91 research outputs found
A high-sensitivity long-lifetime phosphorescent RIE additive to probe free volume-related phenomena in polymers
The photophysical behaviour of phosphorescent rigidification-induced emission (RIE) dyes is highly affected by their micro- and nanoenvironment. The lifetime measure of RIE dyes dispersed in polymers represents an effective approach to gain valuable information on polymer free volume and thus develop materials potentially able to self-monitor physical ageing and mechanical stresses
Development of an Innovative Soft Piezoresistive Biomaterial Based on the Interconnection of Elastomeric PDMS Networks and Electrically-Conductive PEDOT:PSS Sponges
A deeply interconnected flexible transducer of polydimethylsiloxane (PDMS) and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) was obtained as a material for the application of soft robotics. Firstly, transducers were developed by crosslinking PEDOT:PSS with 3-glycidyloxypropryl-trimethoxysilane (GPTMS) (1, 2 and 3% v/v) and using freeze-drying to obtain porous sponges. The PEDOT:PSS sponges were morphologically characterized, showing porosities mainly between 200 and 600 µm2; such surface area dimensions tend to decrease with increasing degrees of crosslinking. A stability test confirmed a good endurance for up to 28 days for the higher concentrations of the crosslinker tested. Consecutively, the sponges were electromechanically characterized, showing a repeatable and linear resistance variation by the pressure triggers within the limits of their working range (∆RR0 max = 80% for 1-2% v/v of GPTMS). The sponges containing 1% v/v of GPTMS were intertwined with a silicon elastomer to increase their elasticity and water stability. The flexible transducer obtained with this method exhibited moderately lower sensibility and repeatability than the PEDOT:PSS sponges, but the piezoresistive response remained stable under mechanical compression. Furthermore, the transducer displayed a linear behavior when stressed within the limits of its working range. Therefore, it is still valid for pressure sensing and contact detection applications. Lastly, the flexible transducer was submitted to preliminary biological tests that indicate a potential for safe, in vivo sensing applications
Angiosarcoma of the breast: a new therapeutic approach?
Introduction Angiosarcomas are highly malignant endothelial cell tumors with poor prognosis. These can be due to breast cancer itself or to subsequent therapeutic modalities. No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Presentation of the case We report the case of a 76-year-old woman who developed an exuberant and aggressive post radiation angiosarcoma of the breast and discuss different aspects of therapy for this disease. A total left mastectomy was performed, followed by a right mastectomy. The lesions into the chest wall, and multiple abdominal skin nodules were treated with local Electrochemotherapy (ECT) with intravenous bleomicin. Discussion No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Electrochemotherapy (ECT) is an efficient palliative treatment of cutaneous and subcutaneous tumor nodules. It consists of the combination of a cytotoxic drug and electroporation, using appropriate electrical parameters; destabilization of the membrane is reversible, ensuring a high survival of permeabilized cells and the delivery of non-permeant molecules inside the cell. Conclusion Due to the rarity of the disease, prospective studies concerning adjuvant or neoadjuvant therapy are limited and no evidence-based guidelines exist. The response to chemotherapy seems to be poor. Treatment with ECT in addition to systemic chemotherapy achieves a complete response in all the lesions and improving patient body image perception
Psychological Distress in Morbid Obesity in Relation to Weight History
Background: Very few data are available on psychological
distress in morbidly obese subjects in relation
to the history of their weight. In subjects with childhood
obesity, psychological distress might be better
than in adult-onset obesity, because of progressive
adaptation to the social stigma.
Methods: Psychological distress was tested in relation
to BMI at age 20 years (BMI-20), weight history
and somatic co-morbidities in 632 treatment-seeking,
morbidly obese participants from the QUOVADIS
cohort (130 men, 502 women; mean age 45.5 years).
The number of dieting attempts/year, BMI increase
and cumulative BMI loss since age 20 were calculated
as weight cycling parameters.The Symptom Check
List-90 (SCL-90), the Psychological General Well-
Being (PGWB), the Binge-Eating Scale, and the
ORWELL-97 questionnaire were used to score psychometry
and health-related quality of life (HRQL).
Complications were quantitatively assessed by a
modified Charlson\u2019s score.
Results: BMI-20 was normal in 35% of cases and >35
kg/m2 in only 14%. Psychometric scores were not different
in relation to BMI-20, when corrected for age,
with the exception of the General Health scale of
PGWB, showing a greater distress in subjects with
normal BMI-20. In most cases, the prevalence of
pathological results of questionnaires showed a Jshaped
curve, with participants with normal BMI-20 or
those with Class II-III obesity in early adulthood having
the highest prevalence of psychological/psychiatric
distress and poor HRQL.Weight cycling was a risk factor
for binge-eating, depression and interpersonal
sensitivity in SCL-90, whereas somatic co-morbidities
adversely affected most SCL-90 and all PGWB scales.
Conclusion: Weight cycling and somatic co-morbidities,
but not age of onset of obesity, are the main
factors negatively influencing psychological health in
treatment-seeking, morbidly obese subjects
Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS
Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis
Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy
Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons
Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care
Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42% 60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe
Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis
Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p
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