Continuous evaluation of cost-to-go for flexible reaching control and online decisions.

Humans consider the parameters linked to movement goal during reaching to adjust their control strategy online. Indeed, rapid changes in target structure or disturbances interfering with their initial plan elicit rapid changes in behavior. Here, we hypothesize that these changes could result from the continuous use of a decision variable combining motor and cognitive components. We combine an optimal feedback controller with a real-time evaluation of the expected cost-to-go, which considers target- and movement-related costs, in a common theoretical framework. This model reproduces human behaviors in presence of changes in the target structure occurring during movement and of online decisions to flexibly change target following external perturbations. It also predicts that the time taken to decide to select a novel goal after a perturbation depends on the amplitude of the disturbance and on the rewards of the different options, which is a direct result of the continuous monitoring of the cost-to-go. We show that this result was present in our previously collected dataset. Together our developments point towards a continuous evaluation of the cost-to-go during reaching to update control online and make efficient decisions about movement goal.

Age assessment in unaccompanied minors: assessing uniformity of protocols across Europe.

Age assessment of migrants is crucial, particularly for unaccompanied foreign minors, a population facing legal, social, and humanitarian challenges. Despite existing guidelines, there is no unified protocol in Europe for age assessment.The Forensic Anthropology Society of Europe (FASE) conducted a comprehensive questionnaire to understand age estimation practices in Europe. The questionnaire had sections focusing on the professional background of respondents, annual assessment numbers, requesting parties and reasons, types of examinations conducted (e.g., physical, radiological), followed protocols, age estimation methods, and questions on how age estimates are reported.The questionnaire's findings reveal extensive engagement of the forensic community in age assessment in the living, emphasizing multidisciplinary approaches. However, there seems to be an incomplete appreciation of AGFAD guidelines. Commonalities exist in examination methodologies and imaging tests. However, discrepancies emerged among respondents regarding sexual maturity assessment and reporting assessment results. Given the increasing importance of age assessment, especially for migrant child protection, the study stresses the need for a unified protocol across European countries. This can only be achieved if EU Member States wholeheartedly embrace the fundamental principles outlined in EU Directives and conduct medical age assessments aligned with recognized standards such as the AGFAD guidelines.

Definition of a Threshold for the Plasma Aß42/Aß40 Ratio Measured by Single-Molecule Array to Predict the Amyloid Status of Individuals without Dementia.

Alzheimer's disease (AD) is characterized by amyloid beta (Aß) plaques and hyperphosphorylated tau in the brain. Aß plaques precede cognitive impairments and can be detected through amyloid-positron emission tomography (PET) or in cerebrospinal fluid (CSF). Assessing the plasma Aß42/Aß40 ratio seems promising for non-invasive and cost-effective detection of brain Aß accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aß42/Aß40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n = 88) and some volunteers (n = 66) were subject to evaluation of amyloid status by CSF Aß quantification or PET analysis. Thresholds of plasma Aß42/Aß40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden's index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

Separability of Human Motor Memories during reaching adaptation with force cues.

Judging by the breadth of our motor repertoire during daily activities, it is clear that learning different tasks is a hallmark of the human motor system. However, for reaching adaptation to different force fields, the conditions under which this is possible in laboratory settings have remained a challenging question. Previous work has shown that independent movement representations or goals enabled dual adaptation. Considering the importance of force feedback during limb control, here we hypothesised that independent cues delivered by means of background loads could support simultaneous adaptation to various velocity-dependent force fields, for identical kinematic plan and movement goal. We demonstrate in a series of experiments that indeed healthy adults can adapt to opposite force fields, independently of the direction of the background force cue. However, when the cue and force field were in the same direction but differed by heir magnitude, the formation of different motor representations was still observed but the associated mechanism was subject to increased interference. Finally, we highlight that this paradigm allows dissociating trial-by-trial adaptation from online feedback adaptation, as these two mechanisms are associated with different time scales that can be identified reliably and reproduced in a computational model.

Ultrastable Silver Nanoparticles for Rapid Serology Detection of Anti-SARS-CoV-2 Immunoglobulins G.

Dipstick assays using silver nanoparticles (AgNPs) stabilized by a thin calix[4]arene-based coating were developed and used for the detection of Anti-SARS-CoV-2 IgG in clinical samples. The calixarene-based coating enabled the covalent bioconjugation of the SARS-CoV-2 Spike Protein via the classical EDC/sulfo-NHS procedure. It further conferred remarkable stability to the resulting bioconjugated AgNPs, as no degradation was observed over several months. In comparison with lateral-flow immunoassays (LFIAs) based on classical gold nanoparticles, our AgNP-based system constitutes a clear step forward, as the limit of detection for Anti-SARS-CoV-2 IgG was reduced by 1 order of magnitude and similar signals were observed with 10 times fewer particles. In real clinical samples, the AgNP-based dipstick assays showed impressive results: 100% specificity was observed for negative samples, while a sensitivity of 73% was determined for positive samples. These values match the typical sensitivities obtained for reported LFIAs based on gold nanoparticles. These results (i) represent one of the first examples of the use of AgNP-based dipstick assays in the case of real clinical samples, (ii) demonstrate that ultrastable calixarene-coated AgNPs could advantageously replace AuNPs in LFIAs, and thus (iii) open new perspectives in the field of rapid diagnostic tests.

Effector-dependent stochastic reference frame transformations alter decision-making.

Psychophysical, motor control, and modeling studies have revealed that sensorimotor reference frame transformations (RFTs) add variability to transformed signals. For perceptual decision-making, this phenomenon could decrease the fidelity of a decision signal's representation or alternatively improve its processing through stochastic facilitation. We investigated these two hypotheses under various sensorimotor RFT constraints. Participants performed a time-limited, forced-choice motion discrimination task under eight combinations of head roll and/or stimulus rotation while responding either with a saccade or button press. This paradigm, together with the use of a decision model, allowed us to parameterize and correlate perceptual decision behavior with eye-, head-, and shoulder-centered sensory and motor reference frames. Misalignments between sensory and motor reference frames produced systematic changes in reaction time and response accuracy. For some conditions, these changes were consistent with a degradation of motion evidence commensurate with a decrease in stimulus strength in our model framework. Differences in participant performance were explained by a continuum of eye-head-shoulder representations of accumulated motion evidence, with an eye-centered bias during saccades and a shoulder-centered bias during button presses. In addition, we observed evidence for stochastic facilitation during head-rolled conditions (i.e., head roll resulted in faster, more accurate decisions in oblique motion for a given stimulus-response misalignment). We show that perceptual decision-making and stochastic RFTs are inseparable within the present context. We show that by simply rolling one's head, perceptual decision-making is altered in a way that is predicted by stochastic RFTs.

Confidence in predicted position error explains saccadic decisions during pursuit.

A fundamental problem in motor control is the coordination of complementary movement types to achieve a common goal. As a common example, humans view moving objects through coordinated pursuit and saccadic eye movements. Pursuit is initiated and continuously controlled by retinal image velocity. During pursuit, eye position may lag behind the target. This can be compensated by the discrete execution of a catch-up saccade. The decision to trigger a saccade is influenced by both position and velocity errors, and the timing of saccades can be highly variable. The observed distributions of saccade frequency and trigger time remain poorly understood, and this decision process remains imprecisely quantified. Here, we propose a predictive, probabilistic model explaining the decision to trigger saccades during pursuit to foveate moving targets. In this model, expected position error and its associated uncertainty are predicted through Bayesian inference across noisy, delayed sensory observations (Kalman filtering). This probabilistic prediction is used to estimate the confidence that a saccade is needed (quantified through log-probability ratio), triggering a saccade upon accumulating to a fixed threshold. The model qualitatively explains behavioral observations on the frequency and trigger time distributions of saccades during pursuit over a range of target motion trajectories. Furthermore, this model makes novel predictions that saccade decisions are highly sensitive to uncertainty for small predicted position errors, but this influence diminishes as the magnitude of predicted position error increases. We suggest that this predictive, confidence-based decision-making strategy represents a fundamental principle for the probabilistic neural control of coordinated movements.NEW & NOTEWORTHY This is the first stochastic dynamical systems model of pursuit-saccade coordination accounting for noise and delays in the sensorimotor system. The model uses Bayesian inference to predictively estimate visual motion, triggering saccades when confidence in predicted position error accumulates to a threshold. This model explains saccade frequency and trigger time distributions across target trajectories and makes novel predictions about the influence of sensory uncertainty in saccade decisions during pursuit.

Online modification of goal-directed control in human reaching movements.

Humans are able to perform very sophisticated reaching movements in a myriad of contexts based on flexible control strategies influenced by the task goal and environmental constraints such as obstacles. However, it remains unknown whether these control strategies can be adjusted online. The objective of this study was to determine whether the factors that determine control strategies during planning also modify the execution of an ongoing movement following sudden changes in task demand. More precisely, we investigated whether, and at which latency, feedback responses to perturbation loads followed the change in the structure of the goal target or environment. We changed the target width (square or rectangle) to alter the task redundancy, or the presence of obstacles to induce different constraints on the reach path, and assessed based on surface electromyography (EMG) recordings when the change in visual display altered the feedback response to mechanical perturbations. Task-related EMG responses were detected within 150 ms of a change in target shape. Considering visuomotor delays of ∼ 100 ms, these results suggest that it takes 50 ms to change control policy within a trial. An additional 30-ms delay was observed when the change in context involved sudden appearance or disappearance of obstacles. Overall, our results demonstrate that the control policy within a reaching movement is not static: contextual factors that influence movement planning also influence movement execution at surprisingly short latencies. Moreover, the additional 30 ms associated with obstacles suggests that these two types of changes may be mediated via distinct processes.NEW & NOTEWORTHY The present work demonstrates that the control strategies used to perform reaching movements are adjusted online when the structure of the target or the presence of obstacles are altered during movements. Thus, the properties of goal-directed reaching control are not simply selected during the planning stage of a movement prior to execution. Rather, they are dynamically and rapidly adjusted online, within ∼150 ms, according to changes in environment.

Measuring fingerpad deformation during active object manipulation.

During active object manipulation, the finger-object interactions give rise to complex fingertip skin deformations. These deformations are in turn encoded by the local tactile afferents and provide rich and behaviorally relevant information to the central nervous system. Most of the work studying the mechanical response of the finger to dynamic loading has been performed under a passive setup, thereby precisely controlling the kinematics or the dynamics of the loading. However, to identify aspects of the deformations that are relevant to online control during object manipulation, it is desirable to measure the skin response in an active setup. To that end, we developed a device that allows us to monitor finger forces, skin deformations, and kinematics during fine manipulation. We describe the device in detail and test it to precisely describe how the fingertip skin in contact with the object deforms during a simple vertical oscillation task. We show that the level of grip force directly influences the fingerpad skin strains and that the strain rates are substantial during active manipulation (norm up to 100%/s). The developed setup will enable us to causally relate sensory information, i.e. skin deformation, to online control, i.e. grip force adjustment, in future studies.NEW & NOTEWORTHY We present a novel device, a manipulandum, that enables to image the contact between the finger and the contact surface during active manipulation of the device. The device is tested in a simple vertical oscillation task involving 18 participants. We demonstrate that substantial surface skin strains take place at the finger-object interface and argue that those deformations provide essential information for grasp stability during object manipulation.

Influence of prior and visual information on eye movements in amblyopic children.

This study analyzed the characteristics of pursuit and assessed the influence of prior and visual information on eye velocity and saccades in amblyopic and control children, in comparison to adults. Eye movements of 41 children (21 amblyopes and 20 controls) were compared to eye movements of 55 adults (18 amblyopes and 37 controls). Participants were asked to pursue a target moving at a constant velocity. The target was either a 'standard' target, with a uniform color intensity, or a 'noisy' target, with blurry edges, to mimic the blurriness of an amblyopic eye. Analysis of pursuit patterns showed that the onset was delayed, and the gain was decreased in control children with a noisy target in comparison to amblyopic or control children with a standard target. Furthermore, a significant effect of prior and visual information on pursuit velocity and saccades was found across all participants. Moreover, the modulation of the effect of visual information on the pursuit velocity by group, that is amblyopes or controls with a standard target, and controls with a noisy target, was more limited in children. In other words, the effect of visual information was higher in control adults with a standard target compared to control children with the same target. However, in the case of a blurry target, either in control participants with a noisy target or in amblyopic participants with a standard target, the effect of visual information was larger in children.

Frontotemporal dementia patients exhibit deficits in predictive saccades.

Prediction and time estimation are all but required for motor function in everyday life. In the context of eye movements, for instance, they allow predictive saccades and eye re-acceleration in anticipation of a target re-appearance. While the neural pathways involved are not fully understood, it is known that the frontal lobe plays an important role. As such, neurological disorders that affect it, such as frontotemporal (FTD) dementia, are likely to induce deficits in such movements. In this work, we study the performances of frontotemporal dementia patients in an oculomotor task designed to elicit predictive saccades at different rates, and compare them to young and older adults. Clear deficits in the production of predictive saccades were found in patients, in particular when the time between saccades was short (~500 ms). Furthermore, one asymptomatic C9ORF72 mutation bearer showed patterns of oculomotor behavior similar to FTD patients. He exhibited FTD symptoms within 3 years post-measure, suggesting that an impairment of oculomotor function could be an early clinical sign. Taken together, these results argue in favor of a role of the frontal lobe in predictive movements timing over short timescales, and suggest that predictive saccades in FTD patients warrant further investigation to fully assess their potential as a diagnostic aid.

Recognizing Manual Activities Using Wearable Inertial Measurement Units: Clinical Application for Outcome Measurement.

The ability to monitor activities of daily living in the natural environments of patients could become a valuable tool for various clinical applications. In this paper, we show that a simple algorithm is capable of classifying manual activities of daily living (ADL) into categories using data from wrist- and finger-worn sensors. Six participants without pathology of the upper limb performed 14 ADL. Gyroscope signals were used to analyze the angular velocity pattern for each activity. The elaboration of the algorithm was based on the examination of the activity at the different levels (hand, fingers and wrist) and the relationship between them for the duration of the activity. A leave-one-out cross-validation was used to validate our algorithm. The algorithm allowed the classification of manual activities into five different categories through three consecutive steps, based on hands ratio (i.e., activity of one or both hands) and fingers-to-wrist ratio (i.e., finger movement independently of the wrist). On average, the algorithm made the correct classification in 87.4% of cases. The proposed algorithm has a high overall accuracy, yet its computational complexity is very low as it involves only averages and ratios.

The biomechanical role of the lacertus fibrosus of the biceps brachii Muscle.

PURPOSE: The lacertus fibrosus (LF) is involved in various surgeries. However, the biomechanical contribution of the LF remains unclear. The aim of this study was to determine the role of the lacertus fibrosus on the elbow and forearm kinematics and on the biceps brachii muscle lever arms. METHODS: This biomechanical study was performed on seven fresh-frozen upper limbs of cadavers. Elbow flexion, forearm supination, and biceps brachii muscle lever arms were analyzed in the intact conditions (I) and after superficial (R) and deep part (R2) of the lacertus fibrosus release, respectively. RESULTS: Elbow flexion shows a significant difference (p < 0.0001) between I, R, R2. Abduction/adduction shows a significant difference between I-R (p < 0.0001) and I-R2 (p < 0.0001). Supination does not show a significant difference in mean maximum amplitude, but between 40 and 70%, there are significant differences. There is a significant mean decrease of lever arm in flexion (28%) and supination (50%) after superficial and deep part of the lacertus fibrosus release. CONCLUSION: The results of this study show that the lacertus fibrosus increases the lever arm during flexion and supination. It limits the flexion and abduction of the elbow and supination of the forearm. Lacertus fibrosus maintains the rhythmicity between the elbow flexion and supination of the forearm. LEVEL OF EVIDENCE: Basic science study, biomechanics.

Structure-Property Relationship of Amorphous Maltitol as Tableting Excipient.

Maltitol shows interesting properties compared with mannitol or sorbitol, two other polyols, which are widely used as a pharmaceutical excipients for tablet compaction. For this study, the properties of an amorphous polyol, maltitol, were investigated using a tablet press simulator. The aim of this study was to evaluate the behavior of amorphous maltitol compared to SweetPearl® P 200, a pure product, and SweetPearl® P 300 DC, a textured crystalline maltitol excipient for direct compression. The physicochemical and pharmacotechnical properties were compared, revealing a major change in properties after amorphization. The study of the tabletability, mean yield pressure, elastic properties, etc. shows that the compression behavior of amorphous powders has been significantly altered. The results showed specific properties of amorphous maltitol with good tabletability at low compaction pressure. The stability of the amorphous and the evolution of its behavior in compression were then studied, showing a direct link between its recrystallization and the change in its properties. The use of a stabilizing agent, maltotriitol, slowed down the recrystallization, maintaining the specific properties of the amorphous material in compression for a longer period of time.

