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"Volpe, R."
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Soft elasticity optimises dissipation in 3D-printed liquid crystal elastomers
2021
Soft-elasticity in monodomain liquid crystal elastomers (LCEs) is promising for impact-absorbing applications where strain energy is ideally absorbed at constant stress. Conventionally, compressive and impact studies on LCEs have not been performed given the notorious difficulty synthesizing sufficiently large monodomain devices. Here, we use direct-ink writing 3D printing to fabricate bulk (>cm
3
) monodomain LCE devices and study their compressive soft-elasticity over 8 decades of strain rate. At quasi-static rates, the monodomain soft-elastic LCE dissipated 45% of strain energy while comparator materials dissipated less than 20%. At strain rates up to 3000 s
−1
, our soft-elastic monodomain LCE consistently performed closest to an ideal-impact absorber. Drop testing reveals soft-elasticity as a likely mechanism for effectively reducing the severity of impacts – with soft elastic LCEs offering a Gadd Severity Index 40% lower than a comparable isotropic elastomer. Lastly, we demonstrate tailoring deformation and buckling behavior in monodomain LCEs via the printed director orientation.
Soft-elasticity in monodomain liquid crystal elastomers (LCEs) is promising for impact-absorbing applications but due to the lack of synthetic procedures which give monodomain devices of sufficient size, impact studies on LCEs have not been performed. Here the authors use direct-ink writing to fabricate bulk monodomain LCE devices and study their compressive soft-elasticity.
Journal Article
Microscale damper prototype: A preliminary study on suppressing air flow oscillations within microchannels
2024
This research introduces a novel micro-damper designed to mitigate pressure and velocity oscillations from a piezoelectric micropump in microfluidic environments. Unlike existing research focusing on damping in incompressible liquid flows with methods like elastic films and PDMS membranes, this study proposes a novel micro-damper prototype. Integrated into a microdevice for particle granulometric separation and detection, the damper connects to a piezoelectric micropump outlet and to a focusing microchannel inlet, followed by a capacitive sensor for size-based particle counting. Preliminary analysis determined an optimal airflow velocity at w = 0.5 m/s for accurate focusing and counting under laminar conditions. The micro-damper, constrained by the piezoelectric pump’s geometry, features a 27 µm high and 1000 µm wide cross section. Its outlet supports two potential focusing microchannel inlet configurations of 30 µm or 40 µm. Distinctively, it incorporates two symmetrical backward micro-channels connecting to the atmosphere, allowing direct piezometric contact between the main flow and an infinite compliant volume. OpenFOAM simulations confirm the damper’s effectiveness in maintaining laminar outlet flow and suppressing micropump disturbances. Thus, the proposed micro-damper ensures optimal inlet conditions for subsequent microchannel processes, enabling stable particle separation and detection in controlled airflow samples.
Journal Article
Peripersonal space plasticity, Self-disorders and intersubjectivity in patients with early-onset and adult-onset schizophrenia
2023
IntroductionIn schizophrenia, there is evidence for anomalies in the extension and plasticity of the peripersonal space (PPS), the portion of space surrounding our body, plastically shaped through motor experiences. An impaired multisensory integration at the PPS level would underpin the disembodiment, a core feature of the disorder linked to subjective perturbations of the sense of self (“Self-disorders”) and of the intersubjective dimension (“schizophrenic autism”).ObjectivesThe present study was aimed at: 1) exploring possible associations between PPS data, psychopathological dimensions, and subjective experiences in schizophrenia; 2) identifying a specific PPS profile in patients with early-onset schizophrenia.MethodsA motor training with a tool was used to assess the PPS size and boundaries demarcation in twenty-seven schizophrenia outpatients. Moreover, they underwent a thorough psychopathological evaluation with the Positive And Negative Syndrome Scale (PANSS), the Examination of Anomalous Self Experience scale (EASE) and the Autism Rating Scale (ARS). Subsequently, the sample was divided into early (EOS) and adult-onset (AOS) subgroups, that were compared with respect to their PPS and psychopathological profiles.ResultsPPS features (size and boundaries demarcation) were associated with PANSS negative score, subjective experiences of existential reorientation (EASE Domain 5 scores) and traits of schizophrenic autism (ARS scores; Fig. 1). PPS parameters (Fig. 2) and ARS scores, but not PANSS and EASE differentiated between early and adult-onset subgroups.Image:Image 2:ConclusionsOur results suggest a link between PPS patterns, negative symptoms, and disturbances of the subjective experience, particularly in the intersubjective domain, in schizophrenia. Moreover, they candidate specific PPS profiles and schizophrenic autism traits as EOS markers.Disclosure of InterestNone Declared
