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.

Study of mitochondrial DNA alteration in the exhaled breath condensate of patients affected by obstructive lung diseases.

Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9 ± 4.9 versus 6.51 ± 0.21, p < 0.05; 7.9 ± 2.5 versus 6.51 ± 0.21, p = 0.06; 18.3 ± 3.4 versus 6.51 ± 0.21, p < 0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.

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.

THz-Frequency Modulation of the Hubbard U in an Organic Mott Insulator.

We use midinfrared pulses with stable carrier-envelope phase offset to drive molecular vibrations in the charge transfer salt ET-F_{2}TCNQ, a prototypical one-dimensional Mott insulator. We find that the Mott gap, which is probed resonantly with 10 fs laser pulses, oscillates with the pump field. This observation reveals that molecular excitations can coherently perturb the electronic on-site interactions (Hubbard U) by changing the local orbital wave function. The gap oscillates at twice the frequency of the vibrational mode, indicating that the molecular distortions couple quadratically to the local charge density.

Pressure-dependent relaxation in the photoexcited mott insulator ET-F2TCNQ: influence of hopping and correlations on quasiparticle recombination rates.

We measure the ultrafast recombination of photoexcited quasiparticles (holon-doublon pairs) in the one dimensional Mott insulator ET-F(2)TCNQ as a function of external pressure, which is used to tune the electronic structure. At each pressure value, we first fit the static optical properties and extract the electronic bandwidth t and the intersite correlation energy V. We then measure the recombination times as a function of pressure, and we correlate them with the corresponding microscopic parameters. We find that the recombination times scale differently than for metals and semiconductors. A fit to our data based on the time-dependent extended Hubbard Hamiltonian suggests that the competition between local recombination and delocalization of the Mott-Hubbard exciton dictates the efficiency of the recombination.

Impaired bone metabolism in glycogen storage disease type 1 is associated with poor metabolic control in type 1a and with granulocyte colony-stimulating factor therapy in type 1b.

BACKGROUND: Glycogen storage disease type 1 (GSD1) is a rare and genetically heterogeneous metabolic defect of gluconeogenesis due to mutations of either the G6PC gene (GSD1a) or the SLC37A4 gene (GSD1b). Osteopenia is a known complication of GSD1. OBJECTIVES: The aim of this study was to investigate the effects of poor metabolic control and/or use of GSD1-specific treatments on bone mineral density (BMD) and metabolism in GSD1 patients. METHODS: In a multicenter, cross-sectional case-control study, we studied 38 GSD1 (29 GSD1a and 9 GSD1b) patients. Clinical, biochemical and instrumental parameters indicative of bone metabolism were analyzed; BMD was evaluated by dual-emission X-ray absorptiometry and quantitative ultrasound. RESULTS: Both GSD1a and GSD1b patients showed reduced BMD compared with age-matched controls. In GSD1a patients, these abnormalities correlated with compliance to diet and biochemical indicators of metabolic control. In GSD1b patients, BMD correlated with the age at first administration and the duration of granulocyte colony-stimulating factor (G-CSF) therapy. CONCLUSIONS: Our data indicate that good metabolic control and compliance with diet are highly recommended to improve bone metabolism in GSD1a patients. GSD1b patients on G-CSF treatment should be carefully monitored for the risk of osteopenia/osteoporosis.

Optical properties of a vibrationally modulated solid state Mott insulator.

Optical pulses at THz and mid-infrared frequencies tuned to specific vibrational resonances modulate the lattice along chosen normal mode coordinates. In this way, solids can be switched between competing electronic phases and new states are created. Here, we use vibrational modulation to make electronic interactions (Hubbard-U) in Mott-insulator time dependent. Mid-infrared optical pulses excite localized molecular vibrations in ET-F2TCNQ, a prototypical one-dimensional Mott-insulator. A broadband ultrafast probe interrogates the resulting optical spectrum between THz and visible frequencies. A red-shifted charge-transfer resonance is observed, consistent with a time-averaged reduction of the electronic correlation strength U. Secondly, a sideband manifold inside of the Mott-gap appears, resulting from a periodically modulated U. The response is compared to computations based on a quantum-modulated dynamic Hubbard model. Heuristic fitting suggests asymmetric holon-doublon coupling to the molecules and that electron double-occupancies strongly squeeze the vibrational mode.

Adherence to diet and quality of life in patients with phenylketonuria.

AIM: To investigate adherence to dietary treatment and quality of life (QoL) in patients with phenylketonuria (PKU). METHODS: In the setting of a tertiary paediatric hospital, 41 early-treated patients affected by PKU aged more than 3 years old were enrolled in a cross-sectional study. Three-days dietary assessment, QoL questionnaires for patients<18 years old (Child Health Questionnaire) and Short Form for adults were completed. RESULTS: Of 41 patients, 23 (56.1%) were considered adherent to the dietary prescriptions as their phenylalanine intake was less than prescribed. Phenylalanine intake was significantly in excess of prescribed if mothers had a lower level of education. Adherence was not correlated with age. Metabolic control was obtained in 41.5-51.2% of the patients depending on the target. QoL was reduced in children and adolescents. There was no significant correlation between adherence and QoL, except for the domains of Global Health and Family Activities (ρ=0.42 and 0.46, respectively). The overall agreement between adherence and metabolic control varied according to different targets of metabolic control (51.2-65.9%). CONCLUSIONS: It is necessary to improve the adherence to diet and the QoL in children and adolescents affected by PKU.

Charmed baryonium.

We reanalyze the published data on the Y(4630)-->Lambda(c) Lambda(c) and the Y(4660)-->psi(2S)pi pi with a consistent ansatz and we find that the two observations are likely to be due to the same state Y(B), produced via initial state radiation (ISR), with M(Y(B))=4660.7+/-8.7 MeV and Gamma(Y(B))=61+/-23 MeV. Under this hypothesis and reanalyzing the e+e- -->J/psi pi pi gamma(ISR) spectrum we find B(Y(B))-->Lambda(c) Lambda(c))/B(Y(B))-->psi(2S)pi pi)=117+/-44, B(Y(B))-->J/psi pi pi)/B(Y(B))-->psi(2S)pi pi)<0.46@90% C.L., B(Y(4350)-->J/psi pi pi)/B(Y(4350)-->psi(2S)pi pi)<3.4x10(-3)@90% C.L., and B(Y(B))-->psi(2S)sigma)/B(Y(B))-->psi(2S)f0)=2.0+/-0.3. These conclusions strongly support the hypothesis of Y(B) being the first observation of a charmed baryonium constituted by four quarks. Analyzing the mass spectrum we show that Y(4350) and Y(B) are, respectively, consistent with the ground state and first radial excitation of the l=1 state.

Cerebro-reno-digital (Meckel-like) syndrome with Dandy-Walker malformation, cystic kidneys, hepatic fibrosis, and polydactyly.

We report on a boy with several findings of the Meckel syndrome, such as hepatic fibrosis, polycystic kidneys, post-axial hexadactyly, and genital abnormalities, but a Dandy-Walker malformation rather an occipital meningocele. Progressive deterioration of renal function beginning at 37 months led to death at 43 months. Both Dandy-Walker malformation and survival to the fourth year are unusual findings in Meckel syndrome. This uncommon combination represents a further demonstration of the pleiotropy/heterogeneity of the cerebro-reno-digital syndromes.