Seeing the piles of the velvet bending under our finger sliding over a tactile stimulator improves the feeling of the fabric.

Using friction modulation to simulate fabrics with a tactile stimulator (i.e. virtual surface) is not sufficient to render fabric touch and even more so for hairy fabrics. We hypothesized that seeing the pile of the velvet darken or lighten depending on changes in the finger movement direction on the virtual surface should improve the velvet fabric rendering. Participants actively rubbed a tactile device or a velvet fabric looking at a screen that showed a synthesized image of a velvet that either remained static (V-static) or darkening/lightening with the direction of touch (V-moving). We showed that in V-moving condition, the touched surface was always perceived rougher, which is a descriptor of a real velvet (Experiment 1). Using electroencephalography and sources localization analyses, we found increased activity in the occipital and inferior parietal lobes (Experiment 2) when seeing dark and shining traces during back-and-forth finger movements over the virtual surface. This suggests that these two posterior cortical regions work together to evaluate visuo-tactile congruence between the seen and the felt (tactile). The visuo-tactile binding, evidenced by neural synchronization (specifically, theta band (5-7 Hz) oscillation) in the left inferior posterior parietal lobule, is consistent with enhanced integration of information and probably contributed to the emergence of a more realistic velvet representation.

Interactions during falls with environmental objects: evidence from real-life falls in long-term care captured on video.

BACKGROUND: Falls are the leading cause of injuries in older adults. Environmental objects (such as furniture, walls, and handrails) may act as hazards or facilitators to balance maintenance and safe landing. There is lack of objective evidence on how older adults interact with objects during falls. We addressed this gap by characterizing body part contacts with objects other than the floor during real-life falls in long-term care. METHODS: We analyzed videos of 1759 falls experienced by 584 residents to characterize the prevalence of contacts with objects before, during, and after fall initiation. Using generalized estimating equations, we compared the prevalence of falls with versus without contact to objects after fall initiation. Using linear mixed models, we tested for differences across body parts in the probability of contacting objects after fall initiation. RESULTS: In nearly one-third of falls, interactions with objects (e.g., trips over objects, loss of support with objects) or with other people (e.g., being pushed by another person) had a primary role in causing imbalance and initiating the fall. After fall initiation, participants contacted objects in 60% of falls, with intentional hand contacts to objects via reach-to-grasp or bracing being the most common type of interaction (Probability ± SE = 0.32 ± 0.01), followed by unintentional impacts to the torso (0.21 ± 0.01) and head (0.16 ± 0.01). Intentional hand contact to an object was more common during forward than backward falls (p < 0.001), while head and torso contacts to objects were more common during backward and sideways falls than forward falls (multiple p values ≤ 0.003). The hand most often contacted chairs, wheelchairs or couches, followed by tables or counters, walls, other people, walkers, and handrails. The head, torso, and shoulder most often contacted a wall. CONCLUSIONS: Most falls in long-term care involved contacts with objects other than the ground, indicating that complex environments often accompany falls in long-term care. Higher probabilities of intentional hand contacts in forward falls, versus unintentional head and torso impacts in backward and sideways falls may reflect the influence of being able to visualize and adjust one's falling patterns to nearby objects.

Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.

Background: Mutations in the GCK gene cause Maturity Onset Diabetes of the Young (GCK-MODY) by impairing glucose-sensing in pancreatic beta cells. During pregnancy, managing this type of diabetes varies based on fetal genotype. Fetuses carrying a GCK mutation can derive benefit from moderate maternal hyperglycemia, stimulating insulin secretion in fetal islets, whereas this may cause macrosomia in wild-type fetuses. Modulating maternal glycemia can thus be viewed as a form of personalized prenatal therapy, highly beneficial but not justifying the risk of invasive testing. We therefore developed a monogenic non-invasive prenatal diagnostic (NIPD-M) test to reliably detect the transmission of a known maternal GCK mutation to the fetus. Methods: A small amount of fetal circulating cell-free DNA is present in maternal plasma but cannot be distinguished from maternal cell-free DNA. Determining transmission of a maternal mutation to the fetus thus implies sequencing adjacent polymorphisms to determine the balance of maternal haplotypes, the transmitted haplotype being over-represented in maternal plasma. Results: Here we present a series of such tests in which fetal genotype was successfully determined and show that it can be used to guide therapeutic decisions during pregnancy and improve the outcome for the offspring. We discuss several potential hurdles inherent to the technique, and strategies to overcome these. Conclusion: Our NIPD-M test allows reliable determination of the presence of a maternal GCK mutation in the fetus, thereby allowing personalized in utero therapy by modulating maternal glycemia, without incurring the risk of miscarriage inherent to invasive testing.

Recurrent spontaneous pneumothorax in an NF1 patient with a novel causative variant: broadening genotype-phenotype correlations.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance, most commonly known to affect the skin and eyes. Although lung involvement in the form of cysts and bullae occurs in up to 20% of adults, the seemingly intuitive association of NF1 and spontaneous pneumothorax is not widely recognised among clinicians. Here, we report the second case of recurring spontaneous pneumothorax in the context of NF1 with a confirmed molecular diagnosis. In both cases, the NF1 variants featured a premature stop codon in the C-terminal protein domain. Interestingly, our patient had mild skin symptoms, suggesting that spontaneous pneumothorax may not be correlated with cutaneous disease severity. More genotype-phenotype correlation studies are needed for NF1 in general and for its link to spontaneous pneumothorax in particular.

CRISPR editing to mimic porphyria combined with light: A new preclinical approach for prostate cancer.

Thanks to its very high genome-editing efficiency, CRISPR-Cas9 technology could be a promising anticancer weapon. Clinical trials using CRISPR-Cas9 nuclease to ex vivo edit and alter immune cells are ongoing. However, to date, this strategy still has not been applied in clinical practice to directly target cancer cells. Targeting a canonical metabolic pathway essential to good functioning of cells without potential escape would represent an attractive strategy. We propose to mimic a genetic metabolic disorder in cancer cells to weaken cancer cells, independent of their genomic abnormalities. Mutations affecting the heme biosynthesis pathway are responsible for porphyria, and most of them are characterized by an accumulation of toxic photoreactive porphyrins. This study aimed to mimic porphyria by using CRISPR-Cas9 to inactivate UROS, leading to porphyrin accumulation in a prostate cancer model. Prostate cancer is the leading cancer in men and has a high mortality rate despite therapeutic progress, with a primary tumor accessible to light. By combining light with gene therapy, we obtained high efficiency in vitro and in vivo, with considerable improvement in the survival of mice. Finally, we achieved the preclinical proof-of-principle of performing cancer CRISPR gene therapy.

Preventing hyperhomocysteinemia using vitamin B6 supplementation in Givosiran-treated acute intermittent porphyria: Highlights from a case report and brief literature review.

Acute hepatic porphyrias are inherited metabolic disorders of heme biosynthesis characterized by the accumulation of toxic intermediate metabolites responsible for disabling acute neurovisceral attacks. Givosiran is a newly approved siRNA-based treatment of acute hepatic porphyria targeting the first and rate-limiting δ-aminolevulinic acid synthase 1 (ALAS1) enzyme of heme biosynthetic pathway. We described a 72-year old patient who presented with severe inaugural neurological form of acute intermittent porphyria evolving for several years which made her eligible for givosiran administration. On initiation of treatment, the patient developed a major hyperhomocysteinemia (>400 µmol/L) which necessitated to discontinue the siRNA-based therapy. A thorough metabolic analysis in the patient suggests that hyperhomocysteinemia could be attributed to a functional deficiency of cystathionine ß-synthase (CBS) enzyme induced by givosiran. Long-term treatment with vitamin B6, a cofactor of CBS, allowed to normalize homocysteinemia while givosiran treatment was maintained. We review the recently published cases of hyperhomocysteinemia in acute hepatic porphyria and its exacerbation under givosiran therapy. We also discuss the benefits of vitamin B6 supplementation in the light of hypothetic pathophysiological mechanisms responsible for hyperhomocysteinemia in these patients. Our results confirmed the importance of monitoring homocysteine metabolism and vitamin status in patients with acute intermittent porphyria in order to improve management by appropriate vitamin supplementation during givosiran treatment.

