Ultra-broadband high-resolution microdroplet spectrometers for the near infrared.

By stabilizing the evaporation dynamics of a microliter fluorocarbon droplet, we demonstrate a fast-scan optofluidic Fourier transform (FT) spectrometer on the tip of an optical fiber operating in the 1000-2000 nm window with a resolution of 3.5 cm-1 (i.e., <1 nm at 1560 nm). Compared with other FT near-infrared (NIR) small-scale spectrometers reported in the literature, the fluorocarbon droplet spectrometer shows the largest wavelength span and span/resolution ratio, allowing spectral analysis of broadband or narrowband radiation to be easily performed. Our results open the way for the practical application of droplet spectrometers as advanced optofluidic NIR analyzers with small size and low cost that are capable of operating in harsh environments, even in the absence of electrical power sources.

Light pressure in droplet micro-resonators excited by free-space scattering.

A droplet optical resonator is a unique environment to investigate light-matter interaction and optomechanics in liquids. Here, we report on light pressure effects derived from whispering gallery modes excited in a liquid-polymer droplet micro-resonator by free-space laser scattering. From the nonlinear resonance spectrum observed in the visible, we provide evidence of photon pressure exerted at the liquid-air boundary and quantify it with a coherent physical model. Our findings pave the way to studies on micro-rheology and nonlinear optofluidics, where droplets serve as miniature liquid laboratories.

A kinetics-based approach to amyloid PET semi-quantification.

PURPOSE: To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. METHODS: The TDr method requires two static scans per subject: one early (~ 0-10 min after the injection) and one late (typically 50-70 min or 90-100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical-cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. RESULTS: TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. CONCLUSIONS: TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.

Approaching the transit time limit for high-precision spectroscopy on metastable CO around 6 µm.

As molecular spectroscopy makes its comeback to the limelight of fundamental sciences, scientists need ever better coherent light sources and diagnostic methods. Of particular importance for molecular spectroscopy is the mid infrared spectral region, where strong and narrow ro-vibrational excitations have their fundamental transition frequencies. Unfortunately, much technology in some portions of this spectral region is still rather pioneering. Here we present a high-resolution spectroscopy experiment, based on a molecular beam setup, which pushes the measured linewidth close to the transit time limit, on the order of 100 kHz. Moreover, we discuss the issue of frequency-noise characterization and the linewidth measurement of the ultrastable infrared laser used in the experiment.

Prognostic Value of 18F-Fluorocholine PET Parameters in Metastatic Castrate-Resistant Prostate Cancer Patients Treated with Docetaxel.

Background and Aim: The availability of new treatments for metastatic castrate-resistant prostate cancer (mCRPC) patients increases the need for reliable biomarkers to help clinicians to choose the better sequence strategy. The aim of the present retrospective and observational work is to investigate the prognostic value of 18F-fluorocholine (18F-FCH) positron emission tomography (PET) parameters in mCRPC. Materials and Methods: Between March 2013 and August 2016, 29 patients with mCRPC were included. They all received three-weekly docetaxel after androgen deprivation therapy, and they underwent 18F-FCH PET/computed tomography (CT) before and after the therapy. Semi-quantitative indices such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) with partial volume effect (PVC-SUV) correction, metabolically active tumour volume (MATV), and total lesion activity (TLA) with partial volume effect (PVC-TLA) correction were measured both in pre-treatment and post-treatment 18F-FCH PET/CT scans for each lesion. Whole-body indices were calculated as sum of values measured for each lesion (SSUVmax, SPVC-SUV, SMATV, and STLA). Progression-free survival (PFS) and overall survival (OS) were considered as clinical endpoints. Univariate and multivariate hazard ratios for whole-body 18F-FCH PET indices were performed, and p < 0.05 was considered as significant. Results: Cox regression analysis showed a statistically significant correlation between PFS, SMATV, and STLA. No correlations between OS and 18F-FCH PET parameters were defined probably due to the small sample size. Conclusions: Semi-quantitative indices such as SMATV and STLA at baseline have a prognostic role in patients treated with docetaxel for mCRPC, suggesting a potential role of 18F-FCH PET/CT imaging in clinical decision-making.

