Loss-free shaping of few-cycle terawatt laser pulses.

We demonstrate loss-free generation of 3 mJ, 1 kHz, few-cycle (5 fs at 750 nm central wavelength) double pulses with a pulse peak separation from 10 to 100 fs, using a helium-filled hollow core fiber (HCF) and chirped mirror compressor. Crucial to our scheme are simulation-based modifications to the spectral phase and amplitude of the oscillator seed pulse to eliminate the deleterious effects of self-focusing and nonlinear phase pickup in the chirped pulse amplifier. The shortest pulse separations are enabled by tunable nonlinear pulse splitting in the HCF compressor.

Polarity reversal of wakefields driven by ultrashort pulse laser.

Using an analytical model and computer simulation, we show that the wakefield driven by an ultrashort laser pulse in high-density plasma periodically reverses its polarity due to the carrier-envelope phase shift of the driver. The wakefield polarity reversal occurs on spatial scales shorter than the typical length considered for electron acceleration with the laser-wakefield mechanism. Consequently, the energies of accelerated electrons are significantly affected. The results obtained are important for the laser-wakefield acceleration under the conditions relevant to present-day high-repetition-rate laser systems.

Trichophyton concentricum in skin lesions in children from the Salomon Islands.

AIM: Aim of the paper was to report cases of Tinea imbricata, a mycosis caused by the anthropophilic dermatophyte Trichophyton concentricum, observed in 2012 in Guadalcanal, the largest of the Salomon islands. METHODS: During 2012, several cases of Tinea imbricata, called bakwa by local people, were observed in the Little Samaritan Hospital in Guadalcanal. Skin scrapings collected from three young patients were examined in Italy to confirm the clinical diagnosis. The fungus grown on culture was morphologically identified and submitted to sequencing of the ITS1-ITS2 region. RESULTS: The diagnosis obtained by visual inspection of the skin lesions, characterised by concentric and lamellar plaques of scale often involving large part of the body, was confirmed mycological investigations. A prevalence of 15% of Tinea imbricata in this population was hypothesized. The fungus grown on culture was morphologically identified as Trichophyton concentricum and identification was confirmed sequencing the ITS1-ITS2 region. Patients were treated with potassium permanganate solution soaked gauze followed by colloidal sulfur and salicylic acid cream application. However, the efficacy of the antifungal treatment was difficult to evaluate due to the poor compliance of the patients and the remoteness of the villages. CONCLUSION: Italian clinicians and mycologists should be aware of this fungal infection because the increased number of international travels and of migration rise the spread of infections previously restricted to limited geographical areas.

A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade.

PURPOSE: The aim of this study was to assess the epidemiology of candidemia and antifungal susceptibility profiles of Candida isolates in Italy through a prospective surveillance study and to evaluate changes compared to a previous survey performed in one Italian region (Lombardy) in 1997-1999. METHODS: A prospective laboratory-based surveillance of candidemia was performed in Italy from January to December 2009. For each case a questionnaire was filled in, and the first isolate was collected and tested for in vitro antifungal susceptibility. RESULTS: During our 12-month survey, 467 episodes of candidemia were reported from 34 centres (30 located in Lombardy) and 464 isolates collected. Candida albicans was the predominant species (overall incidence 50.4 %), but the proportion varied considerably from 52.1 % in Lombardy hospitals to 45.2 % hospitals located outside this region. The second most frequent species was C. glabrata in Lombardy and C. parapsilosis in other regions. Comparison of the 1997-1999 and 2009 data on episodes of candidemia in Lombardy revealed a threefold increase in incidence (from 0.38 to 1.19 per 1,000 admissions), aging of infected patients, decline in crude mortality (from 35 to 27.1 %) and an increased proportion of C. glabrata etiology (from 12.8 to 20.3 %). Susceptibility testing confirmed the broad activity of amphotericin B and echinocandins. Decreased susceptibility to fluconazole was found in 24.9 % of the tested isolates. CONCLUSIONS: The results of this latest survey confirm the high rate of candidemia in Italy and show changes in some of the epidemiological tracts, such as aging of infected patients, increased proportion of C. glabrata infections, increased diagnosis in medical wards, and improvement in patients' survival.

Increased mortality in young candidemia patients associated with presence of a Candida albicans general-purpose genotype.

The yeast Candida albicans causes life-threatening candidemia. A general-purpose genotype (GPG; corresponds to clade 1) causes more infections than other C. albicans genotypes. To investigate if GPG strains also cause higher mortality, we developed a duplex PCR assay which was 98% accurate in identifying GPG strains in an international collection of strains typed with probe Ca3. We applied the assay to 635 European C. albicans candidemia isolates. Of these, 18% conformed to the GPG genotype, 4% were of a borderline genotype, and 78% were of a non-GPG genotype, broadly consistent with genotype distributions in earlier studies. The prevalence of GPG strains was increased in females and in younger patients, exceeding 40% in infants aged ≤1 year. Logistic regression confirmed sex and age as significant determinants of GPG prevalence. Across the entire patient cohort, there was no difference in mortality for patients infected with GPG strains or other strains (36% versus 37%). However, mortality in patients aged ≤48 years was 33% for infection with GPG strains but only 15% for infection with other strains (z test; P < 0.01). Mortality rates associated with GPG and non-GPG strains were comparable in older patients (39% versus 46%). A logistic regression analysis confirmed the age-dependent impact of genotype on mortality. Thus, GPG strains may be more virulent than other strains in younger patients. Because candidemia is usually caused by endogenous strains, our PCR assay could potentially be used as a risk assessment tool for identifying younger patients most at risk of death from candidemia.

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the present data show that the initial block of 5-HT reuptake is revealed by the selective increase in 5-HT levels (extracellular content) measured in PRP (not in insulated platelets, IPs) the 1st day of fluoxetine treatment. The initial action of this SSRI upon the 5-HT transporter in brain has also been confirmed by in vivo voltammetric data showing selective increase in the serotonergic signal following local injection of fluoxetine into the brain region studied. Successively, the major effect monitored is a decrease in 5-HT levels, which is more evident in IPs than in PRP. However, it is known that following 2 weeks treatment with an SSRI, 5-HT autoreceptors are desensitized and the serotonin synthesis is restored, together with the intracellular 5-HT levels. The present data showing that the levels of 5-HT in IPs tend to return to control values 12 days after the beginning of chronic fluoxetine treatment suggest that 5-HT levels in IPs (intracellular environment) mirror the influence of SSRI treatment upon the central 5-HT system. On the other hand, at day 12 of the chronic fluoxetine treatment, 5-HT content remains low in PRP. Similarly, low levels of 5-HT have been monitored in brain homogenate of rats chronically treated with fluoxetine. This would support the similarity between PRP preparation and brain homogenate as in both cases cells are disrupted by sample preparation. In conclusion this work supports the literature in proposing platelets as a peripheral model of central functions. In particular, the present data support the idea that peripheral 5-HT platelet levels can reflect the state of the central 5-HT system in conditions of depression. Furthermore, the main outcome of this study is that PRP may mirror central extracellular 5-HT levels, whilst IPs mirror neuronal 5-HT changes.

Electrochemical evidence that lacidipine stimulates release of nitrogen monoxide in rat aorta.

Dihidropyridines (DHPs) such as amlodipine, lercanidipine and lacidipine, are compounds capable of vascular protection via their calcium antagonist activity. In addition, they present vascular dilatation function, which has been related to an anti endothelin efficacy, particularly for lacidipine. Recent works have suggested that DHPs modulate vascular relaxation via increase in the release of nitrogen monoxide (NO). Using voltammetry with selective biosensors the present experiments performed in rat aortic rings demonstrate the capability of DHPs to implement endothelial NO at 'useful' and not toxic nanomolar levels, with a maximum efficacy for lacidipine. This activity joins the already described positive effects of these compounds upon vascular functions.

Voltammetric and functional evidence that N-methyl-D-aspartate and substance P mediate rat vascular relaxation via nitrogen monoxide release.

It is known that substance P acts as a vasodilator via activation of the enzyme nitrogen monoxide synthase (NOS) in endothelial tissue and it is suggested that N-methyl-D-aspartate (NMDA) could stimulate nitrogen monoxide (NO) release within nervous tissue. However, the data reported concern NO metabolites (nitrites, nitrates), while there is no clear evidence to date of the action of the latter compound within the aortic tissue. In this study, amperometry with specifically prepared carbon fiber electrodes has been applied to examine the effect of NMDA or substance P upon NO release. In particular, the data obtained confirm that NMDA can stimulate NO release in vivo, in the striatum of anaesthetized rats, and that substance P can stimulate NO release in rat aortic rings (ex vivo experiments). In addition, they indicate that NMDA also stimulates NO release in rat aortic rings. This original data has been confirmed by the observation of a vasorelaxant action of NMDA within noradrenaline precontracted aortic rings. Thus, these experiments provide the first direct evidence that NMDA can mediate vascular relaxation via NO release.