Intersubband Polariton-Polariton Scattering in a Dispersive Microcavity.

The ultrafast scattering dynamics of intersubband polaritons in dispersive cavities embedding GaAs/AlGaAs quantum wells are studied directly within their band structure using a noncollinear pump-probe geometry with phase-stable midinfrared pulses. Selective excitation of the lower polariton at a frequency of ∼25 THz and at a finite in-plane momentum k_{‖} leads to the emergence of a narrowband maximum in the probe reflectivity at k_{‖}=0. A quantum mechanical model identifies the underlying microscopic process as stimulated coherent polariton-polariton scattering. These results mark an important milestone toward quantum control and bosonic lasing in custom-tailored polaritonic systems in the mid and far infrared.

Caregivers in home palliative care: gender, psychological aspects, and patient's functional status as main predictors for their quality of life.

PURPOSE: This study aims to investigate the impact of possible predictors of quality of life (QoL) in a group of Italian caregivers assisting a cancer patient in home palliative care. METHODS: Data from 570 adult informal caregivers and their cancer-affected relatives were collected. A multivariate regression analysis was conducted to assess the effect of three groups of variables on Caregivers Quality of Life Index-Cancer (CQOLC) scale: (a) socio-demographic characteristics of caregivers; (b) psychological characteristics of caregivers assessed by Profile Mood of States (POMS), Caregiver Burden Inventory (CBI), and Preparedness for Caregiving Scale (PCS); (c) Socio-demographic characteristics and functional status of the patients assessed by Karnofsky Performance Status (KPS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL). RESULTS: Regression analysis shows that some variables from each of these clusters are significantly associated with CQOLC, in particular: (a) the gender of the caregiver (st.ß = .115, t = 2.765, p = .006) and the time spent for caregiving (st.ß = - .165, t = - 3.960, p < .001); (b) the scores obtained by the caregivers in POMS,CBI (st.ß = - .523, t = - 16.984, p < .001 and st.ß = - .373, t = - 12.950, p < .001, respectively) and PCS (st.ß = .092, t = 3.672, p < .001); (c) the gender (st.ß = - .081, t = - 1.933, p = .045) and the IADL score (st.ß = .195, t = 4.643, p < .001) of the patient. CONCLUSIONS: A multidimensional evaluation is a key strategy to identify the most vulnerable caregivers. Apart from the condition of the patient, the gender of the caregivers, the time spent for caregiving and, above all, their psychological condition are strong predictors of caregivers' QoL.

Multiple predator effects on juvenile prey survival.

Predicting multiple predator effects (MPEs) on shared prey remains one of the biggest challenges in ecology. Empirical evidence indicates that interactions among predators can alter predation rates and modify any expected linear effects on prey survival. Knowledge on predator density, identity and life-history traits is expected to help predict the behavioral mechanisms that lead to non-linear changes in predation. Yet, few studies have rigorously examined the effects of predator-predator interactions on prey survival, particularly with marine vertebrate predators. Using an additive-substitutive design, we experimentally paired reef piscivores with different hunting mode [active predator, Pseudochromis fuscus (F); ambush predators, Cephalopholis boenak (B), Epinephelus maculatus (M)] to determine how behavioral interactions modified their combined impacts on damselfish prey. Results showed that behavioral patterns among predators matched those predicted from their hunting mode. However, it was the identity of the predators what determined the strength of any positive or negative interactions, and thus the nature and magnitude of MPEs on prey survival (i.e., risk-enhancing effects: treatments BB, MM and FM; risk-reducing: BM; and linear effects: FF, FB). Given the specificity of predator-predator interactions, none of the predators were fully functionally redundant. Even when two species seemed substitutable (i.e., predators F and M), they led to vastly diverse effects when paired with additional predator species (i.e., B). We concluded that knowledge of the identity of the predator species and the behavioral interactions among them is crucial to successfully predict MPEs in natural systems.

Exhaled breath temperature measurement: influence of circadian rhythm.

