Pyroligneous acid from Mimosa tenuiflora and Eucalyptus urograndis as an antimicrobial in dairy goats.

AIMS: To evaluate the applicability of the Mimosa tenuiflora and Eucalyptus urograndis pyroligneous acids (PAs) as alternative antiseptics in dairy goats. METHODS AND RESULTS: Cytotoxicity was evaluated in vitro using bacteria, as well as in vivo using goats, and the influence of PAs on the physicochemical parameters of fresh milk were examined. The cytotoxicity of PAs was evaluated in terms of morphology, cell viability and metabolic activity of goat tegumentary cells. The PA of M. tenuiflora had results similar to those of 2% iodine. For the in vitro tests, strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were used with the well technique, demonstrating inhibition halos greater than 9 mm. In the in vivo test, 15 animals were used per phase of the experiment, and the plate counting technique showed that there was antiseptic action of both extracts, with emphasis on the M. tenuiflora PA. Physicochemical analysis of the milk showed that neither PAs interfered with its physical-chemical parameters. CONCLUSIONS: The PA of M. tenuiflora presented potential as an alternative antiseptic in dairy goats. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the use of PA as an antimicrobial agent in animals.

Mandibular incisive canal-related prevalence, morphometric parameters, and implant placement implications: a multicenter study of 847 CBCT scans.

BACKGROUND: This study evaluated the epidemiological and morphological features of the mandibular incisive canal (MIC) using cone beam computed tomography (CBCT) in a significant sample of subjects in Brazil. MATERIAL AND METHODS: This retrospective, multicenter study assessed 847 CBCT scans performed at four oral imaging centers. The sample comprised CBCT images acquired from dentate individuals who presented at least from tooth 35 to tooth 45 in the anterior mandible region. Data regarding patient sex and age, and MIC linear measurements (length and diameter in mm), anatomical distances (to the alveolar, buccal and lingual cortexes, inferior border of the mandible, and adjacent teeth apexes), and location were obtained. RESULTS: The MIC was more prevalent in women (76.3% [p<0.001]) between the fourth and sixth decades of life (p<0.001). It was present bilaterally (p<0.001) and exhibited a mean length of 7.7 mm (standard deviation [SD]=3.7 mm). Spearman correlation and logistic regression analysis revealed collinearity between age and linear measurements (p<0.05). The mean distances varied from the initial to the final portion of the MIC, respectively, in relation to the buccal cortex (mean=2.6 mm, SD=1.27; mean=3.96 mm; SD=1.43), to lingual cortex (mean=5.13 mm; SD=1.7; mean=4.61 mm, SD = 1.65), and to the inferior mandibular border (mean = 9.32 mm, SD=1.92; mean=8.76 mm, SD=2.07 mm). The difference in the proximity of the MIC to the apex of the inferior lateral incisor was statistically significant (p<0.05). CONCLUSIONS: Results of this study revealed a high prevalence of MIC with a bilateral pattern in women who were between the fourth and sixth decades of life. Both the distance between the MIC and the lingual cortex of the mandibular alveolar bone, and the diameter of the MIC, decreased as its trajectory assumed a more anterior position.

Total polyphenol intake, polyphenol subtypes and incidence of cardiovascular disease: The SUN cohort study.

BACKGROUND AND AIMS: Polyphenol-rich diets have been associated with reduced risk of cardiovascular disease (CVD). However, few prospective epidemiological studies have examined the relationship between classes of ingested polyphenols and risk of CVD. Our aim was to evaluate the association between polyphenol intake and risk of major cardiovascular events in a prospective Spanish cohort. METHODS AND RESULTS: We included 17,065 university graduates (60.7% women, mean age: 37.2 years, age range: 20-89) followed-up for a mean of 10.1 years. Polyphenol intake was assessed at baseline using a validated semi-quantitative 136-item food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for incident cardiovascular events (myocardial infarction, stroke or cardiovascular death). Cherries, chocolate, coffee, apples, and olives were the major sources of variability in polyphenol intake. Participants with higher flavonoids intake (fifth quintile) had a 47% lower incidence of cardiovascular events compared to those in the lowest quintile (HR: 0.53, 95% CI: 0.29-0.98; P for trend = 0.09) after adjusting for potential confounders. The results were non-significant for other polyphenol types. CONCLUSION: The intake of flavonoids showed an inverse association with risk of cardiovascular events in a prospective cohort of Spanish middle-aged adult university graduates. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT02669602 in Clinical Trials.

