Coordination Mechanisms along the Supply Chain: a Key-Factor for Competitiveness

The purpose of this paper is to contribute to a better understanding of the role of relationships between stakeholders in the supply chain as a potential source of competitive advantage. In the case study, we focus on the wine industry in the Lazio Region (Italy). We observe a significant loss of competitiveness in this industry and we suggest that a higher level of communication and different coordination mechanisms among stakeholders could help in recovering a better market position. We focus on the linkages between farmers and the other food chain stakeholders through the perspective of Institutional Economics and Economics of Organization, in order to identify the key factors that determine the competitiveness of the supply chain’s product. The Lazio wine supply chain is investigated through the analysis of official data, integrated with primary data, collected through in-person interviews and questionnaires addressed to producers and experts. It emerges that the wine supply chain in the Lazio Region is characterized by a serious decline, suggested by a sharp decrease in production and sales, low reputation among experts, widespread negative consumers perception. We interpret this turn-down through the structural features of the market and through the low level of communication and coordination between the agents. This leads to the identification of potential instruments able to deal with the difficulties highlighted. We emphasize the role of public institutions in fostering communication and cooperation among firms and suggest the potential role of a web portal, in linking sellers and buyers in a common network

High-risk HPVs, microbiota and epithelial carcinogenesis: state of the art and research contribution of in vitro 3D models

Persistent high-risk human papillomavirus (HR-HPV) infection is associated with anogenital and head & neck squamous epithelial (HNSCC) tumors, which altogether cause about 550,000 new cases every year. Several evidences suggest that the microbiota could have a role on the inflammatory, epithelial mesenchymal transition and tumorigenesis processes promoted by HR-HPV infection, yet the mechanisms involved remain to be clarified. In this review we report the state of the art on this topic and on the most promising in vitro developed models for studying the host-pathogen interactions. Using MEDLINE, several terms were searched and combined to select the most pertinent papers. The investigation was limited to the international indexed articles published in PubMed in the last 10 years. This review reports the latest knowledge in the field of the microbial-associated anogenital tumors and HNSCC. In addition, we also discuss the in vitro epithelial culture systems that reproduce the pathophysiological features of the tumoral microenvironment and the in vivo response to microbial agents, thus representing a useful tool for analyzing at cellular and molecular levels the role played by infective agents in tumorigenesis

Laparoscopic Treatment of Gastric Duplication in a Child

Introduction: Gastric duplication is a rare congenital anomaly with an incidence of 4-8% of all gastrointestinal duplications; enteric duplications are ectopic cystic or tubular structures with a mucous and muscular tunics and they can be in contiguity/continuity with the intestinal lumen.1 Gastric duplication is often an occasional finding, associated to aspecific sintomatology for which pre-operative diagnosis is not univoque; differential diagnosis with other retroperitoneal diseases or mesenteric cysts can be difficult.1 (Run time 8min). Material and Methods: We present a case of a one-year-old child with a pre-natal ultrasound (US) finding of endo-abdominal cystic lesion. After birth, US scans showed an anechogenic-cyst of 33x28mm in the left upper quadrant, between stomach, spleen and kidney. The magnetic resonance confirmed the presence of the lesion (40x34mm), imprinting the posterior gastric wall, the spleen and the anterior side of left kidney. An esophagous-stomach-duodenum contrast study was also performed, showing the imprinting cyst on the great curvature close to the gastric fundus without communication with gastric lumen. On follow-up, the child underwent to periodic US scans and no growth or ultrasonographic changes were described. At 13-months, the diagnosis was still unclear and the patient underwent explorative laparoscopy with esophagous-gastric-duodenoscopy (EGDS). The preliminary EGDS showed a 35mm convexity on the posterior wall of gastric fundus with no evidence of orifice. A 5mm trans-umbilical trocar was placed and 5mm trocar in the epigastric region and 10-12mm trocar in the left side were positioned. At the abdominal exploration the cyst resulted to be in continuity with the posterior gastric wall on the superior third of the great curvature. The lesion was isolated from other tissues, but the postero-medial wall of neoformation appeared to be not dissociable and in continuity with the stomach; a complete resection of the cyst, using 45mm linear stapler, was performed including a small portion of the great gastric curvature. At the following intra-operative endoscopic control no more evidence of irregularity of the gastric wall was seen and the suture was assured. Results: The operative time was 140-minutes. No complications occurred and the blood loss was minimal. The patient started oral intake on 5’ post-operative-day and was discharged on 6’ post-operative-day. The histological examination confirmed the gastric nature of cyst. At 1-year of follow-up no recurrences were diagnosed and the child presents in good health with a regular growth. Conclusion: We can assume that laparoscopic surgery is the correct procedure for gastric duplication cysts, to get both definitive diagnosis and treatment, and the radical surgical excision represents the treatment of choice in order to avoid neoplastic degeneration of internal lining mucosa.2 Furthermore surgical laparoscopy appears to be a feasible and safe technique

