Hybrid-integrated diode laser in the visible spectral range.

Generating visible light with wide tunability and high coherence based on photonic integrated circuits is of high interest for applications in biophotonics, precision metrology, and quantum technology. Here we present, to our knowledge, the first demonstration of a hybrid-integrated diode laser in the visible spectral range. Using an AlGaInP optical amplifier coupled to a low-loss Si3N4 feedback circuit based on microring resonators, we obtain a spectral coverage of 10.8 nm around 684.4 nm wavelength with up to 4.8 mW output power. The measured intrinsic linewidth is 2.3±0.2kHz.

In vitro effects of particulate bone substitute materials on the resorption activity of human osteoclasts.

Much research has been done on bone cells, but only a few studies deal with biomaterial-induced effects on human osteoclasts, which may take on an important role in the successful regeneration of bone. In order to highlight such effects, human peripheral blood mononuclear cells (PBMCs) were extracted from venous blood, differentiated to osteoclasts and then cultured in, the presence of five particulate hydroxyapatite (HA)/ß-tricalcium phosphate (TCP) biomaterials, on bovine bone slices and glass cover slips. The biomaterials, AlgOSS 50/50 (50 % HA/50 % TCP), AlgOSS 20/80 (20 % HA/80 % TCP), Algipore (98 % HA), Cerasorb (100 % TCP) and Bio-Oss (100 % HA) were chosen to assess their influence on cell morphology and numbers. Light microscopic evaluation was performed during ongoing cell culture. After 21 d of cultivation, the biomaterial-induced effects on osteoclastic resorption of the bone slices were evaluated by scanning electron microscopy (SEM). Osteoclast-like cells were identified by TRAP staining. All five biomaterials showed larger area fractions of resorbed bone than the control (5.6 ± 6.8 %), as measured on SEM images. The purely hydroxyapatite-based Algipore (9.8 ± 9.7 %) and Bio-Oss (7.9 ± 8.8 %) showed significantly elevated area fraction rates (p ≤ 0.05) of bone resorption. Light microscope evaluation revealed a significant, but inhibiting effect of Cerasorb (p = 0.05). These data indicated that introducing of small biomaterial hydroxyapatite particles may have improved the performance of bone substitute materials.

Sodium caprate transiently opens claudin-5-containing barriers at tight junctions of epithelial and endothelial cells.

Claudin-5 is a tight junction (TJ) protein which limits the diffusion of small hydrophilic molecules. Thus, it represents a potential pharmacological target to improve drug delivery to the tissues protected by claudin-5-dependent barriers. Sodium caprate is known as an absorption enhancer which opens the paracellular space acting on TJ proteins and actin cytoskeleton. Its action on claudin-5 is not understood so far. Epithelial and endothelial systems were used to evaluate the effect of caprate on claudin-5 in TJ-free cells and on claudin-5 fully integrated in TJ. To this aim, confocal microscopy on live and fixed cells and isolated mouse brain capillaries, Western blotting and permeability assays were employed. Caprate reversibly reduced claudin-5 trans-interactions in TJ-free human embryonic kidney-293 cells expressing claudin-5-YFP. It decreased the membranous claudin-5 and the F-actin content in Madin-Darby canine kidney-II cells expressing Flag-claudin-5, thereby increasing the permeability to the small molecule lucifer yellow. Interestingly, zonula occludens protein 1 (ZO-1), which links transmembranous TJ proteins to the actin cytoskeleton, was not affected by caprate treatment. Similarly, endogenous claudin-5 in the membrane of brain endothelia was displaced together with F-actin, whereas ZO-1 remained unaffected. Caprate transiently opens the paracellular space, reducing the intercellular claudin-5/claudin-5 interactions and the polymerized actin at the perijunctional region of endothelial and epithelial cells. In conclusion, the study further elucidates the cellular effects of caprate at the tight junctions.

Accuracy of diagnostic tests in multiple sclerosis--a systematic review.

New diagnostic criteria for multiple sclerosis (MS) have been recently proposed and further updates are upcoming. This systematic literature review summarizes diagnostic studies in suspected MS to clarify the value of diagnostic tests. We included studies of at least 40 patients followed up for 2 years. All studies are limited by the fact that no gold standard to validate diagnostic tests is available. A second relapse is used as a surrogate in relapsing-remitting MS, but long follow-up of at least 5 years is necessary to detect all cases. Many studies showed selection bias, partly because of the vague definition of a clinically isolated syndrome. Based on these limitations, sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%. Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%. Combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%). Studies on evoked potentials did not justify conclusions about their value. A combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis. However, the value of a very early diagnosis stays questionable as patients' benefit of new diagnostic criteria has never been addressed.

Five years' experience in endovenous laser therapy of lower extremity varicose veins.

The authors performed a total of 237 endolaser treatments for insufficiency of great and small saphenous veins and assessed 5-year results. It was found that this method, especially if performed with a 1470-nm-wavelength laser combined with instrumental removal of some lateral veins, was very effective. It was delicate for patients, and it significantly shortened the length of their work incapacity. The benefits of removal of insufficient veins in a whole leg during a single session with the patient under total anesthesia are stressed.

[Partial mastectomy vs. breast ablation in treatment of invasive lobulary carcinoma]. / Parciální mastektomie nebo ablace prsu v terapii invazivního lobulárního karcinomu?

The aim of this paper is presentation a new knowledge about surgical therapy of the invasive lobular breast cancers. Invasive lobular carcinoma (ILC) accounts for 5% to 10% of all invasive breast cancers. Although breast conservation therapy using local excision and postoperative irradiation is a standard therapy for early invasive ductal breast cancer, the result of this strategy in ILC is not well documented. Overall survival and local recurrance (ILC) is not affected by the type of surgical treatment- breast conservation surgery or total mastectomy.

Discounts on fruit and vegetables combined with a space management intervention increased sales in supermarkets.

BACKGROUND/OBJECTIVES: To examine the effects of two interventions on consumer purchases of fruits and vegetables (F&V) on the Danish island of Bornholm: a 20% discount on F&V combined with improved shelf-space allocation, and improved shelf-space allocation alone. SUBJECTS/METHODS: A space management intervention to promote F&V sales was performed in two large discount supermarkets on Bornholm in Denmark for 3 months (September-November 2012). In addition, a 20% discount on F&V was introduced for 3 months in one of the supermarkets ('space + price'). The effect was evaluated using sales data from the two intervention supermarkets and three control supermarkets from the same supermarket chain but in Odsherred, Denmark (control area). Both the effect on sales of fresh F&V and potential unhealthy substitution effects were evaluated using multi-level regression analyses. RESULTS: During the price intervention period, the index number for sales of fresh vegetables increased by 22.2% (P=0.001) in the 'space + price' intervention supermarket compared with the control supermarkets. Furthermore, the index number for the sale of organic fresh fruit and vegetables increased by 12.1% (P=0.04) and the sale of the total amount of fruit and vegetables (fresh, frozen, dried and canned) increased by 15.3% (P=0.01) compared with the control supermarkets. In the 'space only' intervention supermarket no significant increase in the sale of fruit and vegetables was found. No unhealthy substitution effects were found. CONCLUSIONS: In conclusion, a 20% price reduction on F&V significantly increased sales of F&V. The effect was most pronounced on vegetables and no negative/unhealthy substitution effects were found.

Neural correlates of naturalistic social cognition: brain-behavior relationships in healthy adults.

Being able to infer the thoughts, feelings and intentions of those around us is indispensable in order to function in a social world. Despite growing interest in social cognition and its neural underpinnings, the factors that contribute to successful mental state attribution remain unclear. Current knowledge is limited because the most widely used tasks suffer from two main constraints: (i) They fail to capture individual variability due to ceiling effects and (ii) they use highly simplistic, often artificial stimuli inapt to mirror real-world socio-cognitive demands. In the present study, we address these problems by employing complex depictions of naturalistic social interactions that vary in both valence (positive vs negative) and ambiguity (high vs low). Thirty-eight healthy participants (20 female) made mental state judgments while brain responses were obtained using functional magnetic resonance imaging (fMRI). Accuracy varied based on valence and ambiguity conditions and women were more accurate than men with highly ambiguous social stimuli. Activity of the orbitofrontal cortex predicted performance in the high ambiguity condition. The results shed light on subtle differences in mentalizing abilities and associated neural activity.

The visceral yolk sac--an important site of synthesis and secretion of apolipoprotein B containing lipoproteins in the feto-placental unit of the rat.

Rat fetuses exhibit a high serum LDL concentration at term. Delivery caused a marked decrease of the LDL apolipoprotein (apo) B concentration independent of whether this occurred on days 21, 22 or 23 of gestation. The interruption of the yolk sac circulation by a ligature in situ for 6 h led to the same alterations of the LDL-apo B concentration as Caesarean section. Immunoelectronmicroscopic studies provided evidence that the epithelial cells of the visceral yolk sac exhibited electron dense LDL-sized and apo B containing particles which were localized over the compartments of the Golgi complexes, endoplasmatic reticulum, secretory vesicles and intercellular spaces, but not over the cell nuclei, mitochondria or lysosomes. ApoB containing LDL-sized particles could be obtained by ultracentrifugation from the disrupted material of the microsomal fraction of yolk sac homogenates. Isolated segments of the yolk sac membranes were capable to secrete apoB containing lipoproteins floating in the d less than 1.020 g/ml as well as in the d = 1.020-1.064 g/ml fraction with a 10-fold higher amount of apoB in the higher density class. Incorporation experiments with [35S] methionine gave evidence that these lipoproteins were at least partially provided with newly synthesized apoB predominantly found in the LDL fraction. The size of the negatively stained particles in the d = 1.020-1.064 g/ml fraction secreted from yolk sac segments corresponded to that of LDL from fetal rat serum. In contrast their acylglycerol content was significantly higher, whereas the percentage contribution of total cholesterol and protein was markedly reduced in comparison with serum LDL of the fetus. In summary, biochemical and ultrastructural studies provide clear cut evidence that the rat yolk sac is able to synthesize and to deliver apo B containing lipoproteins in the density ranges of VLDL, IDL and particular of LDL thus contributing to the supply of serum lipoproteins in the rat fetus. By recalculation of recent tracer kinetic data (Plonné et al. (1990) J. Lipid Res. 31, 747) using a mathematical step function model it was possible to assess the contribution of the rat yolk sac to the LDL influx into the fetal serum.

Influenza A virus alters structural and biochemical functions of the neutrophil cytoskeleton.

Influenza A virus (IAV) has previously been shown to alter chemotactic, oxidative, and secretory functions of polymorphonuclear leukocytes (PMNL). Because of the role of cytoskeletal proteins in these processes, studies were carried out to determine if IAV altered the PMNL cytoskeleton. PMNL were incubated with buffer of IAV, stimulated with f-met-leu-phe (FMLP), fixed and stained with NBD-phallacidin (NBD-Ph) and studied by flow cytometry. Mean F-actin fluorescence was increased 18% in virus treated cells pre-FMLP stimulation and 13% 5 and 10 min post-FMLP (P less than .03); no significant difference in F-actin fluorescence was noted in virus treated PMNL 15-30 s post-FMLP compared to control cells. PMNL exposed to the same conditions were solubilized and actin content was determined following SDS-PAGE of triton insoluble precipitates. Increased actin was recovered from virus treated compared to buffer treated cells before and after FMLP stimulation in the 8,000g precipitates (P less than .001). Immunofluorescent microscopy studies of F-actin distribution were done in PMNL stained with NBD-Ph following FMLP stimulation for 10 min. These studies showed an increased lamellipod F-actin/uropod F-actin ratio in PMNL pre-incubated with IAV compared to controls (4.6 vs. 1.0; P less than .025). Phosphorylation of specific cytoskeletal proteins was examined after immunoprecipitation. IAV alone altered phosphorylation of both vimentin and vinculin, and in stimulated PMNL virus led to decreased phosphorylation of vimentin and vinculin. These data show distributional and biochemical effects of IAV on PMNL cytoskeletal proteins, indicating additional targets for IAV interference in the PMNL signal-transduction-function process.

Endogenous lipoproteins modify the thromboxane formation capacity of platelets.

A significantly negative correlation was demonstrated between HDL-cholesterol levels of serum and the thromboxane B2 (TXB2) formation in clotted whole blood, whereas a significantly positive correlation was estimated between the LDL cholesterol or apolipoprotein B (apo B) levels and the TXB2 formation in clotted whole blood. Similar relationships were observed between the HDL and apo B serum levels and the thrombin-induced malondialdehyde formation in platelet-rich plasma. The levels of HDL2 cholesterol, total cholesterol, apo A-I and of triglycerides were not significantly correlated with the TXB2 or malondialdehyde formation in both systems. The results in this study support the hypothesis that the TXB2 formation may be modulated by endogenous lipoproteins: high level of LDL stimulates and high level of HDL inhibits the TXB2 formation.

Hybrid hybridomas producing bispecific antibodies to CEA and peroxidase isolated by a combination of HAT medium selection and fluorescence activated cell sorting.

A combination of fluorescence-activated cell sorting and HAT medium selection has been used to establish bispecific antibody (biAbs)-producing hybrid hybridomas. For this purpose hypoxanthine-guanine phosphoribosyl transferase (HGPRT)-deficient mutants were isolated from a hybridoma line (D11-DG2) producing anti-CEA antibodies by 8-azaguanine treatment. The resulting HAT-sensitive hybrid cells were stained with the fluorescence marker tetramethyl rhodamine isothiocyanate (TRITC) and fused by polyethylene glycol (PEG) with HAT-non-sensitive unstained hybrid cells producing antibodies to horseradish peroxidase (POD). Fluorescent fused hybrid hybridomas as well as non-fused stained anti-CEA cells were separated from the unstained anti-POD cells using a fluorescent activated cell sorter (FACS). Finally, non-fused enzyme-deficient anti-CEA cells were eliminated by cultivation in HAT selection medium which permits only an outgrowth of HAT-resistant hybrid hybridoma cells containing the genes for producing both antibodies.

Endocrine pancreatic secretion in patients after acute pancreatitis.

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.

Plasma from atherosclerotic patients exerts an increased degradation of platelet-activating factor.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that exerts diverse biological activities. In the present study the degradation of PAF as well as lipid concentrations were measured both in plasma from 28 patients suffering from peripheral vascular disease and 18 healthy volunteers of comparable age. Beside some changes of the lipoprotein pattern it was also found that the capacity to degrade PAF is significantly elevated in the patient group. In view of this finding the question arises whether there is any link between the degradation of PAF and the development of atherosclerosis.

The degradation of platelet-activating factor in serum and its discriminative value in atherosclerotic patients.

Platelet-activating factor (PAF) is transformed in vivo rapidly into the biologically inactive lyso-PAF. This reaction as well as lipid parameters were quantified in serum from 40 survivors of myocardial infarction and 36 healthy controls matched for age and body weight. The PAF-degrading capacity was 23% (p less than 0.001) higher in patients compared with the control group. Using the degradation of PAF as an univariate discriminator more than 70% of subjects were classified correctly. This is comparable with the discriminatory value of the best lipid variables, apolipoprotein B and HDL-cholesterol. Statistically significant differences in the degradation of PAF were found also by comparing subgroups which were matched for plasma levels of total cholesterol, VLDL/LDL-cholesterol or apolipoprotein B. The ratio by 48% (p less than 0.0001) in the case group was identified as an additional good discriminator between both groups. In contrast, platelet aggregation tests which were performed in acetylsalicyclic acid treated platelet-rich plasma discriminated poorly between patients and controls.

The role of lipoproteins in the degradation of platelet-activating factor.

Measuring both platelet-stimulating activity and liberation of acetate, the capacity of serum and individual lipoproteins to degrade the platelet-activating factor (PAF) was studied. The highest degrading effect relative to the protein content was found in very low density lipoproteins (VLDL) and in low density lipoproteins (LDL). The effect is about 10- and 100-fold higher than that of high density lipoproteins (HDL) and serum, respectively. In lipoprotein deficient serum (LPDS) less than 5% of serum activity is detectable. Considerable individual variations are observed measuring the degradation of PAF under standard conditions in plasma from 37 healthy volunteers. Moreover, this activity is shown to correlate strongly with the plasma concentration of LDL. On the other hand, a significant negative correlation was found between the PAF-degrading capacity and the plasma concentration of HDL. In contrast, the PAF-degradation is unrelated to the concentration of plasma triglycerides. The results point to a possible role of plasma lipoproteins in regulating the degradation of PAF released into the circulation.

Headspace analysis of volatile flower scent constituents of bat-pollinated plants.

The flower scents of 11 bat-pollinated plant species have been investigated using the 'closed-loop-stripping'-adsorption technique. GC and GC/MS analyses of the headspace samples resulted in the identification of 49 compounds, comprising amongst others sulphur compounds, terpenoids and aliphatic compounds.

Concentration and composition of the lipoprotein classes in human umbilical cord serum.

The concentration and composition of the lipoprotein density classes d less than 1.006 (VLDL), d = 1.006 - 1.064 (LDL), and d = 1.064 - 1.21 (HDL) of human umbilical cord serum were investigated by means of preparative ultracentrifugation. The concentrations of all the density classes, in particular that of the VLDL, are lower than in adults; the values correspond to 8.1 (VLDL), 59.2 (LDL), and 77.4 (HDL) mg/100 ml. About 15% of the total cholesterol and roughly 40% of the total lipid phosphorus did not float at the highest density of 1.21. The composition of the LDL and the HDL was principally in agreement with the pattern obtained in adults. The VLDL of the cord serum, however, showed a lower amount of triglycerides (45%) and a higher content of proteins (22%) than the VLDL from serum of adults. In cord serum only 25% of the total triglycerides are associated with the VLDL fraction, while more than 50% of the triglycerides circulate as a constituent of the LDL.

Increase in plasma total and lipoprotein cholesterol during incubation of whole blood samples at 37 degrees C--influence of LCAT inhibitors.

Incubation of whole blood samples at 37 degrees C caused a time-dependent increase in plasma cholesterol concentrations. In samples from 40 fasting healthy males, plasma cholesterol rose by 13.6 +/- 3% during 24 h (P less than 0.001). Changes in cholesterol concentrations were found in both the HDL fraction and the VLDL/LDL fraction. The increase in lipoprotein cholesterol concentrations correlated positively with the initial levels of HDL cholesterol and apo A-I; and with the original levels of VLDL/LDL cholesterol, apo B and triglycerides. The increase in plasma total cholesterol was not related to the HDL cholesterol and apo A-I concentrations. It was more pronounced in samples with elevated plasma concentrations of total cholesterol, VLDL/LDL cholesterol, apo B and triglycerides. The elevation in plasma total cholesterol resulted from an increase in cholesteryl esters, whereas free cholesterol decreased. After LCAT inhibition no changes in total, free and esterified cholesterol were observed. Therefore, increase in plasma cholesterol seems to represent a LCAT-dependent cholesterol transport out of blood cells.

Immunohistochemical expression of steroid receptors and glycodelin A in isolated proliferative human endometrial glandular cells after stimulation with tamoxifen and phytoestrogens (genistein and daidzein).

INTRODUCTION: The aims of this study were an evaluation of the distribution patterns of steroid hormone receptors (ER, PR) and glycodelin A (GdA) expression of proliferative endometrial glandular cells after stimulation with tamoxifen (TAM) and phytoestrogens (PE) (genistein, daidzein). MATERIALS AND METHODS: Human endometrium was obtained from 4 premenopausal women. Glands were stimulated after isolation with single doses of TAM, genistein and daizein (0.1, 1 and 10 mumol/l) and characterised with ER, PR and GdA after 9 days of culture. RESULTS: ER showed a significant decline with the highest TAM and genistein concentration (p < 0.05), whereas PR increased significantly with TAM and genistein concentrations of 1 mumol/l and 10 mumol/l (p < 0.05). GdA did not show any significant expression under TAM and genistein stimulation. Stimulation with daidzein resulted in no statistically relevant alterations in ER, whereas the PR significantly increased with all three concentrations (p < 0.05) and GdA also showed a significant increase with 1 mumol/l (p < 0.05). DISCUSSION: TAM showed anti-estrogenic properties in premenopausal endometrium. PE showed a similar ER, PR expression pattern as TAM, so therefore PE (genistein and daidzein) could also act as antiestrogens. GdA marked a cell transformation from proliferative to secretory status or the antiestrogen effects of TAM and PE.