Search

Introduction Complete blood counts ( CBC) performed for infected children admitted for fever mostly disclose leukocytosis. Yet, the recently developed XN-10® provides novel CBC parameters which could be useful to ascertain infection and discriminate between bacterial and viral etiologies. These were the main objectives of the study presented here. Methods Blood samples from 90 children, 1 month to 5 years old, admitted to an emergency unit for fever benefited from a CBC, C-reactive protein, and procalcitonin assays. For 58, a bacterial infection was documented while a viral cause was disclosed for 32. Concomitantly, 30 healthy children of the same age range were selected as a control group. Results Complete blood counts parameters and leukocyte differentials allowed to statistically significantly disclose infection, compared to reference children, in the age group of 1-5 years old. Among the eight novel discriminant parameters, a particular interest appeared for Neutr- RI and Delta-He. They both were successfully incorporated in a score together with age and immature granulocytes ( IG). ROC curves and AUCs were calibrated using a Hosmer-Lemeshow test. Moreover, novel lymphocyte parameters allowed to segregate bacterial and viral infections in the whole group of 90 febrile children. Conclusion Complete blood counts is the most broadly performed rapid laboratory investigation. Here, we show that XN-10® provides complementary information allowing to confirm infection in febrile children, moreover discriminating between bacterial or viral origin. [ABSTRACT FROM AUTHOR]

Introduction: Cachexia is strongly associated with digestive cancers, particularly oesogastric cancer. Mitochondria in adipose tissue are involved in the regulation of metabolism and physiopathology of cancer cachexia in animal studies. Chemotherapeutic regimens used to control tumour development could also alter mitochondrial function in adipose tissue. We hypothesise that cachexia induces an increase in adipose tissue mitochondrial energy metabolism and that chemotherapy can mitigate this. The purpose of the ChiFMeOE study is to identify adipocyte factors involved in the energy imbalance associated with the cachectic process and their response to chemotherapeutic treatments in patients with oesogastric cancer., Methods and Analysis: ChiFMeOE is a single-centre observational study that will prospectively include 60 patients referred to chemotherapy and surgery for oesophageal and gastro-oesophageal junction adenocarcinomas at the University Hospital of Clermont-Ferrand, France. Visceral and subcutaneous adipose tissue biopsies will be collected during surgery scheduled before and after neoadjuvant chemotherapy administration, as well as cachexia and nutritional assessment. The primary outcome is the maximum mitochondrial respiration rate (Vmax) measured by high-resolution respirometry. Secondary outcomes are other mitochondrial parameters (ie, enzymatic activities, proteins content and gene expression), tumour characteristics, nutritional status and body composition., Ethics and Dissemination: The study was approved by an independent institutional review board on June 2023 (Comité de protection des personnes Sud-Méditerranée V; 2023-A00582-43) and declared to the French regulatory authority for research. Written informed consent will be obtained prior to patient inclusion. The principal investigator will be notified of any changes in patient's health status requiring a modification of his management and/or treatment during the course of the protocol. Results will be published in peer-reviewed journals., Trial Registration Number: ClinicalTrials.gov, NCT05954117., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The entity entitled bleeding disorder of unknown cause (BDUC) qualifies individuals displaying a mild haemorrhagic profile but normal routine coagulation tests. This study was designed to evaluate whether collagen-binding assay for von Willebrand Factor (VWF) measurement (VWF:CB) could allow to diagnose VW disease in such patients., Methods: A large screening was conducted prospectively in two University Hospitals, using the bleeding assessment tool (BAT) recommended by the International Society of Thrombosis and Hemostasis. Patients with an abnormal BAT were confirmed to have a normal complete hemostatic evaluation. A large range of VWF assays was then carried out on a new blood sample for the 68 individuals (91% women) thus identified. Of note, five VWF:CB using different types of collagen were performed, as well as a comprehensive sequencing of the VWF gene., Results: Of this cohort, only 3 individuals (all blood group O), had a VWF:CB between 40 and 50 IU/dL. No unknown anomaly of the VWF gene was disclosed. Of note, 54% of these patients had unexplained abnormal occlusion times on PFA-200., Conclusion: This study identified 68 cases of BDUC, after screening of a large population, indicating a low incidence. Only 3 cases were potentially confirmed as displaying moderate von Willebrand disease. VWF:CB tests were globally normal in the 65 other patients of the cohort., Trial Registration: ClinicalTrials.gov identifier: NCT0279220., (© 2024 John Wiley & Sons Ltd.)