Exhaled breath temperature (EBT) is an expression of airway inflammation, an event that drives several lung diseases. The measurement of the exhaled breath temperature has recently been proposed as a popular tool in the diagnosis and monitoring of inflammatory lung diseases due to the fact that it is a non-invasive method. The influence of external factors on EBT, its reproducibility, and its sensitivity to treatment have already been explored. However, to reach clinical practice, EBT requires a complete validation that is still lacking. The aim of this study was to analyse the possible influence of an important internal variable, i.e the circadian rhythm on EBT values in a group of 24 healthy adult volunteers. We repeated measurement of EBT at different hours of the day: 8.00 AM, 12.00 AM, 4.00 PM, 8.00 PM and analysed the correlation with axillary temperature measurement at these times. The EBT resulted significantly different during daily measurements (8.00 AM vs 12.00 AM vs 4.00 PM vs 8.00 PM: 28.01±1.64°C vs 28.8±1.82°C vs 29.34±1.79°C vs 28.06±1.34°C). The highest EBT was reported at 4.00 PM and the lowest at 8.00 AM. For the first time we found an influence of the circadian rhythm on EBT. These data support the validation of the EBT necessary for its promotion in clinical practice.

Analysis of mitochondrial DNA alteration in new phenotype ACOS.

BACKGROUND: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD. METHODS: Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR. RESULTS: ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56). CONCLUSION: We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.

Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in stable atopic severe asthma.

Severe asthma (SA) is associated with neutrophil recruitment and T helper (TH )17 chemokine overexpression in bronchial biopsies. We aimed to evaluate IL-17A and IL-17F expression in nasal/bronchial lamina propria of atopic mild-to-severe asthmatics and controls in relation to neutrophilia and asthma exacerbations. Cryostat sections of nasal/bronchial biopsies obtained from 14 SA and 14 mild asthma (MA) stable atopic patients with rhinitis, and seven healthy controls were analyzed by immunohistochemistry for neutrophils, IL-17A and IL-17F expression. Atopic SA showed an increase in asthma exacerbations number, IL-17F and IL-17A expression in nasal/bronchial lamina propria compared to MA and controls, and a higher expression of bronchial neutrophils in SA compared to MA and controls. In all asthmatics, significant relationships were found between bronchial IL-17F and neutrophils/FEV1 , nasal IL-17F and bronchial neutrophil/IL-17 markers and between the latter and exacerbations, suggesting that nasal IL-17F might be informative on bronchial IL17-driven neutrophilia in atopic SA.

Atrial fibrillation in patients with haemophilia: a cross-sectional evaluation in Europe.

Atrial fibrillation (AF) is a common health problem in the general population, but data on prevalence or management in patients with haemophilia (PWH) are lacking. The aims of this study were to analyse the prevalence of AF and risk factors for stroke using a cross-sectional pan-European design and to document current anticoagulation practice. The ADVANCE Working Group consists of members from 14 European haemophilia centres. Each centre retrieved data on their PWH with AF. From the total of 3952 adult PWH, 33 had AF with a mean age of 69 years (IQR 62-76). Haemophilia was severe in seven (21%), moderate in six (18%) and mild in 20 (61%) patients. The overall AF prevalence was 0.84% and increased with age; 0.42% in patients 40-60 years and 3.4% in patients >60 years. The mean CHA2 DS2 -Vasc score was 1.3 (range 0-4), predominantly determined by age and hypertension. Hypertension was reported in 48% of PWH with AF. In 11 patients (33%), anticoagulation was started of whom nine aspirin and two vitamin K antagonists. Of these 11 patients, nine had mild haemophilia. Anticoagulation was given in 42% of patients with a CHA2 DS2 -Vasc score ≥2. During follow-up (mean 57 months), there were no thrombotic events reported, nor increases in bleeding severity. The prevalence of AF in haemophilia increases with age and is predominantly present in mild haemophilia. PWH have a low stroke risk based on their CHA2 DS2 -Vasc scores, that might be even lower considering the hypocoagulable state. Only 33% of PWH with AF receives any form of anticoagulation therapy.

TNF-alpha, IL-4R-alpha and IL-4 polymorphisms in mild to severe asthma from Italian Caucasians.

Asthma is a chronic airway inflammatory disease associated with airway hyperresponsiveness which affects subjects with genetic predisposition. An association has been reported between some polymorphisms in various cytokine genes and asthma. Most of them are single nucleotide polymorphisms (SNPs). These polymorphisms are detected in the protein coding sequence or in the promoter region thus influencing cytokine production. We investigated the involvement of SNP mapping in 5 cytokine genes in mild to severe asthmatics of Italian Caucasians. The frequency of alleles and genotypes, relatively to 10 allelic specificities of the cytokine genes, was defined in 57 asthmatics and in 124 control subjects by a Polymerase Chain Reaction-Sequence Specific Primer method. TNF-alpha -308A and TNF-alpha -238A allele frequencies were higher in asthmatics than in controls (p less than 0.001). Significant differences in the frequency of IL-4 -590T allele and of IL-4Ralpha +1902A allele were also detected in asthmatics in comparison with controls (pless than 0.001 and p=0.005, respectively). Similarly, IL-1alpha -889C allele was present in 84.1 percent of asthmatics and in 70.2 percent of controls (p=0.013). Furthermore, the IL-4Ralpha +1902A/A and IL-1alpha -889C/C homozygous conditions and the TNF-alpha -308G/A, TNF-alpha -238G/A, IL-4 -590T/C and IL-10 -1082G/A heterozygous conditions were significantly associated with asthma (p less than 0.05). ACA haplotype of IL-10 was observed only in asthmatic patients. This study reports, for the first time, the frequency of 10 different single nucleotide polymorphisms in 5 cytokine genes in the Italian Caucasians. Furthermore, we also indicate that in our population some single nucleotide polymorphisms are associated with mild to severe bronchial asthma.

Exhaled nitric oxide is related to bronchial eosinophilia and airway hyperresponsiveness to bradykinin in allergen-induced asthma exacerbation.

Exhaled nitric oxide (FeNO) has been associated with bronchial eosinophilia and with airway hyperresponsiveness (AHR) in mild stable asthma. We previously demonstrated in a large project that allergen exposure is able to raise FeNO and to worsen AHR to bradykinin. We postulated that allergen-induced increase in FeNO could be related to heightened mucosal eosinophils and AHR to bradykinin in atopic asthma. We performed a new immunohistochemical analysis on bronchial biopsy specimens, previously obtained from the same large project, in order to assess the number of mucosal eosinophils (EG-2+ cell) and other inflammatory cells at 48 hours after diluent and allergen exposures. Inflammatory cell counts were related to FeNO and AHR to BK (expressed as logPD20 bradykinin). In 10 atopic mild asthmatics, we found that the numbers of EG-2+ and CD4+ cells in bronchial submucosa were significantly increased after allergen compared to the respective counts after diluent (p < 0.01). EG-2+ cells in the bronchial submucosa were negatively correlated with logPD20 bradykinin only after allergen challenge (rho = -0.709, p = 0.027). We also found a positive strong correlation between EG-2+ cells and FeNO values in atopic asthmatics at 48 hours after both diluent (rho = 0.746, p = 0.017) and allergen (rho = 0.644, p = 0.049) challenge. FeNO values negatively correlated with responsiveness to bradykinin only after allergen challenge (rho = -0.675, p = 0.039). This study indicates that after allergen exposure heightened level of exhaled NO may reflect augmented airway eosinophilic inflammation and airway responsiveness to bradykinin indicating loss of asthma control.

Determinants of success.

In chronic obstructive pulmonary disease (COPD) patients, pulmonary rehabilitation is a nonpharmacological intervention aimed at improving physical exercise tolerance, dyspnoea and perceived quality of life. However, identifying predictors of clinical response and which patients achieve benefit remains a difficult question to answer with no conclusive data available. Baseline characteristics of COPD patients, such as degree of breathlessness, body weight and arterial partial pressure of oxygen, generally appear to be too direct to have a correlation with improvement of post-rehabilitation outcomes. Furthermore, some additional benefits of patients treated with rehabilitation are simply not detected by usual measures (social interaction, sleep quality and confidence). Although there are some data suggesting that some medical conditions frequently associated with COPD (osteoporosis, metabolic syndrome and heart diseases) may negatively influence rehabilitation outcomes, at present the evidence is contradictory.

Exhaled nitric oxide as a marker of lung involvement in Crohn's disease.

Crohn's disease is an inflammatory bowel disease associated with a variety of systemic manifestations, including large and small airway involvement. The latter is most often a subclinical one, and requires expensive and invasive diagnostic approaches. Nitric oxide (NO) can be detected non-invasively in the exhaled air (eNO) and be considered as a surrogate marker of airway inflammation. eNO tested at multiple expiratory flows can be used to distinguish the alveolar concentration of NO (CalvNO) from the total amount of fractional eNO (FeNO). The aim of our study is to compare FeNO and concentration of alveolar nitric oxide (CalvNO) levels and to assess their relationship with pulmonary involvement in Crohn's patients differing in clinical stage and therapeutic regimens versus a group of healthy subjects. Thirty Crohn's patients not showing clinical evidence of pulmonary diseases and 21 non-smoking, non-atopic healthy controls were enrolled. FeNO (14.9±10.2 ppb vs 10.1±6.3 ppb, p=0.049) and CalvNO (4.4±2.2 ppb vs 2.6±1.9; p=0.006) values were found to be significantly higher in Crohn's patients than in healthy controls. Both FeNO and CalvNO correlated positively with the Crohn's Disease Activity Index. In conclusion, our results for FeNO and CalvNO confirm the presence of subclinical pulmonary involvement in Crohn's disease. eNO measurement may be of clinical value in the follow-up of Crohn's patients.

