The TexiSense « Smart Sock » - a device for a daily prevention of pressure ulcers in the diabetic foot

International audienceGoals.– The term « diabetic foot » refers to a set of foot pathologies essentially stemming from the neuropathy and arteriopathy of the lower limb associated with diabetes mellitus. Chronic ischemia weakens the healing potential and favors the development of wounds on a more vulnerable foot. Friction or repeated micro-traumas can lead to an ulceration (which in turn can end up in an amputation) that will remain unnoticed because of the somato-sensory deficiency. The current prevention techniques largely relying on visual inspection of the foot and enhancement of the foot/insole interface are not fully satisfying as the prevalence of plantar ulcers remains very high.Patients and methods.– A device for the prevention of plantar ulcers–called “Smart Sock” is described. It consists of:– a sock made of a 100% textile pressure sensing fabric developed by the TexiSense company;– a microcontroller running a biomechanical model of the soft tissues of the foot of the diabetic person;– a vibrating watch (and eventually a smartphone) used to warn the bearer if a pressure pattern threatens the soft tissues integrity.Results.– Internal overpressures within the soft tissues, especially nearby bony prominences are likely to develop into deep foot ulcerations. The biomechanical model gives an estimation of their magnitude based on the external pressures measured by the sock/sensor. This modeling relies on a faithful representation of the morphology of the diabetic subject. The device sends a vibro-tactile alert in case of occasional overpressure or excessive stress dose accumulated during daytime activities.Discussion.– The continuous use of the device, compatible with daytime activities of the diabetic person, helps compensate for the lack of attention in the prevention of pressure ulcer formation. The TexiSense “Smart Sock” can be designed so that when worn, pressure sensors fall onto sensitive anatomical areas such as the dorsal side of the toes or the posterior side of the heel, which makes it also possible to monitor regions located outside the sole of the foot

Body numerical phantoms for estimating soft tissue pains or injuries when interacting with shoes, seats and mattresses

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Influence of the calcaneus shape on the risk of posterior heel ulcer using 3D patient-specific biomechanical modeling.

International audienceMost posterior heel ulcers are the consequence of inactivity and prolonged time lying down on the back. They appear when pressures applied on the heel create high internal strains and the soft tissues are compressed by the calcaneus. It is therefore important to monitor those strains to prevent heel pressure ulcers. Using a biomechanical lower leg model, we propose to estimate the influence of the patient-specific calcaneus shape on the strains within the foot and to determine if the risk of pressure ulceration is related to the variability of this shape. The biomechanical model is discretized using a 3D Finite Element mesh representing the soft tissues, separated into four domains implementing Neo Hookean materials with different elasticities: skin, fat, Achilles' tendon, and muscles. Bones are modelled as rigid bodies attached to the tissues. Simulations show that the shape of the calcaneus has an influence on the formation of pressure ulcers with a mean variation of the maximum strain over 6.0 percentage points over 18 distinct morphologies. Furthermore, the models confirm the influence of the cushion on which the leg is resting: a softer cushion leading to lower strains, it has less chances of creating a pressure ulcer. The methodology used for patient-specific strain estimation could be used for the prevention of heel ulcer when coupled with a pressure sensor

Pressure ulcer prevention in spinal cord injury subjects using the TexiSense pressure sensing textile

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Interactions with M cells and macrophages as key steps in the pathogenesis of enterohemorrhagic Escherichia coli infections

Enterohemorrhagic Escherichia coli (EHEC) are food-borne pathogens that can cause serious infections ranging from diarrhea to hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). Translocation of Shiga-toxins (Stx) from the gut lumen to underlying tissues is a decisive step in the development of the infection, but the mechanisms involved remain unclear. Many bacterial pathogens target the follicle-associated epithelium, which overlies Peyer's patches (PPs), cross the intestinal barrier through M cells and are captured by mucosal macrophages. Here, translocation across M cells, as well as survival and proliferation of EHEC strains within THP-1 macrophages were investigated using EHEC O157:H7 reference strains, isogenic mutants, and 15 EHEC strains isolated from HC/HUS patients. We showed for the first time that E. coli O157:H7 strains are able to interact in vivo with murine PPs, to translocate ex vivo through murine ileal mucosa with PPs and across an in vitro human M cell model. EHEC strains are also able to survive and to produce Stx in macrophages, which induce cell apoptosis and Stx release. In conclusion, our results suggest that the uptake of EHEC by M cells and underlying macrophages in the PP may be a critical step in Stx translocation and release in vivo. A new model for EHEC infection in humans is proposed that could help in a fuller understanding of EHEC-associated diseases

Ribosomal RNA 2′O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

International audienceRecent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2′O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2′O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2′O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2′O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2′O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2′O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer

Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer

International audienceBackground: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. Methods: Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levelsrelated breast tumours. Results: We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. Conclusion: Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper-but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors