Avenues for non-conventional robotics technology applications in the food industry.

Robots in manufacturing alleviate hazardous environmental conditions, reduce the physical/mental stress of the workers, maintain high precision for repetitive movements, reduce errors, speed up production, and minimize production costs. Although robots have pervaded many industrial sectors and domestic environments, the experiments in the food sectors are limited to pick-and-place operations and meat processing while we are assisting new attention in gastronomy. Given the great performances of the robots, there would be many other intriguing applications to explore which could usher the transition to precision food manufacturing. This review wants open thoughts and opinions on the use of robots in different food operations. First, we reviewed the recent advances in common applications - e.g. novel sensors, end-effectors, and robotic cutting. Then, we analyzed the use of robots in other operations such as cleaning, mixing/kneading, dough manipulation, precision dosing/cooking, and additive manufacturing. Finally, the most recent improvements of robotics in gastronomy with their use in restaurants/bars and domestic environments, are examined. The comprehensive analyses and the critical discussion highlighted the needs of further scientific understanding and exploitation activities aimed to fill the gap between the laboratory-scale results and the validation in the relevant environment.

Free-electron lasing with compact beam-driven plasma wakefield accelerator.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators1-4. The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL)5, a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations6,7. So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators8. This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications9.

CXCR3+ Monocytes Increase Significantly in Graft Blood Compared to Peripheral Blood in Patients With Stable Kidney Graft Function.

INTRODUCTION: We have recently reported that some lymphocyte populations do not maintain the same proportion in kidney graft blood as in peripheral blood, despite a stable function of the transplanted kidney. These results suggest that a comparative study between leukocyte cells from graft blood and those obtained from peripheral blood could provide information about the inflammatory state of the transplanted organ. In this work we selected the population of CD4+ lymphocytes and monocytes expressing CXCR3 to test this hypothesis. MATERIAL AND METHODS: The study was performed by flow cytometry during month 3, 6, and 12 after transplantation in 58 patients who received an isolated kidney transplant and the same immunosuppressive regimen. The peripheral blood sample was obtained by venipuncture and the graft blood by fine needle aspiration. RESULTS: We found a significant percentage decrease in CXCR3+ monocytes throughout the first year of transplantation in peripheral blood (15.9 ± 20.7 vs. 12.6 ± 12.4 vs. 6.3 ± 9.0, at 3, 6, and 12 months, respectively; P = .001), whereas the percentage of CXCR3+ monocytes in graft blood did not change over this period. This situation resulted in a significant percentage difference between the CXCR3+ monocytes from the graft blood and those from the peripheral blood at the sixth (15.8 ± 8.1 vs. 12.6 ± 12.4, respectively; P = .008) and 12th months (12.9 ± 8.1 vs. 6.3 ± 9.0, respectively; P < .001). CONCLUSIONS: Therefore, we can conclude that the significant percentage increase of CXCR3+ monocytes in graft blood with respect to peripheral blood suggests the presence of inflammatory activity despite renal function being stable during the second half of the first year post-transplantation.

Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

Impact of time to surgery after neoadjuvant chemotherapy in operable breast cancer patients.

BACKGROUND: The optimal time interval between the end of neoadjuvant systemic therapy (NST) and breast surgery is still unclear. It is not known if a delay in surgery might influence the benefit of primary chemotherapy. The aim of this study is to evaluate the relationship between time to surgery (TTS) and survival outcomes. PATIENTS AND METHODS: According to TTS, women with diagnosis of BC treated with NST were divided into two cohorts: group A = 21 days or fewer and group B = longer than 21 days. OS and RFS were estimated and compared according to TTS and known prognostic factors. RESULTS: A total of 319 patients were included in the study: 61 in group A and 258 in group B. Median TTS was 34 days. No association between clinical stage, nuclear grade, type of chemotherapy, type of surgery and TTS was detected. OS and RFS were significantly worse for group B compared with group A, with a hazard ratio of 3.1 (95% CI, 1.1-8.6 p = 0.03) and 3.1 (95% CI, 1.3-7.1 p = 0.008) respectively. Multivariate analysis confirmed that TTS was an independent prognostic factor in term of OS (p = 0.03) and RFS (p = 0.01). Even in the subgroup of patients with pCR, TTS continued to be an independent prognostic factor for both OS and RFS (p = 0.05 and p = 0.03). CONCLUSIONS: TTS after NST seems to influence survival outcomes. BC patients underwent surgery within 21 days experienced maximal benefit from previous treatment: this advantage is consistent and maintained over time.