Measuring molecular frequencies in the 1-10 µm range at 11-digits accuracy.

High-resolution spectroscopy in the 1-10 µm region has never been fully tackled for the lack of widely-tunable and practical light sources. Indeed, all solutions proposed thus far suffer from at least one of three issues: they are feasible only in a narrow spectral range; the power available for spectroscopy is limited; the frequency accuracy is poor. Here, we present a setup for high-resolution spectroscopy, whose approach can be applied in the whole 1-10 µm range. It combines the power of quantum cascade lasers (QCLs) and the accuracy achievable by difference frequency generation using an orientation patterned GaP crystal. The frequency is measured against a primary frequency standard using the Italian metrological fibre link network. We demonstrate the performance of the setup by measuring a vibrational transition in a highly-excited metastable state of CO around 6 µm with 11 digits of precision.

First description of the soft part anatomy of Ilyocypris ramirezi Cusminsky & Whatley (Crustacea, Ostracoda) from Argentina, South America.

The anatomy of the soft parts of Ilyocypris ramirezi Cusminsky & Whatley, 1996 is described and illustrated for the first time, based on findings of this species from water bodies in the shallow areas of the Llancanelo basin, south-west of Mendoza Province, Argentina. This species is common in Quaternary and extant environments of the Pampa and Patagonian regions. Its distribution is now extending in Argentina to the Central-West area, locally named "Cuyo region". Ilyocypris ramirezi is a good environmental indicator and constitutes a useful tool in paleolimnological studies.

Environmental pollution due to cadmium: measure of semen quality as a marker of exposure and correlation with reproductive potential.

PURPOSE: Contradictory reports exist in the literature regarding an association of cadmium with parameters of semen quality. The aim of the study was to assess cadmium levels in both blood and seminal plasma and to analyze the relationships between cadmium concentrations and lifestyle and semen parameters. MATERIAL AND METHODS: Fifty healthy male volunteers were recruited to provide semen and blood samples. Each patient completed an extensive questionnaire regarding his occupation, residence, social status, diet, water source, smoking habits, and medical and surgical history. Semen analysis was carried out according to WHO guidelines. Detection of cadmium in both semen and blood samples was carried out by means of atomic absorption spectrophotometer. RESULTS: Mean concentrations of cadmium were 8.18 ± 1.6 ng/ml in blood samples and 2.56 ± 0.9 ng/ml in semen samples. Cadmium blood levels were significantly higher in men from industrialized areas and in current smokers, but were not correlated with semen levels. A significant positive correlation was found between cadmium blood levels, number of immotile spermatozoa, and teratozoospermia index (TZI). Significant inverse relationships between cadmium blood concentration and type-a and type a + b motility were found. CONCLUSIONS: The present data show a significant correlation between blood cadmium concentrations, cigarette smoking, occupational exposure, and parameters of semen quality. Such a reduction in spermiogenetic function could be an early marker of a toxic effect by cadmium pollution.

Clinical pharmacology of ponesimod, a selective S1P1 receptor modulator, after uptitration to supratherapeutic doses in healthy subjects.

