Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease.

INTRODUCTION: Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. METHODS: Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. RESULTS: 48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. CONCLUSION: Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.

Sleep-Disordered Breathing Is Associated with Metabolic Syndrome in Outpatients with Diabetes Mellitus Type 2.

BACKGROUND: Metabolic syndrome (MS) and sleep-disordered breathing (SDB) are highly prevalent in patients with diabetes mellitus type 2 (DM2). The present study examined whether there is an independent association between SDB and MS in a sample of outpatients with DM2. METHODS: MS was determined in 679 patients of the DIACORE-SDB substudy, a study of outpatients with DM2. According to the National Cholesterol Education Program (NCEP) criteria, MS is defined by at least three of the following five criteria: waist circumference of >102 cm (men)/>88 cm (women), blood pressure of ≥130/85 mmHg, a fasting triglyceride level of >150 mg/dl, high-density lipoprotein (HDL) of <40 mg/dl (men)/<50 mg/dl (women), and a fasting glucose level of ≥110 mg/dl. The apnea-hypopnea index (AHI) was assessed with a 2-channel ambulatory monitoring device and used to define the severity of SDB (AHI < 15.0: no/mild SDB; AHI 15.0-29.9: moderate SDB; AHI ≥ 30.0: severe SDB). RESULTS: 228 (34%) of the 679 participants (mean age 66 years, mean body mass index (BMI) 31.2 kg/m2, and mean AHI 14/hour) had SDB. MS was significantly more frequent in patients with more severe SDB (no/mild SDB vs. moderate SDB vs. severe SDB: 72% vs. 79% vs. 85%, respectively, p = 0.038). Logistic regression analysis adjusted for sex, age, obesity (BMI ≥ 30 kg/m2), and the HOMA index showed a significant association between the AHI and the presence of MS (OR (95%CI) = 1.039 (1.011; 1.068); p = 0.007). Further, male sex, obesity, and the HOMA index were significantly associated with MS. CONCLUSION: SDB is significantly and independently associated with MS in outpatients with DM2.

Sex Differences in the Prevalence and Modulators of Sleep-Disordered Breathing in Outpatients with Type 2 Diabetes.

In patients with type 2 diabetes, sleep-disordered breathing is a widespread cause of deteriorated quality of life. However, robust prevalence estimates for sleep-disordered breathing in patients with type 2 diabetes are limited due to scarce data. We investigated sex differences in sleep-disordered breathing prevalence and its modulators in the DIACORE SDB substudy, a sample of outpatient type 2 diabetes. 721 participants were tested for sleep-disordered breathing using a two-channel sleep apnoea monitoring device. Patients were stratified according to the severity of sleep-disordered breathing, defined as an apnoea-hypopnoea index < 15, ≥15 to 29, and ≥30 events per hour as no/mild, moderate, and severe sleep-disordered breathing, respectively. In the 679 analysed patients (39% women, age 66 ± 9 years, body mass index 31.0 ± 5.4 kg/m2), the prevalence of sleep-disordered breathing was 34%. The prevalence of sleep-disordered breathing was higher in men than in women (41% versus 22%, p < 0.001) and increased with age (15%, 21%, and 30% in women and 35%, 40%, and 47% in men in those aged 18-59, 60-69, or ≥70, respectively; age trend p = 0.064 in women and p = 0.15 in men). In linear regression analysis, age, BMI, and waist-hip ratio were associated with apnoea-hypopnoea index. Modulators for higher apnoea-hypopnoea index seem to be similar in men and women.

[Comorbidities of heart failure: sleep apnea]. / Schlafapnoe als Komorbidität bei Herzinsuffizienz.

BACKGROUND: Since sleep apnea often occurs in heart failure, physicians regularly need to decide whether further diagnostic procedures and/or treatment are required. OBJECTIVES: Which types of sleep apnea occur in heart failure patients? When is treatment needed? Which treatments and treatment goals are appropriate? MATERIALS AND METHODS: Clinical trials and guidelines as well as their implementation in clinical practice are discussed. RESULTS: At least 40% of patients with heart failure, both with reduced and preserved left ventricular ejection fraction (HFrEF and HFpEF, respectively), suffer from relevant sleep apnea. In heart failure patients both obstructive and central sleep apnea are associated with increased mortality. In HFrEF as well as in HFpEF patients with obstructive sleep apnea, treatment with continuous positive airway pressure (CPAP) achieves symptomatic and functional improvements. In patients with HFpEF, positive airway pressure treatment of central sleep apnea may be beneficial. In patients with HFrEF and left ventricular ejection fraction ≤45%, adaptive servoventilation is contraindicated. CONCLUSIONS: Sleep apnea is highly prevalent in heart failure patients and its treatment in specific patient groups can improve symptoms and functional outcomes. Thus, testing for sleep apnea is recommended.

Men with unilateral Achilles tendinopathy have impaired balance on the symptomatic side.

OBJECTIVES: To investigate single leg standing balance in males with mid-portion Achilles tendinopathy (AT). DESIGN: Cross sectional case study. METHODS: Centre of pressure (COP) path length was measured using a Wii Balance Board (WBB) in 21 male participants (20-60 years) with unilateral mid-portion AT during single-limb standing on each limb with eyes open and closed. Ultrasound imaging of both Achilles tendons was also performed by one blinded assessor, and the anteroposterior (AP) thickness and presence of pathology was determined. Comparisons were made between symptomatic and asymptomatic sides for key outcomes, and correlation between COP path length and variables of interest were investigated. RESULTS: Symptomatic Achilles tendons demonstrated significantly increased AP tendon thickness (p<0.001). Participants with AT demonstrated increased COP path length (sway amplitude) on their affected side during the eyes closed task (p=0.001). Increased tendon thickness was associated with increased sway amplitude during the eyes open task on both the affected (rho=0.44, p=0.045) and unaffected sides (rho=0.62, p=0.003). CONCLUSIONS: In males with AT, single-leg standing balance with eyes closed is impaired on the symptomatic side. This indicates that neuromuscular deficits affecting functional ability may be present in people with AT during more challenging balance activities. It is unclear if this deficit precedes the onset of symptoms, or is a consequence of tendon pain. Work is now needed to understand the mechanisms that may explain standing balance deficits among people with AT.

Polyaspartic acid facilitates oxolation within iron(iii) oxide pre-nucleation clusters and drives the formation of organic-inorganic composites.

The interplay between polymers and inorganic minerals during the formation of solids is crucial for biomineralization and bio-inspired materials, and advanced material properties can be achieved with organic-inorganic composites. By studying the reaction mechanisms, basic questions on organic-inorganic interactions and their role during material formation can be answered, enabling more target-oriented strategies in future synthetic approaches. Here, we present a comprehensive study on the hydrolysis of iron(iii) in the presence of polyaspartic acid. For the basic investigation of the formation mechanism, a titration assay was used, complemented by microscopic techniques. The polymer is shown to promote precipitation in partly hydrolyzed reaction solutions at the very early stages of the reaction by facilitating iron(iii) hydrolysis. In unhydrolyzed solutions, no significant interactions between the polymer and the inorganic solutes can be observed. We demonstrate that the hydrolysis promotion by the polymer can be understood by facilitating oxolation in olation iron(iii) pre-nucleation clusters. We propose that the adsorption of olation pre-nucleation clusters on the polymer chains and the resulting loss in dynamics and increased proximity of the reactants is the key to this effect. The resulting composite material obtained from the hydrolysis in the presence of the polymer was investigated with additional analytical techniques, namely, scanning and transmission electron microscopies, light microscopy, atomic force microscopy, zeta potential measurements, dynamic light scattering, and thermogravimetric analyses. It consists of elastic, polydisperse nanospheres, ca. 50-200 nm in diameter, and aggregates thereof, exhibiting a high polymer and water content.

PdTe: a strongly coupled superconductor.

We report the electrical transport, magnetic, and thermodynamic properties of polycrystalline PdTe which exhibits superconductivity below 4.5 K. Using the measured values for the lower (H(c1)) and upper (H(c2)) critical fields, and the specific heat C(p), we estimate the thermodynamic critical field H(c)(0), coherence length ξ(0), penetration depth λ(0), and the Ginzburg-Landau parameter κ. Compared with band structure calculations, the density of states at the Fermi level is enhanced due to electron-phonon coupling with λ(ep) = 1.4. Furthermore, the large values of ΔC(p)/γ(n)T(c) and 2Δ(0)/k(B)T(c) suggest that PdTe is a strongly coupled superconductor.

Distinct eosinophil cytokine expression patterns in skin diseases - the possible existence of functionally different eosinophil subpopulations.

BACKGROUND: The function of eosinophils has been attributed to host defense, immunomodulation, and fibrosis. Although eosinophils are found among infiltrating cells in a broad spectrum of skin diseases, their pathogenic role remains uncertain. This study aimed to analyze the cytokine expression by eosinophils in different skin diseases. METHODS: Skin specimens from different skin diseases [allergic/reactive, infectious, autoimmune, and tumors/lymphomas (LY)] were stained by antibodies directed to eosinophil cationic protein, cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10, IL-11, IL-13, IL-17, IL-25, IL-33, interferon-γ, transforming growth factor (TGF)-ß, and thymic stromal lymphopoietin], eotaxins (CCL11, CCL24, and CCL26), metalloproteinase (MMP)-9 as well as extracellular matrix proteins (tenascin-C and procollagen-3) and then analyzed by laser scanning microscopy. RESULTS: The number of eosinophils varied considerably in and between disease groups and did not correlate with the numbers of accompanying inflammatory cells. The expression of IL-5, IL-6, IL-11, TGF-ß, CCL24, and MMP-9 by eosinophils significantly differed between disease groups. Eosinophils in tumors/LY predominantly expressed IL-6, TGF-ß, and CCL24, but not IL-11. On the other hand, in autoimmune diseases, eosinophils largely contributed to MMP-9 production. IL-5-generating eosinophils were particularly obvious in allergic and infectious diseases. CONCLUSION: In skin diseases, eosinophil expresses a broad spectrum of cytokines. The different cytokine expression patterns suggest distinct functional roles of eosinophils in these diseases that might be related to host defense, immunomodulation, fibrosis, and/or tumor development.

Spin-resolved tunneling studies of the exchange field in EuS/Al bilayers.

We use spin-resolved electron tunneling to study the exchange field in the Al component of EuS/Al bilayers, in both the superconducting and normal-state phases of the Al. Contrary to expectation, we show that the exchange field H(ex) is a nonlinear function of applied field, even in applied fields that are well beyond the EuS coercive field. Furthermore, the magnitude H(ex) is unaffected by the superconducting phase. In addition, H(ex) decreases significantly with increasing temperature in the temperature range of 0.1-1 K. We discuss these results in the context of recent theories of generalized spin-dependent boundary conditions at a superconductor-ferromagnet interface.

Successful treatment of equine sarcoids by topical aciclovir application.

Based on the anecdotally reported eradication of a sarcoid using aciclovir cream, the curative potential of this ointment was investigated in 22 sarcoid-affected horses referred to the Equine Clinic Tillysburg, Austria, between 2006 and 2009. Sarcoid disease was diagnosed by clinical examination and bovine papillomavirus types 1 and 2 from intact skin and tumour tissue. As nine horses had more than one lesion, a total of 47 sarcoids were treated by daily topical application of aciclovir 5 per cent cream for a period of two to six months; in four horses, surgical tumour ablation was performed before treatment. Disease parameters, including the tumour type, number, location and size, were recorded before and after aciclovir therapy. All 47 (100 per cent) of the sarcoids responded to treatment, with complete tumour regression observed for 32 (68 per cent) lesions and no recurrences reported thus far. Incomplete resolution was observed for 15 (32 per cent) lesions, probably due to their thickness. Aciclovir is proposed to be routinely used for the treatment of mild-type sarcoids and as an adjuvant therapeutic agent in combination with surgery.

Tracer test with As(V) under variable redox conditions controlling arsenic transport in the presence of elevated ferrous iron concentrations.

To study transport and reactions of arsenic under field conditions, a small-scale tracer test was performed in an anoxic, iron-reducing zone of a sandy aquifer at the USGS research site on Cape Cod, Massachusetts, USA. For four weeks, a stream of groundwater with added As(V) (6.7 muM) and bromide (1.6 mM), was injected in order to observe the reduction of As(V) to As(III). Breakthrough of bromide (Br(-)), As(V), and As(III) as well as additional parameters characterizing the geochemical conditions was observed at various locations downstream of the injection well over a period of 104 days. After a short lag period, nitrate and dissolved oxygen from the injectate oxidized ferrous iron and As(V) became bound to the freshly formed hydrous iron oxides. Approximately one week after terminating the injection, anoxic conditions had been reestablished and increases in As(III) concentrations were observed within 1 m of the injection. During the observation period, As(III) and As(V) were transported to a distance of 4.5 m downgradient indicating significant retardation by sorption processes for both species. Sediment assays as well as elevated concentrations of hydrogen reflected the presence of As(V) reducing microorganisms. Thus, microbial As(V) reduction was thought to be one major process driving the release of As(III) during the tracer test in the Cape Cod aquifer.

Physical and chemical properties of sputter-deposited TaC(x)N(y) films.

