stress (UCMS) protocol. Neurotransmitters and melatonin were quantified in prefrontal cortex and plasma, respectively. A different drug biodistribution behavior was unveiled for a CNS-acting drug administered by means of the IN route. For the first time, IN administration of sertraline exhibited heightened systemic exposure (bioavailability = 166 %), and a sustained drug release into the brain, in opposition to IV and oral routes, avoiding drug fluctuation. The lower lung exposition (given by normalized area under the curve) observed after IN instillation envisions the reduction of sertraline pulmonary side effects and similarly other peripheral side effects. IN sertraline treatment displayed significant efficacy in ameliorating anhedonia after one week of administration while the 14-day IN treatment regimen translated into decreased immobility time and increased swimming time in the forced swimming test, suggesting an improvement of the depressive-like behavior displayed by the animal depressive-model. Remarkably, these effects were absent with oral sertraline, despite the higher used dose. Noteworthy neurotransmitter alterations were observed, with IN sertraline markedly reducing adrenaline in the prefrontal cortex, while serotonin and melatonin increased following both administration routes. With its sustained brain delivery and serotonin- and melatonin-enhancing potential, the innovative strategy of IN sertraline holds the potential not only to effectively address depressive symptoms but also to mitigate challenges inherent to classic treatments.

Intranasal delivery of paroxetine: A preclinical study on pharmacokinetics, depressive-like behaviour, and neurochemical sex differences.

Treatment of major depressive disorder remains a major unmet clinical need. Given the advantages of intranasal administration for targeted brain delivery, the present study aimed at investigating the pharmacokinetics of paroxetine, after its intranasal instillation and assessing its potential therapeutic effect on female and male mice subjected to unpredictable chronic mild stress (UCMS) protocol. IN administration revealed direct nose-to-brain paroxetine delivery but dose- and sex-dependent differences. Pharmacokinetics was nonlinear and paroxetine concentrations were consistently higher in plasma and brain of male mice. Additionally, UCMS decreased animal preference for sucrose in both male and female mice following acute (p < 0.01) and chronic stress (p < 0.05), suggesting anhedonia. Both male and female mice exhibited depressive-like behavior in the forced swimming test. UCMS females displayed a significantly longer immobility time and shorter climbing time than the control group (p < 0.05), while no differences were found between male mice. Two weeks of paroxetine intranasal administration reduced immobility time and lengthened climbing and swimming time, approaching values similar to those observed in the healthy control group. The therapeutic effect was stronger on female mice. Importantly, melatonin plasma levels were significantly decreased in female mice following UCMS (p < 0.05), while males exhibited heightened corticosterone levels. On the other hand, treatment with IN paroxetine significantly increased corticosterone and melatonin levels in both sexes compared to healthy mice (p < 0.05). Intranasal paroxetine delivery undoubtedly ameliorated the behavioral despair, characteristic of depressive-like animals. Despite its efficiency in male and female mice subjected to UCMS, females were more prone to this novel therapeutic strategy.

Disability after breast cancer surgery: Proposal of linkage between the International Classification of Functioning, Disability and Health and the Grocery Shelving Task Test.

PURPOSE: To link the concepts measured by the Grocery Shelving Task Test (GST) to the codes and qualifiers of the activity and participation component of the International Classification of Functioning, Disability and Health (ICF). METHODS: The linkage was performed by two professionals who applied the 10 standardized binding rules. The linking process was performed through the model of extraction and identification of the concepts that were found in each item of the GST Test. RESULTS: The GST test includes 1 domain of the activity and participation component (d4 mobility). The link with the qualifiers allowed quantifying the impairment of the limitations of activities in the postoperative period, being observed that 21.27% of the sample did not present any problem, 61.70% presented the qualifier "0.1" (mild problem), 8.50% had a moderate problem (qualifier '0.2') and 8.50% had a severe problem (qualifier '0.3'). No complete impairment was observed in any study participant. DISCUSSION: The linking of the GST to the ICF codes and qualifiers allowed quantifying the functional impairment in the postoperative period of breast cancer, allowing a comprehensive and standardized view, and being a guiding tool for treatment plans.

Content analysis of the Measure of the Quality of the Environment by linkage with the International Classification of Functioning, Disability and Health.

BACKGROUND: This study explores the linkage between the Measurement of Environmental Quality (MQE) and the International Classification of Functioning, Disability, and Health (ICF). Stemming from the Human Development Model-Disability Creation Process (HDM-DCP), MQE enhances understanding of how environmental quality impacts disability development across diverse socio-cultural contexts. Integrating MQE with ICF expands the perspective on disability formation beyond HDM-DCP, encompassing ICF's functioning approach. OBJECTIVE: To link the MQE with the concepts and categories of the ICF. METHODS: Two health professionals with adequate taxonomic knowledge of the ICF performed the initial linkage, which was based on updated standardized rules considering all hierarchical levels of the ICF. Linkage agreement between the first two assessors was measured using the Kappa (k) coefficient and respective 95% confidence intervals. In the absence of a consensus between the two assessors (k > 0.60), a third assessor was consulted to make the arbitrary decision of the final categories linked to the MQE. RESULTS: Insufficient agreement between the two assessors was found for the linkage process (k = 0.52; p < 0.001), requiring the final decision from the third assessor. At the end of the process, 26 ICF categories were linked to the main concepts (MC) measured by the 26 items of the short version of the MQE. Ten ICF categories were linked to the additional concepts (AC) measured by the MQE. Moreover, the MQE addresses the five domains of the ICF component "environmental factors," with a predominance of the "services, systems and policies" domain (MC = 45.8% and AC = 40%). CONCLUSION: The linkage of the concepts measured by the MQE to ICF categories enabled mapping the content of the MQE, identifying it as a promising tool for measuring environmental factors in accordance with ICF percepts.