PURPOSE: The aim of this study was to assess in healthy subjects the safety, tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an oral selective sphingosine-1-phosphate receptor 1 (S1P1) modulator in development for multiple sclerosis, by using an uptitration scheme up to supratherapeutic doses. METHODS: This was a double-blind, placebo-controlled, randomised, parallel group, uptitration study. Male and female subjects received ascending oral doses of ponesimod (n=12) or placebo (n=4) once daily for 3 days at each dose level (10-20-40-60-80-100mg). RESULTS: The most frequent adverse events were chest discomfort, headache, dizziness, dyspnoea, abdominal pain, and night sweats. Chest discomfort and dyspnoea were considered dose-limiting. A transient decrease in heart rate was observed following the first 10-mg ponesimod dose (maximum mean decrease of 9 beats per minute (bpm) (placebo: 2 bpm)). After uptitration, effects on heart rate were indistinguishable from placebo. A dose-dependent effect on pulmonary function tests was observed and reached a plateau with 60-80 mg ponesimod (maximum mean decrease from baseline of 1.24l (-30.5%) in forced expiratory volume in 1s). A plateau in mean lymphocyte count reduction of approximately 70% from baseline was reached at the 40 mg dose level. Observed effects were fully reversible within 10days after treatment discontinuation. No relevant sex differences were observed. CONCLUSIONS: At supratherapeutic doses, symptoms of chest discomfort and dyspnoea were dose-limiting. An uptitration dosing scheme is to be preferred in clinical studies in patients in order to limit effects of ponesimod on heart rate and atrioventricular (AV) conduction.

Benign pulmonary metastasizing leiomyomatosis: case report.

The authors report a rare case of leiomyomatosis of the lung diagnosed in a 43-year-old woman, with uterine intravenous leiomyomatosis. Benign metastasizing leiomyoma (BML) is an extremely rare lesion characterized by usually multiple, benign-appearing smooth muscle tumors of the lung in females with coexisting uterine leiomyoma. On the basis of their histological and immunohistological features, a unified histogenetic view of leiomyomas with vascular invasion (LWVI) and BML of the uterus is proposed. LWVI and BML may be the same pathological entity and microscopic vascular invasion may represent the metastatic mechanism of BML. LWVI seems to be the precursor of BML.

Low-dose estrogen and drospirenone combination: effects on metabolism and endothelial function in postmenopausal women with metabolic syndrome.

PURPOSE: Metabolic syndrome and endothelial dysfunction play a relevant role in the cardiovascular risk in post-menopause. The aim of the study was to assess the effects of a low-dose hemihydrate estradiol and drospirenone combination on cardiovascular risk parameters in postmenopausal women with metabolic syndrome. MATERIALS AND METHODS: Twenty-eight healthy women (group A) and 28 women with metabolic syndrome (group B) were treated with hemihydrate estradiol one mg + drospirenone two mg. At recruitment and after six months, clinical and laboratory parameters of metabolic syndrome were evaluated. Endothelial function was assessed measuring the flow-mediated dilatation of the brachial artery and the intima-media thickness of the common carotid artery. RESULTS: After six months an overall improvement of metabolism was observed in both groups reaching statistical significance for triglycerides, total cholesterolemia, and systolic pressure in group B. A trend to lower baseline flow-mediated dilatation was also found in group B. CONCLUSIONS: Drospirenone improves cardiovascular risk factors and does not impair endothelial function in menopausal women with metabolic syndrome.

Screening for trisomy 21 by maternal age fetal nuchal translucency thickness and maternal serum sample.

AIM: The aim of this paper was to examine the performance of two-stage first-trimester combined screening based on maternal age, fetal nuchal translucency (NT) thickness and maternal serum sample "free beta-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A)". METHODS: A combined screening for chromosomal anomalies was performed in 713 singleton pregnancies. We performed a two-stage screening with the blood taken at 8+0 to 10+6 weeks and the measurement of NT performed at 12+0 to 12+6 weeks. The maternal age related risk for trisomy 21 was calculated and adjusted according to the gestational age at the time of screening to derive the a-priori risk. The measured free beta-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were converted into a multiple of the median (MoM) for gestational age, adjusted for maternal weight, smoking status, ethnicity, method of conception (spontaneous or IVF) and parity. The measured NT was assessed in relationship of mesasure of CRL. Finally, the risk resulting by NT thickness and biochemical markers were multiplied by the a-priori risk to derive the patient-specific risk. RESULTS: The ultrascreen was considered positive in the case where the risk was greater than 1:250. In this case it was suggested the study of the fetal karyotype through an invasive test. In our study we had 23 positive cases after the combined screening: all patients have opted for the study of fetal karyotype, and in 5 cases the result was abnormal (trisomy 21). We had 1 case where the test was negative but the fetal karyotype was abnormal (trisomy 21). We have calculated sensitivity and false positive rate of the test. CONCLUSION: In our study there were 707 cases with a normal karyotype or delivery of a phenotypically normal baby and 6 cases with trisomy 21. The detection rate of the first trimester screening for chromosomal anomalies was 83% with a false positive rate of 3,2%. The aim of the study was estimated the performance of two-step strategy screening. In our study, the performance of the screening model, based on the two-stage, was not higher than the performance of screening based on a single-step reported in literature. In our opinion, there is no potential advantage in terms of detection rate.