Grip force preparation for collisions.

Grip force has been studied widely in a variety of interaction and movement tasks, however, not much is known about the timing of the grip force control in preparation for interaction with objects. For example, it is unknown whether and how the temporal preparation for a collision is related to (the prediction of) the impact load. To study this question, we examined the anticipative timing of the grip force in preparation for impact loads. We designed a collision task with different types of load forces in a controlled virtual environment. Participants interacted with a robotic device (KINARM, BKIN Technologies, Kingston) whose handles were equipped with force sensors which the participants held in precision grip. Representations of the hand and objects were visually projected on a virtual reality display and forces were applied onto the participant's hand to simulate a collision with the virtual objects. The collisions were alternating between the two hands to allow transfer and learning between the hands. The results show that there is immediate transfer of object information between the two hands, since the grip force levels are (almost) fully adjusted after one collision with the opposite hand. The results also show that the grip force levels are nicely adjusted based on the mass and stiffness of the object. Surprisingly, the temporal onset of the grip force build up did not depend on the impact load, so that participants avoid slippage by adjusting the other grip force characteristics (e.g., grip force level and rate of change), therefore considering these self-imposed timing constraints. With the use of catch trials, for which no impact occurred, we further analyzed the temporal profile of the grip force. The catch trial data showed that the timing of the grip force peak is also independent of the impact load and its timing, which suggests a time-locked planning of the complete grip force profile.

Misperception of motion in depth originates from an incomplete transformation of retinal signals.

Depth perception requires the use of an internal model of the eye-head geometry to infer distance from binocular retinal images and extraretinal 3D eye-head information, particularly ocular vergence. Similarly, for motion in depth perception, gaze angle is required to correctly interpret the spatial direction of motion from retinal images; however, it is unknown whether the brain can make adequate use of extraretinal version and vergence information to correctly transform binocular retinal motion into 3D spatial coordinates. Here we tested this hypothesis by asking participants to reconstruct the spatial trajectory of an isolated disparity stimulus moving in depth either peri-foveally or peripherally while participants' gaze was oriented at different vergence and version angles. We found large systematic errors in the perceived motion trajectory that reflected an intermediate reference frame between a purely retinal interpretation of binocular retinal motion (not accounting for veridical vergence and version) and the spatially correct motion. We quantify these errors with a 3D reference frame model accounting for target, eye, and head position upon motion percept encoding. This model could capture the behavior well, revealing that participants tended to underestimate their version by up to 17%, overestimate their vergence by up to 22%, and underestimate the overall change in retinal disparity by up to 64%, and that the use of extraretinal information depended on retinal eccentricity. Since such large perceptual errors are not observed in everyday viewing, we suggest that both monocular retinal cues and binocular extraretinal signals are required for accurate real-world motion in depth perception.

Optimal use of limb mechanics distributes control during bimanual tasks.

Bimanual tasks involve the coordination of both arms, which often offers redundancy in the ways a task can be completed. The distribution of control across limbs is often considered from the perspective of handedness. In this context, although there are differences across dominant and nondominant arms during reaching control ( Sainburg 2002 ), previous studies have shown that the brain tends to favor the dominant arm when performing bimanual tasks ( Salimpour and Shadmehr 2014 ). However, biomechanical factors known to influence planning and control in unimanual tasks may also generate limb asymmetries in force generation, but their influence on bimanual control has remained unexplored. We investigated this issue in a series of experiments in which participants were instructed to generate a 20-N force with both arms, with or without perturbation of the target force during the trial. We modeled the task in the framework of optimal feedback control of a two-link model with six human-like muscles groups. The biomechanical model predicted a differential contribution of each arm dependent on the orientation of the target force and joint configuration that was quantitatively matched by the participants' behavior, regardless of handedness. Responses to visual perturbations were strongly influenced by the perturbation direction, such that online corrections also reflected an optimal use of limb biomechanics. These results show that the nervous system takes biomechanical constraints into account when optimizing the distribution of forces generated across limbs during both movement planning and feedback control of a bimanual task. NEW & NOTEWORTHY Here, we studied a bimanual force production task to examine the effects of biomechanical constraints on the distribution of control across limbs. Our findings show that the central nervous system optimizes the distribution of force across the two arms according to the joint configuration of the upper limbs. We further show that the underlying mechanisms influence both movement planning and online corrective responses to sudden changes in the target force.

