Co-circulation of classic and novel astrovirus strains in patients with acute gastroenteritis in Germany

Objectives

In order to analyze the molecular epidemiology of human astroviruses (HAstV) in Germany, a retrospective long-term study was performed to characterize circulating human astrovirus in patients with acute gastroenteritis in Germany.

Secretory products from human adipocytes impair endothelial function via nuclear factor kappaB

Hyperplasia and hypertrophy of fat cells can be found in obesity, and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial function. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs), and human coronary artery endothelial cells (HCAECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, incubation of HUVECs and HCAECs with Adipo significantly increased monocyte adhesion 7.3 and 2.2-fold, respectively. VCAM-1, ICAM-1, and E-selectin in HUVECs were upregulated 3.9, 3.0, and 9.5-fold, respectively, under these conditions. Furthermore, Adipo significantly stimulated NFkappaB activity 1.9-fold. The NFkappaB inhibitor MG-132 and heat inactivation significantly reversed Adipo-stimulated monocyte adhesion. TNFalpha-neutralizing antibodies partly reversed Adipo-induced monocyte adhesion. In contrast, thiazolidinedione-pretreatment of human adipocytes did not alter the effects of Adipo. Adipo did not show cytotoxic effects. Taken together, we demonstrate that endothelial dysfunction is induced by adipocyte-secreted factors via NFkappaB partly dependent on TNFalpha.     

Rules of formation of H–C–N–O compounds at high pressure and the fates of planetary ices

The solar system’s outer planets, and many of their moons, are dominated by matter from the H–C–N–O chemical space, based on solar system abundances of hydrogen and the planetary ices H2O, CH4, and NH3. In the planetary interiors, these ices will experience extreme pressure conditions, around 5 Mbar at the Neptune mantle–core boundary, and it is expected that they undergo phase transitions, decompose, and form entirely new compounds. While temperature will dictate the formation of compounds, ground-state density functional theory allows us to probe the chemical effects resulting from pressure alone. These structural developments in turn determine the planets’ interior structures, thermal evolution, and magnetic field generation, among others. Despite its importance, the H–C–N–O system has not been surveyed systematically to explore which compounds emerge at high-pressure conditions, and what governs their stability. Here, we report on and analyze an unbiased crystal structure search among H–C–N–O compounds between 1 and 5 Mbar. We demonstrate that simple chemical rules drive stability in this composition space, which explains why the simplest possible quaternary mixture HCNO—isoelectronic to diamond—emerges as a stable compound and discuss dominant decomposition products of planetary ice mixtures.

Crystal structure prediction coupled to electronic structure calculations has emerged as a powerful tool in computational materials science, in particular in the area of high-pressure science, where it can overcome the chemical imagination attuned to ambient conditions: The predictions—and subsequent experimental confirmations—of unusual compounds such as Na2He, H3S, or LaH10 attest to the predictive power of these approaches (1–6). The planetary ices H2O, CH4, and NH3 may dominate the interiors of icy planets, but under extreme conditions (7–10). High-pressure phases of these ices have been explored computationally, and some predictions of exotic phases of individual ices have also been confirmed by experiments (11–15). Arguably, computational predictions in this field are of crucial importance because of the challenges for laboratory experiments and the indirect nature of astronomical observations. However, with increasing number of constituents the structure searches become computationally much more demanding. Hence, while structure predictions for elemental and binary systems are routine there are far fewer extensive searches of ternary systems, and none for quaternary systems.The situation in the H–C–N–O quaternary system reflects this. A vast number of publications exist on the high-pressure evolution of the individual constituents H, C, N, and O (16–19). Binary systems have also been looked at in great detail (20–24). The ternary systems are much less investigated: While H–C–O, H–N–O, and C–N–O phase diagrams have been reported (25–27), the H–C–N ternary has not, for example. The PubChem database (28) lists just under 4.8 million molecular H–C–N compounds. Overall, it contains 44.6 million H–C–N–O compounds at ambient pressure, 78% of which are of true quaternary composition—this highlights both the complexity and the relevance of this quaternary system for organic chemistry. Back in the high-pressure area, some binary mixtures of planetary ices, for instance H2O–NH3 or N2–CH4 mixtures, which form a subset of the H–N–O and H–C–N ternaries, have been studied in simulations into the megabar pressure range (29–32). However, despite the overall importance of H–C–N–O both to planetary science and Earth-bound chemical and life sciences, to our knowledge there are no computational high-pressure studies of this system, or even subsets that include all four elements, for example binary or ternary molecular mixtures such as CO2–NH3 or NH3–H2O–CH4. Here, we explore the full H–C–N–O chemical space via crystal structure searches performed at 500 GPa. This resembles the pressure—if not the temperature—at Neptune’s core–mantle boundary and therefore helps illuminate potential pressure-induced chemical reactions in the deep interiors of the outer planets and giant icy exoplanets. It also helps us understand more generally what rules govern a familiar composition space at highly unfamiliar external conditions.     

Serodiagnosis of Schistosoma mansoni infections in an endemic area of Burkina Faso: performance of several immunological tests with different parasite antigens

The performance of indirect haemagglutination assays (IHA), enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescent antibody tests (IFAT) were compared with 450 sera from a Schistosoma mansoni-endemic area in Burkina Faso. All participants in this survey provided at least one sample each of stool, urine and serum. From those with an egg-negative Kato-Katz thick smear, a second stool sample was examined. IHA was based on either extracts of adult S. mansoni worms (SmIHA) or S. japonicum egg antigen (SjIHA). For ELISA, three antigen preparations were used, namely: (i) soluble S. mansoni adult worm antigens (SWAP); (ii) soluble S. mansoni egg antigens (SEA); and (iii) a cationic exchange fraction of S. mansoni eggs (CEF6). IFAT was performed with S. mansoni male worm sections. Among the egg-excretors, the sensitivity of ELISA was high and egg antigens performed slightly better (SEA, 96%; CEF6, 97%) than worm antigen (94%). Sensitivity of IHA was satisfactory with homologous (Sm, >85%), but not heterologous (Sj, 56%) parasite antigen. In IFAT, the parenchyma-associated fluorescence showed high sensitivity (95%), but gut-associated fluorescence, which is known to be a sensitive diagnostic marker for schistosome-infected European travelers, was observed only in 76% of a sub-sample of 100 of the endemic sera. Among sera from egg-negative individuals, many gave positive reactions in several or all of the tests employed. These reactions (formally "false positive") are considered to represent true infections, since chemotherapy had not yet been delivered to this population. For the purpose of further surveys in Burkina Faso or other resource-poor settings, we suggest IHA as an accurate diagnostic test and propose to further improve its performance by including egg rather than worm antigens.     

Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2

OBJECTIVE: The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2. METHODS: A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months. RESULTS: HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p < .0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p < .0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p < .0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p < .0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p < .0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group. CONCLUSIONS: Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.     

Prospective pilot evaluation of a new needle prototype for endoscopic ultrasonography-guided fine-needle aspiration: comparison of cytology and histology yield

OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine needle aspiration has become an important diagnostic modality in gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on cytology; data are scarce that compare cytology and histology. While testing a 22-gauge prototype needle, we prospectively compared the yield for both. METHODS: Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range: 17-90 years) were included. In each patient we aimed to make two needle passes, and if the material acquired appeared insufficient macroscopically (no in-room cytopathology was available), further passes were done. The material was sent for cytological and histological assessment. RESULTS: A median number of two passes (range: 2-3) were uneventfully performed for pancreatic lesions (n=30), mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4) and yielded adequate material for cytology, histology or at least one of the two investigations in 62, 67 and 74% of patients, respectively. No false positive results were found (specificity 100%). Sensitivities were 58.6 and 65.5%, respectively, for cytology and histology alone; combined assessment increased sensitivity to 79.3%. When adjusted values were calculated, based only on those cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for histology, and increased to 100% with combined assessment. CONCLUSION: The new needle achieves sensitivities similar to those previously reported with no significant differences in sensitivity between cytology and histology. More effective tissue acquisition methods must be sought to improve overall results.     

Color Doppler ultrasonography of hand and finger arteries to differentiate primary from secondary forms of Raynaud's phenomenon

OBJECTIVE: Modern ultrasound (US) equipment allows rheumatologists to directly visualize hand and finger arteries. How does US aid in diagnosis of Raynaud's phenomenon (RP)? METHODS: Color Doppler US of the proper and common palmar digital, radial, and ulnar arteries and the superficial palmar arch of both hands was performed in 135 consecutive patients who presented with suspected RP. RESULTS: US was pathologic in 63% of patients with secondary RP, in 6% with primary RP, and in none with pseudo-RP (p < 0.0001). We found 3 types of vascular pathology: Type 1 showed narrowing or chronic occlusion of some proper digital arteries; Type 2 was characterized by the same finding in all proper digital arteries; and Type 3 involved acute occlusions. Type 1 was found in 3 of 53 patients with primary RP and in 19 patients with secondary RP including 5 of 9 patients with anti-centromere positive systemic sclerosis (SSc); Type 2 occurred in 16 patients with SSc, MCTD, and dermatomyositis; and Type 3 was found in 8 patients with antiphospholipid antibody syndrome, thromboangiitis obliterans, vibration trauma, or vasculitis. The ulnar arteries were more commonly affected than the radial arteries. The 2nd radial, 3rd radial, 4th ulnar, and 5th ulnar proper palmar digital arteries were most commonly involved. CONCLUSION: Aiding in differentiating primary versus secondary RP, severe versus less severe disease, and acute versus chronic vascular occlusion, digital artery US depicts the same anatomical structures as angiography, but it is cheaper, faster, and noninvasive.     

Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats

Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatment in vivo induces alpha(1b)-adrenoreceptor mRNA and increases the density of alpha(1B)-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic alpha(1)-adrenoceptors also facilitates estrogen-dependent lordosis. To investigate the cellular mechanisms of adrenergic effects on VMN neurons, whole-cell patch-clamp recordings were carried out on hypothalamic slices from control and estradiol-treated female rats. In control slices, bath application of the alpha(1)-agonist phenylephrine (PHE; 10 microM) depolarized 10 of 25 neurons (40%), hyperpolarized three neurons (12%), and had no effect on 12 neurons (48%). The depolarization was associated with decreased membrane conductance, and this current had a reversal potential close to the K(+) equilibrium potential. The alpha(1b)-receptor antagonist chloroethylclonidine (10 microM) blocked the depolarization produced by PHE in all cells. From estradiol-treated rats, significantly more neurons in slices depolarized (71%) and fewer neurons showed no response (17%) to PHE. PHE-induced depolarizations were significantly attenuated with 4-aminopyridine (5 mM) but unaffected by tetraethylammonium chloride (20 mM) or blockers of Na(+) and Ca(2+) channels. These data indicate that alpha(1)-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K(+). Estradiol amplifies alpha(1b)-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of alpha(1b)-adrenergic receptors, which is expected in turn to promote lordosis.