[Phytoestrogens and menopause]. / Fitoestrogeni e menopausa.

Menopause is the interruption of menstrual and reproductive capacity, therefore, that occurs naturally in all women between 48 and 55 years, due to a lower production of gonadal steroids. The period becomes progressively irregular and lack of ovulation and menstrual flow decrease, and finally disappears. The time between the first symptoms and the cessation of the menstrual cycle is called menopause. With the onset of menopause the woman undergoes a series of changes related to estrogen deficiency, which occur in all tissues of the body. In this period one can distinguish an early stage, characterized by hot flashes, mood swings, night sweats and insomnia, and a late phase in which we highlight more symptoms related to the interruption of hormonal such as osteoporosis, obesity, at urogenital and increased incidence of cardiovascular disease. In Italy, only 5.2% of women aged 45-64 years used hormone replacement therapy, and only 20-30% follow a therapy for more than two years, both for psychological reasons, and for fear of side effects. Not surprisingly, therefore, phytoestrogens are given a high importance, as they are considered a natural alternative tank to to their plant origin. Interest in phytoestrogens was born from the observation that postmenopausal women who live in the East have a lower incidence of symptoms, cardiovascular disease, cancer and osteoporosis hormone use, compared to Western women.

Accurate modeling of a DOI capable small animal PET scanner using GATE.

In this work we developed a Monte Carlo (MC) model of the Sedecal Argus pre-clinical PET scanner, using GATE (Geant4 Application for Tomographic Emission). This is a dual-ring scanner which features DOI compensation by means of two layers of detector crystals (LYSO and GSO). Geometry of detectors and sources, pulses readout and selection of coincidence events were modeled with GATE, while a separate code was developed in order to emulate the processing of digitized data (for example, customized time windows and data flow saturation), the final binning of the lines of response and to reproduce the data output format of the scanner's acquisition software. Validation of the model was performed by modeling several phantoms used in experimental measurements, in order to compare the results of the simulations. Spatial resolution, sensitivity, scatter fraction, count rates and NECR were tested. Moreover, the NEMA NU-4 phantom was modeled in order to check for the image quality yielded by the model. Noise, contrast of cold and hot regions and recovery coefficient were calculated and compared using images of the NEMA phantom acquired with our scanner. The energy spectrum of coincidence events due to the small amount of (176)Lu in LYSO crystals, which was suitably included in our model, was also compared with experimental measurements. Spatial resolution, sensitivity and scatter fraction showed an agreement within 7%. Comparison of the count rates curves resulted satisfactory, being the values within the uncertainties, in the range of activities practically used in research scans. Analysis of the NEMA phantom images also showed a good agreement between simulated and acquired data, within 9% for all the tested parameters. This work shows that basic MC modeling of this kind of system is possible using GATE as a base platform; extension through suitably written customized code allows for an adequate level of accuracy in the results. Our careful validation against experimental data confirms that the developed simulation setup is a useful tool for a wide range of research applications.

Cloning and molecular characterization of Trypanosoma cruzi U2, U4, U5, and U6 small nuclear RNAs.

Small nuclear RNAs (snRNAs) are important factors in the functioning of eukaryotic cells that form several small complexes with proteins; these ribonucleoprotein particles (U snRNPs) have an essential role in the pre-mRNA processing, particularly in splicing, catalyzed by spliceosomes, large RNA-protein complexes composed of various snRNPs. Even though they are well defined in mammals, snRNPs are still not totally characterized in certain trypanosomatids as Trypanosoma cruzi. For this reason we subjected snRNAs (U2, U4, U5, and U6) from T. cruzi epimastigotes to molecular characterization by polymerase chain reaction (PCR) and reverse transcription-PCR. These amplified sequences were cloned, sequenced, and compared with those other of trypanosomatids. Among these snRNAs, U5 was less conserved and U6 the most conserved. Their respective secondary structures were predicted and compared with known T. brucei structures. In addition, the copy number of each snRNA in the T. cruzi genome was characterized by Southern blotting.

Cloning and molecular characterization of Trypanosoma cruzi U2, U4, U5, and U6 small nuclear RNAs

Small nuclear RNAs (snRNAs) are important factors in the functioning of eukaryotic cells that form several small complexes with proteins; these ribonucleoprotein particles (U snRNPs) have an essential role in the pre-mRNA processing, particularly in splicing, catalyzed by spliceosomes, large RNA-protein complexes composed of various snRNPs. Even though they are well defined in mammals, snRNPs are still not totally characterized in certain trypanosomatids as Trypanosoma cruzi. For this reason we subjected snRNAs (U2, U4, U5, and U6) from T. cruzi epimastigotes to molecular characterization by polymerase chain reaction (PCR) and reverse transcription-PCR. These amplified sequences were cloned, sequenced, and compared with those other of trypanosomatids. Among these snRNAs, U5 was less conserved and U6 the most conserved. Their respective secondary structures were predicted and compared with known T. brucei structures. In addition, the copy number of each snRNA in the T. cruzi genome was characterized by Southern blotting.

Frailty predicts long-term mortality in elderly subjects with chronic heart failure.

BACKGROUND: The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. MATERIALS AND METHODS: The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a 'Frailty Staging System'. RESULTS: Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75.9 +/- 6.7); subjects without CHF were prevalently female (56.4%) and younger than 75 years (mean 74.0 +/- 6.3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70.0% to 94.4%, P < 0.03) than in those without (43.8.% to 88.3%, P < 0.0001) CHF. The Kaplan-Meier analysis shows that at 9 years the probability of survival progressively decreased as frailty increased (45.5% to 0%) in subjects with CHF and from 62.8% to 25.9% in subjects without CHF. The Cox regression analysis indicated that frailty is predictive of mortality in the multivariate model adjusted for several variables including sex and age in subjects with and without CHF. Moreover, the analysis showed that frailty is more predictive of mortality in elderly subjects with CHF when it was analyzed either as continuous (1.48 vs. 1.36) or as a dummy (3 vs. 1 = 1.62 vs. 1.24) variable. CONCLUSIONS: Thus mortality among elderly subjects with or without CHF increases with frailty. Moreover, frailty is more predictive of long-term mortality in elderly subjects with than in those without CHF. Hence, frailty represents a new independent variable for predicting long-term mortality in elderly subjects with CHF.

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs.

Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing which involves excision of introns and union of exons in two independent transcripts. For the first time, we present the standardization of Trypanosoma cruzi permeable cells (Y strain) as a model for trans-splicing study of mRNAs in trypanosomes, following by RNase protection reaction, which localizes the SL exon and intron. This trans-splicing reaction in vitro was also used to analyze the influence of NFOH-121, a nitrofurazone-derivative, on this mechanism. The results suggested that the prodrug affects the RNA processing in these parasites, but the trans-splicing reaction still occurred.

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs

Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing which involves excision of introns and union of exons in two independent transcripts. For the first time, we present the standardization of Trypanosoma cruzi permeable cells (Y strain) as a model for trans-splicing study of mRNAs in trypanosomes, following by RNase protection reaction, which localizes the SL exon and intron. This trans-splicing reaction in vitro was also used to analyze the influence of NFOH-121, a nitrofurazone-derivative, on this mechanism. The results suggested that the prodrug affects the RNA processing in these parasites, but the trans-splicing reaction still occurred.