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Abstract Integrating artificial limbs as part of one's body involves complex neuroplastic changes resulting from various sensory inputs. While somatosensory feedback is crucial, plastic processes that enable embodiment remain unknown. We investigated this using somatosensory evoked fields (SEFs) in the primary somatosensory cortex (S1) following the Rubber Hand Illusion (RHI), known to quickly induce artificial limb embodiment. During electrical stimulation of the little finger and thumb, 19 adults underwent neuromagnetic recordings before and after the RHI. We found early SEF displacement, including an illusion-brain correlation between extent of embodiment and specific changes to the first cortical response at 20 ms in Area 3b, within S1. Furthermore, we observed a posteriorly directed displacement at 35 ms towards Area 1, known to be important for visual integration during touch perception. That this second displacement was unrelated to extent of embodiment implies a functional distinction between neuroplastic changes of these components and areas. The earlier shift in Area 3b may shape extent of limb ownership, while subsequent displacement into Area 1 may relate to early visual-tactile integration that initiates embodiment. Here we provide evidence for multiple neuroplastic processes in S1—lasting beyond the illusion—supporting integration of artificial limbs like prostheses within the body representation.

Abstract The broad spread of cooperative robots into many application domains has resulted in a demand for intuitive and effective solutions for teleoperated control. A relevant role in teleoperation has been assumed by impedance controllers, that allow the increase of stability and accuracy during interaction. This paper aims to test a teleoperation method based on an impedance controller, namely tele-impedance control, that is usable in unstructured environments since it relies only on wearable sensors. The proposed solution maps the joint stiffness and position of the human user, computed through six EMG and two M-IMU sensors, into the remote system to be teleoperated. We developed a 2-DoFs virtual task involving virtual physical interactions to compare the performance of our solution with the one of a traditional position-based controller. The study has been conducted on five healthy participants, who experienced both controllers in two different sessions. The tele-impedance approach has proved to be less physically demanding and more intuitive than the position-based one. Experimental data also allow us to investigate the strategy employed by the volunteers in the case of remote interactions, while using the two controllers. Of note, even though with the position controller the variation of subject impedance has no effect on the virtual arm, participants still tend to regulate both impedance and position of their own arm.

Abstract Background In the last years, the classical pattern of diabetic kidney disease (DKD) has been partially overcome, because of the uncovering of a new DKD phenotype with significant renal dysfunction without presence of albuminuria: the non-albuminuric DKD (NA-DKD). To date, the cardiovascular risk associated with this phenotype is still debated. We investigated the cardiovascular risk and renal injury profile of NA-DKD subjects in comparison with other DKD phenotypes. Methods Pulse wave velocity (PWV), intima-media thickness, presence of carotid atherosclerotic plaque, renal resistive index (RRI), and a panel of urinary biomarkers of kidney injury were evaluated in 160 subjects with type 2 diabetes, stratified according to estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) into four groups: controls (UACR

Summary: Background: Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D. Methods: We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function. Findings: We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR 30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m2 (95% C.I. from 1.13 to 2.48; p

Background and aimsFH women are less likely to receive intensive statin treatment and to obtain a 50% reduction of LDL-C from baseline compared to men with FH. SLCO1B1 rs4149056 might influence statin therapy compliance and thus LDL-C target achievement. Our aim was to evaluate the impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy (LLT) optimization in men and women with FH.MethodsThis was a retrospective observational study involving 412 FH subjects with a probable or defined clinical diagnosis of FH who had had genetic analysis from June 2016 to September 2022. Biochemical analysis was obtained from all subjects at baseline and at the last follow-up after LLT optimization.ResultsAfter LLT optimization the percentage of FH subjects on high-intensity statins decreased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was found in LDL-C target distribution (for both p for trend < 0.01). The prevalence of SASE fear increased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was observed in reported myalgia distribution (for both p for trend < 0.01). Logistic regression analysis showed that the W/SCLO1B1-, M/SCLO1B1+ and W/SCLO1B1+ groups were inversely associated with LDL-C target achievement (p for trend < 0.001) and the W/SCLO1B1+ group exhibited the strongest association.ConclusionA low prevalence of FH women with SLCO1B1 rs4149056 were on high intensity statins and they rarely achieved LDL-C target. The genotype effect of SLCO1B1 rs4149056 could be more pronounced in FH women than men.