Journal Article
Peripersonal space plasticity in Schizophrenia: a motor training
2022
IntroductionA primary disruption of the bodily self is considered a core feature of schizophrenia patients (SCZ). The “disembodied” self would be underpinned by an inefficient body-related multisensory integration mechanism occurring in the Peripersonal Space (PPS). PPS is a plastic sector of space surrounding our body, whose extent is altered in SCZ. Although PPS represents a malleable interface marking the perceptual border between self and others, no study has investigated the potential alteration of its plasticity in SCZ.ObjectivesWe investigated the PPS extension and its plasticity in SCZ and their potential correlations with the clinical scales.MethodsThirty SCZ and thirty healthy controls (HC) underwent a multisensory task to estimate PPS boundary before and after a motor training. Patients were also administered the Positive And Negative Syndrome Scale (PANSS) and the Examination of Anomalous Self-Experience (EASE).ResultsData confirm a narrower PPS extent in SCZ than in HC, whereas no differences in PPS expansion was found in the two groups after the motor training (Figure 1). Positive symptoms were associated directly with PPS extent and inversely with PPS plasticity. No associations were found between PPS and EASE domains. Figure1: Graphical representation of PPS expansion in SCZ and HC. Both panels show individual normalized sigmoid fitsConclusionsThe present study suggests a narrower PPS extent and a preserved PPS plasticity in SCZ with respect to HC. Both PPS extent and plasticity are related to the severity of positive symptoms. These results highlight the potential role of rehabilitation interventions in order to improve patients’ weakened body boundary.DisclosureNo significant relationships.
Journal Article
Family SES Is Associated with the Gut Microbiome in Infants and Children
by
Lewis, Candace R.
,
McCann, Shelley Hoeft
,
Lemery-Chalfant, Kathryn
in
Antibiotics
,
Bacteroides
,
Breast feeding
2021
Background: While early life exposures such as mode of birth, breastfeeding, and antibiotic use are established regulators of microbiome composition in early childhood, recent research suggests that the social environment may also exert influence. Two recent studies in adults demonstrated associations between socioeconomic factors and microbiome composition. This study expands on this prior work by examining the association between family socioeconomic status (SES) and host genetics with microbiome composition in infants and children. Methods: Family SES was used to predict a latent variable representing six genera abundances generated from whole-genome shotgun sequencing. A polygenic score derived from a microbiome genome-wide association study was included to control for potential genetic associations. Associations between family SES and microbiome diversity were assessed. Results: Anaerostipes, Bacteroides, Eubacterium, Faecalibacterium, and Lachnospiraceae spp. significantly loaded onto a latent factor, which was significantly predicted by SES (p < 0.05) but not the polygenic score (p > 0.05). Our results indicate that SES did not predict alpha diversity but did predict beta diversity (p < 0.001). Conclusions: Our results demonstrate that modifiable environmental factors influence gut microbiome composition at an early age. These results are important as our understanding of gut microbiome influences on health continue to expand.
Journal Article
EWHETA (Eat Well for a HEalthy Third Age) Project: novel foods to improve the nutrition in the elderly people
2021
Cardiovascular diseases (CVD) are the leading cause of mortality. However, by treating modifiable cardiovascular risk factors and following a healthy diet as the Mediterranean diet, we have opportunity to prevent CVD. In the EWHETA (Eat Well for a HEalthy Third Age) Project, our goal has been to develop novel foods (“Mediterranean Lasagne”, MLs) in versions all nutritionally complete and well balanced in terms of calories, whole carbohydrates, fibers, source of vegetable proteins, and vegetable fats. MLs can be easy prepared at home (inexpensively) and used as fresh food or can be pre-prepared and used in residences for elderly people or in health care residencies. The project has saw the alliance between nutritionists and food and sensor scientists and the active involvement of older people in tasting the novel foods to achieve the final tasty versions of the MLs. We think that the nutritional components of these novel foods and its well-accepted taste, insert in a healthy diet and life style (fundamental aspects at every age), and could contribute to improve diet in the elderly people and prevent malnutrition.
