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We investigated the Phase Change Memory (PCM) capabilities of In-doped Sb nanowires (NWs) with diameters of (20-40) nm, which were self-assembled by Metalorganic Chemical Vapor Deposition (MOCVD) via the vapor-liquid-solid (VLS) mechanism. The PCM behavior of the NWs was proved, and it was shown to have relatively low reset power consumption (~ 400 μW) and fast switching capabilities with respect to standard Ge-Sb-Te based devices. In particular, reversible set and reset switches by voltage pulses as short as 25 ns were demonstrated. The obtained results are useful for understanding the effects of downscaling in PCM devices and for the exploration of innovative PCM architectures and materials. Keywords: Phase change memories, Nanowires, MOCVD, In-Sb, TEM, XRD

Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections.This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months.HbA1c (8.4 vs. 7.4%; p0.0001) and body weight (94.1 vs. 93 kg; p0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p0.0001).These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.

Osteoarthritis (OA) is a chronic degenerative condition involving the joints caused by metabolic changes in chondrocytes metabolism. Treatment with magnetic fields (EMFs) produces benefits to patients affected by this pathology. The present research has the aim to investigate, by a proteomic approach, the effect of magnetic fields on cultured chondrocytes, because EMFs interferes greatly with OA chondrocytes metabolism. Human osteoarthritic chondrocytes were obtained from the femur head of osteoarthritis adult patients and were cultured under standard conditions and exposed for precise times both to extremely low-frequency (ELF; 100-Hz) electromagnetic fields and to the Therapeutic Application of Musically Modulated Electromagnetic Fields (TAMMEF), which are characterized by variable frequencies, intensities, and wave shapes. We tested the effects of the different exposure by 2-DE analysis and demonstrated that chondrocytes metabolism was highly influenced by the treatment with EMFs; in fact many proteins change their expression after the stimulation, but differently, depending on whether we use ELF or TAMMEF system.

The study and observation of electromagnetic phenomena have followed the evolution of human thought from the dawn of civilization to the present day; also magnetotherapy has followed a similar path. Magnetotherapy has been applied and continues to be applied in many branches and fields of medicine, as it accelerates the healing of fractures, has analgesic and anti-inflammatory properties that can help in inflammatory or degenerative diseases of bones, joints and the peripheral nervous system, and stimulates the healing of open skin lesions (such as bed sores, diabetic ulcers) etc. If magnetotherapy has so many fields of application in medicine, we may therefore ask why doubts, prejudice and limitations to its therapeutic use still exist. This brief historical excursion wants to give a small contribution to answer the question.

The utility and the safety of the extremely low frequencies (ELF) electromagnetic fields in the treatment of numerous diseases have been demonstrated. Moreover, the effects of these fields seem to depend on their respective codes (frequency, intensity, waveform). We want to value the effects and the safety of the therapeutic application of a musically modulated electromagnetic field (TAMMEF) system, which field is piloted by a musical signal and its parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all possible codes can occur during a single application. Sixty subjects, affected by shoulder periarthritis were enrolled in the study and randomly divided into three groups of 20 patients each: the first exposed to TAMMEF, the second exposed to ELF, the third exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 min each and a clinical examination upon enrolment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later. All the patients of TAMMEF group and ELF group completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In those exposed to a simulated field group, there was no improvement of the pain symptoms or articular functionality. This study suggests that the TAMMEF system is efficacious and safe in the control of pain symptoms and in the reduction of functional limitation in patients with shoulder periarthritis. Moreover, the effects of the TAMMEF system cover those produced by the ELF field.

A rapid, sensitive, and specific method based on liquid chromatography/tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of propranolol in human plasma using metoprolol as internal standard. The drugs were extracted from plasma by liquid-liquid extraction and separated isocratically on a Phenomenex Synergi Fusion-RP C18 analytical column, 4 µm (150 mm × 4.6 mm i.d.) maintained at 30°C, with acetonitrile/water (95/5, v/v): 100 mM ammonium acetate: 100 mM acetic acid (65:15:20 v/v/v) as mobile phase, run at a flow rate of 1 mL min−1 (split 1:3). Detection was carried out by positive electrospray ionization (ESI +) in selected reaction monitoring (SRM) mode. The chromatographic separation was obtained within 3.0 min and was linear in the concentration range of 2–150 ng mL−1 (r2 = 0.9969). The method was successfully applied for the bioequivalence study of two tablet formulations (test and reference) of propranolol 80 mg after single oral dose administration to 36 ...

Numerous studies have demonstrated the utility of extremely low frequencies (ELF) electromagnetic fields in the treatment of pain. Moreover, the effects of these fields seems to depend on their respective codes. In our study we want to value the effects and the safety of the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system, which field is piloted by a musical signal and its parameters are modified in time, randomly varying within the respective ranges, so that all possible codes can occur during a single application. Ninety subjects, affected by chronic low back pain, were enrolled in the study and randomly divided into three groups of 30 patients each: A exposed to TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon enrolment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later. All the patients of groups A and B completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In group C, there was no improvement of the pain symptoms or articular functionality. This study suggests that the TAMMEF system is efficacious and safe in the treatment of patients with chronic low back pain.

Background: The effect of pulsed electromagnetic fields (PEMFs) on bone formation and remodeling has been evaluated in several studies in the last 30 years, but the results of these studies have been equivocal. Objective: The aim of this study was to investigate the effects of PEMFs on bone mineral density (BMD) and the biochemical markers of bone turnover in patients with postmenopausal osteoporosis. Methods: In this single-blind, randomized study, 40 outpatients were exposed to 100-Hz PEMFs (n = 20) or to a placebo electromagnetic field (n = 20) for 60 minutes per day, 3 times a week for 3 months. BMD was measured at baseline and at the end of treatment, and biochemical markers of bone metabolism were measured at baseline, after 3 months' treatment, and 1 month after treatment cessation. Results: Treatment with PEMFs did not cause a significant increase in BMD in either group. However, in the group treated with 100-Hz PEMFs, a significant increase in serum osteocalcin and serum procollagen type I C-terminal propeptide was observed during treatment ( P Conclusions: These findings suggest that PEMFs may stimulate osteogenesis, possibly by increasing osteoblastic activity, in postmenopausal women with osteoporosis.

A new Radioactive Ion Beam (RIB) facility (SPES) is presently under construction at the Legnaro National Laboratories of INFN. The SPES facility is based on the ISOL method using an UCx Direct Target able to sustain a power of 8 kW. The primary proton beam is provided by a high current Cyclotron accelerator with energy of 35-70 MeV and a beam current of 0.2-0.7 mA. Neutron-rich radioactive ions are produced by proton induced fission on an Uranium target at an expected fission rate of the order of 1013 fissions per second. After ionization and selection the exotic isotopes are re-accelerated by the ALPI superconducting LINAC at energies of 10A MeV for masses in the region A=130 amu. The expected secondary beam rates are of the order of 107 - 109 pps. Aim of the SPES facility is to deliver high intensity radioactive ion beams of neutron rich nuclei for nuclear physics research as well as to be an interdisciplinary research centre for radio-isotopes production for medicine and for neutron beams.

A specific, fast and sensitive high performance liquid chromatography coupled to an electro spray tandem triple quadrupole mass spectrometer (LC-MS/MS) assay was developed for the determination of nimesulide in human plasma using carbamazepine as the internal standard. The lower limit of quantification (LLOQ) was 50 ng/ml and the calibration curves were linear in the concentration range of 50 - 6,000 ng/ml. Method inter-batch precision and accuracy ranged from 2.78 to 10.80%, and 94.92 to 102.46%, respectively. Intra-batch precision ranged from 2.44 to 7.74%, while intra-batch accuracy ranged from 91.70 to 104.73%. The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of two different pharmaceutical formulations containing nimesulide, one tablet and one oral suspension, manufactured by the same pharmaceutical factory, comparing with two reference Nisulid formulations in 52 volunteers of both sexes previously divided in two groups of 26 subjects (13 men and 13 females each group). The test tablet formulation was not bioequivalent to the Nisulid 100 mg tablet with respect to the rate of absorption, but was bioequivalent according to the extent of drug absorption. On the other hand, since the 90% CI for Cmax, AUC0-t and AUCinf were within the 80 - 125% interval in the oral suspension study, it was concluded that test oral suspension were bioequivalent to Nisulid 50 mg/ml with respect to both the rate and extent of absorption.

