Transcriptome-wide expression profiling in skin fibroblasts of patients with joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients

Mesh Fixation Methods in Groin Hernia Surgery

No unanimous consent has been reached by surgeons in terms of a method for mesh fixation in laparoscopic and open surgery for inguinal hernia repair. Many different methods of fixation are available, and the choice of which one to use is still based on surgeons’ preferences. At present, tissue glues, sutures, and laparoscopic tacks are the most common fixating methods. In open technique, sutures have been the method of choice for their reduced costs and surgeons’ habits. Nevertheless, tissue glues have been demonstrated to be effective and safe. Similarly, tacks can be considered the most common means of fixation in laparoscopic hernia repair, but they are connected to a higher risk of complication and morbidity. In this chapter, we present these types of mesh fixation, their characteristics and potential risks, and advantages of their use

GLUT10 deficiency leads to oxidative stress and non-canonical αvβ3 integrin-mediated TGFβ signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts

Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10). The role of GLUT10 in ATS pathogenesis remains an enigma, and the transported metabolite(s), i.e. glucose and/or dehydroascorbic acid, have not been clearly elucidated. To discern the molecular mechanisms underlying the ATS aetiology, we performed gene expression profiling and biochemical studies on skin fibroblasts. Transcriptome analyses revealed the dysregulation of several genes involved in TGFβ signalling and extracellular matrix (ECM) homeostasis as well as the perturbation of specific pathways that control both the cell energy balance and the oxidative stress response. Biochemical and functional studies showed a marked increase in ROS-induced lipid peroxidation sustained by altered PPARγ function, which contributes to the redox imbalance and the compensatory antioxidant activity of ALDH1A1. ATS fibroblasts also showed activation of a non-canonical TGFβ signalling due to TGFBRI disorganization, the upregulation of TGFBRII and connective tissue growth factor, and the activation of the αvβ3 integrin transduction pathway, which involves p125FAK, p60Src and p38 MAPK. Stable GLUT10 expression in patients' fibroblasts normalized redox homeostasis and PPARγ activity, rescued canonical TGFβ signalling and induced partial ECM re-organization. These data add new insights into the ATS dysregulated biological pathways and definition of the pathomechanisms involved in this disorder

All-in-One Mesh Hernioplasty: A New Procedure for Inguinal Hernia Repair

Since the 1970s, when biocompatible meshes were introduced with the consequent decrease of recurrence, one of the priorities in inguinal hernia surgery was that of minimizing postoperative chronic pain. All technical variations, proposed during the past years in order to improve patient’s comfort, reported a variable incidence of chronic neuralgia. The procedure we describe, applicable to all cases of primary inguinal hernia, employs a smaller pre-cut single mesh that covers all weak areas of the inguinal canal and is enveloped in a fibro-cremasteric sheath, avoiding contact of the prosthesis with neural structures. The new procedure, already performed on 250 patients, aims to improve patients’ comfort and to reduce the incidence of chronic neuralgia

Modelling soil water conent in a tomato field: proximal gamma ray spectroscopy and soil-crop system models

Proximal soil sensors are taking hold in the understanding of soil hydrogeological processes involved in precision agriculture. In this context, permanently installed gamma ray spectroscopy stations represent one of the best space-time trade off methods at field scale. This study proved the feasibility and reliability of soil water content monitoring through a seven-month continuous acquisition of terrestrial gamma radiation in a tomato test field. By employing a 1 L sodium iodide detector placed at a height of 2.25 m, we investigated the gamma signal coming from an area having a ~25 m radius and from a depth of approximately 30 cm. Experimental values, inferred after a calibration measurement and corrected for the presence of biomass, were corroborated with gravimetric data acquired under different soil moisture conditions, giving an average absolute discrepancy of about 2%. A quantitative comparison was carried out with data simulated by AquaCrop, CRITeRIA, and IRRINET soil-crop system models. The different goodness of fit obtained in bare soil condition and during the vegetated period highlighted that CRITeRIA showed the best agreement with the experimental data over the entire data-taking period while, in presence of the tomato crop, IRRINET provided the best results.Comment: 18 pages, 9 Figures, 3 Table

Neuroselling: applying neuroscience to selling for a new business perspective. An analysis on teleshopping advertising.