During development, motor axons are guided toward muscle target by various extrinsic cues including extracellular matrix (ECM) proteins whose identities and cellular source remain poorly characterized. Here, using single-cell RNAseq of sorted GFP + cells from smyhc1:gfp -injected zebrafish embryos, we unravel the slow muscle progenitors (SMP) pseudotemporal trajectory at the single-cell level and show that differentiating SMPs are a major source of ECM proteins. The SMP core-matrisome was characterized and computationally predicted to form a basement membrane-like structure tailored for motor axon guidance, including basement membrane-associated ECM proteins, as collagen XV-B, one of the earliest core-matrisome gene transcribed in differentiating SMPs and the glycoprotein Tenascin C. To investigate how contact-mediated guidance cues are organized along the motor path to exert their function in vivo, we used microscopy-based methods to analyze and quantify motor axon navigation in tnc and col15a1b knock-out fish. We show that motor axon shape and growth rely on the timely expression of the attractive cue Collagen XV-B that locally provides axons with a permissive soft microenvironment and separately organizes the repulsive cue Tenascin C into a unique functional dual topology. Importantly, bioprinted micropatterns that mimic this in vivo ECM topology were sufficient to drive directional motor axon growth. Our study offers evidence that not only the composition of ECM cues but their topology critically influences motor axon navigation in vertebrates with potential applications in regenerative medicine for peripheral nerve injury as regenerating nerves follow their original path., Competing Interests: Competing interests statement:The authors declare no competing interest.

The survival of animals depends, among other things, on their ability to identify threats in their surrounding environment. Senses such as olfaction, vision and taste play an essential role in sampling their living environment, including microorganisms, some of which are potentially pathogenic. This study focuses on the mechanisms of detection of bacteria by the Drosophila gustatory system. We demonstrate that the peptidoglycan (PGN) that forms the cell wall of bacteria triggers an immediate feeding aversive response when detected by the gustatory system of adult flies. Although we identify ppk23+ and Gr66a+ gustatory neurons as necessary to transduce fly response to PGN, we demonstrate that they play very different roles in the process. Time-controlled functional inactivation and in vivo calcium imaging demonstrate that while ppk23+ neurons are required in the adult flies to directly transduce PGN signal, Gr66a+ neurons must be functional in larvae to allow future adults to become PGN sensitive. Furthermore, the ability of adult flies to respond to bacterial PGN is lost when they hatch from larvae reared under axenic conditions. Recolonization of germ-free larvae, but not adults, with a single bacterial species, Lactobacillus brevis, is sufficient to restore the ability of adults to respond to PGN. Our data demonstrate that the genetic and environmental characteristics of the larvae are essential to make the future adults competent to respond to certain sensory stimuli such as PGN., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

Background: Insects living in nutritionally poor environments often establish long-term relationships with intracellular bacteria that supplement their diets and improve their adaptive and invasive powers. Even though these symbiotic associations have been extensively studied on physiological, ecological, and evolutionary levels, few studies have focused on the molecular dialogue between host and endosymbionts to identify genes and pathways involved in endosymbiosis control and dynamics throughout host development., Results: We simultaneously analyzed host and endosymbiont gene expression during the life cycle of the cereal weevil Sitophilus oryzae, from larval stages to adults, with a particular emphasis on emerging adults where the endosymbiont Sodalis pierantonius experiences a contrasted growth-climax-elimination dynamics. We unraveled a constant arms race in which different biological functions are intertwined and coregulated across both partners. These include immunity, metabolism, metal control, apoptosis, and bacterial stress response., Conclusions: The study of these tightly regulated functions, which are at the center of symbiotic regulations, provides evidence on how hosts and bacteria finely tune their gene expression and respond to different physiological challenges constrained by insect development in a nutritionally limited ecological niche. Video Abstract., (© 2023. The Author(s).)