A rapid, sensitive and specific method to quantify diclofenac in human plasma using indomethacin as the internal standard (IS) is described. Samples were extracted using protein precipitation protocol and analyzed by high performance liquid chromatography coupled to ultraviolet detection at 276 nm. Chromatography was performed isocratically with a run time of 8.0 min and the retention time observed for diclofenac and IS was 6.0 and 7.0 min, respectively. The calibration curve was linear over the range 50 - 4,000 ng/ml (r2 > 0.9995). The mean recovery of diclofenac ranged from 88.76 to 99.14% and the limit of quantification was 50 ng/ml. Intrabatch precision and accuracy (%CV) of the method ranged from 0.86 to 7.60%, and 99.34 to 103.8%, respectively. Interbatch precision (%CV) and accuracy ranged from 0.26 to 11.4%, and 92.00 to 105.34%, respectively. This HPLC method was used to determine the relative pharmacokinetics of two diclofenac-cholestyramine 140 mg capsule formulations. The study was conducted using an open, randomized and crossover design with a 1-week washout interval. A single 140 mg dose (equivalent to 70 mg of diclofenac) of each formulation was administered to 26 healthy volunteers (13 males and 13 females) and blood samples were obtained over 12-h interval. The geometric mean of diclofenac-cholestyramine/Flotac ratio was 90.53% for AUC0-12 and 100.22% for Cmax. Since the 90% CI for Cmax and AUCs ratios were all inside the 80 - 125% interval, it was concluded that the diclofenac-cholestyramine test formulation is bioequivalent to Flotac regarding both the rate and the extent of absorption.

A specific, fast and sensitive LC–MS/MS assay was d e- veloped for the determination of bupropion and its me- tabolite hydroxybupropion in human plasma using lidocaine as the internal standard. The limit of qu antifica- tion was 3.13 ng/ml for bupropion and 7.81 ng/ml fo r hydroxybupropion. The method was linear in the stud ied range of 3.13 – 400.00 ng/ml for bupropion and 7.81 – 1000 ng/ml for hydroxybupropion. This analytical me thod was applied to a comparative pharmacokinetic study, in which seventy eight volunteers (39 men and 39 femal e) aged between 18 and 50 years received a single oral dose of 150 mg of reference and test bupropion formulati on, in an open, two-period, balanced randomized, crossover pro- tocol. Group 1 received the medication without any addi- tional meal. Group two received a hyperlipemic meal 30 min before the medication. Based on the 90% confide nce interval of the individual ratios for C max and AUC 0-inf , it was concluded that the test formulation is bioequiv alent to the reference formulation with respect to the ra te and extent of absorption of both bupropion and hydroxybupropion and that food intake before the dr ug administration had no effect in the relative pharma coki- netic parameters. However, the hyperlipemic meal si gnifi- cantly increased the bupropion absorption.

With reference to experimental data in the literature, we present a model consisting of two elastic elements, conceived to simulate resistance to stretching, at constant velocity of elongation, of corneal tissue affected by keratoconus, treated with riboflavin and ultraviolet irradiation to induce cross-linking. The function describing model behaviour adapted to stress and strain values. It was found that the Young's moduli of the two elastic elements increased in cross-linked tissues and that cross-linking treatment therefore increased corneal rigidity. It is recognized that this observation is substantially in line with the conclusion reported in the literature, obtained using an exponential fitting function. It is observed, however, that the latter function implies a condition of non-zero stresses without strain, and does not provide interpretative insights for lack of any biomechanical basis. Above all, the function fits a singular trend, inexplicably claimed to be viscoelastic, with surprising perfection. In any case, using the reported data, the study demonstrates that a fitting equation obtained by a modelling approach not only shows the evident efficacy of the treatment, but also provides orientations for studying modifications induced in cross-linked fibres.

TPG is the acronym for a 3D imaging gas chamber with GEM amplification, hexaboard read-out and FADC electronics. We have constructed a TPG-head with three GEM foils (30 cm diameter) and a read-out board (30 cm diameter active surface) covered with 710000 hexagonal pads of 300 /spl mu/m size. The aligned pads are connected in parallel to one strip out of three sets of 576 parallel strips (500 /spl mu/m pitch). The three sets of strips run at 120 degrees from each other and at three different depths inside the hexaboard multi-layer structure. Each strip is read by FADC electronics. The TPG-head is under initial test in a small container with a drift volume 33 mm long and of 30 cm diameter. A 150 cm long drift volume inside a 0.7 Tesla solenoidal magnetic field has been prepared by using HARP-TPC instrumentation as a test bed.