This paper presents an innovative research project that aims to study the emotional factors influencing decision-making elicited by infomercials, a powerful sales technique that uses emotional communication to engage viewers, capture attention, and build trust. Using cutting-edge consumer neuroscience techniques, this study focuses on the identification of the variables that most impact the Call-to-Action and Purchase Intention. Forty participants were selected and divided into two groups, with each group exposed to one of two infomercials (condition A = male seller; condition B = female seller). EEG signals were recorded as well as Eye-tracking data. After the viewing, participants completed a self-report questionnaire. Results show that seller characteristics such as Performance and Trustworthiness, as well as Neurophysiological variables such as Approach-Withdrawal Index, Willingness to Pay, Attention and Engagement, significantly impact the final Call-to-Action, Purchase Intention, and infomercial Likeability responses. Moreover, eye-tracking data revealed that the more time is spent observing crucial areas of the infomercial, the more it will increase our Willingness to Pay and our interest and willingness to approach the infomercial and product. These findings highlight the importance of considering both the Seller attributes and the consumers’ Neurophysiological responses to understand and predict their behaviors in response to marketing stimuli since they all seem to play a crucial role in shaping consumers’ attitudes and purchase intentions. Overall, the study is a significant pilot in the new field of neuroselling, shedding light on crucial emotional aspects of the seller/buyer relationship and providing valuable insights for researchers and marketers

"All-in-one mesh" hernioplasty: A new procedure for primary inguinal hernia open repair.

Summary: Background: We propose a new open mesh hernia repair procedure for the treatment of inguinal hernias in adults aiming to improve patients' comfort and to reduce the incidence of chronic neuralgia. Methods: From September 2012 to August 2015, 250 consecutive patients were treated with "all in-one" mesh hernioplasty procedure in our Institution. According to the devised technique, a new smaller prosthesis was placed on the floor of the inguinal canal in order to strengthen all areas of weakness from which hernias may originate. The mesh was enveloped by a fibro-cremasteric sheath avoiding contact with neural structures. Follow-up was carried out at 3, 6, 12, 18 and 24 months for evaluation of postoperative pain using Visual Analogue Scale score, need of medication, patients' comfort and short or long-term complications. Results: All patients were discharged within 24 h from surgery. Slight pain was reported by the majority of patients and 47.6% of them did not require pain medication at home. After the 1st postoperative week 96.8% reported no pain and no other symptoms. No relevant limitation of normal activities was reported. There has been no postoperative neuralgia. One recurrence was observed. Conclusions: This new hernioplasty technique respects the anatomy of the inguinal canal, uses a smaller mesh, and seems to avoid neuralgia with maximum comfort for the patients. Keywords: Inguinal hernioplasty, Tension free hernia repair, Hernioplasty technique, Mesh for groin hernia, Neuralgia post-hernioplast

Transcranial sonography: a technique for the study of the temporal lobes of the human and non-human primate brain

We developed a modified transcranial sonography technique to study the morphology of the temporal lobe, a brain region involved in language, memory and social functions in humans that can be visualized in correspondence of the acoustic window of the temporal squama. Previous studies raise the possibility that a unique derived feature of Homo sapiens is a relatively larger temporal lobe compared to those of other hominins and apes. Such a brain reorganization might have contributed to the evolution of various “higher” cognitive functions of Homo sapiens, including language. Hence, the importance of further comparative analyses of the temporal region. With the technique that we developed we were able to study the meninges, the subarachnoidal space and the cortex of the human temporal lobe. The spatial resolution and the ability to visualize structures of 200-300 μm size led us to hypothesize that the linear structures parallel to the subarachnoidal space might be referred to the neuronal layers of the cortex. The low cost, simplicity and safety of the procedure suggest that this technique may have a significant potential in the comparative study of the primate temporal lobe. Furthermore, the procedure described here can also be used for the study of vascularization of the meninges, in order to better understand the evolutionary relationships between the neurocranial shape and the middle meningeal vessels in living and fossil human species

Metopic suture and RUNX2, a key transcription factor in osseous morphogenesis with possible important implications for human brain evolution

Background. Overall, the comparative data available on the timing of metopic suture closure in present-day and fossil members of human lineage, as well as great apes, seem to indicate that human brain evolution occurred within a complex network of fetopelvic constraints, which required modification of frontal neurocranial ossification patterns, involving delayed fusion of the metopic suture. It is very interesting that the recent sequencing of the Neanderthal genome has revealed signs of positive selection in the modern human variant of the RUNX2 gene, which is known to affect metopic suture fusion in addition to being essential for osteoblast development and proper bone formation. It is possible that an evolutionary change in RUNX2, affecting aspects of the morphology of the upper body and cranium, was of importance in the origin of modern humans. Thus, to contribute to a better understanding of the molecular evolution of this gene probably implicated in human evolution, we performed a comparative bioinformatic analysis of the coding sequences of RUNX2 in Homo sapiens and other non-human Primates.Results. We found amino-acid sequence differences between RUNX2 protein isoforms of Homo sapiens and the other Primates examined, that might have important implications for the timing of metopic suture closure. Conclusions. Further studies are needed to clear the potential distinct developmental roles of different species-specific RUNX2 N-terminal isoforms. Meantime, our bioinformatic analysis, regarding expression of the RUNX2 gene in Homo sapiens and other non-human Primates, has provided a contribution to this important issue of human evolution