EVALUATION OF THE INTERACTION AMONG HPV16 E6 AND E7 ONCOPROTEINS AND THE DNA DAMAGE SENSOR 53BP1 IN 2D AND 3D EPITHELIAL CULTURES BY THE PROXIMITY LIGATION ASSAY

INTRODUCTION. Human papillomaviruses (HPV) group several viruses able to infect squamous stratified epithelia and cause benign papillomas, warts and anogenital lesions. They also correlate to oropharyngeal and anogenital malignancies, mainly promoted by the high risk (HR) \u3b1-HPV16 E6E7 oncoproteins. Despite scientific progresses and the development of vaccines, these tumors are still common and represent one of the major causes of women\u2019s death. Host\u2019s cell replication fidelity depends by the DNA Damage Response (DDR). Unlike from other DNA viruses, HR-HPVs encourage cells proliferation without inactivating the DDR: the mechanisms at the basis haven\u2019t been clarified yet. During HPV16 infection, E6 binds and degrades p53 through the E6AP LXXLL domain. Similarly, E7 competes with E2F1-pRb interaction, thus inactivating pRb, and promoting the linking the pRb-like proteins CBP/p300 and p107, that also harbor a LXXLL sequence. Unfortunately, E6 E7 role in the DDR activation is not elucidated yet. EXPERIMENTAL MODEL. To gain new information, we reproduced an in vitro 3D HPV16-E6E7 infected epithelium, already characterized for HPVs studies, and checked for cellular and viral markers, among them HPV16E6E7 oncoproteins and the double strand breaks (DSB) sensor 53BP1; we then made a Co-IF for E6 and E7 with 53BP1. Since E6 and E7 both interact with LXXLL containing proteins, we analyzed 53BP1 BRCT2 domain and we explored the binding hypothesis via the in situ PLA technique in 2D in CaSki and E6E7HPV16 keratinocytes and in the 3D model. RESULTS. The in vitro infected epithelium resembles the in vivo tissue. E6E7HPV16, both in basal and differentiated strata, induce a 53BP1 increase in nuclear foci. After highlighting E6 and E7 co-expression with 53BP1 and a LKVLL sequence within the 53BP1 BRCT2 domain, we demonstrated the binding in all the employed cellular models. CONCLUSION. Our results add new information on HPV16 oncoproteins capability in overcome cellular defense strategies

In Vitro Reconstructed Human Epithelial Models for Microbial Infection Research: Why Do We Need them?

In the last 50 years, the Replacement, Reduction and Refinement principles have become a framework for conducting high quality academic, pre-clinical, clinical and industrial research experimentation studies, in order to respond to the European Union legislative demand of alternatives to animal-based experimentation, often difficult to translate to human applications, expensive and not ethically approved. Thanks to the improvement of cellular isolation protocols, culture and co-culture conditions, together with the increased clinical demand, several novel in vitro three-dimensional tissue engineered human epithelial models, able to create sophisticate pre-clinical tests and produce results more reliable than the traditional bi-dimensional flat cell culture systems, have been developing also for microbial infection research purposes

The Development of Spatial Memory Analyzed by means of Ecological Walking Task

The present study is aimed at investigating the development of spatial memory in pre-school children aged 4-6 years using an ecological walking task with multiple rewards. The participants were to explore an open space in order to find nine rewards placed in buckets arranged in three spatial configurations: a Cross, a 3x3 Matrix and a Cluster composed of three groups of three buckets each. Clear age-related improvements were evident in all the parameters analysed. In fact, there was a general trend for younger children to display worse performances than the older ones. Moreover, males performed better than females in both the search efficiency and visiting all buckets. Additionally, the search efficiency proved to be a function of the difficulty of the configuration to be explored: the Matrix and Cluster configurations were easier to explore than the Cross configuration. Taken altogether, the present findings suggest that there is a general improvement in the spatial memory abilities in preschoolers, and that solving an open space task could be influenced by gender. Moreover, it can be proposed that both the procedural competences and the memory load requested to explore a specific environment are determined by its specific features