Sub-clinical left ventricular diastolic dysfunction in early stage of chronic obstructive pulmonary disease.

Sub-clinical cardiac dysfunction may be significantly associated with chronic obstructive pulmonary disease (COPD) with a different degree of severity. In a cross-sectional design we aimed to evaluate the frequency of left ventricular diastolic dysfunction (LVdd) and its correlation with lung function, pulmonary arterial pressure and systemic inflammation in a selected population of COPD at an early stage of their disease. Fifty-five COPD patients with no clinical signs of cardiovascular dysfunction were recruited and compared to 40 matched healthy controls. All the subjects underwent pulmonary function testing, doppler echocardiography, and interleukin-6 blood sampling. Presence of LVdd was defined according to the significant change in both the ratio between early and late diastolic transmitral flow velocity (E/A ratio), isovolumetric relaxation time (IVRT), and deceleration time (DT). The frequency of LVdd was higher in the COPD group (70.9 percent) compared to controls (27.5 percent). In these patients decreased E/A ratio, and prolonged IVRT and DT clearly pointed to left ventricular filling impairment, a condition we found to be especially severe in those patients suffering from lung static hyperinflation as expressed by inspiratory-to-total lung capacity ratio (IC/TLC) <0.25. Circulating levels of interleukin-6 were also higher among COPD patients compared to controls. The results of the present study suggest that subclinical left ventricular filling impairment is frequently found in COPD patients at the earlier stage of the disease even in the absence of any other cardiovascular dysfunction. Doppler echocardiography may help the early identification of LVdd in COPD patients.

Single Stapler Parachute Technique (SSPT): a new procedure for large hemorroidal prolapse.

Procedure for Prolapse and Hemorrhoids (PPH or Longo procedure), a stapled circumferential anal mucosectomy, has proven to be very popular as it is considered safe and successful. However, a high haemorrhoid recurrence rate is reported, specially due to insufficient mucosal resection. The authors have come up with a technical modification to the mucoprolapsectomy, notably the Single Stapler Parachute Technique (SSPT), in order to obtain more abundant mucosal resection. In this study they will present the results obtained in 80 patients treated for muco-haemorrhoidal prolapse, 40 of whom underwent traditional PPH, while the remaining 40 patients underwent SSPT, both performed in two different specialised centres located in Rome, Italy.

Impact of exclusive e-cigarettes and heated tobacco products use on muco-ciliary clearance.

BACKGROUND: Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact on STTT of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) is not known. METHODS: We report STTT of exclusive EC and HTP users. Test results were compared with those obtained in current, former, and never smokers. RESULTS: STTT were obtained from 39 current, 40 former, 40 never smokers, and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups (p < 0.00001) with current smokers having a median [interquartile range (IQR)] STTT of 13.15 min, which was significantly longer compared with that of all other study groups. In particular, compared with former (7.26 min) and never smokers (7.24 min), exclusive EC users and exclusive HTP users had similar STTT at 7.00 and 8.00 min, respectively. CONCLUSION: Former smokers who have switched to exclusive regular use of combustion-free nicotine delivery systems (i.e., ECs and HTPs) exhibit similar saccharin transit time as never and former smokers. This suggests that combustion-free nicotine delivery technologies are unlikely to have detrimental effects on MCC function.

C-reactive protein and markers for thrombophilia in patients with chronic plaque psoriasis.

Chronic plaque psoriasis is associated to an increased risk of cardiovascular events. The aim of our study is to test patients with psoriasis for common markers of acquired and inherited thrombophilia. A cross-sectional study on 172 patients with psoriasis and 198 controls was carried out. The plasma levels of coagulation protein C, coagulation protein S, homocysteine, folic acid, C-reactive protein (CRP) and fibrinogen as well as activated protein C resistance and antithrombin III activity, were measured. CRP and homocysteine levels were higher in patients with psoriasis than in controls (5.9 ± 7.1 vs 3.1 ± 2.4 mg/L, p=0.0003 and 16.3 ± 12.8 vs 10.4 ± 4.6 umol/L, p=0.0001; mean ± SD) whereas folic acid was lower in psoriatic patients compared to controls (4.3 ± 7.2 vs 12.6 ± 7.9 p=0.006). Levels of coagulation protein C, coagulation protein S, fibrinogen as well as activated protein C resistance, antithrombin III activity were within normal ranges both in cases and controls. In a multivariate regression analysis, psoriasis severity was an independent predictor of higher CRP. In conclusion, high levels of serum CRP and homocysteine were found in patients with psoriasis, related to the severity of the disease. These data suggest that the increased risk of thrombotic cardiovascular events observed in psoriasis patients should be ascribed to an acquired rather than inherited thrombophilic status.

