Pulmonary Epithelial Integrity in Children: Relationship to Ambient Ozone Exposure and Swimming Pool Attendance

Airway irritants such as ozone are known to impair lung function and induce airway inflammation. Clara cell protein (CC16) is a small anti-inflammatory protein secreted by the nonciliated bronchiolar Clara cells. CC16 in serum has been proposed as a noninvasive and sensitive marker of lung epithelial injury. In this study, we used lung function and serum CC16 concentration to examine the pulmonary responses to ambient O(3) exposure and swimming pool attendance. The measurements were made on 57 children 10–11 years of age before and after outdoor exercise for 2 hr. Individual O(3) exposure was estimated as the total exposure dose between 0700 hr until the second blood sample was obtained (mean O(3) concentration/m(3) × hours). The maximal 1-hr value was 118 μg/m(3) (59 ppb), and the individual exposure dose ranged between 352 and 914 μg/m(3)hr. These O(3) levels did not cause any significant changes in mean serum CC16 concentrations before or after outdoor exercise, nor was any decrease in lung function detected. However, children who regularly visited chlorinated indoor swimming pools had significantly lower CC16 levels in serum than did nonswimming children both before and after exercise (respectively, 57 ± 2.4 and 53 ± 1.7 μg/L vs. 8.2 ± 2.8 and 8.0 ± 2.6 μg/L; p < 0.002). These results indicate that repeated exposure to chlorination by-products in the air of indoor swimming pools has adverse effects on the Clara cell function in children. A possible relation between such damage to Clara cells and pulmonary morbidity (e.g., asthma) should be further investigated

Design, synthesis and <i>in vitro</i> and <i>in vivo</i> biological evaluation of flurbiprofen amides as new fatty acid amide hydrolase/cyclooxygenase-2 dual inhibitory potential analgesic agents

Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds

Мотивация и ее методы социально-психологического стимулирования

Материалы XVIII Междунар. науч.-техн. конф. студентов, аспирантов и молодых ученых, Гомель, 26–27 апр. 2018 г

Tillstånd och trender för arter och deras livsmiljöer

2015 års upplaga av den svenska rödlistan är den fjärde i ordningen. Den är baserad på IUCN:s rödlistningskriterier och revideras vart femte år. I rödlistan bedöms risken som enskilda arter av djur, växter och svampar löper att försvinna från Sverige. Bedömningen utförs av ArtDatabankens medarbetare i samverkan med över 100 externa experter, indelade i 14 expertkommittéer för olika organismgrupper. Under arbetet med 2015 års rödlista har tillstånd och trender bedömts för 21 600 arter och 1 318 lägre taxa (apomiktiska arter, underarter och varieteter), sammanlagt ca 22 900 taxa. Av de bedömda arterna klassificerades 2 029 som hotade (kategorierna CR, EN och VU) och 4 273 som rödlistade (inkluderar även kategorierna NT, RE och DD). Förhållandet mellan antalet rödlistade och antalet bedömda arter ar 19,8 %, vilket är ungefär samma värde som 2010 och 2005. I denna rapport jämförs antalet och andelen rödlistade arter mellan olika organismgrupper, biotoper, substrat och påverkansfaktorer. Texten ar indelad i en allmän del och åtta kapitel inriktade på olika landskapstyper. Landskapstyperna utgör en grov indelning av landets miljöer enligt följande kategorier: Skog, Jordbrukslandskap, Urbana miljöer, Fjäll, Våtmarker, Sötvatten, Havsstränder och Havsmiljöer. Skogen och jordbrukslandskapet är de artrikaste landskapstyperna med 1 800 respektive 1 400 arter som har en stark anknytning dit, och ytterligare flera hundra arter som förekommer där mer sporadiskt. De faktorer som påverkar flest rödlistade arter i Sverige är skogsavverkning och igenväxning, som båda utgör ett hot mot vardera ca 30 % av de rödlistade arterna. Avverkning minskar arealen av skog där naturliga strukturer och naturlig dynamik upprätthålls, och den orsakar därmed förlust av livsmiljöer. Igenväxning orsakas av ett antal faktorer, bland annat upphörande hävd (bete och slåtter), gödsling, trädplantering och brist på naturliga störningsregimer som t.ex. regelbundna översvämningar kring vattendrag och sjöar. Andra viktiga påverkansfaktorer är fiske, torrläggning av våtmarker, tillbakagång hos värdarter (främst alm och ask som drabbats av invasiva svampsjukdomar), klimatförändringar och konkurrens från invasiva arter. IUCN:s rödlisteindex beräknas för ett urval av de bedömda organismgrupperna. Rödlisteindex visar att skillnaderna mellan rödlistorna från 2000, 2005, 2010 och 2015 är små. Ett par undantag finns dock. Groddjur och stora däggdjur har fått en något förbättrad situation sedan 2000. Totalt förefaller det ändå som att trycket mot Sveriges artstock har förblivit relativt konstant under de senaste 15 åren

Human bocavirus (HBoV) in children with respiratory tract infection by enzyme linked immunosorbent assay (ELISA) and qualitative polymerase chain reaction (PCR)