Learning to stand with sensorimotor delays generalizes across directions and from hand to leg effectors.

Humans receive sensory information from the past, requiring the brain to overcome delays to perform daily motor skills such as standing upright. Because delays vary throughout the body and change over a lifetime, it would be advantageous to generalize learned control policies of balancing with delays across contexts. However, not all forms of learning generalize. Here, we use a robotic simulator to impose delays into human balance. When delays are imposed in one direction of standing, participants are initially unstable but relearn to balance by reducing the variability of their motor actions and transfer balance improvements to untrained directions. Upon returning to normal standing, aftereffects from learning are observed as small oscillations in control, yet they do not destabilize balance. Remarkably, when participants train to balance with delays using their hand, learning transfers to standing with the legs. Our findings establish that humans use experience to broadly update their neural control to balance with delays.

Vestibular control of deep and superficial lumbar muscles.

The active control of the lumbar musculature provides a stable platform critical for postures and goal-directed movements. Voluntary and perturbation-evoked motor commands can recruit individual lumbar muscles in a task-specific manner according to their presumed biomechanics. Here, we investigated the vestibular control of the deep and superficial lumbar musculature. Ten healthy participants were exposed to noisy electrical vestibular stimulation while balancing upright with their head facing forward, left, or right to characterize the differential modulation in the vestibular-evoked lumbar extensor responses in generating multidirectional whole body motion. We quantified the activation of the lumbar muscles on the right side using indwelling [deep multifidus, superficial multifidus, caudal longissimus (L4), and cranial longissimus (L1)] and high-density surface recordings. We characterized the vestibular-evoked responses using coherence and peak-to-peak cross-covariance amplitude between the vestibular and electromyographic signals. Participants exhibited responses in all lumbar muscles. The vestibular control of the lumbar musculature exhibited muscle-specific modulations: responses were larger in the longissimus (combined cranio-caudal) compared with the multifidus (combined deep-superficial) when participants faced forward (P < 0.001) and right (P = 0.011) but not when they faced left. The high-density surface recordings partly supported this observation: the location of the responses was more lateral when facing right compared with left (P < 0.001). The vestibular control of muscle subregions within the longissimus or the multifidus was similar. Our results demonstrate muscle-specific vestibular control of the lumbar muscles in response to perturbations of vestibular origin. The lack of differential activation of lumbar muscle subregions suggests the vestibular control of these subregions is co-regulated for standing balance.NEW & NOTEWORTHY We investigated the vestibular control of the deep and superficial lumbar extensor muscles using electrical vestibular stimuli. Vestibular stimuli elicited preferential activation of the longissimus muscle over the multifidus muscle. We did not observe clear regional activation of lumbar muscle subregions in response to the vestibular stimuli. Our findings show that the central nervous system can finely tune the vestibular control of individual lumbar muscles and suggest minimal regional variations in the activation of lumbar muscle subregions.

Severe Perinatal Presentations of Günther's Disease: Series of 20 Cases and Perspectives.

(1) Background: Congenital erythropoietic porphyria (CEP), named Günther's disease, is a rare recessive type of porphyria, resulting from deficient uroporphyrinogen III synthase (UROS), the fourth enzyme of heme biosynthesis. The phenotype ranges from extremely severe perinatal onset, with life-threatening hemolytic anaemia, to mild or moderate cutaneous involvement in late-onset forms. This work reviewed the perinatal CEP cases recorded in France in order to analyse their various presentations and evolution. (2) Methods: Clinical and biological data were retrospectively collected through medical and published records. (3) Results: Twenty CEP cases, who presented with severe manifestations during perinatal period, were classified according to the main course of the disease: antenatal features, acute neonatal distress and postnatal diagnosis. Antenatal symptoms (seven patients) were mainly hydrops fetalis, hepatosplenomegaly, anemia, and malformations. Six of them died prematurely. Five babies showed acute neonatal distress, associated with severe anemia, thrombocytopenia, hepatosplenomegaly, liver dysfunction, and marked photosensitivity leading to diagnosis. The only two neonates who survived underwent hematopoietic stem cell transplantation (HSCT). Common features in post-natal diagnosis (eight patients) included hemolytic anemia, splenomegaly, skin sensitivity, and discoloured teeth and urine. All patients underwent HSCT, with success for six of them, but with fatal complications in two patients. The frequency of the missense variant named C73R is striking in antenatal and neonatal presentations, with 9/12 and 7/8 independent alleles, respectively. (4) Conclusions: The most recent cases in this series are remarkable, as they had a less fatal outcome than expected. Regular transfusions from the intrauterine period and early access to HSCT are the main objectives.