Exhaled nitric oxide levels in alpha-1-antitrypsin PiMZ subjects.

OBJECTIVES: Although the likelihood of intermediate alpha-1-antitrypsin deficiency (PiMZ) patients developing chronic obstructive pulmonary disease (COPD) remains uncertain, several investigators have suggested that a lack of antiprotease inhibitor activity may favour the development of airway inflammation with subsequent pulmonary tissue damage. The levels of exhaled nitric oxide (FeNO) in PiMZ subjects are unknown and polymorphisms in nitric oxide synthase have been linked to lung disease susceptibility in subjects with alpha-1-antitrypsin (AAT) deficiency. This study was aimed at assessing FeNO levels in a group of PiMZ subjects and comparing it with the concentrations found amongst groups of COPD and control patients. DESIGN: A group of 31 PiMZ subjects, 31 COPD patients and 30 controls underwent pulmonary function tests, AAT assay and phenotyping, and FeNO measurement in an ambulatory setting. RESULTS: FeNO values observed in the group of PiMZ subjects (21.6 +/- 8.9 ppb) showed a significant increase compared with COPD (14.5 +/- 8.7 ppb; P < 0.01) and the control groups (9.1 +/- 2.9 ppb; P < 0.01). Within the PiMZ population, a significant, negative correlation was observed between plasma AAT levels and FeNO readings. CONCLUSIONS: Not only did PiMZ subjects show increased FeNO levels compared with COPD patients and controls; FeNO levels proved to be related to the reduced concentration of plasma AAT. Such findings seem to suggest the importance of FeNO measurements on PiMZ subjects for monitoring a possible progression of airway inflammation to obstructive lung disease as observed in some of these patients.

Andolast acts at different cellular levels to inhibit immunoglobulin E synthesis.

The anti-asthmatic agent andolast is thought to inhibit the release of allergic mediators, but its mechanism of action is not fully understood. We investigated whether the compound inhibits immunoglobulin E (IgE) synthesis and tested the hypothesis that andolast affects immunoglobulin class switching. Interleukin (IL)-4 and the interaction of CD40 expressed on B cells with its ligand on T cells are necessary for IgE synthesis. Thus, peripheral blood mononuclear cells (PBMCs) from 40 asthmatic, 16 non-asthmatic allergic, and 9 normal donors were stimulated with IL-4 and/or anti-CD40 antibody. T cells from 9 additional allergic donors were activated with anti-CD3/CD28 antibodies to express IL-4 mRNA. After incubation in the absence or presence of test compounds, immunoglobulin concentrations were measured by enzyme immunoassay, and mRNA levels were analyzed by RT-PCR. Andolast significantly inhibited IgE synthesis by stimulated PBMCs from both asthma patients and combined allergic/normal donors. In mechanistic studies, andolast was found to act at different cellular levels. Firstly, it reduced by about 45 percent (p<0.05) the levels of IL-4 mRNA in T cells stimulated with anti-CD3/CD28. Secondly, andolast reduced by about 36 percent (p<0.05) the expression of epsilon germline transcripts in PBMCs stimulated with IL-4/anti-CD40. Thirdly, the effect of andolast on immunoglobulin synthesis was selective in that the production of IgG4 antibodies was not significantly inhibited. Our findings, while supporting the evidence that andolast is effective for the treatment of asthma, provide new insights into its mechanism of action.

Upper extremity deep vein thrombosis as an uncommon complication of pacemaker implantation: a case report.

Venous complications of pacemaker implantation rarely cause immediate clinical problems. An 89-year-old man, without thrombophilia, 4 weeks after a pacemaker implantation experienced functional impotence of the left arm that appeared warm, reddened, oedematous and painful. Color Doppler Ultrasonography revealed a thrombosis of the axillary vein extended to the proximal third of the ulnar vein. In our opinion, upper extremity deep vein thrombosis (UEDVT) represents an important complication of post-surgical pacemaker implantation that should be suspected early, even without specific symptoms and thrombophilia.