High-order dispersion mapping of an optical fiber.

We report on measurements of high-order dispersion maps of an optical fiber, showing how the ratio between the third and fourth-order dispersion (ß3/ß4) and the zero-dispersion wavelength (λ0) vary along the length of the fiber. Our method is based on Four-Wave Mixing between short pulses derived from an incoherent pump and a weak laser. We find that the variations in the ratio ß3/ß4 are correlated to those in λ0. We present also numerical calculations to illustrate the limits on the spatial resolution of the method. Due to the good accuracy in measuring λ0 and ß3/ß4 (10 -3% and 5% relative error, respectively), and its simplicity, the method can be used to identify fiber segments of good uniformity, suitable to build nonlinear optical devices such as parametric amplifiers and frequency comb generators.

Major cluster of paediatric 'true' primary chilblains during the COVID-19 pandemic: a consequence of lifestyle changes due to lockdown.

BACKGROUND: Over the last months, during the COVID-19 pandemic, a growing number of chilblain-like lesions were reported mainly in children and rarely in young adults. The relationship with SARS-CoV-2 infection was postulated, often without any laboratory, instrumental or clinical confirmation. The disclosure of information about chilblain-like lesions as a COVID-19 manifestation in social media has created concern in children's families and paediatricians. OBJECTIVES: To verify whether the chilblain-like lesions were caused by SARS-CoV-2 infection. METHODS: Prospective study on a case series including children who presented with acral lesions at the Pediatric Dermatology Outpatient and Pediatric Emergency Unit of the University of Bologna, from 1 April to 30 April 2020. We reported demographical, laboratory and clinical features, history of close contact with COVID-19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset. RESULTS: We evaluated eight patients (five females, three males) aged between 11 and 15 years. We excluded acute or previous SARS-CoV-2 infection with RT-PCR nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. Other acute infections causing purpuric lesions at the extremities were negative in all patients. Skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain. PCR assay on skin lesion biopsy for parvovirus B19, Mycoplasma pneumoniae and SARS-CoV-2 was performed in a patient and resulted negative. We identified common precipitating and risk factors: physical (cold and wet extremities, low BMI), cold and wet indoor and outdoor environment, behaviours, habits and lifestyle. We therefore reached a diagnosis of primary chilblains. CONCLUSIONS: During the COVID-19 pandemic, a 'cluster' of primary chilblains developed in predisposed subjects, mainly teenagers, due to cold exposure in the lockdown period. Laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis.

Shift of zero-dispersion wavelength in bent optical fibers.

The understanding of how bending modifies the dispersion of optical fibers, in particular, the zero-dispersion wavelength (λ0), is essential in the development of compact nonlinear optical devices such as parametric amplifiers, wavelength converters, soliton lasers and frequency comb generators. Typically, substantial variations in the parametric gain and/or conversion efficiency are significant for changes in λ0 of ~0.1 nm, which occur for variations on the bending radius (Rb) of 1 cm or less. Measuring λ0 as a function of bending radius (Rb) is challenging, as it requires detecting changes < 0.1 nm and in short fibers. By using a method based on four-wave mixing (FWM) generated by an incoherent-pump with relatively broad spectrum and a weak laser, we report measurements of λ0 as a function of Rb in a dispersion-shifted fiber with <0.1 nm accuracy on λ0. This method is sensitive enough to measure small variations in λ0 of ~0.04 nm in very short fibers (~20 m). We observe that λ0 increases by 12 nm when Rb is decreased from 10 cm to 1 cm, and a change of 1 nm is obtained for Rb = 3 cm. We also present numerical simulations of the bent fiber that are in good agreement with our measurements, and help us to explain the observations and to predict how high-order dispersion is modified with bending. This study can provide insights for dispersion engineering, in which bending could be used as a tuning, equalization, or tailoring mechanism for λ0, which can be used in the development of compact nonlinear optical devices based on fibers or other bent-waveguide structures.

Prospective Epstein-Barr virus-related post-transplant lymphoproliferative disorder prevention program in pediatric allogeneic hematopoietic stem cell transplant: virological monitoring and first-line treatment.