Antibacterial and antifungal activities of pyroligneous acid from wood of Eucalyptus urograndis and Mimosa tenuiflora.

AIMS: This work aimed to evaluate the antibacterial and antifungal activities of two types of pyroligneous acid (PA) obtained from slow pyrolysis of wood of Mimosa tenuiflora and of a hybrid of Eucalyptus urophylla × Eucalyptus grandis. METHODS AND RESULTS: Wood wedges were carbonized on a heating rate of 1·25°C min-1 until 450°C. Pyrolysis smoke was trapped and condensed to yield liquid products. Crude pyrolysis liquids were bidistilled under 5 mmHg vacuum yielding purified PA. Multi-antibiotic-resistant strains of Escherichia coli, Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923) had their sensitivity to PA evaluated using agar diffusion test. Two yeasts were evaluated as well, Candida albicans (ATCC 10231) and Cryptococcus neoformans. GC-MS analysis of both PAs was carried out to obtain their chemical composition. Regression analysis was performed, and models were adjusted, with diameter of inhibition halos and PA concentration (100, 50 and 20%) as parameters. Identity of regression models and equality of parameters in polynomial orthogonal equations were verified. Inhibition halos were observed in the range 15-25 mm of diameter. CONCLUSIONS: All micro-organisms were inhibited by both types of PA even in the lowest concentration of 20%. SIGNIFICANCE AND IMPACT OF THE STUDY: The feasibility of the usage of PAs produced with wood species planted in large scale in Brazil was evident and the real potential as a basis to produce natural antibacterial and antifungal agents, with real possibility to be used in veterinary and zootechnical applications.

The synthetic peptide PnPP-19 induces peripheral antinociception via activation of NO/cGMP/KATP pathway: Role of eNOS and nNOS.

BACKGROUND: and purpose: The peptide PnPP-19, derived from the spider toxin PnTx2-6 (renamed as δ-CNTX-Pn1c), potentiates erectile function by activating the nitrergic system. Since NO has been studied as an antinociceptive molecule and PnPP-19 is known to induce peripheral antinociception, we intended to evaluate whether PnPP-19 could induce peripheral antinociception through activation of this pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PGE2 (2 µg/paw) was administered intraplantarly together with PnPP-19 and inhibitors/blockers of NOS, guanylyl cyclase and KATP channels. The nitrite concentration was accessed by Griess test. The expression and phosphorylation of eNOS and nNOS were determined by western blot. KEY RESULTS: PnPP-19 (5, 10 and 20 µg/paw) induced peripheral antinociception in rats. Administration of NOS inhibitor (L-NOarg), selective nNOS inhibitor (L-NPA), guanylyl cyclase inhibitor (ODQ) and the blocker of KATP (glibenclamide) partially inhibited the antinociceptive effect of PnPP-19 (10 µg/paw). Tissue nitrite concentration increased after PnPP-19 (10 µg/paw) administration. Expression of eNOS and nNOS remained the same in all tested groups, however the phosphorylation of nNOS Ser852 (inactivation site) increased and phosphorylation of eNOS Ser1177 (activation site) decreased after PGE2 injection. Administration of PnPP-19 reverted this PGE2-induced effect. CONCLUSIONS AND IMPLICATIONS: The peripheral antinociceptive effect induced by PnPP-19 is resulting from activation of NO-cGMP-KATP pathway. Activation of eNOS and nNOS might be required for such effect. Our results suggest PnPP-19 as a new drug candidate to treat pain and reinforce the importance of nNOS and eNOS activation, as well as endogenous NO release, for induction of peripheral antinociception.

Dynamic structure of NGF and proNGF complexed with p75NTR: pro-peptide effect.

Crystallographic structures of NGF/p75NTR and proNGF/p75NTR were previously obtained in 2:1 and 2:2 stoichiometries, respectively. However, evidence shows that both stoichiometries can occur for mature neurotrophins and pro-neurotrophins. We used Molecular Dynamics (MD) simulations to examine the energetic and structural characteristics of these two complete systems as well as the uncomplexed forms of NGF and understand how these could translate in a new view of different biological outcomes. Here, we show that one chain at the 2:2 proNGF complex seems to be preferentially lost creating a 2:1 structure able to interact with sortilin. We also demonstrated that the structure of the neurotrophin dimers is not pre-established and suffers large structural modifications upon p75NTR binding. Moreover, our data suggests an elegant explanation for the dual role of NGF in neuronal cell death and survival, where different stoichiometries induce conformational changes that might be the basis for the different biological outcomes observed with the mature and proforms of neurotrophins.

Ligand-induced structural changes in TEM-1 probed by molecular dynamics and relative binding free energy calculations.

The TEM family of enzymes has had a crucial impact on the pharmaceutical industry due to their important role in antibiotic resistance. Even with the latest technologies in structural biology and genomics, no 3D structure of a TEM-1/antibiotic complex is known previous to acylation. Therefore, the comprehension of their capability in acylate antibiotics is based on the protein macromolecular structure uncomplexed. In this work, molecular docking, molecular dynamic simulations, and relative free energy calculations were applied in order to get a comprehensive and thorough analysis of TEM-1/ampicillin and TEM-1/amoxicillin complexes. We described the complexes and analyzed the effect of ligand binding on the overall structure. We clearly demonstrate that the key residues involved in the stability of the ligand (hot-spots) vary with the nature of the ligand. Structural effects such as (i) the distances between interfacial residues (Ser70-Oγ and Lys73-Nζ, Lys73-Nζ and Ser130-Oγ, and Ser70-Oγ-Ser130-Oγ), (ii) side chain rotamer variation (Tyr105 and Glu240), and (iii) the presence of conserved waters can be also influenced by ligand binding. This study supports the hypothesis that TEM-1 suffers structural modifications upon ligand binding.

Radiation protection measures used in Portuguese interventional radiology departments: A national survey.

INTRODUCTION: This study aimed to characterise radiation protection (RP) measures used in interventional radiology (IR) departments in Portugal with respect to European and national recommendations. METHODS: An online national survey was created to characterise the fluoroscopy technology as well as analyse the frequency of body fluoroscopy-guided intervention procedures (FGIP), RP education and training of the staff, and RP measures used daily. RESULTS: In Portugal, most equipment for FGIP are single-sourced and have a flat panel detector (70%). The most commonly FGIP are percutaneous biliary drainage, percutaneous arterial and venous thrombolysis/thrombectomy, arteriovenous malformations embolization, and percutaneous transluminal balloon angioplasty for arteriovenous fistulas. Only a few staff members had received postgraduate education and training in RP (30%), with most nurses having not received RP education and training (40%). Some of the recommended RP measures lacked harmonisation. Additionally, >50% of the IR departments do not consider examination dose values to identify patients eligible for tissue reactions follow-up. CONCLUSION: This is the first study to examine the characteristics of IR departments in Portugal. We observed a lack of RP education and training among staff members; further, there was a need to update some RP measures in some IR departments according to the recommendations. IMPLICATIONS FOR PRACTICE: Our findings will be presented to the participating IR departments in order to update and promote RP best practices. Moreover, our findings will be presented to the national societies of the different professional groups in order to inform strategies for harmonising RP education and training of the staff.

Geographical and seasonal patterns in the carbonate chemistry of Narragansett Bay, RI.