TPG is the acronym for Time Projection chamber with GEM amplification, hexaboard read-out and FADC electronics. We are constructing a TPG read-out module with three GEM foils (30 cm diameter) and a read-out board (30 cm diameter active surface) covered with hexagonal pads of 300 μm size. Aligned pads are connected in parallel to one strip out of three sets of parallel strips. Each strip is read by FADC electronics. The test bench for the TPG head will be the HARP-TPC field cage. TPG characteristics, design and expected performances are discussed

The analgesic-therapeutic efficacy and tolerability of a low-frequency electromagnetic field (ELF), modulated at a frequency of 100 Hz with a sinusoidal waveform and mean induction of a few gauss, has been demonstrated by the authors in numerous previous studies of various hyperalgic pathologies, particularly of the locomotor apparatus. In the present study, the authors tested a new type of all-inclusive field, denoted TAMMEF, whose parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all the possible codes can occur during a single application. For the comparison, 150 subjects (118 women and 32 men, between 37 and 66 years of age) were enrolled. They were affected by cervical spondylosis (101 cases) or shoulder periarthritis (49 cases). Unbeknownst to them, they were randomly divided into three groups of 50 subjects. One group was exposed to the new TAMMEF, another group to the usual ELF, and the third group to simulated treatment. The results show that the effects of the new TAMMEF therapy are equivalent to those obtained with the ELF.

The transcutaneous pO2 (tcpO2) changes induced by the increase of temperature to 45 degrees C after electrode stabilization at 37 degrees C were continuously recorded. The mathematical analysis of the curve led us to identify three different parameters: the half-slope "b" time, the angular "mT" coefficient and the angular "mb" parameter, which are not simply the expression of the maximum vasodilation capacity but mainly of the dynamic response of the microcirculatory system to skin heating. These parameters derived from the computerized mathematical analysis of the curve can be also obtained by a graphical approach with a very good approximation. The angular "mb" coefficient was shown to possess the highest statistical power in discriminating the POAD patients from normal controls. The clinical relevance and the possible pathophysiological meaning of these preliminary observations have to be confirmed.

Current evidence suggests that several cellular activities may be influenced by weak electromagnetic fields (EMFs). The understanding of these interactions would be of considerable importance in biology, and peripheral blood mononuclear cells (PBMC) are being employed as a sensitive model1. Activated lymphocytes release cytokines which are regulatory proteins, active at a concentration of pg and produced by a variety of immune cells. Cytokines may be used as a sensitive indicator of perturbation of the immunoregulatory network by EMFs. Many cytokines have interactive effects which may result synergistic or additive. Among these cytokines that have interactive effects are tumor necrosis factor α (TNF α), interferon γ (IFN γ) and some interleukins (IL). Moreover one of the primary biological effects of TNF is to trigger the release of other cytokines such as IL-1 and IFN γ, which amplify and extend the effect of TNF α alone. Once initiated, this cascade persists for hours or days and is relatively dissociated in time from the initiating event.2 It is well known that TNF α synergizes with IL-2 to stimulate T-cell proliferation3 and that both TNF α and IL-2 interact synergistically with IFN γ.4,5

A recent review of a century of studies describes the different conditions in which subjective estimates of time deviate, sometimes considerably, from clock time. With reference to experimental data published a few years ago, showing that prolonged observation of a scene in miniature induces the observer to ascribe durations contracted by the scale factor to events imaginable therein, it is demonstrated that a simple comparison with the time of the experimenter does not always reveal all the effects obtainable from the data. Avoiding questions of interpretation belonging to the field of psychology, the author applies the physical law of time contraction to a miniaturized scene to provide a time reference dependent on the scale factor, to be exact, proportional to its square root.

Demonstration that a hypothetical primitive man, smaller in size than a contemporary man but with the same anthropometrical proportions, is not only intrinsically stronger but is structurally more robust.

The inverse proportionality between body size and strength/weight ratio, at the same somatic proportions, show that for the purpose of survival the small size of primitive man was an essential advantage.

Three hundred-fifty-three patients with chronic pain have been treated with pulsed electromagnetic fields. In this work the Authors show the result obtained in the unsteady follow-up (2-60 months). The eventual progressive reduction of benefits is valued by Spearman's test. We noted the better results in the group of patients with post-herpetic pain (deafferentation) and in patients simultaneously suffering from neck and low back pain.