Investigation into the applicability of a passive upper-limb exoskeleton in automotive industry

The fourth industrial revolution faces the technological challenge of human-robot cooperation in manufacturing process. Aim of this study was to investigate the effectiveness and user’s acceptance of a passive exoskeleton for upper limbs. Three different tests, involving static and dynamic tasks, were performed by 29 automotive operators without and with the exoskeleton. Main aspects and results of the testing campaign are presented in the paper. Potential issues associated to the introduction of these auxiliary devices in the automotive industry are briefly addressed, together with the open questions on how to assess the biomechanical workload risk, especially in the design phase

Nonintegrating Lentiviral Vector-Based Vaccine Efficiently Induces Functional and Persistent CD8+ T Cell Responses in Mice

CD8+ T cells are an essential component of an effective host immune response to tumors and viral infections. Genetic immunization is particularly suitable for inducing CTL responses, because the encoded proteins enter the MHC class I processing pathway through either transgene expression or cross-presentation. In order to compare the efficiency and persistence of immune response induced by genetic vaccines, BALB/c mice were immunized either twice intramuscularly with DNA plasmid expressing a codon-optimized HIV-1 gp120 Envelope sequence together with murine GM-CSF sequence or with a single immunization using an integrase defective lentiviral vector (IDLV) expressing the same proteins. Results strongly indicated that the schedule based on IDLV vaccine was more efficient in inducing specific immune response, as evaluated three months after the last immunization by IFNγ ELISPOT in both splenocytes and bone marrow- (BM-) derived cells, chromium release assay in splenocytes, and antibody detection in sera. In addition, IDLV immunization induced high frequency of polyfunctional CD8+ T cells able to simultaneously produce IFNγ, TNFα, and IL2

Successful Immunization with a Single Injection of Non-integrating Lentiviral Vector

We evaluated the ability of an integrase (IN)-defective self-inactivating lentiviral vector (sinLV) for the delivery of human immunodeficiency virus-1 (HIV-1) envelope sequences in mice to elicit specific immune responses. BALB/c mice were immunized with a single intramuscular injection of the IN-defective sinLV expressing the codon optimized HIV-1 JR-FL gp120 sequence, and results were compared with those for the IN-competent counterpart. The IN-defective sinLV elicited specific and long-lasting immune responses, as evaluated up to 90 days from the immunization by enzyme-linked immunosorbent spot (ELISPOT) and intracellular staining (ICS) for interferon- γ (IFN- γ ) assays in both splenocytes and bone marrow (BM) cells, chromium release assay in splenocytes, and antibody detection in sera, without integration of the vector into the host genome. These data provide evidence that a single administration of an IN-defective sinLV elicits a significant immune response in the absence of vector integration and may be a safe and useful strategy for vaccine development

oxidative stress affects responsiveness to hypotonicity of renal cells

Oxidative stress plays a critical role in the pathophysiology of several kidney diseases and is the consequence of alterations like ischemic events. The regulatory volume decrease (RVD) is an homeostatic response essential to many cells, including renal cells, to counteract changes in the osmolarity of the external medium. The aim of the present work is to verify whether oxidative stress affects RVD in a model of renal cells (human embryonic kidney cells, HEK 293 Phoenix). To accomplish this aim, the experimental procedure consisted in: i) cell culture preparation and treatment with 200 μM H2O2; and ii) measurement of cell volume changes in isotonic conditions or following hypotonic stress. H2O2 added to the extracellular isotonic solution induced a significant reduction in cell volume, and added to the extracellular hypotonic solution dramatically impaired the expected osmotic cell swelling. Pre-incubation of cells in an extracellular isotonic solution containing H2O2 prevented cell from swelling after hypotonic stress application. In conclusion, H2O2 leads to cell shrinkage in isotonic conditions, inhibits the hypotonicity-induced cell swelling and consequently prevents RVD, hypothetically due to an activation of transport pathways determining ion loss and, in turn, water efflux. Cell shrinkage in isotonic conditions is a hallmark of apoptosis and is known as the apoptotic volume decrease

regulatory volume decrease in isolated nematocytes is affected by crude venom from the jellyfish pelagia noctiluca

Crude venom from nematocysts of the Scyphozoan Pelagia noctiluca possesses hemolytic and cytotoxic power on cultured cells and elicits local and systemic inflammation reactions in vivo. The ability of regulating their volume after exposure to an anisosmotic solution is a fundamental feature common to cells from vertebrates and invertebrates, including Cnidarians. The aim of the present work i s to assay whether crude venom from Pelagia noctiluca may affect the regulatory volume decrease (RVD) of nematocytes isolated from the Anthozoan Aiptasia mutabilis, here employed as a cell model. For this purpose, nematocytes were isolated by 605 mM NaSCN plus 0.01 mM Ca2+ application on acontia of Aiptasia mutabilis, while crude venom was obtained by sonication of a population of, respectively, 10, 25 and 50 nematocysts/µL (n/µL). Isolated nematocytes were pre-treated for 30 min with crude venom, submitted to hypotonic stress and their osmotic response and RVD were measured optically. Our results show that, after exposure to crude venom, nematocytes were morphologically intact, as shown by the Trypan blue exclusion test, but did not exhibit RVD. This effect was dose-dependent and reversed by the ionopho re gramicidin. The last observation suggests an inhibitory effect of venom on cell membrane ion transport mechanisms involved in RVD. Further studies are needed to verify this hypothesis and ascertain if a similar effect could be observed in human cells

Cabozantinib in neuroendocrine tumours: tackling drug activity and resistance mechanisms

Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines

Insulinoma in pediatric tuberous sclerosis complex: a case report

BackgroundTuberous sclerosis complex (TSC) is a rare multisystemic disorder. This genetically determined disease is characterized by highly variable clinical expression, including epilepsy as a common feature. Seizures can also occur as a manifestation of symptomatic hypoglycemia. The latter could be caused by an insulinoma, whose association to TSC has already been debated. In TSC-associated tumors, dysregulation of the mTOR pathway is believed to be present, leading to significant impacts on cellular metabolism, growht, and proliferation. To date, the association between TSC and insulinoma has been reported in 11 adults. Here, we present the first case of a pediatric patient with TSC diagnosed with an insulinoma and review the existing literature on this topic.Case presentationA 11-year-old female with TSC presented with seizures unresponsive to standard therapy. Further investigation revealed that these seizures were caused by hypoglycemia. Subsequent evaluation led to the diagnosis of a pancreatic insulinoma, which was surgically removed. Following the procedure, the patient was free from seizures.ConclusionsIn individuals with TSC, the recurrence of epileptiform episodes throughout their lifetime, especially if previously well controlled with antiepileptic therapy, should raise suspicion for hypoglycemic events. These events may potentially be associated with the presence of an insulinoma. Further research and increased awareness are necessary to gain a better understanding of the association between TSC and insulinomas, and to guide clinical management strategies

Disrupted Peyer’s Patch Microanatomy in COVID-19 Including Germinal Centre Atrophy Independent of Local Virus

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis