Sauter-Schwinger Effect in a Bardeen-Cooper-Schrieffer Superconductor.

Since the 1960s a deep and surprising connection has followed the development of superconductivity and quantum field theory. The Anderson-Higgs mechanism and the similarities between the Dirac and Bogoliubov-de Gennes equations are the most intriguing examples. In this last analogy, the massive Dirac particle is identified with a quasiparticle excitation and the fermion mass energy with the superconducting gap energy. Here we follow further this parallelism and show that it predicts an outstanding phenomenon: the superconducting Sauter-Schwinger effect. As in the quantum electrodynamics Schwinger effect, where an electron-positron couple is created from the vacuum by an intense electric field, we show that an electrostatic field can generate two coherent excitations from the superconducting ground-state condensate. Differently from the dissipative thermal excitation, these form a new macroscopically coherent and dissipationless state. We discuss how the superconducting state is weakened by the creation of this kind of excitations. In addition to shedding a different light and suggesting a method for the experimental verification of the Sauter-Schwinger effect, our results pave the way to the understanding and exploitation of the interaction between superconductors and electric fields.

The additional role of 18F-FDG PET/CT in prosthetic valve endocarditis.

OBJECTIVE: The purpose of the present review is an update on the diagnosis of prosthetic valve endocarditis (PVE), evaluating the additional value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to the standard modified DUKE criteria on which for a long time is based the diagnostic strategy of the disease. MATERIALS AND METHODS: We did a comprehensive research on the studies reported in the literature and regarding the employment of 18F-FDG PET/CT in the early diagnosis of PVE in patients with suspected disease. Scientific databases have been examined such as Medline and PubMed, followed by a review of citations and reference lists. The research included the following terms: infective endocarditis, prosthetic heart valve and cardiac valve replacement infections, 18F-FDG PET/CT and endocarditis. RESULTS: The recent studies reported in the literature on the PVE diagnostic approaches showed elevated sensitivity and specificity values of 18F-FDG PET/CT ranging from 73 to 96.6% and from 80 to 94%, respectively, reducing the number of misdiagnosed patients. The usefulness of the radioisotopic procedure is even more important when the other diagnostic conventional diagnostic tools, such as echocardiography, are inconclusive or negative in patients in whom the diagnosis of PVE is definitively ascertained. However, false negative and positive results of 18F-FDG PET/CT were also ascertained in some studies interfering with image interpretation even if such limitation can be reduced with an adequate patient preparation, with a better knowledge of clinical course of the disease, of the treatment in progress and of the different technical aspects of the method. CONCLUSIONS: In different studies reported in the literature, 18F-FDG PET/CT proved to improve the diagnostic accuracy of the conventional modified DUKE criteria in patients with suspected IE, and in particular with PVE, giving the highest diagnostic performance and providing additional diagnostic benefits. Thus, the radioisotopic hybrid procedure should be included in the diagnostic protocol of PVE as complementary tool to modified DUKE criteria. Finally, the usefulness of 18F-FDG PET/CT in monitoring the response to antibiotic therapy, although the few data reported in the literature are encouraging, needs more numerous studies and with a major number of cases.

Body fat changes in HIV patients on highly active antiretroviral therapy (HAART): a longitudinal DEXA study.

OBJECTIVE: We aimed to quantitatively evaluate body fat composition in a group of HIV patients treated with Highly Active Anti-retroviral Therapy (HAART) to ascertain both fat loss and fat distribution changes and to identify possible therapeutic and host related associated risk factors. PATIENTS AND METHODS: A total of 180 patients with available total body DEXA scan were assigned to a) Group 1, with clinically evident body fat changes, (BFC) and b) Group 2, without BFC. Clinical and immunovirologic data were collected. We used Student t-test and x2 or Fisher exact test to compare the characteristics of the two groups. Paired t-test was used to compare basal and follow-up data. The relationships between variables were evaluated by calculating Pearson's correlation coefficient and its significance. RESULTS: HAART duration was significantly (p<0.0001) higher for patients in Group 1 than in Group 2, as well as PI (p<0.02) and NRTI (p<0.002) therapy duration. Current CD4 count and CD4 rise from nadir resulted significantly higher in Group 1 than in Group 2 (p<0.02 and 0.006, respectively). Whole Body Fat (WBF), Peripheral Fat (PF) and Leg (L) fat negatively correlated with PI and NRTI therapy duration, while Trunk Fat (TF)/PF positively correlated with PI and NNRTI duration. No significant correlation was found, instead, with NNRTI therapy duration. At 5-year follow-up, we registered a further increase in TF, Arms (A) and L fat, especially in PI-treated patients. CONCLUSIONS: Body fat changes should always be considered when dealing with HIV-affected patients on HAART. The fat loss seemed to involve mainly peripheral regions, while fat accumulation tendency occurred in the trunk.

Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients.

OBJECTIVE: To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss. PATIENTS AND METHODS: In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases. RESULTS: At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol. CONCLUSIONS: The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.

Full distribution of work done on a quantum system for arbitrary initial states.

We propose an approach to define and measure the statistics of work, internal energy and dissipated heat in a driven quantum system. In our framework the presence of a physical detector arises naturally and work and its statistics can be investigated in the most general case. In particular, we show that the quantum coherence of the initial state can lead to measurable effects on the moments of the work done on the system. At the same time, we recover the known results if the initial state is a statistical mixture of energy eigenstates. Our method can also be applied to measure the dissipated heat in an open quantum system. By sequentially coupling the system to a detector, we can track the energy dissipated in the environment while accessing only the system degrees of freedom.

A Josephson radiation comb generator.

We propose the implementation of a Josephson Radiation Comb Generator (JRCG) based on a dc superconducting quantum interference device (SQUID) driven by an external magnetic field. When the magnetic flux crosses a diffraction node of the critical current interference pattern, the superconducting phase undergoes a jump of π and a voltage pulse is generated at the extremes of the SQUID. Under periodic drive this allows one to generate a sequence of sharp, evenly spaced voltage pulses. In the frequency domain, this corresponds to a comb-like structure similar to the one exploited in optics and metrology. With this device it is possible to generate up to several hundreds of harmonics of the driving frequency. For example, a chain of 50 identical high-critical-temperature SQUIDs driven at 1 GHz can deliver up to a 0.5 nW at 200 GHz. The availability of a fully solid-state radiation comb generator such as the JRCG, easily integrable on chip, may pave the way to a number of technological applications, from metrology to sub-millimeter wave generation.

Ultrastructural evidence of a secretory role for melatonin in the human parotid gland.

In vivo animal studies show that pentagastrin, cholecystokinin and melatonin cause the secretion and synthesis of salivary proteins. Melatonin occurs in large amounts in the gut and is released into the blood on food intake. In vitro experiments suggest that pentagastrin exerts secretory activity in human salivary glands, as judged by ultrastructural changes, reflecting secretion, and an actual protein output. Currently, it is hypothesised that melatonin induces secretory exocytotic events in the human parotid gland. Human parotid tissues were exposed to a high single concentration of melatonin in vitro, processed for high resolution scanning electron microscopy and then assessed morphometrically with the emphasis on the membrane of the intercellular canaliculi, a site of protein secretion. Compared with controls and in terms of density, the melatonin-exposed parotid tissues displayed increases in protrusions (signalling anchored granules) and microbuds (signalling membrane recycling and/or vesicle secretion) and decreases in microvilli (signalling cytoskeletal re-arrangement related to exocytosis), phenomena abolished or very largely reduced by the melatonin receptor blocker, luzindole. In conclusion, acinar serous cells of parotid tissue displayed in vitro exocytotic activity to melatonin, signalling protein secretion. Whether, under physiological conditions, melatonin influences the secretion of human parotid glands remains to be explored, however.

Quantum driving and work.

As quantum systems become more experimentally accessible, we are forced to reconsider the notions of control and work to fully account for quantum effects. To this end, we identify the work injected into a quantum system during a general quantum-mechanical driving protocol and quantify the relevant heat flows. The known results that are applicable in the limit of a classical drive are shown to emerge from our equations as a special case. Using the established framework, we show that the Bochkov-Kuzovlev identity for the exclusive work distribution is modified in a nontrivial way by the accumulation of system-drive correlations resulting from quantum back action. Our results accentuate the conceptual and discernible differences between a fully quantum-mechanical and classical driving protocols of quantum systems.

The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands.

OBJECTIVE: Amisulpride is reported to inhibit clozapine-induced sialorrhea. Preclinically, clozapine evokes muscarinic-M1-type-mediated secretion that, however, amisulpride does not reduce. Instead, amisulpride, without causing any overt secretion per se, enhances both nerve- and autonomimetic-evoked salivation by unknown mechanism(s). Hypothesizing that amisulpride prepares the gland for secretion, we looked for ultrastructural events indicating secretory activity in intercellular canaliculi of serous/seromucous cells, that is, density increase in protrusions (reflecting anchored granules) and in microbuds (reflecting recycling membranes and/or vesicle secretion) and decrease in microvilli (reflecting the cytoskeletal re-arrangement related to exocytosis). MATERIAL AND METHODS: Rat parotid and submandibular glands were exposed to amisulpride in vivo or in vitro. Glands were processed for transmission electron and scanning electron microscopy and then morphometrically assessed. RESULTS: Cells were packed with secretory granules. The density of protrusions increased in both glands, whereas significant and parallel changes in microvilli and microbuds occurred only in parotid glands, and in vitro. CONCLUSIONS: Amisulpride induced ultrastructural signs of secretory activity but to varying extent; in submandibular glands, in contrast to parotid glands, changes were not brought beyond the granular anchoring stage. Amisulpride may provide an overall readiness for secretion that will result in augmented responses to agonists, a phenomenon of potential interest in dry-mouth treatment.

Subcellular distribution of melatonin receptors in human parotid glands.

The hormone melatonin influences oral health through a variety of actions, such as anti-inflammatory, anti-oxidant, immunomodulatory and antitumour. Many of these melatonin functions are mediated by a family of membrane receptors expressed in the oral epithelium and salivary glands. Using immunoblotting and immunohistochemistry, recent studies have shown that the melatonin membrane receptors, MT1 and MT2, are present in rat and human salivary glands. To date, no investigation has dealt with the ultrastructural distribution of the melatonin receptors. This was the aim of the present study, using the immunogold method applied to the human parotid gland. Reactivity to MT1 and, with less intensity, to MT2 appeared in the secretory granules of acinar cells and in the cytoplasmic vesicles of both acinar and ductal cells. Plasma membranes were also stained, albeit slightly. The peculiar intracytoplasmic distribution of these receptors may indicate that there is an uptake/transport system for melatonin from the circulation into the saliva.

Environment-governed dynamics in driven quantum systems.

We show that the dynamics of a driven quantum system weakly coupled to the environment can exhibit two distinct regimes. While the relaxation basis is usually determined by the system+drive Hamiltonian (system-governed dynamics), we find that under certain conditions it is determined by specific features of the environment, such as, the form of the coupling operator (environment-governed dynamics). We provide an effective coupling parameter describing the transition between the two regimes and discuss how to observe the transition in a superconducting charge pump.

Diabetes reduces statherin in human parotid: immunogold study and comparison with submandibular gland.

BACKGROUND AND OBJECTIVE: Alteration of salivary gland secretion is one of the consequences of diabetes. In a recent study on the submandibular gland of diabetic subjects, we found changed expression of statherin, a salivary protein of fundamental importance in preserving tooth integrity, whose reduction was related with the high incidence of oral diseases in patients with diabetes. The goal of this report is to extend the study to human parotid gland and to compare the effects of diabetes on statherin expression with those previously described in submandibular gland. MATERIALS AND METHODS: Fragments of parotid glands obtained from diabetic and non-diabetic patients were fixed, dehydrated, embedded in Epon Resin and processed for the immunogold histochemistry. The staining density was expressed as number of gold particles per µm(2) and statistically evaluated. RESULTS AND CONCLUSIONS: In all samples, statherin reactivity was specifically localized in secretory granules of acinar cells. The statistical analysis showed that labelling density was significantly lower in diabetic than in non-diabetic parotid glands and that diabetes affects protein expression at identical extent in parotid and submandibular glands. The results strengthen the hypothesis that a reduced statherin secretion may be responsible for the higher incidence of oral disorders in diabetic subjects.

Geometric Landau-Zener interferometry.

We propose a new type of interferometry, based on geometric phases accumulated by a periodically driven two-level system undergoing multiple Landau-Zener transitions. As a specific example, we study its implementation in a superconducting charge pump. We find that interference patterns appear as a function of the pumping frequency and the phase bias, and clearly manifest themselves in the pumped charge. We also show that the effects described should persist in the presence of realistic decoherence.

Diabetes affects statherin expression in human labial glands.

BACKGROUND AND OBJECTIVE: Salivary statherin, which plays a special role in the defense of tooth integrity, is secreted by both major and minor salivary glands. A significantly reduced expression of this was recently found in human major salivary glands removed from diabetic subjects and was correlated with the high incidence of dental diseases occurring in patients with diabetes. In this study, we measured the density of gold particles indicating statherin immunoreactivity in labial glands to reveal a significant difference between diabetic and non-diabetic patients. MATERIALS AND METHODS: Surgical samples of labial glands obtained from both diabetic and non-diabetic patients were fixed with a glutaraldehyde and paraformaldehyde mixture, embedded in Epon, and treated for immunogold histochemistry using a polyclonal antibody specific for statherin. RESULTS: Statherin immunoreactivity was detected onto small vesicles diffused throughout the cytoplasm of serous cells. Statistical analysis revealed that the number of stained particles was significantly lower in the samples from diabetic subjects than from non-diabetic subjects. CONCLUSIONS: The results indicate that diabetes affects statherin secretion in labial glands and support the hypothesis that the increased susceptibility to oral diseases associated with diabetes could be related with a reduced statherin secretion.

Reduced statherin reactivity of human submandibular gland in diabetes.

BACKGROUND AND OBJECTIVES: Statherin is a salivary protein involved in the formation of enamel pellicle and in regulation of calcium homeostasis. Diabetes and other pathologies affect both salivary flow and protein secretion by salivary glands, causing increased susceptibility to mucosal infections, tooth demineralization, and caries. The purpose of this study was to compare the statherin expression in submandibular glands of healthy and diabetic subjects. MATERIALS AND METHODS: Fragments of submandibular glands obtained from diabetic and non diabetic patients were fixed, dehydrated, embedded in Epon Resin and processed for the immunogold histochemistry. The results were statistically evaluated. RESULTS: Specific statherin labeling was demonstrated in secretory granules of acinar cells in both diabetic and normal samples. The staining was much more intense in the latter compared to those of diabetics. The labeling density was quantified by evaluating the number and spatial distribution of gold particles within the granules. The number of gold particles was significantly lower in glands from diabetics than in control glands. CONCLUSIONS: The results obtained suggest that a reduced statherin secretion by salivary glands might be partly responsible for a less effective protection of the oral tissues, resulting in an higher incidence of caries and oral infections associated with diabetes.

Decoherence in adiabatic quantum evolution: application to cooper pair pumping.

One of the challenges of adiabatic control theory is the proper inclusion of the effects of dissipation. Here we study the adiabatic dynamics of an open two-level quantum system deriving a generalized master equation to consistently account for the combined action of the driving and dissipation. We demonstrate that in the zero-temperature limit the ground state dynamics is not affected by environment. As an example, we apply our theory to Cooper pair pumping, which demonstrates the robustness of ground state adiabatic evolution.

New findings on 3-D microanatomy of cellular structures in human tissues and organs. An HRSEM study.

We present here findings obtained on a large number of human tissues over a period of more than ten years, by our modification of the Osmium maceration method for high resolution scanning electron microscopy (HRSEM). Data are documented by original pictures which illustrate both some 3-D intracellular features not previously shown in human tissues, and results obtained in our current studies on mitochondrial morphology and on the secretory process of salivary glands. We have demonstrated that mitochondria of cells of practically all human tissues and organs have usually tubular cristae, and that even the cristae that look lamellar are joined to the inner mitochondrial membrane by tubular connexions similar to the crista junctions later seen by electron tomography. Concerning salivary glands an important result is the development of a morphometric method that allows the quantitative evaluation of the secretory events.

Bone mass loss and vitamin D metabolism impairment in HIV patients receiving highly active antiretroviral therapy.

