Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

School performance of international adoptees better than expected from cognitive test results

Objective: To investigate school performance of international adoptees in relation to their cognitive competence. Method: From the population of all male Swedish residents born 1973–1976, registered in the census 1985 and with complete test scores from military conscription, the following study groups were identified: Korean adoptees (n = 320), non-Korean adoptees (n = 1,125), siblings (children born by adoptive parents, n = 190) and Swedish majority comparisons (n = 142,024). Global scores from intelligence tests at conscription were compared with grade points from the last compulsory school year (year 9). Linear and logistic regression was applied in statistical analyses. Results: The mean grade points in theoretical subjects were lower in non-Korean adoptees than in the majority population, but when global test scores from military conscription were adjusted for, outcomes were significantly better, equal for physics, than in the majority population. The grade points of Korean adoptees were higher than in the majority population and the same held true after adjusting for global test scores. When SES was taken into account, the risk of poor school performance (only completed lower subject levels) increased in non-Korean adoptees compared to models only adjusted for age and sex. Conclusion: Male international adoptees generally perform better in school than expected by their cognitive competence. A cognitive evaluation is important in the assessment of adoptees with learning difficulties

Muc5ac: a critical component mediating the rejection of enteric nematodes

The mucin Muc5ac is essential for the expulsion of Trichuris muris and other gut-dwelling nematodes

Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production

BACKGROUND: As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS). RESULTS: Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1β, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-α, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5–7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5–7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1β, TNF-α and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol. CONCLUSION: Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC

Cognitive differentiation during childhood: A study on cognitive profiles of 5, 7, and 9-year-old children

No seio do debate sobre se a inteligência é mais bem definida por um fator geral ou por aptidões específicas, ganha relevância a hipótese da diferenciação cognitiva. Análises recentes enfatizam o interesse dessa questão para a investigação e alertam para a relevância das suas implicações na área educativa. Este estudo analisou a possibilidade de a diferenciação das aptidões cognitivas ocorrer já na infância e também o efeito moderador do Quociente de Inteligência na magnitude da relação entre as habilidades cognitivas. Aplicou-se uma bateria de provas que avaliam várias funções cognitivas a uma amostra de 231 crianças com 5, 7 e 9 anos, distribuídas por três grupos de desempenho cognitivo. Os resultados de uma análise de clusters hierárquica e de uma análise de variância apontam para a não diferenciação das funções cognitivas na infância. Contudo, uma análise mais cuidadosa aponta para alguma diferenciação suportada pela heterogeneidade dos perfis cognitivos junto dos alunos com Quociente de Inteligência elevado.Within the debate about whether intelligence is best defined by a general factor or specific skills, the hypothesis of cognitive differentiation gains relevance. Recent analyses have emphasized the importance of this issue in the investigation of cognitive skills and have highlighted its implications in education. This study examined the possibility that the differentiation of cognitive abilities may occur during childhood and investigated the moderating effect of Intelligence Quotient on the magnitude of the relationship between cognitive abilities. A battery of tests for assessing cognitive function was administered to 231 children aged 5, 7, and 9 years old, who were divided into three cognitive performance groups. The results of hierarchical cluster analysis and variance analysis indicate the lack of differentiation of cognitive functions during childhood. However, a more careful analysis suggests some differentiation supported by the heterogeneity of cognitive profiles among students with high Intelligence Quotient.FCT -Fundação para a Ciência e a Tecnologia(SFRH/BD/84153/2012

Blood lactate levels in 31 female dogs with pyometra

<p>Abstract</p> <p>Background</p> <p>Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1) the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2) if these levels are related with the clinical status or other biochemical or hematological disorders.</p> <p>Methods</p> <p>In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome.</p> <p>Results</p> <p>In the pyometra group the median blood lactate level was 1,6 mmol l^-1(range <0.8–2.7 mmol l^-1). In the control group the median lactate level was 1,2 mmol l^-1(range <0.8–2.1 mmol l^-1). Of the 31 bitches 19 (61%) fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32%) fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l^-1) was demonstrated in one female dog with pyometra (3%), and was not associated with longer hospitalisation or presence of SIRS. Lactate measurement was not indicative of peritonitis. None of the bitches died during or within two months of the hospital stay. The measurements of temperature, heart rate, respiratory rate, percentage bandforms of neutrophilic granulocytes, α₂-globulins, creatinin, pvCO₂, TCO₂and base excess showed significant differences between the SIRS positive and the SIRS negative pyometra cases.</p> <p>Conclusion</p> <p>Increased blood lactate concentrations were demonstrated in 3% (1/31), and SIRS was present in 61% (19/31) of the female dogs with pyometra. Preoperative lactate levels were not related with presence of SIRS or prolonged hospitalisation. Lactate measurement was not indicative of peritonitis. The value of a single and repeated lactate analysis in more severely affected cases remains to be determined.</p

Altering Mucus Rheology to “Solidify” Human Mucus at the Nanoscale

The ability of mucus to function as a protective barrier at mucosal surfaces rests on its viscous and elastic properties, which are not well understood at length scales relevant to pathogens and ultrafine environmental particles. Here we report that fresh, undiluted human cervicovaginal mucus (CVM) transitions from an impermeable elastic barrier to non-adhesive objects sized 1 µm and larger to a highly permeable viscoelastic liquid to non-adhesive objects smaller than 500 nm in diameter. Addition of a nonionic detergent, present in vaginal gels, lubricants and condoms, caused CVM to behave as an impermeable elastic barrier to 200 and 500 nm particles, suggesting that the dissociation of hydrophobically-bundled mucin fibers created a finer elastic mucin mesh. Surprisingly, the macroscopic viscoelasticity, which is critical to proper mucus function, was unchanged. These findings provide important insight into the nanoscale structural and barrier properties of mucus, and how the penetration of foreign particles across mucus might be inhibited