Two-Color Radiation Generated in a Seeded Free-Electron Laser with Two Electron Beams.

We present the experimental evidence of the generation of coherent and statistically stable two-color free-electron laser radiation obtained by seeding an electron beam double peaked in energy with a laser pulse single spiked in frequency. The radiation presents two neat spectral lines, with time delay, frequency separation, and relative intensity that can be accurately controlled. The analysis of the emitted radiation shows a temporal coherence and a shot-to-shot regularity in frequency significantly enhanced with respect to the self-amplified spontaneous emission.

Increased extracellular levels of glutamate in the hippocampus of chronically epileptic rats.

An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state.

Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain.

Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.

Multiple myeloma and paget disease with abnormal skull lesions and intracranial hypertension.

We report a 73 years old man with a diagnosis of Paget Disease (PD) and symptomatic Multiple Myeloma (MM). Coexistence of MM and PD has rarely been described. PD mimics many of the features of bone destructive process in MM, making differential diagnosis more complicated. In addition, the presence of serious muscolo-skeletal and metabolic complications in both diseases makes management of patients difficult, worsening the prognosis.The comparison of these two diseases has led to the characterization of a common molecular mechanism represented by the receptor activator of nuclear factor-kB ligand (RANKL)/Osteoprotegerin signaling pathway. The improved comprehension of these mechanisms led to the development of new pharmacologic agents (bisphosphonates, cytokines inhibitors) effective for the treatment of these bone diseases.

Soft x-ray images of the laser entrance hole of ignition hohlraums.

Hohlraums are employed at the national ignition facility to convert laser energy into a thermal x-radiation drive, which implodes a fusion capsule, thus compressing the fuel. The x-radiation drive is measured with a low spectral resolution, time-resolved x-ray spectrometer, which views the region around the hohlraum's laser entrance hole. This measurement has no spatial resolution. To convert this to the drive inside the hohlraum, the size of the hohlraum's opening ("clear aperture") and fraction of the measured x-radiation, which comes from this opening, must be known. The size of the clear aperture is measured with the time integrated static x-ray imager (SXI). A soft x-ray imaging channel has been added to the SXI to measure the fraction of x-radiation emitted from inside the clear aperture. A multilayer mirror plus filter selects an x-ray band centered at 870 eV, near the peak of the x-ray spectrum of a 300 eV blackbody. Results from this channel and corrections to the x-radiation drive are discussed.

High-order-harmonic generation and superradiance in a seeded free-electron laser.

Higher order harmonic generation in a free-electron laser amplifier operating in the superradiant regime [R. H. Dicke, Phys. Rev. 93, 99 (1954).] has been observed. Superradiance has been induced by seeding a single-pass amplifier with the second harmonic of a Ti:sapphire laser, generated in a ß-Barium borate crystal, at seed intensities comparable to the free-electron laser saturation intensity. Pulse energy and spectral distributions of the harmonics up to the 11th order have been measured and compared with simulations.

Critical evaluation of the use of cell cultures for inclusion in clinical trials of patients affected by collagen VI myopathies.

Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1(-/-) mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI-related myopathic patients. However, the mitochondrial phenotype is no longer maintained after nine passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established.

Religious and spiritual beliefs in outpatients suffering from Parkinson Disease.