The structural, electronic, optical, and mechanical properties of stoichiometric TaC(x)N(y = 1-x) were simulated using an ab initio calculation based on density functional theory (DFT) within the generalized gradient approximation. The calculations revealed the theoretical lattice parameter, density of states, refractive index, and elastic constants as a function of carbon and nitrogen content. TaC(x)N(y) films were subsequently produced on Si wafers using unbalanced magnetron sputtering. The structural, optical, and mechanical properties were measured using x-ray diffraction/transmission electron microscopy, vacuum ultraviolet spectroscopic ellipsometry, and nanoindentation, respectively. The computational and experimental properties were compared. The lattice parameter, the energy of the 2p bands in the density of states, and the energy of the interband transitions were found to decrease with increasing C content. No significant changes in the elastic constants were observed as a result of substituting N atoms with C atoms. The hardness and the elastic modulus were in the 40 and 380 GPa range, respectively. The experimental Young's modulus was much smaller than the computational one and this discrepancy was attributed to the nanocrystalline nature of the films. Also, the elastic constants were found to decrease dramatically for over-stoichiometric films.

Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry.

Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is an inborn error of the urea cycle. The leading symptom is progressive hyperammonaemia, which is a life-threatening condition, particularly in patients with a neonatal onset. Early diagnosis and treatment of the hyperammonaemia are necessary to improve survival and the long-term outcome of ASL-deficient patients. Currently, the diagnosis of ASL deficiency is based on the measurement of urea cycle intermediates and amino acids by automated quantitative ion exchange chromatography in plasma and urine. Here, we report a newborn presenting with coma and severe hyperammonaemia. ASL deficiency was suspected on the basis of an adapted tandem mass spectrometric (MS-MS) procedure which allows determination of argininosuccinate in addition to the amino acids in serum samples. MS-MS measurements revealed a characteristic increase of argininosuccinate, a moderate increase of citrulline, and lowered levels of arginine and ornithine in the serum of the patient. The diagnosis was confirmed by the detection of a novel homozygous frameshift mutation in exon 14 of the argininosuccinate lyase gene. We propose MS-MS as a diagnostic tool suitable for the rapid detection of specific alterations in the amino acid spectra caused by ASL deficiency.

Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans.

Quantification of the acid-labile subunit (ALS) has to date been restricted to immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule. For mAb selection, a special screening method was developed. Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition of ALS were investigated after acidification for protein unfolding in different pH ranges and in a time-dependent manner. It was determined that acidification of the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution to 1:100 was the optimal acid-neutralization method. For standardization purposes, a serum pool derived from healthy volunteers was assigned the value 1 U/ml ALS. The sandwich assay has a working range with a linear dose-response curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12 months of growth hormone therapy, ALS levels increased significantly to 1.18+/-0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The change in ALS with growth hormone (GH) therapy correlated closer with the change in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This specific sandwich assay for the measurement of ALS provides a potentially valuable indicator of growth hormone secretory status. With this mAb-based immunofluorometric assay, the nonspecific detection of other proteins containing leucine-rich repeat sequences can be excluded.

Effect of meconium on the hemoglobin-oxygen association curve.

OBJECTIVE: Our purpose was to determine the effect of meconium-stained amniotic fluid on the hemoglobin-oxygen association curve of maternal whole blood. METHODS: Whole blood was obtained from term gravidas in active labor. Hemoglobin-oxygen association curves were generated for blood incubated with meconium vs. controls. Oxygen association curves were determined at pH 7.4 and 37 degrees C utilizing an automated device consisting of a spectrophotometer cuvette fitted with a magnetic stirrer, gas exchange line, and a Clark oxygen electrode. The samples were deoxygenated with nitrogen and association curves recorded while reoxygenating. Data was analyzed with Sigma Plot and Sigma Stat software. Analysis included log transformation, linear regression, and paired t-test. RESULTS: Twenty-eight hemoglobin oxygen association curves were generated. In all 14 pairs, meconium shifted the hemoglobin-oxygen association curve to the right. Partial pressures of oxygen required for various degrees of hemoglobin saturation were higher in meconium-exposed samples; P50 (30.1+/-0.6 vs. 27.8+/-0.4 mmHg, P < 0.01); P75 (46.9+/-0.6 vs. 43.1+/-0.5 mmHg, P < .001); P90 (69.2+/-1 vs. 63.3+/-1 mmHg, P < 0.01). CONCLUSIONS: Meconium-stained amniotic fluid causes a statistically significant, but clinically small, right shift in the hemoglobin-oxygen association curve.

Long-wavelength first hyperpolarizability measurements by hyper-Rayleigh scattering.

A hyper-Rayleigh scattering (HRS) system based on an optical parametric power oscillator is described. The first hyperpolarizability, beta, of Crystal Violet dye was measured at 1450 and 1500 nm. The resonance-free beta value, beta(0), for this octupole was found to be comparable with that of the dipolar dye Disperse Red 1 but with the nonlinearity-transparency trade-off worse for the octupole. The discrepancy in beta(0) with that reported previously is explained in terms of resonance and the adequacy of the octupolar three-state model. The possibility of dye aggregation by solvent-dependent HRS is investigated.