Abstract In human movement augmentation, the number of controlled degrees of freedom could be enhanced by the simultaneous and independent use of supernumerary robotic limbs (SRL) and natural ones. However, this poses several challenges, that could be mitigated by encoding and relaying the SRL status. Here, we review the impact of supplementary sensory feedback on the control and embodiment of SRLs. We classify the main feedback features and analyse how they improve control performance. We report the feasibility of pushing body representation beyond natural human morphology and suggest that gradual SRL embodiment could make multisensory incongruencies less disruptive. We also highlight shared computational bases between SRL motor control and embodiment and suggest contextualizing them within the same theoretical framework. Finally, we argue that a shift towards long term experimental paradigms is necessary for successfully integrating motor control and embodiment.

Abstract Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.

Anderson-Fabry disease (AFD), a genetic disorder caused by mutations in the α-galactosidase-A (GLA) gene, disrupts lysosomal function, leading to vascular complications. The accumulation of globotriaosylceramide (Gb3) in arterial walls triggers upregulation of adhesion molecules, decreases endothelial nitric oxide synthesis, and induces reactive oxygen species production. This cascade results in fibrotic thickening, endothelial dysfunction, hypercontractility, vasospasm, and a pro-thrombotic phenotype. AFD patients display increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating heightened cardiovascular risk. Nailfold capillaroscopy (NFC) shows promise in diagnosing and monitoring microcirculatory disorders in AFD, though it remains underexplored. Morphological evidence of AFD as a storage disorder can be demonstrated through electron microscopy and immunodetection of Gb3. Secondary pathophysiological disturbances at cellular, tissue, and organ levels contribute to the clinical manifestations, with prominent lysosomal inclusions observed in vascular, cardiac, renal, and neuronal cells. Chronic accumulation of Gb3 represents a state of ongoing toxicity, leading to increased cell turnover, particularly in vascular endothelial cells. AFD-related vascular pathology includes increased renin-angiotensin system activation, endothelial dysfunction, and smooth muscle cell proliferation, resulting in IMT increase. Furthermore, microvascular alterations, such as atypical capillaries observed through NFC, suggest early microvascular involvement. This review aims to unravel the complex interplay between inflammation, oxidative stress, and endothelial dysfunction in AFD, highlighting the potential connections between metabolic disturbances, oxidative stress, inflammation, and fibrosis in vascular and cardiac complications. By exploring novel cardiovascular risk factors and potential diagnostic tools, we can advance our understanding of these mechanisms, which extend beyond sphingolipid accumulation to include other significant contributors to disease pathogenesis. This comprehensive approach can pave the way for innovative therapeutic strategies and improved patient outcomes.

The increasing utilization of Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) in managing type 2 diabetes mellitus has raised interest regarding their impact on thyroid function. In fact, while these agents are well known for their efficacy in glycemic control and weight management, their association with thyroid disorders requires clarification due to the complex interplay between thyroid hormones and metabolic pathways. Thyroid dysfunction commonly co-occurs with metabolic conditions such as diabetes and obesity, suggesting a profound interconnection between these systems. This review aims to contribute to a deeper understanding of the interaction between GLP-1 RAs and thyroid dysfunction and to clarify the safety of GLP-1 RAs in diabetic patients with thyroid disorders. By synthesizing existing evidence, this review highlights that, despite various studies exploring this topic, current evidence is inconclusive, with conflicting results. It is important to note that these drugs are relatively recent, and longer-term studies with larger sample sizes are likely needed to draw clearer conclusions. Currently, no existing guidelines provide definitive directions on this clinical issue; however, it is advisable to include thyroid function tests in the routine screening of diabetic patients, particularly those treated with GLP-1 Ras, with the goal of optimizing patient care and management.

Fatty liver disease has been identified as a marker of malnutrition in different clinical settings. Recently, the COntrolling NUTritional status score (CONUT score) emerged as a promising tool for malnutrition assessment. Our aim was to evaluate short-term outcomes among patients with malnutrition-related liver steatosis in an Internal Medicine department. Furthermore, we evaluated the association of the CONUT score with malnutrition-related liver steatosis. Data from 247 patients hospitalized in an Internal Medicine department were retrospectively collected. The study population was stratified into three groups based on hepatic radiodensity assessed with computed tomography: mild steatosis (≥56.1 HU), moderate steatosis (between 49.7 and 56 HU), and severe steatosis (≤49.6 HU). We then calculated the CONUT score. Severe steatosis patients had higher in-hospital mortality (18.2 vs. 15.5%) and longer in-hospital stays compared with the mild steatosis group (length of in-hospital stay longer than 12 days: 45% vs. 40%). Logistic regression analysis showed that severe steatosis was not significantly associated with in-hospital all-cause death, while a high CONUT score was an independent risk factor for sepsis. We found an independent relationship between malnutrition-associated liver steatosis and the CONUT score. These results identified the CONUT score as a tool for nutritional assessment of hospitalized patients.