AIM: Given the few controversial data about the effect of highly active antiretroviral therapy (HAART) on bone mass in HIV patients, we investigated whether a relationship between osteopenia/osteoporosis risk and HAART exists. METHODS: In 172 HIV patients, 152 on HAART, 92 including and 60 not including protease inhibitors (PI), 20 naïve and 64 controls, we measured spine/femur bone mineral density (BMD) by DEXA, and assayed serum osteocalcin (O), bone alkaline phosphatase (BAP), 1,25(OH)2 D, parathormone (PTH), calcium (Ca) and urinary pyridinium cross-links (PYD & DPD). RESULTS: Following WHO BMD t-score criteria, osteopenia was ascertained in >35% of all HAART groups and in 30% of naive. Only HAART patients had osteoporosis, PI patients more frequently, significantly (p<0.03) in spine (21.7% vs 8.3%). Males, intravenous drug users and B-C stage patients have a higher risk for low bone mass. Mean t-score was significantly lower in both spine and femur and O and PYD & DPD higher in PI than non PI patients and controls; 1,25(OH)2 D was significantly lower in all HIV groups than controls, PI patients having the lowest values positively correlating with BMD and negatively with OC and PYD & DPD, and it decreased further in 27 non selected monitored patients continuing on HAART. PTH was higher and Ca lower in HAART patients than controls but not significantly, PTH negatively correlating with BMD. CONCLUSION: HAART could be associated with osteopenia, even osteoporosis, and it could aggravate the loss in bone mass due to HIV infection itself. We hypothesize that HAART may directly affect bone remodelling and/or may indirectly affect vitamin D metabolism.

Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study.

OBJECTIVES: This study investigated the prognostic value of left ventricular (LV) mass at echocardiography in uncomplicated subjects with essential hypertension. BACKGROUND: Only a few single-center studies support the prognostic value of LV mass in uncomplicated hypertension. METHODS: The MAssa Ventricolare sinistra nell'Ipertensione study was a multicenter (45 centers) prospective study. The prespecified aim was to explore the prognostic value of LV mass in hypertension. Admission criteria included essential hypertension, no previous cardiovascular events, and age > or =50. There was central reading of echocardiographic tracings. Treatment was tailored to the single subject. RESULTS: Overall, 1,033 subjects (396 men) were followed for 0 to 4 years (median, 3 years). Mean age at entry was 60 years, and systolic/diastolic blood pressure was 154/92 mm Hg. The rate of cardiovascular events (x100 patient-years) was 1.3 in the group with normal LV mass and 3.2 in the group (28.5% of total sample) with LV mass > or =125 g/body surface area (p = 0.005). After adjustment for age (p < 0.01), diabetes (p < 0.01), cigarette smoking (p < 0.01) and serum creatinine (p = 0.03), LV hypertrophy was associated with an increased risk of events (RR [relative risk] 2.08; 95% CI [confidence interval]: 1.22 to 3.57). For each 39 g/m(2) (1 SD) increase in LV mass there was an independent 40% rise in the risk of major cardiovascular events (95% CI: 14 to 72; p = 0.0013). CONCLUSIONS: Our findings show a strong, continuous and independent relationship of LV mass to subsequent cardiovascular morbidity. This is the first study to extend such demonstration to a large nationwide multicenter sample of uncomplicated subjects with essential hypertension.

99mTc-Tetrofosmin pinhole-SPECT (P-SPECT) and radioguided sentinel node (SN) biopsy and in breast cancer axillary lymph node staging.

We compared 99mTc-Tetrofosmin P-SPECT with radioguided SN biopsy in 101 T1/T2 BC pts to predict axillary lymph node status. The day before surgery all pts underwent lymphoscintigraphy (LS) to mark the SN, following subdermal injection of 99mTc-colloidal sulphur surrounding the breast lesion. LS was combined with pre and intraoperative gamma probe. Previously, all pts had also undergone P-SPECT. ALND was performed in all cases. The SN(s) was detected in 97/101 cases (96%) by LS and gamma probe; in the 4 missed cases P-SPECT predicted lymph node status. In the 97 comparable cases, radioguided SN biopsy showed a slightly higher accuracy than P-SPECT (94.8% vs 93.8%), but a higher false-negative rate (14.3% vs 8.6%); P-SPECT had a higher NPV (95.2% vs 92.5%). The two procedures when combined achieved 100% accuracy. Radioguided SN biopsy alone had 100% accuracy only in pts with BC < 15 mm. P-SPECT had 3 false negative cases, 2 of which were micrometastatic SNs, and 3 false positives. P-SPECT identified 81.2% of cases with a single node, determined the exact number of nodes in 82.6% of cases with 1 to 3 node and correctly classified 93.7% of pts as having < or = 3 or > 3 metastatic nodes. Radioguided SN biopsy seems indicated in selected, early stage, small BC pts, while P-SPECT shows a high sensitivity independent of primary tumor size, giving additional important preoperative prognostic information. The two procedures combined provided a better axillary lymph node status prediction in T1/T2 carcinomas, and could thus improve ALND pt selection.