Substitution of arginine 219 by glycine compromises stability, dimerization, and catalytic activity in a G6PD mutant.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies in humans, present in approximately half a billion people worldwide. More than 230 clinically relevant G6PD mutations of different classes have been reported to date. We hereby describe a patient with chronic hemolysis who presents a substitution of arginine by glycine at position 219 in G6PD protein. The variant was never described in an original publication or characterized on a molecular level. In the present study, we provide structural and biochemical evidence for the molecular basis of its pathogenicity. When compared to the wild-type enzyme, the Arg219Gly mutation markedly reduces the catalytic activity by 50-fold while having a negligible effect on substrate binding affinity. The mutation preserves secondary protein structure, but greatly decreases stability at higher temperatures and to trypsin digestion. Size exclusion chromatography elution profiles show monomeric and dimeric forms for the mutant, but only the latter for the wild-type form, suggesting a critical role of arginine 219 in G6PD dimer formation. Our findings have implications in the development of small molecule activators, with the goal of rescuing the phenotype observed in this and possibly other related mutants.

When mechanical engineering inspired from physiology improves postural-related somatosensory processes.

Despite numerous studies uncovering the neural signature of tactile processing, tactile afferent inputs relating to the contact surface has not been studied so far. Foot tactile receptors being the first stimulated by the relative movement of the foot skin and the underneath moving support play an important role in the sensorimotor transformation giving rise to a postural reaction. A biomimetic surface, i.e., complying with the skin dermatoglyphs and tactile receptors characteristics should facilitate the cortical processes. Participants (n = 15) stood either on a biomimetic surface or on two control surfaces, when a sudden acceleration of the supporting surface was triggered (experiment 1). A larger intensity and shorter somatosensory response (i.e., SEP) was evoked by the biomimetic surface motion. This result and the associated decrease of theta activity (5-7 Hz) over the posterior parietal cortex suggest that increasing the amount of sensory input processing could make the balance task less challenging when standing on a biomimetic surface. This key point was confirmed by a second experiment (n = 21) where a cognitive task was added, hence decreasing the attentional resources devoted to the balance motor task. Greater efficiency of the postural reaction was observed while standing on the biomimetic than on the control surfaces.

Atypical diabetes with spontaneous remission associated with systemic lupus erythematosus in an adolescent girl of African ancestry, a case report.

BACKGROUND: New-onset diabetes in youth encompasses type 1 diabetes, type 2 diabetes, monogenic diabetes, and rarer subtypes like Type B insulin resistance syndrome and ketosis-prone atypical diabetes in African populations. Some cases defy classification, posing management challenges. Here, we present a case of a unique, reversible diabetes subtype. CASE PRESENTATION: We describe an adolescent African girl recently diagnosed with systemic lupus erythematosus. At age 15, she presented with ketoacidosis, HbA1c of 108.7 mmol/mol (12.1%), and positive anti-insulin antibodies. Initially diagnosed with type 1 diabetes, insulin was prescribed. Due to the presence of obesity and signs of insulin resistance, we added metformin. Concurrently, she received treatment for lupus with hydroxychloroquine, mycophenolate mofetil, and prednisone. After discharge, she stopped insulin due to cultural beliefs. Five months later, her glycemia and HbA1c normalized (37 mmol/mol or 5.5%) without insulin, despite corticosteroid therapy and weight gain. Autoantibodies normalized, and lupus activity decreased. Genetic testing for monogenic diabetes was negative, and the type 1 genetic risk score was exceptionally low. CONCLUSIONS: We present a complex, reversible diabetes subtype. Features suggest an autoimmune origin, possibly influenced by overlapping HLA risk haplotypes with lupus. Lupus treatment or immunomodulation may have impacted diabetes remission. Ancestry-tailored genetic risk scores are currently designed to improve diagnostic accuracy.