The disturbance of intercellular communication is one of the hallmarks of aging. The goal of this study is to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. We focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, we described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin.

Competing Interests: Conflicts of interest: F.A. and O.D. have received hospitality and speakers’ honoraria from Kyowa Kirin.

Papillary and reticular dermis show distinct extracellular matrix (ECM) and vascularization corresponding to their specific functions. These characteristics are associated with gene expression patterns of fibroblasts freshly isolated from their native microenvironment. In order to assess the relevance of these fibroblast subpopulations in a tissue engineering context, we investigated their contribution to matrix production and vascularization using cell sheet culture conditions. We first performed RNA-seq differential expression analysis to determine whether several rounds of cell amplification and high-density culture affected their gene expression profile. Bioinformatics analysis revealed that expression of angiogenesis-related and matrisome gene signatures were maintained, resulting in papillary and reticular ECMs that differ in composition and structure. The impact of secreted or ECM-associated factors was then assessed using two independent 3D angiogenesis assays: -1/ a fibrin hydrogel-based assay allowing investigation of diffusible secreted factors, -2/ a scaffold-free cell-sheet based assay for investigation of fibroblast-produced microenvironment. These analyses revealed that papillary fibroblasts secrete highly angiogenic factors and produce a microenvironment characterised by ECM remodelling capacity and dense and branched microvascular network, whereas reticular fibroblasts produced more structural core components of the ECM associated with less branched and larger vessels. These features mimick the characteristics of both the ECM and the vasculature of dermis subcompartments. In addition to showing that skin fibroblast populations differentially regulate angiogenesis via both secreted and ECM factors, our work emphasizes the importance of papillary and reticular fibroblasts for engineering and modelling dermis microenvironment and vascularization. STATEMENT OF SIGNIFICANCE: Recent advances have brought to the forefront the central role of microenvironment and vascularization in tissue engineering for regenerative medicine and microtissue modelling. We have investigated the role of papillary and reticular fibroblast subpopulations using scaffold-free cell sheet culture. This approach provides differentiated cells conditions allowing the production of their own microenvironment. Analysis of gene expression profiles and characterisation of the matrix produced revealed strong and specific angiogenic properties that we functionally characterized using 3D angiogenesis models targeting the respective role of either secreted or matrix-bound factors. This study demonstrates the importance of cell-generated extracellular matrix and questions the importance of cell source and the relevance of hydrogels for developing physio-pathologically relevant tissue engineered substitutes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adèle Mauroux, Laëtitia Marchand, Sylvie Bordes, and Brigitte Closs are employees of SILAB. Florence Ruggiero and Laurent Muller declare the receipt of a grant from SILAB. PJ, NBJ, HB, BG, SH, CAR, AL, PM, CM and SG state no conflict of interest, (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The ultrasonographic assessment of the caudal vena cava-to-aorta ratio (CVC:Ao) appears to be a promising method for early recognition of alterations of intravascular volume status in veterinary medicine. The primary objective of this study was to establish the reference intervals of the CVC:Ao ratio with ultrasound in nonsedated healthy dogs. Secondary objectives were to determine the influence of the respiratory cycle and to evaluate correlations between ultrasonographic measurements, signalment and physical exam findings. Ultrasonographic measurements of Ao and CVC diameters were successfully obtained for all sixty dogs included. No evidence of a difference was observed between the measurements of Ao and CVC diameters, and CVC:Ao ratio between inspiration and expiration (P = .373, P = .318, and P = .537, respectively). The reference interval for CVC:Ao ratio (95% CI), generated from US measurements performed at any moment of the respiratory cycle was defined as 0.93 (0.91-0.95) -1.32 (1.30-1.34). The CVC:Ao ratio was significantly negatively correlated with age (r = -0.341, P = .008) and positively correlated with respiratory rate (r = 0.423, P < .001), but not with heart rate (P = .573) or arterial systolic blood pressure (P = .166). A low inter- and intraoperator variability in repeated measurements was observed for each operator and between operators. The ultrasonographic measurement of the CVC:Ao ratio appears as a simple method with low inter- and intraoperator variability using the ultrasonographic protocol described in the current study. With the reference interval established in the present study in healthy nonsedated dogs, further studies should evaluate the utility of this simple method in assessing and monitoring volume status in hypo- and hypervolemic dogs., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically defined diets, we found that association with Lp improves the growth of larvae-fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its host's growth through a molecular dialogue that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the general control nonderepressible 2 (GCN2) kinase in Drosophila 's enterocytes. Our data indicate that Lp's r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialogue between host and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons., Competing Interests: TG, JC, MF, HA, LB, YD, IR, PD, BG, SH, CR, RM, FL No competing interests declared, (© 2023, Grenier et al.)