This study examined geographical and seasonal patterns in carbonate chemistry and will facilitate assessment of acidification conditions and the current state of the seawater carbonate chemistry system in Narragansett Bay. Direct measurements of total alkalinity, dissolved inorganic carbon, dissolved oxygen percent saturation, water temperature, salinity and pressure were performed during monthly sampling cruises carried out over three years. These measurements were used to calculate the following biologically relevant carbonate system parameters: total pH (pHT), the partial pressure of carbon dioxide in the gas phase pCO2, and the aragonite saturation state ΩA. The information provided by carbonate chemistry analysis allowed for the characterization of acidification events which have the potential to disrupt the species composition and ecological functioning of coastal biological communities and threaten commercially important aquatic life. We found very robust relationships between salinity and total alkalinity Radjusted2=0.82 and between salinity and dissolved inorganic carbon Radjusted2=0.81 that persisted through all regions, seasons, and depth-layers with mixing of coastal waters with freshwater entering in the upper bay being an important driver on alkalinity and dissolved inorganic carbon distributions. We compared the metabolically linked calculated carbonate system parameters with dissolved oxygen (DO) saturation and found high correlation, with DO percent saturation exhibiting robust correlation with the calculated carbonate system parameters total pH (r=0.70) and with partial pressure of carbon dioxide in the gas phase (r=-0.71). Using a statistical model to correct for the confounded effects of time and space that are a common challenge in marine survey design, we found that acidification events occurred in the Northern Region of the bay, primarily during the Summer and Fall, and likely due to a combination of microbial respiration and stratification. These acidification events, especially in the Northern Region, have the potential to adversely impact aquatic life.

Depression and metabolic syndrome in participants of the "Seguimiento Universidad de Navarra" (SUN) cohort study.

BACKGROUND: Depression is a major public health concern worldwide and its association with metabolic syndrome (MetS) remains unclear. Thus, we prospectively examined the association between depression and the risk of MetS, according to different diagnosis criteria. METHODS: This study included 9,237 participants of a Spanish dynamic prospective cohort of adult university graduates [mean (SD) age: 36.7 year (10.7)], initially free of any specific criterion of MetS, who were followed-up for a median of 8.3 years. The exposure variables were medical diagnosis of depression at baseline or in the first 2-year follow-up questionnaire. The outcome variable was the incidence of MetS, assessed according to each of three different criteria proposed by: International Diabetes Federation (IDF); National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III); IDF/NCEP-ATP III (updated harmonizing definition). Multivariable-adjusted Relative Risks (RR) of new-onset MetS and their 95% Confidence Intervals (95% CI) were estimated, using Poisson regression models. RESULTS: The cumulative incidences of MetS were 475 cases (IDF definition), 288 cases (NCEP-ATP III definition) and 492 cases (update harmonized definition). No association was observed between baseline depression and incidence of MetS, but the presence of depression after 2-years of follow-up was significantly associated with a higher risk of new-onset MetS, according to NCEP-ATP III definition (multivariable-adjusted RR, 2.46; 95% CI, 1.06-5.67). LIMITATIONS: Diagnosis of depression and MetS were self-reported. CONCLUSIONS: In this large prospective cohort of Spanish middle-aged adult university graduates, a direct association between depression and the risk of MetS according to NCEP-ATP III definition was found.

Polyvinyl alcohol/chitosan wound dressings loaded with antiseptics.

Wound care remains a challenge in healthcare. This work aimed to develop a new polyvinyl alcohol (PVA)/chitosan (Ch) based wound dressing able to ensure protection, hydration and a controlled release of antiseptics, as alternative to actual treatments. Two distinct formulations (1:1 and 3:1, w/w) were prepared, sterilized by autoclaving and characterized concerning surface morphology, degradation over the time, mechanical properties and hydrophilicity. Both dressings revealed adequate properties for the intended purpose. The dressings were loaded with chlorhexidine (CHX) and polyhexanide (PHMB) and the drug release profiles were determined using Franz diffusion cells. The release of PHMB was more sustained than CHX, lasting for 2 days. As the amounts of drugs released by PVA/Ch 1:1 were greater, the biological tests were done only with this formulation. The drug loaded dressings revealed antibacterial activity against S. aureus and S. epidermidis, but only the ones loaded with PHMB showed adequate properties in terms of cytotoxicity and irritability. The application of this elastic dressing in the treatment of wounds in a dog led to faster recovery than conventional treatment, suggesting that the material can be a promising alternative in wound care.

Synoptic assessment of coastal total alkalinity through community science.

Comprehensive sampling of the carbonate system in estuaries and coastal waters can be difficult and expensive because of the complex and heterogeneous nature of near-shore environments. We show that sample collection by community science programs is a viable strategy for expanding estuarine carbonate system monitoring and prioritizing regions for more targeted assessment. 'Shell Day' was a single-day regional water monitoring event coordinating coastal carbonate chemistry observations by 59 community science programs and seven research institutions in the northeastern United States, in which 410 total alkalinity (TA) samples from 86 stations were collected. Field replicates collected at both low and high tides had a mean standard deviation between replicates of 3.6 ± 0.3 µmol kg-1 (σ mean ± SE, n = 145) or 0.20 ± 0.02%. This level of precision demonstrates that with adequate protocols for sample collection, handling, storage, and analysis, community science programs are able to collect TA samples leading to high-quality analyses and data. Despite correlations between salinity, temperature, and TA observed at multiple spatial scales, empirical predictions of TA had relatively high root mean square error >48 µmol kg-1. Additionally, ten stations displayed tidal variability in TA that was not likely driven by low TA freshwater inputs. As such, TA cannot be predicted accurately from salinity using a single relationship across the northeastern US region, though predictions may be viable at more localized scales where consistent freshwater and seawater endmembers can be defined. There was a high degree of geographic heterogeneity in both mean and tidal variability in TA, and this single-day snapshot sampling identified three patterns driving variation in TA, with certain locations exhibiting increased risk of acidification. The success of Shell Day implies that similar community science based events could be conducted in other regions to not only expand understanding of the coastal carbonate system, but also provide a way to inventory monitoring assets, build partnerships with stakeholders, and expand education and outreach to a broader constituency.

Proteomic analysis of human mesenchymal stromal cells derived from adipose tissue undergoing osteoblast differentiation.

BACKGROUND AIMS: Stem cells derived from human adipose tissue (ASC) have the capacity for renewal, are easily obtained and have plasticity properties that allow them to differentiate into several cell types, including osteoblast cells. With the aim of understanding the issue of the osteogenic process and finding reliable biomarkers in cells undergoing the osteogeneic differentiation process, this work took advantage of a proteomic approach to identify proteins involved in osteogenesis. METHODS: For this purpose, ASC were analyzed under three conditions: S0, in the absence of stimulation; S1, with 2 weeks of osteogenic medium stimulation; and S2, with 4 weeks of osteogenic medium stimulation. The identification of ASC was carried out by flow cytometry using antibodies specific to known undifferentiated stem cell-surface markers. Cell viability, enzymatic activity, mineral deposition, collagen structure and production and gene analyzes were evaluated for each condition. RESULTS: Phenotypic modifications were observed during the in vitro osteogenic differentiation process by two-dimensional (2-D) differential image gel electrophoresis (DIGE). The proteins were identified by mass espectrometry in tandem (MS/MS) analyzes using Matrix-assisted laser desorption/ionization with TOF/TOF is a tandem mass spectrometry method where two time-of-flight mass spectrometers are used consecutively (MALDI-TOF/TOF). A total of 51 differentially expressed proteins was identified when comparing the three observed conditions. Sixteen different spots were identified in the S0 stage compared with S2, while 28 different spots were found in S2 compared with S0. S1 expressed seven different spots compared with S0 and S2. CONCLUSIONS: These findings suggest the involvement of several proteins directly related to the osteogenic pathway, which can be used to improve understanding of the osteogenic process.

LyeTx I, a potent antimicrobial peptide from the venom of the spider Lycosa erythrognatha.

LyeTx I, an antimicrobial peptide isolated from the venom of Lycosa erythrognatha, known as wolf spider, has been synthesised and its structural profile studied by using the CD and NMR techniques. LyeTx I has shown to be active against bacteria (Escherichia coli and Staphylococcus aureus) and fungi (Candida krusei and Cryptococcus neoformans) and able to alter the permeabilisation of L: -alpha-phosphatidylcholine-liposomes (POPC) in a dose-dependent manner. In POPC containing cholesterol or ergosterol, permeabilisation has either decreased about five times or remained unchanged, respectively. These results, along with the observed low haemolytic activity, indicated that antimicrobial membranes, rather than vertebrate membranes seem to be the preferential targets. However, the complexity of biological membranes compared to liposomes must be taken in account. Besides, other membrane components, such as proteins and even specific lipids, cannot be discarded to be important to the preferential action of the LyeTx I to the tested microorganisms. The secondary structure of LyeTx I shows a small random-coil region at the N-terminus followed by an alpha-helix that reached the amidated C-terminus, which might favour the peptide-membrane interaction. The high activity against bacteria together with the moderate activity against fungi and the low haemolytic activity have indicated LyeTx I as a good prototype for developing new antibiotic peptides.

Nut consumption and incidence of hypertension: the SUN prospective cohort.

BACKGROUND AND AIMS: The consumption of tree nuts could reduce the risk of hypertension, but scarce research has been done to evaluate this potential association. We assessed the association between nut consumption and the incidence of hypertension among 9919 Spanish university graduates followed-up biennially for a median of 4.3 years. METHODS AND RESULTS: Food habits were assessed with a validated 136-item food-frequency questionnaire. Nut consumption was classified into four categories: rarely/never, 1-3/month, 1/week, and 2+/week. A participant was classified as an incident case of hypertension when, being free of hypertension at baseline, he/she subsequently reported a physician-made diagnosis of hypertension in at least one of the follow-up questionnaires. The incidence of hypertension was 12.4 per 1000 person-years. We found no association between nut consumption and incidence of hypertension after adjusting for sex, age and other dietary and non-dietary potential confounders (hazard ratio [HR] for those in the highest vs. lowest nut consumption category=0.77 [IC 95%: 0.46-1.30] p=0.795). Results were not modified when we stratified them analyses according to sex or to body mass index. CONCLUSION: Our data do not provide evidence for an inverse association between nut consumption and incident hypertension in our cohort. Further results from cohorts and trials with a higher baseline risk of hypertension should be obtained to test this relationship.

Early onset gastric cancer no longer presents as an advanced disease with ominous prognosis.

BACKGROUND: This study aimed to characterize the clinicopathological features and prognosis of early onset gastric carcinomas (EOGCs) in a sample of young Portuguese adults. MATERIAL AND METHODS: A subset of 415 patients submitted to gastric resection was divided into 2 groups: A--patients aged 45 years or less (n = 108), and B--patients older than 45 years (n = 307). The groups were compared for several clinicopathological features and the survival of the patients was analyzed by uni- and multivariate analysis. RESULTS: The surgical resection rate was higher in young patients, in whom tumors more frequently displayed an ulcerative shape (p < 0.001) and diffuse/isolated cell-type histology (p < 0.001). In the elderly, the rate of vascular invasion was significantly higher (p = 0.002). Overall, the survival of young patients was higher than in the elderly (p < 0.001). Survival curves were higher in young patients, except for pT4 and pM1 cases. In the multivariate survival analysis, age (p < 0.001), depth of tumor invasion (p < 0.001), nodal status (p < 0.001), vascular invasion (p = 0.011) and distant metastases (p = 0.007) emerged as independent prognostic factors for gastric carcinoma. CONCLUSION: Young gastric cancer patients no longer present with more advanced disease than the elderly and, overall, survival is better in young patients.

Upper Airway Video Endoscopy: Assessment of the response to positive pressure ventilation and mechanical in-exsufflation.

Upper airways (UA) include the nasal cavities, pharynx, and larynx, and its main function is to warm and filter the inspired air. UA dysfunction is in the pathogenesis of various disorders, such as obstructive sleep apnea syndrome (OSAS) and vocal cord dysfunction. In addition, in some neurodegenerative diseases (e.g. Amyotrophic Lateral Sclerosis - ALS), UA dysfunction may also compromise the effective use of ventilatory support (VS). In this context, the endoscopic evaluation of UA may be useful in understanding the OSAS mechanisms, in determining the causes for treatment-induced airway obstruction and even in helping to titrate noninvasive ventilation (NIV) in ALS patients with bulbar or pseudo-bulbar (spastic) dysfunction. Specifically, in OSAS patients, when residual obstructive events persist, although an optimal ventilatory mode has been apparently achieved, along with interface and equipment, the endoscopic evaluation of UA seems to be a valuable tool in understanding its mechanisms, even assisting adjustments to NIV parameters. In addition, it has also been described as being useful in laryngeal response to mechanical in-exsufflation (MI-E) and Exercise-Induced Laryngeal Obstruction (EILO). However, no protocol has yet been published or validated for this. For this reason, a literature review was conducted on UA function and its response to positive pressure and MI-E. Special emphasis has also been given to the current indication for video endoscopy in chronically ventilated patients.

Photodegradation of Si-doped GaAs nanowire.

Researching optical effects in nanowires may require a high pump intensity which under ambient conditions can degrade nanowires due to thermal oxidation. In this work we investigated the photodegradation of a single Si-doped GaAs nanowire by laser heating in air. To understand the changes that occurred on the nanowire we carried out Raman spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and photoluminescence spectroscopy in laser damaged regions as well as in non-affected ones. From Raman Stokes and anti-Stokes measurements we estimated the local temperature that the oxidation process of the nanowire (NW) surface starts at as 661 K, resulting in two new Raman modes at 200 cm-1 and 259 cm-1. Scanning electron microscopy and energy dispersive X-ray spectroscopy measurements showed a significant loss of arsenic in the oxidized regions, but no erosion of the nanowire. Micro-photoluminescence measurements showed the near-band-edge emission of GaAs along the nanowire, as well as a new emission band at 755 nm corresponding to polycrystalline ß-Ga2O3 formation. Our results also indicate that neither amorphous As nor crystalline As were deposited on the surface of the nanowire. Combining different experimental techniques, this study showed the formation of polycrystalline ß-Ga2O3 by oxidation of the nanowire surface and the limits for performing spectroscopic investigations on individual GaAs NWs under ambient air conditions.

The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting.

The formation of brain circuits requires molecular recognition between functionally related neurons. We report the cloning of a molecule that participates in these interactions. The limbic system-associated membrane protein (LAMP) is an immunoglobulin (Ig) superfamily member with 3 Ig domains and a glycosyl-phosphatidylinositol anchor. In the developing forebrain, lamp is expressed mostly by neurons comprising limbic-associated cortical and subcortical regions that function in cognition, emotion, memory, and learning. The unique distribution of LAMP reflects its functional specificity. LAMP-transfected cells selectively facilitate neurite outgrowth of primary limbic neurons. Most striking, administration of anti-LAMP in vivo results in abnormal growth of the mossy fiber projection from developing granule neurons in the dentate gyrus of the hippocampal formation, suggesting that LAMP is essential for proper targeting of this pathway. Rather than being a general guidance cue, LAMP likely serves as a recognition molecule for the formation of limbic connections.

Activation of AMP-activated protein kinase, inhibition of pyruvate dehydrogenase activity, and redistribution of substrate partitioning mediate the acute insulin-sensitizing effects of troglitazone in skeletal muscle cells.

The aim of this study was to investigate the acute effects of troglitazone on several pathways of glucose and fatty acid (FA) partitioning and the molecular mechanisms involved in these processes in skeletal muscle. Exposure of L6 myotubes to troglitazone for 1 h significantly increased phosphorylation of AMPK and ACC, which was followed by approximately 30% and approximately 60% increases in palmitate oxidation and carnitine palmitoyl transferase-1 (CPT-1) activity, respectively. Troglitazone inhibited basal ( approximately 25%) and insulin-stimulated ( approximately 35%) palmitate uptake but significantly increased basal and insulin-stimulated glucose uptake by approximately 2.2- and 2.7-fold, respectively. Pharmacological inhibition of AMPK completely prevented the effects of troglitazone on palmitate oxidation and glucose uptake. Interestingly, even though troglitazone exerted an insulin sensitizing effect, it reduced basal and insulin-stimulated rates of glycogen synthesis, incorporation of glucose into lipids, and glucose oxidation to values corresponding to approximately 30%, approximately 60%, and 30% of the controls, respectively. These effects were accompanied by an increase in basal and insulin-stimulated phosphorylation of Akt(Thr308), Akt(Ser473), and GSK3alpha/beta. Troglitazone also powerfully suppressed pyruvate decarboxylation, which was followed by a significant increase in basal ( approximately 3.5-fold) and insulin-stimulated ( approximately 5.5-fold) rates of lactate production by muscle cells. In summary, we provide novel evidence that troglitazone exerts acute insulin sensitizing effects by increasing FA oxidation, reducing FA uptake, suppressing pyruvate dehydrogenase activity, and shifting glucose metabolism toward lactate production in muscle cells. These effects seem to be at least partially dependent on AMPK activation and may account for potential acute PPAR-gamma-independent anti-diabetic effects of thiazolidinediones in skeletal muscle.