Using Neck Muscle Afferentation to Control an Ongoing Limb Movement? Individual Differences in the Influence of Brief Neck Vibration.

When preparing and executing goal-directed actions, neck proprioceptive information is critical to determining the relative positions of the body and target in space. While the contribution of neck proprioception for upper-limb movements has been previously investigated, we could not find evidence discerning its impact on the planning vs. online control of upper-limb trajectories. To investigate these distinct sensorimotor processes, participants performed discrete reaches towards a virtual target. On some trials, neck vibration was randomly applied before and/or during the movement, or not at all. The main dependent variable was the medio-lateral/directional bias of the reaching finger. The neck vibration conditions induced early leftward trajectory biases in some participants and late rightward trajectory biases in others. These different patterns of trajectory biases were explained by individual differences in the use of body-centered and head-centered frames of reference. Importantly, the current study provides direct evidence that sensory cues from the neck muscles contribute to the online control of goal-directed arm movements, likely accompanied by significant individual differences.

Noninvasive prenatal diagnosis of Mendelian disorders for consanguineous couples by relative genotype dosage.

Noninvasive prenatal diagnosis relies on the presence in maternal blood of circulating cell-free fetal DNA released by apoptotic trophoblast cells. Widely used for aneuploidy screening, it can also be applied to monogenic diseases (NIPD-M) in case of known parental mutations. Due to the confounding effect of maternal DNA, detection of maternal or biparental mutations requires relative haplotype dosage (RHDO), a method relying on the presence of SNPs that are heterozygous in one parent and homozygous in the other. Unavoidably, there is a risk of test failure by lack of such informative SNPs, an event particularly likely for consanguineous couples who often share common haplotypes in regions of identity-by-descent. Here we present a novel approach, relative genotype dosage (RGDO) that bypasses this predicament by directly assessing fetal genotype with SNPs that are heterozygous in both parents (frequent in regions of identity-by-descent). We show that RGDO is as sensitive as RHDO and that it performs well over a large range of fetal fractions and DNA amounts, thereby opening NIPD-M to most consanguineous couples. We also report examples of couples, consanguineous or not, where combining RGDO and RHDO allowed a diagnosis that would not have been possible with only one approach.

Cortical facilitation of tactile afferents during the preparation of a body weight transfer when standing on a biomimetic surface.

Self-generated movement shapes tactile perception, but few studies have investigated the brain mechanisms involved in the processing of the mechanical signals related to the static and transient skin deformations generated by forces and pressures exerted between the foot skin and the standing surface. We recently found that standing on a biomimetic surface (i.e., inspired by the characteristics of mechanoreceptors and skin dermatoglyphics), that magnified skin-surface interaction, increased the sensory flow to the somatosensory cortex and improved balance control compared to standing on control (e.g., smooth) surfaces. In this study, we tested whether the well-known sensory suppression that occurs during movements is alleviated when the tactile afferent signal becomes relevant with the use of a biomimetic surface. Eyes-closed participants (n = 25) self-stimulated their foot cutaneous receptors by shifting their body weight toward one of their legs while standing on either a biomimetic or a control (smooth) surface. In a control task, similar forces were exerted on the surfaces (i.e., similar skin-surface interaction) by passive translations of the surfaces. Sensory gating was assessed by measuring the amplitude of the somatosensory-evoked potential over the vertex (SEP, recorded by EEG). Significantly larger and shorter SEPs were found when participants stood on the biomimetic surface. This was observed whether the forces exerted on the surface were self-generated or passively generated. Contrary to our prediction, we found that the sensory attenuation related to the self-generated movement did not significantly differ between the biomimetic and control surfaces. However, we observed an increase in gamma activity (30-50 Hz) over centroparietal regions during the preparation phase of the weight shift only when participants stood on the biomimetic surface. This result might suggest that gamma-band oscillations play an important functional role in processing behaviorally relevant stimuli during the early stages of body weight transfer.