BACKGROUND: In 28 pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, we aimed to evaluate: (i) the impact of routine Epstein-Barr virus (EBV) DNA monitoring on the development of EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD); (ii) the incidence of EBV infection and the potential risk factors; and (iii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV-PTLD. METHODS: Quantitative real-time polymerase chain reaction assay was performed on WB samples for all patients. EBV DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for the patients at higher risk of developing EBV-PTLD (≥ 10,000 copies/mL WB). RESULTS: High EBV DNAemia levels were observed in 37.5% of the actively infected recipients (57.1%). Severe aplastic anemia, matched-unrelated donor transplant, the reduced-intensity conditioning regimen and, to a lesser extent, the in vivo T-cell depletion with anti-thymocyte immunoglobulin were associated with high viral load. A significant correlation between EBV DNA levels in WB and PBMC samples was obtained (r = 0.755, P < 0.001). A similar kinetics of EBV DNA in the 2 blood compartments was observed. Clinically, both specimen types appeared to be equally informative to assess the risk of patients to develop PTLD. On the basis of EBV DNAemia levels, in 3 patients (10.7%) immunosuppressive therapy was reduced and 1 patient (3.5%) received early treatment for probable EBV disease. No patients developed EBV-PTLD. CONCLUSION: WB proved to be a suitable clinical specimen to monitor EBV DNA load after allo-HSCT for the management of EBV infection and PTLD prevention.

Differential atrial performance at rest and exercise in athletes: Potential trigger for developing atrial dysfunction?

Highly trained athletes show an increased risk of atrial arrhythmias. Little is known about atrial volumes and function during exercise in this population. Our aim was to analyze atrial size and contractile function during exercise. Fifty endurance athletes with 11 ± 8 h of training per week and 30 sedentary control subjects were included. Echocardiography was performed at baseline and during exercise. Left (LA) and right atrial (RA) size and function were assessed by two-dimensional echocardiography. Peak negative strain (Sa) during atrial contraction and active atrial emptying volume (AEV) were measured. Athletes and control subjects showed a significant increment of deformation and AEV of both atria with exercise (P < 0.01 vs baseline for LA and RA). Among athletes, a subgroup with significant LA (n = 8)/RA (n = 15) dilatation (≥40 mL/m2 ) showed a significantly lower increment in AEV with exercise (LA∆AEV: 1.4 ± 1.1 mL/m2 vs 2.1 ± 0.9 mL/m2 , P = 0.04; RA∆AEV: 0.9 ± 0.8 mL/m2 vs 2.3 ± 1.1 mL/m2 , P < 0.01) and lower increment in deformation vs other athletes (LA∆Sa: -3.2 ± 2.9% vs -9.5 ± 4.4%, P < 0.01; RA∆Sa: -2.5 ± 3.3% vs. -9.8 ± 3.3%, P < 0.01). During exercise, active atrial strain increases, but less in athletes compared to controls, but due to larger atrial volumes, they reached similar increases in atrial emptying volume. However, this overall lesser deformation increases from a subgroup with significant atrial dilatation showing impairment in atrial contractile reserve.

Septal flash predicts cardiac resynchronization therapy response in patients with permanent atrial fibrillation.

AIMS: Patients with heart failure (HF) as well as atrial fibrillation (AF) have suboptimal response to cardiac resynchronization therapy (CRT). Identification of mechanical abnormalities, amenable to correction with CRT, might improve the selection of candidates and CRT efficiency. We evaluated whether abnormal septal motion, assessed by the presence of septal flash (SF) is related to CRT response in patients with AF. METHODS AND RESULTS: Ninety-four CRT patients with AF were included. Echocardiography was performed in all subjects at baseline and at 12-month follow-up. Abnormal septal motion was defined by the presence of SF (early septal inward/outward motion within the isovolumic contraction period/QRS duration). Response to CRT was defined as a reduction (>15%) of the end-systolic volume of the left ventricle (LV). Univariate and multivariate analyses were performed to identify the predictors of CRT response. The mean age was 69 ± 8 years, 79% were males, and 59% of patients responded to CRT. Cardiovascular death was 14.4% and all-cause mortality was 16.5% during follow-up. Patients with SF at baseline that was acutely corrected by CRT were significantly more likely to respond than patients without SF. Baseline SF was an independent predictor of CRT response (OR 5.24; 95% CI 1.95-14.11). CONCLUSION: Abnormal septal motion, assessed by the presence of SF, is a mechanism amenable to CRT correction. Its correction is associated with a higher likelihood of CRT response in HF patients with long-standing AF. This could improve the selection of candidates to CRT in a subgroup with particularly poor response and long-term prognosis.

Characterization of volatile fraction of typical Irpinian wines fermented with a new starter yeast.

Non-Saccharomyces yeasts are microorganisms that play an important role in the fermentation dynamics, compositions and flavour of wine. The aromatic compounds responsible for varietal aroma in wine are mainly terpenes, of which the most important group are the monoterpenes because of their volatility and odour if present in a free form. In fact, some terpenyl-glycosides do not contribute to the aroma unless they are hydrolysed. The glycosylated form of terpenes can be converted by hydrolysis with ß-glycosidases produced by yeasts during the winemaking process, into aromatic compounds. In this study we utilized a non-Saccharomyces yeast, with a high extra-cellular glycosidase activity, isolated from grapes of cultivars typical of Irpinia region. This strain, identified as a Rhodotorula mucillaginosa (strain WLR12), was used to carry out an experimental winemaking process and the results were compared with those obtained with a commercial yeast starter. Chemical and sensorial analysis demonstrated that the wines produced with WLR12 strain had a more floral aroma and some sweet and ripened fruit notes compared to those obtained with commercial yeast. The data also showed an increasing of the free terpenes fraction that, however, did not significatively modify the bouquet of the wines.

Exploring language barriers to Evidence-based Health Care (EBHC) in post-graduate medical students: a randomised trial.

BACKGROUND: Understanding the written English language might be a barrier when teaching Evidence-based Health Care (EBHC) to Spanish-speaking physicians. AIM: To quantify the magnitude of this potential barrier. METHOD: Cochrane Review abstracts in English or in Spanish were randomly distributed among first-year residents at the Pontificia Universidad Catolica of Chile. Residents answered investigator-designed questionnaires to measure their comprehension while the time needed to complete the task was recorded. RESULTS: Groups were similar at baseline. Mean score for those reading in Spanish was 11.9 +/- 2.8 (range 5 to 18) compared to 10.5 +/- 3.8 (range 1 to 17) for those reading in English (p=0.04). Low scores ( pound 9) were twice as frequent for the English group than for the Spanish group (16.7% vs 34.7%; p=0.042). The time to complete the task was also longer for the group reading in English. CONCLUSION: Language should be taken into account when teaching EBHC to Spanish-speaking physicians.

The PLAT Study: a multidisciplinary study of hemostatic function and conventional risk factors in vascular disease patients.

In this paper are reported the basal results of a multidisciplinary, multicenter study designed to explore in a population with ischemic disease the relation between hemostatic variables, conventional risk factors and atherothrombotic sequelae. 953 patients less than or equal to 69 yrs with documented coronary, cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months. Examinations included hemostatic and lipid laboratory assays, arterial Doppler examination, cerebral computerized tomography and nuclear magnetic resonance, exercise electrocardiogram and coronary angiography. Fibrinogen (301.4 +/- 71.52 mg/dl) correlated positively with antithrombin III (r = 0.27) and leukocytes (r = 0.25), negatively with HDL-cholesterol (r = 0.18) and tended to increase with smoking. Heavy smokers had higher leukocyte counts than non-smokers (8.0 +/- 2.0 vs. 7.2 +/- 2.1 x 10(3)/microliters), higher triglycerides (1.87 +/- 1.12 vs. 1.53 +/- 1.35 mmol/l) and lower HDL-cholesterol (0.93 +/- 0.27 vs. 1.00 +/- 0.25 mmol/l). FVII correlated positively with triglycerides (r = 0.16) and protein C (r = 0.45). vWF:Ag (145.4 +/- 70.58%) ad FVII:C (139.7 +/- 59.10%) were positively correlated (r = 0.44). FVIII:C correlated positively with fibrinogen (r = 0.21). Myocardial infarction survivors with associated cerebral and peripheral vascular lesions had higher FVIII:C, FVII, fibronogen and vWF:Ag. These findings suggest that hemostatic factors may enhance and/or mediate the effects of conventional risk factors in atherothrombotic ischemic events.

Chromosomal alterations in atherosclerotic plaques.

Alterations of chromosomes 7 and 11 have been involved in the progression of atherosclerosis. Twenty-three carotid endarterectomy specimens were studied for the presence of alterations in chromosomes 7 and 11, and fibroblastic growth factor-3 (FGF-3) gene amplification. Besides classic histological stainings, immunophenotyping of cellular and vascular components and fluorescence in situ hybridization (FISH) were performed. At the caps, unstable plaques (n=18) showed inflammatory infiltration of macrophages, smooth muscle cells, and T-lymphocytes. Specifically in these regions, the FISH showed varying percentages of trisomy (15/18) and tetrasomy (8/15) of chromosome 7. In four cases polisomy 7 was noted in some nuclei. Monosomy of chromosome 11 and gene amplification of FGF-3 gene was observed. The FISH of the five stable plaques and normal arterial walls showed no chromosome alterations; furthermore, chromosome 3, which is not involved in atherosclerotic progression, presented a normal ploidy of smooth muscle cells in stable and unstable plaques and normal arterial walls. In conclusion, chromosome 7 and 11 alterations and FGF-3 gene amplification are components of unstable plaques, and might contribute to the evolution of stable plaques into complicated plaques.

Association of increased fibrin turnover and defective fibrinolytic capacity with leg atherosclerosis. The PLAT Group.

Patients with peripheral arterial disease have a high risk of death from cardiovascular events. As defective fibrinolysis associated with leg atherosclerosis has been suggested as a predisposing factor, we sought a relation among decreased fibrinolysis, the presence of leg atherosclerosis and the incidence of thrombotic events in a case-control study nested in the PLAT. Fifty-eight patients with coronary and/or cerebral atherothrombotic disease, free of leg atherosclerosis at Doppler examination, were compared with 50 atherosclerotic patients with leg involvement. High D-dimer (153.0 vs 81.3 ng/ml, p < 0.001) and tPA antigen before venous stasis (14.4 vs 11.8 ng/ml, p < 0.03), and low tPA antigen (6.7 vs 15.6 ng/ml, p < 0.01) and fibrinolytic activity released after venous stasis (fibrinolytic capacity: 113.2 vs 281.4 mm2, p < 0.001) were found in patients with leg atherosclerosis. D-dimer and fibrinolytic capacity, in addition to age, were selected by stepwise discriminant analysis as characterizing patients with leg atherosclerosis. Moreover, higher D-dimer and tPA inhibitor characterized patients with leg atherosclerosis who subsequently experienced thrombotic events. These findings constitute evidence of high fibrin turnover and impaired fibrinolytic potential in patients with leg atherosclerosis. Thus impaired fibrinolysis may contribute to the prothrombotic state in these patients.

Maternal IgG avidity and IgM detected by blot as diagnostic tools to identify pregnant women at risk of transmitting cytomegalovirus.

In this study, we determined the avidity index (AI) of anticytomegalovirus (CMV) immunoglobulin G (IgG) and the anti-CMV immunoglobulin M (IgM) profile in 124 pregnant women, 87 of whom were considered at risk of transmitting CMV infection to their offspring and 37 of whom were at no risk. IgG avidity and blot for IgM were performed on two serum samples from each woman, at 6-18 weeks' gestation and at 20-23 weeks' gestation. Pregnancy outcomes were monitored. The results obtained showed that the determination of anti-CMV IgG avidity at 6-18 weeks' gestation can identify all women who would have an infected fetus/newborn (100% sensitivity), whereas IgM detected by blot had poorer results (69% sensitivity). Interestingly, at 20-23 weeks' gestation, the sensitivity of IgM detection by blot was higher than that obtained by avidity (75 % and 63%, respectively) and the combination of IgG avidity and IgM by blot yielded the best results (81% sensitivity).

Blood flow in the internal carotid and middle cerebral arteries: effects of continuous oral conjugated equine estrogens administration with monthly progestogen supplementation on postmenopausal women.

OBJECTIVE: This study was designed in order to evaluate the effect of conjugated equine estrogens (CEE) on internal carotid and middle cerebral artery blood flow in postmenopausal women. DESIGN: Thirty-four healthy postmenopausal women with intact uteri were randomly divided into two groups of 17 subjects each. The first group was treated for 24 weeks with continuous CEE medication (0.625 mg daily) and cyclical supplementations of 5 mg/day of medrogestone acetate, given on the last 12 days of every 4-week period (Prempak, Wyeth, Italy). The second group received no treatment. The pulsatility indices (PI) of both the internal carotid artery and middle cerebral artery were measured. RESULTS: In the treated group, the PI of the interior carotid artery and MCA was reduced from respectively 0.736 (0.016) and 0.745 (0.009) at baseline, to 0.669 (0.021) and 0.670 (0.011) after 24 weeks (p = 0.01); in the control group, the PI values remained unchanged. The between-group difference for both arteries was significant (p < 0.01). CONCLUSIONS: The administration of CEE with cyclical medrogestone supplementation to postmenopausal women induces a statistically significant reduction in the PI of cerebral arteries.

Cerebral artery blood flow in relation to age and menopausal status.

OBJECTIVE: To investigate vascular reactivity in women's cerebral arteries from reproductive age to postmenopause. METHODS: The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20-59 years. RESULTS: In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. CONCLUSION: Menopause causes a significant increase in the PI of women's cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and middle cerebral arteries and menopausal but not chronologic age. This effect may be one of the mechanisms by which menopause is associated with the known higher risk for coronary heart disease observed in women.

Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries.

OBJECTIVE: To determine the effect of the androgen supplementation of hormone replacement therapy (HRT) on the vascular reactivity of cerebral arteries. DESIGN: Open randomized study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Forty postmenopausal women who were treated with sequential HRT (transdermal E2 50 microg/d + medroxyprogesterone acetate 10 mg/d for 12 days every other month) for > or =1 year and < or =5 years. INTERVENTION(S): Testosterone undecanoate (40 mg/d, p.o.) was randomly administered to 20 patients during ongoing HRT; the other 20 served as controls. Doppler evaluations of the internal carotid and middle cerebral arteries were performed together with lipid levels assessments. A visual analogue scale (VAS) was used to evaluate various parameters relating to sexual life and well-being. MAIN OUTCOME MEASURE(S): Pulsatility index (PI) of the arteries, VAS assessment of psychophysical well-being. RESULT(S): The administration of testosterone undecanoate during HRT induced an increase in the PI of the middle cerebral artery and a reduction of high-density lipoprotein cholesterol. Sexual desire and satisfaction were greatly improved. CONCLUSION(S): In postmenopausal women, androgen supplementation during HRT can partially counteract the beneficial effects of estrogens on cerebral vascular reactivity and lipid profiles, but sexual desire and satisfaction are greatly improved.

Gonadotropin-releasing hormone agonist-induced hypoestrogenism and blood flows in cerebral arteries.

OBJECTIVE: To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebral vessel blood flow. DESIGN: Open, controlled study. SETTING: Tertiary care units of the University of Milan, Italy. PATIENTS: Young women scheduled to undergo 6 months of therapy with a GnRH-a; a control group was also enrolled. INTERVENTIONS: In both groups, the pulsatility index of both the internal carotid artery (ICA) and middle cerebral artery (MCA) was measured by means of Doppler ultrasound over a period of 6 months. MAIN OUTCOME MEASURE: The ICA and MCA pulsatility index. RESULTS: No variation in the pulsatility index of either artery was found in either group. CONCLUSIONS: A 6-month period of GnRH-a-induced hypoestrogenism in young women does not lead to any variation in the blood flow of cerebral vessels. This provides some reassurance as to the safety of these drugs in relation to the role that the reactivity of peripheral arteries may play in determining risk of cardiovascular disease. Furthermore, our results show that blood flow in the cerebral vessels of young subjects is under extraestrogenic control and that this may counterbalance estrogen deprivation through mechanisms that probably are no longer active in the perimenopausal years.

Modulation of electrically elicited blink reflex components by visual and acoustic prestimuli in man.

The effects of a prestimulus on the electrically elicited blink reflex components were investigated in 20 healthy subjects. In the first group of 10 subjects (warned group), electric shocks were delivered in isolation or preceded, at an interstimulus interval (ISI) of 0.1 s, 1 s, or 10 s, by a visual or acoustic warning stimulus. In the second group of 10 subjects (unwarned group), the electric shocks were delivered either in isolation or preceded, at the same ISI, by visual or acoustic stimuli having no warning value. The modulation of the three blink reflex components was then analysed. Compared to the baseline condition, the R1 oligosynaptic component was enhanced at 0.1 s and 1 s ISI, in the warned group with the visual prestimulus, but only at 0.1 s after a visual and acoustic prestimulus in the unwarned group. On the contrary, the polysynaptic responses showed a different course: R2 was significantly reduced at the 0.1 s interval in the warned group with both the prestimuli, and only with the visual prestimulus in the unwarned group. The R3 was inhibited at all three intervals with the visual prestimulus, and at the 0.1 s and 1 s with the acoustic one in the warned group, and only at 0.1 s in the unwarned group, both after visual and acoustic prestimuli. The decrement in R2 and R3 observed with the shortest interval was probably related to the prepulse inhibition of startle reflex. Furthermore, only R3 was still inhibited at longer intervals, when the sustained processes of attention may have influenced this component. Perhaps this combination of events represents, in the warned group, the best preparation for voluntary reflex reaction.

[New trends in the treatment of trophic sequelae post-phlebitic syndrome]. / Nuovi orientamenti nel trattamento delle sequele trofiche della sindrome post-flebitica.

Authors analyses most recent concepts on pathogenesis of trophic changes in post-phlebitic syndrome: particularly they consider the role of extravascular fibrin deposition, in patients with depressed plasmatic fibrinolytic activity. In this patients, according to recent reports, it seems useful a fibrinolytic therapy to improve trophic conditions of the post-phlebitic limb, particularly in respect to dermatoliposclerosis. Authors refer their experience on a double blind study with stanozolol an anabolizing steroid with fibrinolytic activity: in all treated patients good clinical results were obtained; however no enhancement of plasmatic fibrinolytic activity was demonstrated.