Magnetoencephalography and electroencephalography (M/EEG) seed-based connectivity analysis typically requires regions of interest (ROI)-based extraction of measures. M/EEG ROI-derived source activity can be treated in different ways. For instance, it is possible to average each ROI's time series prior to calculating connectivity measures. Alternatively one can compute connectivity maps for each element of the ROI, prior to dimensionality reduction to obtain a single map. The impact of these different strategies on connectivity estimation is still unclear.Here, we address this question within a large MEG resting state cohort (N=113) and simulated data. We consider 68 ROIs (Desikan-Kiliany atlas), two measures of connectivity (phase locking value-PLV, and its imaginary counterpart- ciPLV), and three frequency bands (theta 4-8 Hz, alpha 9-12 Hz, beta 15-30 Hz). We consider four extraction methods: (i) mean, or (ii) PCA of the activity within the ROI before computing connectivity, (iii) average, or (iv) maximum connectivity after computing connectivity for each element of the seed. Connectivity outputs from these extraction strategies are then compared with hierarchical clustering, followed by direct contrasts across extraction methods. Finally, the results are validated by using a set of realistic simulations.We show that ROI-based connectivity maps vary remarkably across strategies in both connectivity magnitude and spatial distribution. Dimensionality reduction procedures conducted after computing connectivity are more similar to each-other, while PCA before approach is the most dissimilar to other approaches. Although differences across methods are consistent across frequency bands, they are influenced by the connectivity metric and ROI size. Greater differences were observed for ciPLV than PLV, and in larger ROIs. Realistic simulations confirmed that after aggregation procedures are generally more accurate but have lower specificity (higher rate of false positive connections). Although computationally demanding, after dimensionality reduction strategies should be preferred when higher sensitivity is desired. Given the remarkable differences across aggregation procedures, caution is warranted in comparing results across studies applying different extraction methods.

Abstract Pointing at a screen using wrist and forearm movements is a kinematically redundant task, and the Central Nervous System seems to manage this redundancy by using a simplifying strategy, named Donders’ Law for the wrist. In this work we investigated (1) whether this simplifying approach is stable over time and (2) whether a visuomotor perturbation provided in the task space influences the strategy used to solve the redundancy problem. We conducted two experiments asking participants to perform the same pointing task in four different days (first experiment), and providing a visual perturbation, i.e. a visuomotor rotation to the controlled cursor (second experiment), while recording their wrist and forearm rotations. Results showed that the participant-specific wrist redundancy management (described by the Donders’ surfaces) (1) neither changes over time (2) nor varies when a visuomotor perturbation is provided in the task space.

Anderson–Fabry disease (AFD) is a genetic lysosomal storage disorder caused by mutations in the α-galactosidase A gene, leading to impaired lysosomal function and resulting in both macrovascular and microvascular alterations. AFD patients often exhibit increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating non-atherosclerotic arterial thickening and the potential for cardiovascular events. Nailfold capillaroscopy, a non-invasive diagnostic tool, has shown potential in diagnosing and monitoring microcirculatory disorders in AFD, despite limited research. This study evaluates nailfold capillaroscopy findings in AFD patients, exploring correlations with GLA gene variant subgroups (associated with classical or late-onset phenotypes and variants of uncertain significance (VUSs)), and assessing morpho-functional differences between sexes. It aims to determine whether capillaroscopy can assist in the early identification of individuals with multiorgan vascular involvement. A retrospective observational study was conducted with 25 AFD patients from AOUP "G. Rodolico-San Marco" in Catania (2020–2023). Patients underwent genetic testing, enzyme activity evaluation, and nailfold capillaroscopy using Horus basic HS 200 videodermatoscopy. Parameters like angiotectonic disorder, vascular areas, capillary density, and intimal thickening were assessed. The study identified significant differences in capillaroscopy findings among patients with different GLA gene variant subgroups. Classic AFD variant patients showed reduced capillary length and signs of erythrocyte aggregation and dilated subpapillary plexus. No correlation was found between enzymatic activity and capillaroscopy parameters. However, Lyso-Gb3 levels were positively correlated with average capillary length (ῤ = 0.453; p = 0.059). Sex-specific differences in capillaroscopy findings were observed in neoangiogenesis and average capillary length, with distinct implications for men and women. This study highlights the potential of nailfold capillaroscopy in the diagnostic process and clinical management of AFD, particularly in relation to specific GLA gene mutations, as a valuable tool for the early diagnosis and monitoring of AFD. [ABSTRACT FROM AUTHOR]