OBJECTIVE: Personality changes are known to occur in idiopathic Parkinson's Disease (PD). The aim of the study was to evaluate whether religious and spiritual beliefs in PD patients are different from age-matched controls. DESIGN: Eighty-three PD participants, 79 hypertensive individuals not affected by PD and 88 healthy subjects participated to a cross-sectional study. The Royal Free Interview (RFI) was used to evaluate participants' beliefs. The Hospital Anxiety and Depression Scale (HADS) was applied to monitor emotional distress. RESULTS: There was no statistical evidence of a difference between PD participants and the two control groups, the only exception being observed between the left PD onset group and the controls, where the total RFI score was about 5 points higher (t-test: p = 0.0273). RFI total score was uncorrelated with age, severity of illness and depression, but was strongly dependent on the type of beliefs. The percentage of PD participants suffering from anxiety and depression was high (right onset: 54.8%; left onset: 68.6%), while only 15.2% of the hypertensive participants, and none of the healthy controls, had a HADS score above 10 points. Total RFI score was higher in women. CONCLUSION: PD participants maintain their Faith in spite of the disease severity. Differences are found between right and left onset of PD. The possible beneficial effect of religious coping is discussed.

Sigma-2 receptor expression in bovine papillomavirus-associated urinary bladder tumours.

The expression of sigma-2 receptors was investigated in nine urothelial tumours of the urinary bladder of cattle. Each tumour was associated with the presence of DNA of bovine papillomavirus type-2 (BPV-2) and expression of the E5 viral oncoprotein. Five tumours were classified as low-grade carcinoma on the basis of morphological criteria and calculation of mean nuclear area (MNA) and mean nuclear perimeter (MNP). Four tumours were classified as high-grade carcinoma. Sigma-2 receptors were overexpressed in both types of carcinoma. In control normal bovine bladder tissue the density of receptors (expressed as the B(max)) was 0.37 pmol/mg of protein. Low-grade carcinomas had a mean B(max) of 1.37+/-0.32 pmol/mg of protein (range 1.03-1.86) and in high-grade carcinomas the mean B(max) was 10.9+/-2.8 pmol/mg of protein (range 8.2-14). The difference in B(max) between low- and high-grade carcinomas was statistically significant (P=0.0001).

Short communication: Detection of human Torque teno virus in the milk of water buffaloes (Bubalus bubalis).

Forty-four raw milk and 15 serum samples from 44 healthy water buffaloes reared in Caserta, southern Italy, the most important region in Europe for buffalo breeding, were examined to evaluate the presence of Torque teno viruses (TTV) using molecular tools. Furthermore, 8 pooled pasteurized milk samples (from dairy factories having excellent sanitary conditions) and 6 Mozzarella cheese samples were also tested. Four of the cheese samples were commercial Mozzarella cheese; the remaining 2 were prepared with TTV-containing milk. Human TTV were detected and confirmed by sequencing in 7 samples of milk (approximately 16%). No TTV were found in serum, pooled pasteurized milk, or Mozzarella cheese samples. The samples of Mozzarella cheese prepared with TTV-containing milk did not show any presence of TTV, which provides evidence that standard methodological procedures to prepare Mozzarella cheese seem to affect viral structure, making this food fit for human consumption. The 7 TTV species from water buffaloes were identified as genotypes corresponding to the tth31 (3 cases), sle 1981, sle 2031, and NLC030 (2 cases each) human isolates. Although cross-species infection may occur, detection of TTV DNA in milk but not in serum led us to believe that its presence could be due to human contamination rather than a true infection. Finally, the mode of transmission of TTV has not been determined. Contaminated of the food chain with TTV may be a potential risk for human health, representing one of the multiple routes of infection.

The cyclophilin inhibitor Debio 025 normalizes mitochondrial function, muscle apoptosis and ultrastructural defects in Col6a1-/- myopathic mice.