NRF2 is a master regulator of the antioxidative response that was recently proposed as a potential regulator of extracellular matrix (ECM) gene expression. Fibroblasts are major ECM producers in all connective tissues, including the dermis. A better understanding of NRF2-mediated ECM regulation in skin fibroblasts is thus of great interest for skin homeostasis maintenance and aging protection. In this study, we investigate the impact of NRF2 downregulation on matrisome gene expression and ECM deposits in human primary dermal fibroblasts. RNA-sequencing‒based transcriptome analysis of NRF2 silenced dermal fibroblasts shows that ECM genes are the most regulated gene sets, highlighting the relevance of the NRF2-mediated matrisome program in these cells. Using complementary light and electron microscopy methods, we show that NRF2 deprivation in dermal fibroblasts results in reduced collagen I biosynthesis and impacts collagen fibril deposition. Moreover, we identify ZNF469, a putative transcriptional regulator of collagen biosynthesis, as a target of NRF2. Both ZNF469 silenced fibroblasts and fibroblasts derived from Brittle Corneal Syndrome patients carrying variants in ZNF469 gene show reduced collagen I gene expression. Our study shows that NRF2 orchestrates matrisome expression in human skin fibroblasts through direct or indirect transcriptional mechanisms that could be prioritized to target dermal ECM homeostasis in health and disease., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Downy mildew is caused by Plasmopara viticola, an obligate oomycete plant pathogen, a devasting disease of grapevine. To protect plants from the disease, complex III inhibitors are among the fungicides widely used. They specifically target the mitochondrial cytochrome b (cytb) of the pathogen to block cellular respiration mechanisms. In the French vineyard, P. viticola has developed resistance against a first group of these fungicides, the Quinone outside Inhibitors (QoI), with a single amino acid substitution G143A in its cytb mitochondrial sequence. The use of QoI was limited and another type of fungicide, the Quinone inside Inhibitors, targeting the same gene and highly effective against oomycetes, was used instead. Recently however, less sensitive P. viticola populations were detected after treatments with some inhibitors, in particular ametoctradin and cyazofamid. By isolating single-sporangia P. viticola strains resistant to these fungicides, we characterized new variants in the cytb sequences associated with cyazofamid resistance: a point mutation (L201S) and more strikingly, two insertions (E203-DE-V204, E203-VE-V204). In parallel with the classical tools, pyrosequencing and qPCR, we then benchmarked short and long-reads NGS technologies (Ion Torrent, Illumina, Oxford Nanopore Technologies) to sequence the complete cytb with a view to detecting and assessing the proportion of resistant variants of P. viticola at the scale of a field population. Eighteen populations collected from French vineyard fields in 2020 were analysed: 12 showed a variable proportion of G143A, 11 of E203-DE-V204 and 7 populations of the S34L variant that confers resistance to ametoctradin. Interestingly, the long reads were able to identify variants, including SNPs, with confidence and to detect a small proportion of P. viticola with multiple variants along the same cytb sequence. Overall, NGS appears to be a promising method for assessing fungicide resistance of pathogens linked to cytb modifications at the field population level. This approach could rapidly become a robust decision support tool for resistance management in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cherrad 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.)

Biological pathways rely on the formation of intricate protein interaction networks called interactomes. Getting a comprehensive map of interactomes implies the development of tools that allow one to capture transient and low-affinity protein-protein interactions (PPIs) in live conditions. Here we presented an experimental strategy: the Cell-PCA (cell-based protein complementation assay), which was based on bimolecular fluorescence complementation (BiFC) for ORFeome-wide screening of proteins that interact with different bait proteins in the same live cell context, by combining high-throughput sequencing method. The specificity and sensitivity of the Cell-PCA was established by using a wild-type and a single-amino-acid-mutated HOXA9 protein, and the approach was subsequently applied to seven additional human HOX proteins. These proof-of-concept experiments revealed novel molecular properties of HOX interactomes and led to the identification of a novel cofactor of HOXB13 that promoted its proliferative activity in a cancer cell context. Taken together, our work demonstrated that the Cell-PCA was pertinent for revealing and, importantly, comparing the interactomes of different or highly related bait proteins in the same cell context.

Introduction: Acquired hemophilia A (AHA) is a rare autoimmune hemorrhagic disease occurring in several underlying conditions. Drug-associated AHA (D-AHA) is poorly addressed nowadays., Aim: This work aims to identify and characterize which drugs are associated with AHA using the WHO global database of reported potential effects of medicinal products (VigiBase)., Methods: First, we realized a disproportionality analysis using the information component (IC) to identify D-AHA in VigiBase. IC compares observed- and expected-values in order to find associations between drugs and adverse drug reactions (ADRs) using disproportionate Bayesian reporting. IC 025 is the lower end of a 95% credibility interval for the IC. Then, we collected cases of drugs significantly associated with AHA from July 2004 to November 2021., Results: 14 drugs with IC 025 > 0 were identified representing a total of 185 cases. D-AHA occurred more frequently in men (59%) than women (41%). The median (min-max) age at onset was 75 years (8-98). The median [Q1-Q3] time to onset of D-AHA from the start of the suspected drug was 30 days [9.5-73.75] and 10% of cases resulted in a fatality. The drugs associated with the highest IC 025 (IC 025 > 2) were Clopidogrel, Alemtuzumab, Omalizumab. This study retrieved for the first time three usually used drugs (3/14) that exhibit a significant pharmacovigilance signal for D-AHA., Conclusion: This worldwide pharmaco-epidemiologic study updates the list of the drugs associated with AHA. The clinician should be aware of these possible severe ADR, which might require larger epidemiological and pathophysiologic studies., (© 2022 John Wiley & Sons Ltd.)

Background: Many insects house symbiotic intracellular bacteria (endosymbionts) that provide them with essential nutrients, thus promoting the usage of nutrient-poor habitats. Endosymbiont seclusion within host specialized cells, called bacteriocytes, often organized in a dedicated organ, the bacteriome, is crucial in protecting them from host immune defenses while avoiding chronic host immune activation. Previous evidence obtained in the cereal weevil Sitophilus oryzae has shown that bacteriome immunity is activated against invading pathogens, suggesting endosymbionts might be targeted and impacted by immune effectors during an immune challenge. To pinpoint any molecular determinants associated with such challenges, we conducted a dual transcriptomic analysis of S. oryzae's bacteriome subjected to immunogenic peptidoglycan fragments., Results: We show that upon immune challenge, the bacteriome actively participates in the innate immune response via induction of antimicrobial peptides (AMPs). Surprisingly, endosymbionts do not undergo any transcriptomic changes, indicating that this potential threat goes unnoticed. Immunohistochemistry showed that TCT-induced AMPs are located outside the bacteriome, excluding direct contact with the endosymbionts., Conclusions: This work demonstrates that endosymbiont protection during an immune challenge is mainly achieved by efficient confinement within bacteriomes, which provides physical separation between host systemic response and endosymbionts. Video Abstract., (© 2022. The Author(s).)