Journal Article
Structural basis of colibactin activation by the ClbP peptidase
by
Kenney, Grace E.
,
Balskus, Emily P.
,
Volpe, Matthew R.
in
631/535/1266
,
631/92/173
,
631/92/349
2023
Colibactin, a DNA cross-linking agent produced by gut bacteria, is implicated in colorectal cancer. Its biosynthesis uses a prodrug resistance mechanism: a non-toxic precursor assembled in the cytoplasm is activated after export to the periplasm. This activation is mediated by ClbP, an inner-membrane peptidase with an N-terminal periplasmic catalytic domain and a C-terminal three-helix transmembrane domain. Although the transmembrane domain is required for colibactin activation, its role in catalysis is unclear. Our structure of full-length ClbP bound to a product analog reveals an interdomain interface important for substrate binding and enzyme stability and interactions that explain the selectivity of ClbP for the
N
-acyl-
d
-asparagine prodrug motif. Based on structural and biochemical evidence, we propose that ClbP dimerizes to form an extended substrate-binding site that can accommodate a pseudodimeric precolibactin with its two terminal prodrug motifs in the two ClbP active sites, thus enabling the coordinated activation of both electrophilic warheads.
Structure and mutagenesis of the colibactin-activating peptidase ClbP reveals a dimer with a substrate-binding transmembrane domain and a conserved polar network in its periplasmic domain that enforces selectivity for
d
-asparagine prodrug motifs.
Journal Article
A small molecule inhibitor prevents gut bacterial genotoxin production
2023
The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a
clbP
deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.
A substrate-guided design strategy generated highly potent inhibitors of the biosynthesis of the genotoxin colibactin by human gut bacteria. These inhibitors also enable a generalizable approach for chemically guided natural product discovery.
Journal Article
The Experience of Medical Scribing: No Disparities Identified
2024
The chronic failure to significantly increase the number of underrepresented minorities (URM) in medicine requires that we look for new mechanisms for channelling URM students through pre-medical education and into medical school. One potential mechanism is medical scribing, which involves a person helping a physician engage in real-time documentation in the electronic medical record.
As a precursor to evaluating this mechanism, this survey pilot study explored individuals' experiences working as a medical scribe to look for any differences related to URM status. Of 248 scribes, 159 (64% response rate) completed an online survey. The survey was comprised of 11 items: demographics (4 items), role and length of time spent as a scribe (2 items), and experience working as a scribe (5 items).
The vast majority (>80%) of participants reported that working as a medical scribe gave them useful insight into being a clinician, provided valuable mentoring, and reinforced their commitment to pursue a career in medicine. The experiences reported by scribes who identified as URM did not differ from those reported by their majority counterparts.
It remains to be seen whether medical scribing can serve as an effective pipeline for URM individuals to matriculate into medical school. But the present findings suggest that the experience of working as a medical scribe is a positive one for URM.
Journal Article
A Golden Opportunity: Prevention in the Workplace
2016
[...]simply because patients are receiving medical care, this does not mean their condition is under control; we often observe incomplete medication adherence and as a consequence, patients to not achieve the desired results prescribed by the medical treatment guidelines. [...]only about 20 % of patients with diabetes, high cholesterol and hypertension receive appropriate, satisfactory medical care. The Italian data reflect the results of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III), conducted in 22 European countries in 2006–2007, that show that a large proportion of coronary patients do not achieve the desired therapeutic targets for cardiovascular risk factors. [...]the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA), conducted in 12 European countries in 2009–2010, concludes that a lack of control of hypertension, hyperlipidemia, diabetes and smoking was responsible for 30 % of cardiovascular mortality risk.
Journal Article