“Crossmodal correspondences” are the consistent mappings between perceptual dimensions or stimuli from different sensory domains, which have been widely observed in the general population and investigated by experimental psychologists in recent years. At the same time, the emerging field of human movement augmentation (i.e., the enhancement of an individual’s motor abilities by means of artificial devices) has been struggling with the question of how to relay supplementary information concerning the state of the artificial device and its interaction with the environment to the user, which may help the latter to control the device more effectively. To date, this challenge has not been explicitly addressed by capitalizing on our emerging knowledge concerning crossmodal correspondences, despite these being tightly related to multisensory integration. In this perspective paper, we introduce some of the latest research findings on the crossmodal correspondences and their potential role in human augmentation. We then consider three ways in which the former might impact the latter, and the feasibility of this process. First, crossmodal correspondences, given the documented effect on attentional processing, might facilitate the integration of device status information (e.g., concerning position) coming from different sensory modalities (e.g., haptic and visual), thus increasing their usefulness for motor control and embodiment. Second, by capitalizing on their widespread and seemingly spontaneous nature, crossmodal correspondences might be exploited to reduce the cognitive burden caused by additional sensory inputs and the time required for the human brain to adapt the representation of the body to the presence of the artificial device. Third, to accomplish the first two points, the benefits of crossmodal correspondences should be maintained even after sensory substitution, a strategy commonly used when implementing supplementary feedback.

Supernumerary robotic limbs are mainly designed to augment the physical capabilities of able-bodied individuals, in a wide range of contexts from body support to surgery. When they are worn as wearable devices, they naturally provide inherent feedback due to the mechanical coupling with the human body. The user can, thus, perceive the interaction with the environment by relying on a combination of visual and inherent feedback. However, these can be inefficient in accomplishing complex tasks, particularly in the case of visual occlusion or variation in the environment stiffness. Here, we investigated whether, in a force-regulation task using a wearable supernumerary robotic arm (SRA), additional vibrotactile feedback can increase the control performance of participants compared to the inherent feedback. Additionally, to make the scenario more realistic, we introduced variations in the SRA’s kinematic posture and in the environment stiffness. Notably, our findings revealed a statistically significant improvement in user performance over all the evaluated metrics while receiving additional vibrotactile feedback. Compared to inherent feedback alone, the additional vibrotactile feedback allowed participants to exert the required force faster (p < 0.01), to maintain it for longer (p < 0.001), and with lower errors (p < 0.001). No discernible effects related to the SRA’s posture or environment stiffness were observed. These results proved the benefits of providing the user with additional vibrotactile feedback to convey the SRA’s force during interaction tasks.

Host genetic variants may affect oral biofilms, playing a role in the periodontitis–systemic disease axis. This is the first study to assess the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed, assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis testing) and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed and stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics with no genome-wide associations detected for periodontitis severity or Mets components at p < 10−7. Severe periodontitis was associated with pathogenic genera and species. Some SNPs correlated with specific bacterial genera as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and the microbiome.

Abstract Auditory white noise (WN) is widely used in neuroscience to mask unwanted environmental noise and cues, e.g. TMS clicks. However, to date there is no research on the influence of WN on corticospinal excitability and potentially associated sensorimotor integration itself. Here we tested the hypothesis, if WN induces M1 excitability changes and improves sensorimotor performance. M1 excitability (spTMS, SICI, ICF, I/O curve) and sensorimotor reaction-time performance were quantified before, during and after WN stimulation in a set of experiments performed in a cohort of 61 healthy subjects. WN enhanced M1 corticospinal excitability, not just during exposure, but also during silence periods intermingled with WN, and up to several minutes after the end of exposure. Two independent behavioural experiments highlighted that WN improved multimodal sensorimotor performance. The enduring excitability modulation combined with the effects on behaviour suggest that WN might induce neural plasticity. WN is thus a relevant modulator of corticospinal function; its neurobiological effects should not be neglected and could in fact be exploited in research applications.

IntroductionRobotic therapy allow to propose sessions of controlled and identical exercises, customizing settings, and characteristics on the individual patient. The effectiveness of robotic assisted therapy is still under study and the use of robots in clinical practice is still limited. Moreover, the possibility of treatment at home allows to reduce the economic costs and time to be borne by the patient and the caregiver and is a valid tool during periods of pandemic such as covid. The aim of this study is to assess whether a robotic home-based treatment rehabilitation using the iCONE robotic device has effects on a stroke population, despite the chronic condition of patients involved and the absence of a therapist next to the patient while performing the exercises.Materials and methodsAll patients underwent an initial (T0) and final (T1) assessment with the iCONE robotic device and clinical scales. After T0 evaluation, the robot was delivered to the patient's home for 10 days of at-home treatment (5 days a week for 2 weeks).ResultsComparison between T0 and T1 evaluations revealed some significant improvements in robot-evaluated indices such as Independence and Size for the Circle Drawing exercise and Movement Duration for Point-to-Point exercise, but also in the MAS of the elbow. From the analysis of the acceptability questionnaire, a general appreciation of the robot emerged: patients spontaneously asked for the addition of further sessions and to continue therapy.DiscussionTelerehabilitation of patients suffering from a chronic stroke is an area that is still little explored. From our experience, this is one of the first studies to carry out a telerehabilitation with these characteristics. The use of robots can become a method to reduce the rehabilitation health costs, to ensure continuity of care, and to arrive in more distant places or where the availability of resources is limited.ConclusionFrom the data obtained, this rehabilitation seems to be promising for this population. Moreover, promoting the recovery of the upper limb, iCONE can improve patient's quality of life. It would be interesting to conduct RCT studies to compare a conventional treatment in structure with a robotic telematics treatment.

In this Review, the authors discuss recent technological and neuroscientific advances in human body augmentation. They construct a movement augmentation taxonomy, discuss how it is achieved, and propose a vision for the field.

Background and Aims: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase‐associated lipocalin (u‐NGAL), urinary beta‐2‐microglobulin (u‐B2M), urinary osteopontin (u‐OPN), urinary trefoil factor 3 (u‐TFF3) and urinary Cystatin C (u‐Cys). Methods: This is a case‐control study investigating the following urinary biomarkers of tubular damage: u‐NGAL, u‐B2M, u‐OPN, u‐TFF3 and u‐Cys, in patients with mild acute hyperbilirubinemia. Seventy‐four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. Results: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u‐NGAL, u‐B2M, u‐OPN, u‐TFF3 and u‐Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u‐NGAL values (OR = 3.8, 95% CI 1.07–13.5, p =.03) and u‐B2M (OR = 9.4, 95% CI 2.3–38.9, p =.0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. Conclusions: This study demonstrated increased urinary biomarkers of tubular damage (u‐NGAL, u‐B2M, u‐OPN, u‐TFF3, and u‐Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology). [ABSTRACT FROM AUTHOR]

Anderson-Fabry disease (AFD), a genetic disorder caused by mutations in the α-galactosidase-A (GLA) gene, disrupts lysosomal function, leading to vascular complications. The accumulation of globotriaosylceramide (Gb3) in arterial walls triggers upregulation of adhesion molecules, decreases endothelial nitric oxide synthesis, and induces reactive oxygen species production. This cascade results in fibrotic thickening, endothelial dysfunction, hypercontractility, vasospasm, and a pro-thrombotic phenotype. AFD patients display increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating heightened cardiovascular risk. Nailfold capillaroscopy (NFC) shows promise in diagnosing and monitoring microcirculatory disorders in AFD, though it remains underexplored. Morphological evidence of AFD as a storage disorder can be demonstrated through electron microscopy and immunodetection of Gb3. Secondary pathophysiological disturbances at cellular, tissue, and organ levels contribute to the clinical manifestations, with prominent lysosomal inclusions observed in vascular, cardiac, renal, and neuronal cells. Chronic accumulation of Gb3 represents a state of ongoing toxicity, leading to increased cell turnover, particularly in vascular endothelial cells. AFD-related vascular pathology includes increased renin-angiotensin system activation, endothelial dysfunction, and smooth muscle cell proliferation, resulting in IMT increase. Furthermore, microvascular alterations, such as atypical capillaries observed through NFC, suggest early microvascular involvement. This review aims to unravel the complex interplay between inflammation, oxidative stress, and endothelial dysfunction in AFD, highlighting the potential connections between metabolic disturbances, oxidative stress, inflammation, and fibrosis in vascular and cardiac complications. By exploring novel cardiovascular risk factors and potential diagnostic tools, we can advance our understanding of these mechanisms, which extend beyond sphingolipid accumulation to include other significant contributors to disease pathogenesis. This comprehensive approach can pave the way for innovative therapeutic strategies and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Somatosensation greatly increases the ability to control our natural body. This suggests that supplementing vision with haptic sensory feedback would also be helpful when a user aims at controlling a robotic arm proficiently. However, whether the position of the robot and its continuous update should be coded in a extrinsic or intrinsic reference frame is not known. Here we compared two different supplementary feedback contents concerning the status of a robotic limb in 2-DoFs configuration: one encoding the Cartesian coordinates of the end-effector of the robotic arm (i.e., Task-space feedback) and another and encoding the robot joints angles (i.e., Joint-space feedback). Feedback was delivered to blindfolded participants through vibrotactile stimulation applied on participants' leg. After a 1.5-hour training with both feedbacks, participants were significantly more accurate with Task compared to Joint-space feedback, as shown by lower position and aiming errors, albeit not faster (i.e., similar onset delay). However, learning index during training was significantly higher in Joint space feedback compared to Task-space feedback. These results suggest that Task-space feedback is probably more intuitive and more suited for activities which require short training sessions, while Joint space feedback showed potential for long-term improvement. We speculate that the latter, despite performing worse in the present work, might be ultimately more suited for applications requiring long training, such as the control of supernumerary robotic limbs for surgical robotics, heavy industrial manufacturing, or more generally, in the context of human movement augmentation.

Diabetic kidney disease (DKD) is a complication that strongly increases the risk of end-stage kidney disease and cardiovascular events. The identification of novel, highly sensitive, and specific early biomarkers to identify DKD patients and predict kidney function decline is a pivotal aim of translational medicine. In a previous study, after a high-throughput approach, we identified in 69 diabetic patients 5 serum mitochondrial RNAs (MT-ATP6, MT-ATP8, MT-COX3, MT-ND1, and MT-RNR1) progressively downregulated with increasing eGFR stages. Here, we analyzed the protein serum concentrations of three well-validated biomarkers: TNFRI, TNFRII, and KIM-1. The protein biomarkers were gradually upregulated from G1 to G2 and G3 patients. All protein biomarkers correlated with creatinine, eGFR, and BUN. Performing multilogistic analyses, we found that, with respect to single protein biomarkers, the combination between (I) TNFRI or KIM-1 with each RNA transcript and (II) TNFRII with MT-ATP8, MT-ATP6, MT-COX-3, and MT-ND1 determined an outstanding improvement of the diagnostic performance of G3 versus G2 patient identification, reaching values in most cases above 0.9 or even equal to 1. The improvement of AUC values was also evaluated in normoalbuminuric or microalbuminuric patients considered separately. This study proposes a novel, promising multikind marker panel associated with kidney impairment in DKD.

Abstract The successful completion of complex tasks like hanging a picture or laparoscopic surgery requires coordinated motion of more than two limbs. User-controlled supernumerary robotic limbs (SL) have been proposed to bypass the need for coordination with a partner in such tasks. However, neither the capability to control multiple limbs alone relative to collaborative control with partners, nor how that capability varies across different tasks, is well understood. In this work, we present an investigation of tasks requiring three-hands where the foot was used as an additional source of motor commands. We considered: (1) how does simultaneous control of three hands compare to a cooperating dyad; (2) how this relative performance was altered by the existence of constraints emanating from real or virtual physical connections (mechanical constraints) or from cognitive limits (cognitive constraints). It was found that a cooperating dyad outperformed a single user in all scenarios in terms of task score, path efficiency and motion smoothness. However, while the participants were able to reach more targets with increasing mechanical constraints/decreasing number of simultaneous goals, the relative difference in performance between a dyad and a participant performing trimanual activities decreased, suggesting further potential for SLs in this class of scenario.