Body mass prediction from femoral volume and sixteen other femoral variables in the elderly: BMI and adipose tissue effects.

OBJECTIVES: The frequently used prediction equations of body mass do not seem appropriate for elderly individuals. Here, we establish the relationship between femoral dimensions and known body mass in elderly individuals in order to develop prediction formulas and identify the factors affecting their accuracy. MATERIALS AND METHODS: The body mass linear least-squares regression is based on 17 femoral dimensions, including femoral volume, and 66 individuals. Body proportion and composition effects on accuracy are analyzed by means of the body mass index (BMI) and on a subset sample (n = 25), by means of the masses of adipose, bone and muscle tissues. RESULTS: Most variables significantly reflect body mass. Among them, six dimensions (e.g., biepicondylar breadth, femoral volume, and head femoral diameter) present percent standard errors of estimate ranging from 9.5 to 11% (r = 0.72-0.81) in normal BMI samples. Correlations are clearly lower in samples with normal and abnormal BMI [r = 0.38-0.58; % of standard error of estimate (SEE) = 17.3-19.6%] and not significantly correlated in females (femoral volume) who present high proportions of abnormal BMI and adipose tissue. In the subset, femoral volume is well correlated with bone mass (r = 0.88; %SEE = 7.9%) and lean body mass (r = 0.67; %SEE = 17.2%). DISCUSSION: Our body mass estimation equations for elderly individuals are relevant since relatively low correlations are recurrent in studies using younger individuals of known body mass. However, age, sex, lifestyle, and skeleton considerations of studied populations can provide information about the relevance of the body mass estimation, which is dependent on the BMI classification and the proportion of adipose tissue. Our general considerations can be used for studies of younger individuals.

Weighted integration of short-term memory and sensory signals in the oculomotor system.

Oculomotor behaviors integrate sensory and prior information to overcome sensory-motor delays and noise. After much debate about this process, reliability-based integration has recently been proposed and several models of smooth pursuit now include recurrent Bayesian integration or Kalman filtering. However, there is a lack of behavioral evidence in humans supporting these theoretical predictions. Here, we independently manipulated the reliability of visual and prior information in a smooth pursuit task. Our results show that both smooth pursuit eye velocity and catch-up saccade amplitude were modulated by visual and prior information reliability. We interpret these findings as the continuous reliability-based integration of a short-term memory of target motion with visual information, which support modeling work. Furthermore, we suggest that saccadic and pursuit systems share this short-term memory. We propose that this short-term memory of target motion is quickly built and continuously updated, and constitutes a general building block present in all sensorimotor systems.

Aloe Emodin Reduces Phthiodiolone Dimycocerosate Potentiating Vancomycin Susceptibility on Mycobacteria.

Treatment of tuberculosis still represent a major public health issue. The emergence of multi-and extensively-drug resistant (MDR and XDR) Mycobacterium tuberculosis clinical strains further pinpoint the urgent need for new anti-tuberculous drugs. We previously showed that vancomycin can target mycobacteria lacking cell wall integrity, especially those lacking related phthiocerol and phthiodolone dimycocerosates, PDIM A and PDIM B, respectively. As aloe emodin was previously hypothesized to be able to target the synthesis of mycobacterial cell wall lipids, we tested its ability to potentiate glycopeptides antimycobacterial activity. The aloe emodin with the vancomycin induced a combination effect beyond simple addition, close to synergism, at a concentration lower to reported IC50 cytotoxic value, on M. bovis BCG and on H37Rv M. tuberculosis. Interestingly, out of six MDR and pre-XDR clinical strains, one showed a strong synergic susceptibility to the drug combination. Mycobacterial cell wall lipid analyses highlighted a selective reduction of PDIM B by aloe emodin.