<p>Abstract</p> <p>Background</p> <p>Human bocavirus (HBoV) is a recently discovered parvovirus associated with mild to severe lower respiratory tract infections in children, the aim of the work was determination of human bocavirus in nasopharyngeal aspirate (NPA) of infants by qualitative PCR and determination of acute human bocavirus infection by estimation of immunoglobulin M (IgM) antibodies in serum by enzyme linked immunosorbent assay.</p> <p>Results</p> <p>Twenty two (22%) out of the 100 NPA specimens of the patients with respiratory manifestations were positive for HBoV by qualitative PCR, while ELISA revealed positive HBoV IgM antibodies in 18 (18%) patients who were also positive by PCR. Non of the controls were positive by both techniques. The correlation study between ELISA and PCR revealed high significant association, (p < 0.001, X²= 36 and agreement = 96%). Also PCR detected 4 (18.1%) NPA samples as HBoV positive cases among the patients that were not identified by ELISA. This could be due to high sensitivity and efficacy of PCR. ELISA being less sensitive than RT-PCR, sensitivity was (81.8% vs 100%), the efficacy was 97.7% in ELISA versus 99.7% for RT-PCR.</p> <p>Conclusion</p> <p>HBoV infections could be diagnosed in NPA of children by conventional PCR as a rapid and sensitive technique. While ELISA was a reliable serologic analysis for diagnosis of acute HBoV infection by estimation IgM antibodies in serum.</p

Interaction of the N-(3-Methylpyridin-2-yl)amide Derivatives of Flurbiprofen and Ibuprofen with FAAH: Enantiomeric Selectivity and Binding Mode

Background Combined fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) inhibition is a promising approach for pain-relief. The Flu-AM1 and Ibu-AM5 derivatives of flurbiprofen and ibuprofen retain similar COX-inhibitory properties and are more potent inhibitors of FAAH than the parent compounds. However, little is known as to the nature of their interaction with FAAH, or to the importance of their chirality. This has been explored here. Methodology/Principal Findings FAAH inhibitory activity was measured in rat brain homogenates and in lysates expressing either wild-type or FAAHT488A-mutated enzyme. Molecular modelling was undertaken using both docking and molecular dynamics. The (R)- and (S)-enantiomers of Flu-AM1 inhibited rat FAAH with similar potencies (IC50 values of 0.74 and 0.99 μM, respectively), whereas the (S)-enantiomer of Ibu-AM5 (IC50 0.59 μM) was more potent than the (R)-enantiomer (IC50 5.7 μM). Multiple inhibition experiments indicated that both (R)-Flu-AM1 and (S)-Ibu-AM5 inhibited FAAH in a manner mutually exclusive to carprofen. Computational studies indicated that the binding site for the Flu-AM1 and Ibu-AM5 enantiomers was located between the acyl chain binding channel and the membrane access channel, in a site overlapping the carprofen binding site, and showed a binding mode in line with that proposed for carprofen and other non-covalent ligands. The potency of (R)-Flu-AM1 was lower towards lysates expressing FAAH mutated at the proposed carprofen binding area than in lysates expressing wild-type FAAH. Conclusions/Significance The study provides kinetic and structural evidence that the enantiomers of Flu-AM1 and Ibu-AM5 bind in the substrate channel of FAAH. This information will be useful in aiding the design of novel dual-action FAAH: COX inhibitors

Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity and Insulin Resistance

Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.acceptedVersio

A strong association between non-musculoskeletal symptoms and musculoskeletal pain symptoms: results from a population study

<p>Abstract</p> <p>Background</p> <p>There is a lack of knowledge about the pattern of symptom reporting in the general population as most research focuses on specific diseases or symptoms. The number of musculoskeletal pain sites is a strong predictor for disability pensioning and, hence, is considered to be an important dimension in symptom reporting. The simple method of counting symptoms might also be applicable to non-musculoskeletal symptoms, rendering further dimensions in describing individual and public health. In a general population, we aimed to explore the association between self-reported non-musculoskeletal symptoms and the number of pain sites.</p> <p>Methods</p> <p>With a cross-sectional design, the Standardised Nordic Questionnaire and the Subjective Health Complaints Inventory were used to record pain at ten different body sites and 13 non-musculoskeletal symptoms, respectively, among seven age groups in Ullensaker, Norway (n = 3,227).</p> <p>Results</p> <p>Results showed a strong, almost linear relationship between the number of non-musculoskeletal symptoms and the number of pain sites (r = 0.55). The <it>number </it>and <it>type </it>of non-musculoskeletal symptoms had an almost equal explanatory power in the number of pain sites reported (27.1% vs. 28.2%).</p> <p>Conclusion</p> <p>The linear association between the number of non-musculoskeletal and musculoskeletal symptoms might indicate that the symptoms share common characteristics and even common underlying causal factors. The total burden of symptoms as determined by the number of symptoms reported might be an interesting generic indicator of health and well-being, as well as present and future functioning. Research on symptom reporting might also be an alternative pathway to describe and, possibly, understand the medically unexplained multisymptom conditions.</p

Identifisering av fokus i korttids dynamisk psykoterapi

Brief dynamic psychotherapy has its origins in traditional psychodynamic therapy. The most important features of brief dynamic psychotherapy include preplanned time-limited therapy, identifying and holding on to a focus, and an active therapist stance. More specifically, this thesis will address the concept of focus and how focus is identified in Hanna Levensons integrative model, called Time-Limited-Dynamic Psychotherapy (TLDP). The model is a further development of the TLDP model originally proposed by Hans Strupp and Jeffery Binder. We describe the historic development of TLDP, from the classical drive/structural models until todays brief dynamic psychotherapy, represented by Levensons integrative, relation-oriented TLDP. The Cyclic Maladaptiv Pattern (CMP) guides the process of identifying a focus. CMP works as a guideline for selecting relevant information about the patient, and the way the patient relates to other people. This lays the foundation for the therapy process. How a focus is identified in practice is demonstrated by analyzing authentic video material with Levenson as therapist