Behavioral and Electrocortical Response to a Sensorimotor Conflict in Individuals with Fibromyalgia.

People with fibromyalgia have been shown to experience more somatosensory disturbances than pain-free controls during sensorimotor conflicts (i.e., incongruence between visual and somatosensory feedback). Sensorimotor conflicts are known to disturb the integration of sensory information. This study aimed to assess the cerebral response and motor performance during a sensorimotor conflict in people with fibromyalgia. Twenty participants with fibromyalgia and twenty-three pain-free controls performed a drawing task including visual feedback that was either congruent with actual movement (and thus with somatosensory information) or incongruent with actual movement (i.e., conflict). Motor performance was measured according to tracing error, and electrocortical activity was recorded using electroencephalography. Motor performance was degraded during conflict for all participants but did not differ between groups. Time-frequency analysis showed that the conflict was associated with an increase in theta power (4-8 Hz) at conflict onset over the left posterior parietal cortex in participants with fibromyalgia but not in controls. This increase in theta suggests a stronger detection of conflict in participants with fibromyalgia, which was not accompanied by differences in motor performance in comparison to controls. This points to dissociation in individuals with fibromyalgia between an altered perception of action and a seemingly unaltered control of action.

Cortical facilitation of somatosensory inputs using gravity-related tactile information in humans with vestibular hypofunction.

A few years after their bilateral vestibular loss, patients usually show a motor repertoire that is almost back to normal. This recovery is thought to involve an upregulation of the visual and proprioceptive information that compensates for the lack of vestibular information. Here, we investigated whether plantar tactile inputs, which provide body information relative to the ground and to the Earth vertical, contribute to this compensation. More specifically, we tested the hypothesis that somatosensory cortex response to electric stimulation of the plantar sole in standing adults will be greater in humans (n = 10) with bilateral vestibular hypofunction (VH) than in an age-matched healthy group (n = 10). Showing significantly greater somatosensory evoked potentials (i.e., P1N1) in VH than in control subjects, the electroencephalographic recordings supported this hypothesis. Furthermore, we found evidence that increasing the differential pressure between both feet, by adding a 1-kg mass at each pendant wrist, enhanced the internal representation of body orientation and motion relative to a gravitational reference frame. The large decrease in alpha power in the right posterior parietal cortex (and not in the left) is in line with this assumption. Finally, behavioral analyses showed that trunk oscillations were smaller than head oscillations in VH and showed a reverse pattern for healthy participants. These findings are consistent with a tactile-based postural control strategy in the absence of vestibular input and a vestibular-based control strategy in healthy participants where the head serves as a reference for balance control.NEW & NOTEWORTHY Somatosensory cortex excitability is greater in participants with bilateral vestibular hypofunction than in age-matched healthy humans. To control balance, healthy humans "locked" the head whereas participants with vestibular hypofunction "locked" their pelvis. For participants with vestibular hypofunction, increasing loading/unloading of the feet enhances the internal representation of body state in the posterior parietal cortex.

A peripheral signature of Alzheimer's disease featuring microbiota-gut-brain axis markers.

BACKGROUND: Increasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD. METHODS: We included 34 patients with cognitive impairment due to AD (CI-AD), 37 patients with cognitive impairment not due to AD (CI-NAD), and 13 cognitively unimpaired persons (CU). We studied the following systems: (1) fecal GM, with 16S rRNA sequencing; (2) a panel of putative MGBA mediators in the blood including immune and endothelial markers as bacterial products (i.e., lipopolysaccharide, LPS), cell adhesion molecules (CAMs) indicative of endothelial dysfunction (VCAM-1, PECAM-1), vascular changes (P-, E-Selectin), and upregulated after infections (NCAM, ICAM-1), as well as pro- (IL1ß, IL6, TNFα, IL18) and anti- (IL10) inflammatory cytokines; (3) the amyloid cascade with amyloid PET, plasma phosphorylated tau (pTau-181, for tau pathology), neurofilament light chain (NfL, for neurodegeneration), and global cognition measured using MMSE and ADAScog. We performed 3-group comparisons of markers in the 3 systems and calculated correlation matrices for the pooled group of CI-AD and CU as well as CI-NAD and CU. Patterns of associations based on Spearman's rho were used to validate the study hypothesis. RESULTS: CI-AD were characterized by (1) higher abundance of Clostridia_UCG-014 and decreased abundance of Moryella and Blautia (p < .04); (2) elevated levels of LPS (p < .03), upregulation of CAMs, Il1ß, IL6, and TNFα, and downregulation of IL10 (p < .05); (3) increased brain amyloid, plasma pTau-181, and NfL (p < 0.004) compared with the other groups. CI-NAD showed (1) higher abundance of [Eubacterium] coprostanoligenes group and Collinsella and decreased abundance of Lachnospiraceae_ND3007_group, [Ruminococcus]_gnavus_group and Oscillibacter (p < .03); (2) upregulation of PECAM-1 and TNFα (p < .03); (4) increased plasma levels of NfL (p < .02) compared with CU. Different GM genera were associated with immune and endothelial markers in both CI-NAD and CI-AD but these mediators were widely related to amyloid cascade markers only in CI-AD. CONCLUSIONS: Specific bacterial genera are associated with immune and endothelial MGBA mediators, and these are associated with amyloid cascade markers in sporadic AD. The physiological mechanisms linking the GM to the amyloid cascade should be further investigated to elucidate their potential therapeutic implications.

Seeing our hand or a tool during visually-guided actions: Different effects on the somatosensory and visual cortices.

The processing of proprioceptive information in the context of a conflict between visual and somatosensory feedbacks deteriorates motor performance. Previous studies have shown that seeing one's hand increases the weighting assigned to arm somatosensory inputs. In this light, we hypothesized that the sensory conflict, when tracing the contour of a shape with mirror-reversed vision, will be greater for participants who trace with a stylus seen in their hand (Hand group, n = 17) than for participants who trace with the tip of rod without seen their hand (Tool group, n = 15). Based on this hypothesis, we predicted that the tracing performance with mirror vision will be more deteriorated for the Hand group than for the Tool group, and we predicted a greater gating of somatosensory information for the Hand group to reduce the sensory conflict. The participants of both groups followed the outline of a shape in two visual conditions. Direct vision: the participants saw the hand or portion of a light 40 cm rod directly. Mirror Vision: the hand or the rod was seen through a mirror. We measured tracing performance using a digitizing tablet and the cortical activity with electroencephalography. Behavioral analyses revealed that the tracing performance of both groups was similarly impaired by mirror vision. However, contrasting the spectral content of the cortical oscillatory activity between the Mirror and Direct conditions, we observed that tracing with mirror vision resulted in significantly larger alpha (8-12 Hz) and beta (15-25 Hz) powers in the somatosensory cortex for participants of the Hand group. The somatosensory alpha and beta powers did not significantly differ between Mirror and Direct vision conditions for the Tool group. For both groups, tracing with mirror vision altered the activity of the visual cortex: decreased alpha power for the Hand group, decreased alpha and beta power for the Tool group. Overall, these results suggest that seeing the hand enhanced the sensory conflict when tracing with mirror vision and that the increase of alpha and beta powers in the somatosensory cortex served to reduce the weight assigned to somatosensory information. The increased activity of the visual cortex observed for both groups in the mirror vision condition suggests greater visual processing with increased task difficulty. Finally, the fact that the participants of the Tool group did not show better tracing performance than those of the Hand group suggests that tracing deterioration resulted from a sensorimotor conflict (as opposed to a visuo-proprioceptive conflict).