Novel immunomodulatory properties of adenosine analogs promote their antiviral activity against SARS-CoV-2.

The COVID-19 pandemic reminded us of the urgent need for new antivirals to control emerging infectious diseases and potential future pandemics. Immunotherapy has revolutionized oncology and could complement the use of antivirals, but its application to infectious diseases remains largely unexplored. Nucleoside analogs are a class of agents widely used as antiviral and anti-neoplastic drugs. Their antiviral activity is generally based on interference with viral nucleic acid replication or transcription. Based on our previous work and computer modeling, we hypothesize that antiviral adenosine analogs, like remdesivir, have previously unrecognized immunomodulatory properties which contribute to their therapeutic activity. In the case of remdesivir, we here show that these properties are due to its metabolite, GS-441524, acting as an Adenosine A2A Receptor antagonist. Our findings support a new rationale for the design of next-generation antiviral agents with dual - immunomodulatory and intrinsic - antiviral properties. These compounds could represent game-changing therapies to control emerging viral diseases and future pandemics.

Tibiofemoral articulation and axial tibial rotation of the knee after a cruciate retaining total knee arthroplasty.

PURPOSE: Numerous research has reported that total knee arthroplasty (TKA) cannot reproduce axial tibial rotations of normal knees. The objective of this study was to measure the tibiofemoral articular contact motions and axial tibial rotations of TKA knees to investigate the mechanism causing the knee kinematics change of after TKAs. METHODS: Eleven patients with unilateral cruciate retaining (CR) TKA were tested for measurements of knee motion during a weight-bearing flexion from 0° to 105° using an imaging technique. The tibiofemoral contact kinematics were determined using the contact points on medial and lateral surfaces of the tibia and femoral condyles. Axial tibial rotations were calculated using the differences between the medial and lateral articulation distances on the femoral condyles and tibial surfaces at each flexion interval of 15°. RESULTS: On femoral condyles, articular contact distances are consistently longer on the medial than on the lateral sides (p < 0.05) up to 60° of flexion, corresponding to internal tibial rotations (e.g., 1.3° ± 1.0° at 15-30° interval). On tibial surfaces, the articular contact point on the medial side moved more posteriorly than on the lateral side at low flexion angles, corresponding to external tibial rotations (e.g., -1.4° ± 1.8° at 15-30° interval); and more anteriorly than on the lateral sides at mid-range flexion, corresponding to internal tibial rotations (e.g., 0.8° ± 1.7° at 45-60° interval). At higher flexion, articular motions on both femoral condyles and tibial surfaces caused minimal changes in tibial rotations. CONCLUSIONS: These results indicate that the axial tibial rotations of these TKA knees were mainly attributed to asymmetric articulations on the medial and lateral femoral condyles and tibial surfaces. The data can help understand the mechanisms causing axial tibial rotations of TKA knees and help improve implant designs for restoration of normal knee kinematics.

RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression.

Functional selectivity in the context of serotonin 2A (5-HT2A) receptor agonists is often described as differences psychedelic compounds have in the activation of Gq vs ß-arrestin signaling in the brain and how that may relate to inducing psychoactive and hallucinatory properties with respect to each other. However, the presence of 5-HT2A receptors throughout the body in several cell types, including endothelial, endocrine, and immune-related tissues, suggests that functional selectivity may exist in the periphery as well. Here, we examine functional selectivity between two 5-HT2A receptor agonists of the phenylalkylamine class: (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] and (R)-2,5-dimethoxy-4-trifluoromethylamphetamine [(R)-DOTFM]. Despite comparable in vitro activity at the 5-HT2A receptor as well as similar behavioral potency, (R)-DOTFM does not exhibit an ability to prevent inflammation or elevated airway hyperresponsiveness (AHR) in an acute murine ovalbumin-induced asthma model as does (R)-DOI. Furthermore, there are distinct differences between protein expression and inflammatory-related gene expression in pulmonary tissues between the two compounds. Using (R)-DOI and (R)-DOTFM as tools, we further elucidated the anti-inflammatory mechanisms underlying the powerful anti-inflammatory effects of certain psychedelics and identified key mechanistic components of the anti-inflammatory effects of psychedelics, including suppression of arginase 1 expression.