Regenerating animals have the ability to reproduce body parts that were originally made in the embryo and subsequently lost due to injury. Understanding whether regeneration mirrors development is an open question in most regenerative species. Here, we take a transcriptomics approach to examine whether leg regeneration shows similar temporal patterns of gene expression as leg development in the embryo, in the crustacean Parhyale hawaiensis . We find that leg development in the embryo shows stereotypic temporal patterns of gene expression. In contrast, the dynamics of gene expression during leg regeneration show a higher degree of variation related to the physiology of individual animals. A major driver of this variation is the molting cycle. We dissect the transcriptional signals of individual physiology and regeneration to obtain clearer temporal signals marking distinct phases of leg regeneration. Comparing the transcriptional dynamics of development and regeneration we find that, although the two processes use similar sets of genes, the temporal patterns in which these genes are deployed are different and cannot be systematically aligned.

Estrogen related receptors are orphan members of the nuclear receptor superfamily acting as transcription factors (TFs). In contrast to classical nuclear receptors, the activities of the ERRs are not controlled by a natural ligand. Regulation of their activities thus relies on availability of transcriptional co-regulators. In this paper, we focus on ERRα, whose involvement in cancer progression has been broadly demonstrated. We propose a new approach to identify potential co-activators, starting from previously identified ERRα-activated genes in a breast cancer (BC) cell line. Considering mRNA gene expression from two sets of human BC cells as major endpoint, we used sparse partial least squares modeling to uncover new transcriptional regulators associated with ERRα. Among them, DDX21, MYBBP1A, NFKB1, and SETD7 are functionally relevant in MDA-MB-231 cells, specifically activating the expression of subsets of ERRα-activated genes. We studied SET7 in more details and showed its co-localization with ERRα and its ERRα-dependent transcriptional and phenotypic effects. Our results thus demonstrate the ability of a modeling approach to identify new transcriptional partners from gene expression. Finally, experimental results show that ERRα cooperates with distinct co-regulators to control the expression of distinct sets of target genes, thus reinforcing the combinatorial specificity of transcription., (© 2022. The Author(s).)

Background: To reduce the rate of anterior cruciate ligament (ACL) graft rupture, recent surgeries have involved anterolateral ligament reconstruction (ALLR). This reconstruction procedure harvests more knee flexor muscle tendons than isolated ACL reconstruction (ACLR), but its influence on knee muscle strength recovery remains unknown. This study aimed to assess the influence of ALLR with a gracilis graft on the strength of the knee extensor and flexor muscles at 6 months postoperatively., Hypothesis: The additional amount of knee flexor harvest for ALLR would result in impairment in knee flexor muscle strength at 6 months postoperatively., Study Design: Retrospective cohort study., Level of Evidence: Level 2., Methods: A total of 186 patients were assigned to 2 groups according to the type of surgery: ACL + ALLR (graft: semitendinosus + gracilis, n = 119) or isolated ACLR (graft: semitendinosus, n = 67). The strength of the knee extensor and flexor muscles was assessed using an isokinetic dynamometer at 90, 180, and 240 deg/s for concentric and 30 deg/s for eccentric contractions and compared between groups using analysis of variance statistical parametric mapping., Results: Regardless of the surgery and the muscle, the injured leg produced significantly less strength than the uninjured leg throughout knee flexion and extension from 30° to 90° for each angular velocity (30, 90, 180, and 240 deg/s). However, the knee muscle strength was similar between the ACL + ALLR and ACLR groups., Conclusion: The addition of ALLR using the gracilis tendon during ACLR does not alter the muscle recovery observed at 6 months postoperatively., Clinical Relevance: Although more knee flexor muscle tendons were harvested in ACL + ALLR, the postoperative strength recovery was similar to that of isolated ACLR.