BACKGROUND AND PURPOSE: We have investigated the therapeutic effects of the selective cyclophilin inhibitor D-MeAla(3)-EtVal(4)-cyclosporin (Debio 025) in myopathic Col6a1(-/-) mice, a model of muscular dystrophies due to defects of collagen VI. EXPERIMENTAL APPROACH: We studied calcineurin activity based on NFAT translocation; T cell activation based on expression of CD69 and CD25; propensity to open the permeability transition pore in mitochondria and skeletal muscle fibres based on the ability to retain Ca(2+) and on membrane potential, respectively; muscle ultrastructure by electronmicroscopy; and apoptotic rates by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assays in Col6a1(-/-) mice before after treatment with Debio 025. KEY RESULTS: Debio 025 did not inhibit calcineurin activity, yet it desensitizes the mitochondrial permeability transition pore in vivo. Treatment with Debio 025 prevented the mitochondrial dysfunction and normalized the apoptotic rates and ultrastructural lesions of myopathic Col6a1(-/-) mice. CONCLUSIONS AND IMPLICATIONS: Desensitization of the mitochondrial permeability transition pore can be achieved by selective inhibition of matrix cyclophilin D without inhibition of calcineurin, resulting in an effective therapy of Col6a1(-/-) myopathic mice. These findings provide an important proof of principle that collagen VI muscular dystrophies can be treated with Debio 025. They represent an essential step towards an effective therapy for Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy, because Debio 025 does not expose patients to the potentially harmful effects of immunosuppression.

Microtransplantation of ligand-gated receptor-channels from fresh or frozen nervous tissue into Xenopus oocytes: a potent tool for expanding functional information.

Despite huge improvements in neurobiological approaches for investigating the functional properties of neurotransmitter receptors and ion channels, many difficulties are still encountered when focusing on the human brain. Electrophysiological studies aimed at performing direct determinations on human nervous tissue are limited by neurosurgery and also by pathophysiological conditions prevailing before and after the resective operation. The electrophysiological study of receptors and channels becomes difficult also in animal models when the cells are not accessible and/or the experiments last many hours, during which the examined nervous tissue usually becomes unhealthy. To increase the possibility of doing optimal electrophysiological recordings, addressed to investigate the functional properties of receptors and channels, more than two decades ago, foreign mRNAs were injected into Xenopus oocytes to heterologously express the receptors; and about a decade ago cell membranes were injected into the oocytes to directly transplant the native receptors. While the first approach needs complex procedures for mRNA isolation, the membrane preparations are simpler to obtain and the embedded receptors are transplanted in their own membrane, with their own glycosylation and together with any ancillary proteins they may have. Using injections of membranes isolated from fresh nervous tissues several issues have already been addressed and many questions can be answered in the near future. Strikingly, with this approach it has been possible to "resuscitate" receptors and ion channels from tissues kept frozen for many years. This review focuses on recently obtained information and on some new lines of biological research using receptor microtransplantation into oocytes.

Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor.

The ephrinA1 ligand exerts antioncogenic effects in tumor cells through activation and downregulation of the EphA2 receptor and has been described as a membrane-anchored protein requiring clustering for function. However, while investigating the ephrinA1/EphA2 system in the pathobiology of glioblastoma multiforme (GBM), we uncovered that ephrinA1 is released from GBM and breast adenocarcinoma cells as a soluble, monomeric protein and is a functional form of the ligand in this state. Conditioned media containing a soluble monomer of ephrinA1 caused EphA2 internalization and downregulation, dramatic alteration of cell morphology and suppression of the Ras-MAPK pathway. Moreover, soluble monomeric ephrinA1 was functional in a physiological context, eliciting collapse of embryonic neuronal growth cones. We also found that ephrinA1 is cleaved from the plasma membrane of GBM cells, an event which involves the action of a metalloprotease. Thus, the ephrinA1 ligand can, indeed, function as a soluble monomer and may act in a paracrine manner on the EphA2 receptor without the need for juxtacrine interactions. These findings have important implications for further deciphering the function of these proteins in pathology and physiology, as well as for the design of ephrinA1-based EphA2-targeted antitumor therapeutics.