Low-Dose Antithymocyte Globulin: A Pragmatic Approach to Treating Stage 2 Type 1 Diabetes.

OBJECTIVE: Low-dose antithymocyte globulin (ATG) (2.5 mg/kg) preserves C-peptide and reduces HbA1c in new-onset stage 3 type 1 diabetes, yet efficacy in delaying progression from stage 2 to stage 3 has not been evaluated. RESEARCH DESIGN AND METHODS: Children (n = 6) aged 5-14 years with stage 2 type 1 diabetes received off-label, low-dose ATG. HbA1c, C-peptide, continuous glucose monitoring, insulin requirements, and side effects were followed for 18-48 months. RESULTS: Three subjects (50%) remained diabetes free after 1.5, 3, and 4 years of follow-up, while three developed stage 3 within 1-2 months after therapy. Eighteen months posttreatment, even disease progressors demonstrated near-normal HbA1c (5.1% [32 mmol/mol], 5.6% [38 mmol/mol], and 5.3% [34 mmol/mol]), time in range (93%, 88%, and 98%), low insulin requirements (0.17, 0.18, and 0.34 units/kg/day), and robust C-peptide 90 min after mixed meal (1.3 ng/dL, 2.3 ng/dL, and 1.4 ng/dL). CONCLUSIONS: These observations support additional prospective studies evaluating ATG in stage 2 type 1 diabetes.

Investigation of Characteristic Motion Patterns of the Knee Joint During a Weightbearing Flexion.

This study aimed to develop and validate a novel flexion axis concept by calculating the points on femoral condyles that could maintain constant heights during knee flexion. Twenty-two knees of 22 healthy subjects were investigated when performing a weightbearing single leg lunge. The knee positions were captured using a validated dual fluoroscopic image system. The points on sagittal planes of the femoral condyles that had minimal changes in heights from the tibial plane along the flexion path were calculated. It was found that the points do formulate a medial-lateral flexion axis that was defined as the iso-height axis (IHA). The six degrees of freedom (6DOF) kinematics data calculated using the IHA were compared with those calculated using the conventional transepicondylar axis and geometrical center axis. The IHA measured minimal changes in proximal-distal translations and varus-valgus rotations along the flexion path, indicating that the IHA may have interesting clinical implications. Therefore, identifying the IHA could provide an alternative physiological reference for improvement of contemporary knee surgeries, such as ligament reconstruction and knee replacement surgeries that are aimed to reproduce normal knee kinematics and medial/lateral soft tissue tensions during knee flexion.

Farm size limits agriculture's poverty reduction potential in Eastern India even with irrigation-led intensification.

CONTEXT: Millions of people living in the Eastern Gangetic Plains (EGP) of India engage in agriculture to support their livelihoods yet are income poor, and food and climate insecure. To address these challenges, policymakers and development programs invest in irrigation-led agricultural intensification. However, the evidence for agricultural intensification to lift farmers' incomes above the poverty line remains largely anecdotal. OBJECTIVE: The main objective of this study is to use a large household survey (n = 15,572; rice: 8244, wheat: 7328; 2017/18) to assess the link between agricultural intensification and personal daily incomes from farming (FPDI) in the rice-wheat systems of the EGP - the dominant cropping system of the region. METHODS: We use the Intensification Benefit Index (IBI), a measure that relates farm size and household size to FPDI, to assess how daily incomes from rice-wheat production change with irrigation-led intensification across the EGP. RESULTS AND CONCLUSIONS: Relative to the international poverty line of 1.90 Purchasing Power Parity (PPP)$ day-1 and accounting for variations in HH size in the analysis, we found that small farm sizes limit the potential for agricultural intensification from irrigation to transform the poverty status of households in the bottom three quartiles of the IBI. The estimated median FPDI of households with intensified systems in the bottom three quartiles is only 0.51 PPP$ day-1 (a 0.15 PPP$ gain). The median FPDI increases to 2.10 PPP$ day-1 for households in the upper quartile of the IBI distribution (a 0.30 PPP$ gain). Irrigation-led agricultural intensification of rice-wheat systems in the EGP may provide substantial benefits for resilience to climatic change and food security but achieving meaningful poverty reduction will require complementary investments. SIGNIFICANCE: Transforming the poverty status of most smallholder farmers in the EGP requires diversified portfolios of rural on- and off-farm income-generating opportunities. While bolstering food- and climate security, agronomic intervention programs should consider smallholders' limited monetary incentives to invest in intensification. Irrigation-led agricultural intensification programs and policies should explicitly account for the heterogeneity in household resources, irrigation levels, and degree of dependence on agricultural income.

Identifying links between monsoon variability and rice production in India through machine learning.

Climate change poses a major threat to global food security. Agricultural systems that rely on monsoon rainfall are especially vulnerable to changes in climate variability. This paper uses machine learning to deepen understanding of how monsoon variability impacts agricultural productivity. We demonstrate that random forest modelling is effective in representing rice production variability in response to monsoon weather variability. Our random forest modelling found monsoon weather predictors explain similar levels of detrended anomaly variation in both rice yield (33%) and area harvested (35%). The role of weather in explaining harvested rice area highlights that production area changes are an important pathway through which weather extremes impact agricultural productivity, which may exacerbate losses that occur through changes in per-area yields. We find that downwelling shortwave radiation flux is the most important weather variable in explaining variation in yield anomalies, with proportion of area under irrigation being the most important predictor overall. Machine learning modelling is capable of representing crop-climate variability in monsoonal agriculture and reveals additional information compared to traditional parametric models. For example, non-linear yield and area responses of irrigation, monsoon onset and season length all match biophysical expectations. Overall, we find that random forest modelling can reveal complex non-linearities and interactions between climate and rice production variability.

Central-line-associated bloodstream infections and central-line-associated non-CLABSI complications among pediatric oncology patients.

OBJECTIVE: To assess central venous catheter (CVC) harm in pediatric oncology patients, we explored risks for central-line-associated bloodstream infections (CLABSIs) and central-line-associated non-CLABSI complications (CLANCs). DESIGN: Retrospective cohort study. SETTING: Midwestern US pediatric oncology program. PATIENTS: The study cohort comprised 592 pediatric oncology patients seen between 2006 and 2016. METHODS: CLABSIs were defined according to Centers for Disease Control and Prevention (CDC)/National Health Safety Network (NHSN) definitions. CLANCs were classified using a novel definition requiring CVC removal. Patient-level and central-line-level risks were calculated using a negative binomial model to adjust for correlations between total events and line numbers. RESULTS: CVCs were inserted in 62% of patients, with 175,937 total catheter days. The inpatient CLABSI and CLANC rates were 5.8 and 8.5 times higher than outpatient rates. At the patient level, shared risks included acute myeloid leukemia (AML) and age <1 year at diagnosis. At the line level, shared risks included age <1 year at diagnosis, non-mediports, and >1 lumen. AML was a CLABSI-specific risk. CLANC-specific risks included non-brain-tumor diagnosis, younger age at diagnosis or central-line placement, and age <1 year at diagnosis or line placement. Multivariable risks were for CLABSI >1 lumen and for CLANC age <1 year at placement. CONCLUSIONS: Among patients with CVCs, CLABSI and CLANC rates were similar, higher among inpatients than outpatients. For both CLABSIs and CLANCs, infants and patients with AML were at higher risk. In both univariate and multivariate models, lines with >1 lumen were associated with CLABSIs and placement during infancy with CLANCs.

Physiological Axial Tibial Rotation of the Knee During a Weightbearing Flexion.

Axial tibial rotation is a characteristic motion of the knee, but how it occurs with knee flexion is controversial. We investigated the mechanisms of tibial rotations by analyzing in vivo tibiofemoral articulations. Twenty knees of 20 living human subjects were investigated during a weightbearing flexion from full extension to maximal flexion using a dual fluoroscopic imaging system. Tibiofemoral articular contact motions on medial and lateral femoral condyles and tibial surfaces were measured at flexion intervals of 15 deg from 0 deg to 120 deg. Axial tibial rotations due to the femoral and tibial articular motions were compared. Articular contact distances were longer on femoral condyles than on tibial surfaces at all flexion intervals (p < 0.05). The articular distance on medial femoral condyle is longer than on lateral side during flexion up to 60 deg. The internal tibial rotation was 6.8 ± 4.5 deg (Mean ± SD) at the flexion interval of 0-15 deg, where 6.1 ± 2.6 deg was due to articulations on femoral condyles and 0.7 ± 5.1 deg due to articulations on tibial surfaces (p < 0.05). The axial tibial rotations due to articulations on femoral condyles are significantly larger than those on tibial surfaces until 60 deg of flexion (p < 0.05). Minimal additional axial tibial rotations were observed beyond 60 deg of flexion. The axial tibial rotations were mainly attributed to uneven articulations on medial and lateral femoral condyles. These data can provide new insights into the understanding of mechanisms of axial tibial rotations and serve as baseline knowledge for improvement of knee surgeries.

Allantodapsone is a Pan-Inhibitor of Staphylococcus aureus Adhesion to Fibrinogen, Loricrin, and Cytokeratin 10.

Staphylococcus aureus infections have become a major challenge in health care due to increasing antibiotic resistance. We aimed to design small molecule inhibitors of S. aureus surface proteins to be developed as colonization inhibitors. We identified allantodapsone in an initial screen searching for inhibitors of clumping factors A and B (ClfA and ClfB). We used microbial adhesion assays to investigate the effect of allantodapsone on extracellular matrix protein interactions. Allantodapsone inhibited S. aureus Newman adhesion to fibrinogen with an IC50 of 21.3 µM (95% CI 4.5-102 µM), minimum adhesion inhibitory concentration (MAIC) of 100 µM (40.2 µg/mL). Additionally, allantodapsone inhibited adhesion of Lactococcus lactis strains exogenously expressing the clumping factors to fibrinogen (L. lactis ClfA, IC50 of 3.8 µM [95% CI 1.0-14.3 µM], MAIC 10 µM, 4.0 µg/mL; and L. lactis ClfB, IC50 of 11.0 µM [95% CI 0.9-13.6 µM], MAIC 33 µM, 13.3 µg/mL), indicating specific inhibition. Furthermore, the dapsone and alloxan fragments of allantodapsone did not have any inhibitory effect. Adhesion of S. aureus Newman to L2v loricrin is dependent on the expression of ClfB. Allantodapsone caused a dose dependent inhibition of S. aureus adhesion to the L2v loricrin fragment, with full inhibition at 40 µM (OD600 0.11 ± 0.01). Furthermore, recombinant ClfB protein binding to L2v loricrin was inhibited by allantodapsone (P < 0.0001). Allantodapsone also demonstrated dose dependent inhibition of S. aureus Newman adhesion to cytokeratin 10 (CK10). Allantodapsone is the first small molecule inhibitor of the S. aureus clumping factors with potential for development as a colonization inhibitor. IMPORTANCE S. aureus colonization of the nares and the skin provide a reservoir of bacteria that can be transferred to wounds that can ultimately result in systemic infections. Antibiotic resistance can make these infections difficult to treat with significant associated morbidity and mortality. We have identified and characterized a first-in-class small molecule inhibitor of the S. aureus clumping factors A and B, which has the potential to be developed further as a colonization inhibitor.

Herpes Simplex Virus-1 Induced Serotonin-Associated Metabolic Pathways Correlate With Severity of Virus- and Inflammation-Associated Ocular Disease.

Herpes simplex virus-associated diseases are a complex interaction between cytolytic viral replication and inflammation. Within the normally avascular and immunoprivileged cornea, HSV ocular infection can result in vision-threatening immune-mediated herpetic keratitis, the leading infectious cause of corneal blindness in the industrialized world. Viral replicative processes are entirely dependent upon numerous cellular biosynthetic and metabolic pathways. Consistent with this premise, HSV infection was shown to profoundly alter gene expression associated with cellular amino acid biosynthetic pathways, including key tryptophan metabolism genes. The essential amino acid tryptophan is crucial for pathogen replication, the generation of host immune responses, and the synthesis of neurotransmitters, such as serotonin. Intriguingly, Tryptophan hydroxylase 2 (TPH2), the neuronal specific rate-limiting enzyme for serotonin synthesis, was the most significantly upregulated gene by HSV in an amino acid metabolism PCR array. Despite the well-defined effects of serotonin in the nervous system, the association of peripheral serotonin in disease-promoting inflammation has only recently begun to be elucidated. Likewise, the impact of serotonin on viral replication and ocular disease is also largely unknown. We therefore examined the effect of HSV-induced serotonin-associated synthesis and transport pathways on HSV-1 replication, as well as the correlation between HSV-induced ocular serotonin levels and disease severity. HSV infection induced expression of the critical serotonin synthesis enzymes TPH-1, TPH-2, and DOPA decarboxylase (DDC), as well as the serotonin transporter, SERT. Concordantly, HSV-infected cells upregulated serotonin synthesis and its intracellular uptake. Increased serotonin synthesis and uptake was shown to influence HSV replication. Exogenous addition of serotonin increased HSV-1 yield, while both TPH-1/2 and SERT pharmacological inhibition reduced viral yield. Congruent with these in vitro findings, rabbits intraocularly infected with HSV-1 exhibited significantly higher aqueous humor serotonin concentrations that positively and strongly correlated with viral load and ocular disease severity. Collectively, our findings indicate that HSV-1 promotes serotonin synthesis and cellular uptake to facilitate viral replication and consequently, serotonin's proinflammatory effects may enhance the development of ocular disease.

Probes for Fluorescent Visualization of Specific Cellular Organelles.

The defining characteristic of eukaryotic cells is the segregation of critical cellular functions within various membrane bound cellular organelles, including the nucleus, endoplasmic reticulum, Golgi apparatus, lysosomes, and mitochondria. Cell biologists therefore have extensively utilized organelle specific counterstains to help identify the localization of specific proteins or other targets of interest in order to garner an understanding of either their potential functions or their effects on the cell. There currently is a wide array of fluorescent dyes and reagents that can be utilized in live and fixed cells to identify organelles, thereby creating challenges in both choosing between the plethora of options and optimizing their use. Here we present a discussion of commonly utilized commercially available organelle dyes and summarize the factors that influence selection of the various dyes for: a given organelle; live versus fixed cellular conditions; adaptation to a specific protocol; spectral multiplexing; or matching excitation/emission spectra to available imaging equipment. Also presented are recommended protocols for a typical example reagent that can be reliably utilized to visualize its target cellular organelle.

Investigation of femoral condyle height changes during flexion of the knee: implication to gap balance in TKA surgery.

BACKGROUND: Gap balance of the knee at 0° and 90° of flexion has been pursued in total knee arthroplasty (TKA) with the trans-epicondyle axis (TEA) as a reference. This study investigated the height changes of the tibiofemoral articulation and compared the data with the femoral condyle height changes measured using different flexion axes. MATERIALS AND METHODS: Twenty healthy knees were investigated during an in vivo weightbearing flexion using a technique combining MRI and a dual fluoroscopic imaging system (DFIS). The tibiofemoral contact points and the femoral condyle heights [measured using: TEA, geometric center axis (GCA), and iso-height axis (IHA)] were determined at each flexion angle. The height changes of the articular contact points and the femoral condyles were compared along the flexion path. RESULTS: The changes of the medial and lateral contact point heights were within 2.5 mm along the flexion path. The changes of the medial and lateral condyle heights were within 8.9 mm for TEA, within 4.2 mm for GCA and within 3.0 mm for IHA. The height changes measured by the contact points and IHA are similar (p > 0.05), and both are significantly smaller than those measured using the TEA and GCA (p < 0.05). CONCLUSIONS: The TEA and GCA measured varying femoral condyle heights, but the IHA resulted in minimal condyle height changes and could better represent the articulation characteristics of the knee. The data suggested that the IHA could be used as an alternative reference to guide surgical preparation of gap balance along the knee flexion path during TKA surgeries.

Mapping land suitability for informal, small-scale irrigation development using spatial modelling and machine learning in the Upper East Region, Ghana.

Small-scale irrigation has gained momentum in recent years as one of the development priorities in Sub-Saharan Africa. However, farmer-led irrigation is often informal with little support from extension services and a paucity of data on land suitability for irrigation. To map the spatial explicit suitability for dry season small-scale irrigation, we developed a method using an ensemble of boosted regression trees, random forest, and maximum entropy machine learning models for the Upper East Region of Ghana. Both biophysical predictors including surface and groundwater availability, climate, topography and soil properties, and socio-economic predictors which represent demography and infrastructure development such as accessibility to cities and proximity to roads were considered. We assessed that 179,584 ± 49,853 ha is suitable for dry-season small-scale irrigation development when only biophysical variables are considered, and 158,470 ± 27,222 ha when socio-economic variables are included alongside the biophysical predictors, representing 77-89% of the current rainfed-croplands. Travel time to cities, accessibility to small reservoirs, exchangeable sodium percentage, surface runoff that can be potentially stored in reservoirs, population density, proximity to roads, and elevation percentile were the top predictors of small-scale irrigation suitability. These results suggested that the availability of water alone is not a sufficient indicator for area suitability for small-scale irrigation. This calls for strategic road infrastructure development and an improvement in the support to farmers for market accessibility. The suitability for small-scale irrigation should be put in the local context of market availability, demographic indicators, and infrastructure development.

A Model of Collaboration Can Expand the Opportunities in Adaptive Sports Equipment.

ABSTRACT: Physical medicine and rehabilitation requires teamwork and innovation to help patients reach their goals and to optimize their quality of life, and one way is through participation in sports ( Sports Med Arthrosc Rev . 2019;27:73-82; PM R . 2015;7(10):1081-8; PM R . 2012;4(11):851-6; Phys Med Rehabil Clin N Am . 2019;30(1):289-99). Unfortunately, people with disabilities participate in sports ~20% less than their peers, and reasons for this disparity include equipment cost and availability ( Sports Med Arthrosc Rev . 2019;27:73-82; PM R . 2015;7(10):1081-8; Pediatrics . 2008;121(5):1057-61; Res Dev Disabil . 2017;67:9-18). A unique way for physical medicine and rehabilitation clinicians to aid in overcoming these barriers is to collaborate with other fields to make adaptive equipment that meets patients' needs.A multidisciplinary team including a physical medicine and rehabilitation resident physician and biomedical engineer, physical therapist, and machinist collaborated through a local nonprofit organization to design and build adaptive equipment solutions. This team designed two types of adaptive putters that are useable by golfers of various ages and functional ranges and a removable golf club grip for a player with limited grip strength.Implementation of a design team for creating adaptive equipment solutions is possible and can be done in the community setting or as part of a hospital system. In the authors' experience, taking a multidisciplinary team approach allowed developing more innovative and diverse solutions, and the athletes benefited by being able to participate in their desired sports activities.

Articulation of the femoral condyle during knee flexion.

Femoral condyle motion of the knee is generally reported using a morphological trans-epicondyle axis (TEA) or geometric center axis (GCA) in the investigation of the knee kinematics. Axial rotation of the femur is recognized as a characteristic motion of the knee during flexion, but is controversial in the literature. This study investigated the biomechanical factors that could be associated to the axial rotations of the femur using both physiological and morphological measurement methods. Twenty healthy knees were investigated during a weightbearing flexion from 0° to 120° at a 15° increment using an imaging technique. A 3D model was constructed for each knee using MR images. Tibiofemoral cartilage contact points were determined at each flexion position to represent physiological knee motion. The contact distance on each condyle was measured between consecutive contact points. The TEA and GCA were used to measure morphological anteroposterior translations of the femoral condyles. The differences between the medial and lateral condyle motions were used to calculate the physiological and morphological axial rotations of the femur. Both the physiological and morphological methods measured external rotations of the femur at low flexion range (0°-45°) and minimal rotations at higher flexion angles. However, the morphological method measured larger posterior translations of the lateral femoral condyle than the medial condyle (p < 0.05), implying a medial pivoting rotation; in contrast, the physiological method measured larger contact distances on the medial condyle than on the lateral condyle (p < 0.05), implying a lateral pivoting rotation. These data could provide useful references for future investigation of kinematics of the knee before and after surgical repair, such as using total knee arthroplasty.