FIRST CASE OF LAPAROSCOPIC PARTIAL SPLENECTOMY IN A CHILD WITH HAMARTOMA: CASE REPORT AND REVIEW OF THE LITERATURE

INTRODUCTION To date, laparoscopic surgery has played a key role in the treatment of not only splenic hematologic pathologies but also solid ones. Hamartoma is a rare disease; only twenty percent of them are of pediatric relevance; it is a benign tumor, but radiological features never allow proper differentiation from malignant neoplasms. In children, hamartoma may be associated with other morbid conditions, such as sickle cell disease or other hematological alterations. PRESENTATION OF THE CASE We report a case of hamartoma in a 7-year-old child treated with partial laparoscopic splenectomy After a multidisciplinary evaluation, the indication of laparoscopic splenectomy was decided; upon evaluating the age of the patient and the affected spleen portion, a partial splenectomy was proposed. The histological examination during surgery was performed to exclude any form of malignancy. The intraoperative frozen section of the specimen was negative for malignancies, and a partial splenectomy was performed. DISCUSSION Surgery remains the first choice in the definitive treatment of solid lesions of the spleen; minimally invasive technique, namely, laparoscopy, has set itself as the technique of choice for surgical treatment. In this case, the possibility of obtaining an intraoperative pathological diagnosis by frozen section of the specimen, confirming the benign nature of the lesion, allowed the surgeon to decide in favor of a laparoscopic partial splenectomy. CONCLUSION Partial laparoscopic splenectomy can be considered a safe, effective and reproducible alternative in patients suffering from benign solid diseases, safeguarding the hematological functions of the organ itself in pediatric age

The progressive loss of brain network fingerprints in Amyotrophic Lateral Sclerosis predicts clinical impairment

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by functional connectivity alterations in both motor and extra-motor brain regions. Within the framework of network analysis, fingerprinting represents a reliable approach to assess subject-specific connectivity features within a given population (healthy or diseased). Here, we applied the Clinical Connectome Fingerprint (CCF) analysis to source-reconstructed magnetoencephalography (MEG) signals in a cohort of seventy-eight subjects: thirty-nine ALS patients and thirty-nine healthy controls. We set out to develop an identifiability matrix to assess the extent to which each patient was recognisable based on his/her connectome, as compared to healthy controls. The analysis was performed in the five canonical frequency bands. Then, we built a multilinear regression model to test the ability of the “clinical fingerprint” to predict the clinical evolution of the disease, as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r), the King’s disease staging system, and the Milano-Torino Staging (MiToS) disease staging system. We found a drop in the identifiability of patients in the alpha band compared to the healthy controls. Furthermore, the “clinical fingerprint” was predictive of the ALSFRS-r (p = 0.0397; β = 32.8), the King’s (p = 0.0001; β = − 7.40), and the MiToS (p = 0.0025; β = − 4.9) scores. Accordingly, it negatively correlated with the King’s (Spearman’s rho = -0.6041, p = 0.0003) and MiToS scales (Spearman’s rho = − 0.4953, p = 0.0040). Our results demonstrated the ability of the CCF approach to predict the individual motor impairment in patients affected by ALS. Given the subject-specificity of our approach, we hope to further exploit it to improve disease management

a rare case of diaphragmatic hernia after cytoreductive surgery and hypertermic intraperitoneal chemotherapy

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective therapeutic approach for selected patients with gastrointestinal and gynecological malignancies with peritoneal spread. The most frequent postoperative surgical complications are anastomotic leakage, digestive perforations, fistulas, intestinal obstruction, abscess and peripancreatitis. This report presents case of a patient with late postoperative diaphragmatic hernia after CRS and HIPEC. A 50- year-old woman previously treated with CRS and HIPEC for a pseudomyxoma peritonei was admitted to our unit with diagnosis of intestinal obstruction. At the CT scan a left diaphragmatic hernia involving the splenocolic flexure was found. Both stripping of the diaphragmatic peritoneum during CRS, sometimes combined with diaphragmatic resection and the heat of HIPEC might be responsible for such complication. The diaphragmatic hernia is rarely diagnosed after CRS and HIPEC. Surgical techniques for repair can be the direct suture of the defect or closure with synthetic or biological tissue, both are possible surgical techniques for repair with a good long term results

Dual, HLA-B27 Subtype-dependent Conformation of a Self-peptide

The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens