Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway.

BACKGROUND Elevated levels of interleukin-6 (IL-6) have been identified in a variety of systemic inflammatory states that are associated with endothelial barrier dysfunction, but the specific effect of IL-6 on endothelial permeability and the mechanism of action have not been fully examined. The current study evaluated the effect of IL-6 on endothelial permeability and on the distribution of the tight junctional protein ZO-1 and cytoskeletal actin. We also assessed the role of protein kinase C (PKC) in this process. METHODS Confluent monolayers of human umbilical vein endothelial cells (n = 6) were exposed to IL-6 (50-500 ng/ml) in the presence or absence of the PKC inhibitor Gö6976 (0.1 microM). Transendothelial electrical resistance (TEER) was measured at the onset of exposure and at 6-h intervals and compared with that of control cells using ANOVA with a Bonferroni multiple comparison test. Additional monolayers were exposed to IL-6, stained for ZO-1 and F-actin, and evaluated via fluorescence microscopy. RESULTS Interleukin-6 increased endothelial permeability as measured by TEER in a dose- and time-dependent manner. In the presence of PKC inhibitor, the IL-6-mediated increase in permeability was attenuated (18-h TEER 73% of control with IL-6 exposure vs 95% of control with IL-6 + Gö6976 inhibitor, P < 0.01). Microscopy revealed that permeability changes were accompanied by a redistribution of the tight junctional protein ZO-1 and cytoskeletal actin, increased cell contraction, and disorganization of the intercellular borders. Conclusions. The inflammatory cytokine IL-6 is an important mediator of increased endothelial permeability via alterations in the ultrastructural distribution of tight junctions and morphologic changes in cell shape. PKC is a critical intracellular messenger in these IL-6-mediated changes. A better understanding of this mechanism should allow the determination of rational treatment strategies for endothelial barrier dysfunction which occurs in inflammatory states.
PGE2‐EP2 signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF‐κB

BACKGROUND AND PURPOSE Cerebral aneurysm is a frequent cerebrovascular event and a major cause of fatal subarachnoid haemorrhage, but there is no medical treatment for this condition. Haemodynamic stress and, recently, chronic inflammation have been proposed as major causes of cerebral aneurysm. Nevertheless, links between haemodynamic stress and chronic inflammation remain ill‐defined, and to clarify such links, we evaluated the effects of prostaglandin E2 (PGE2), a mediator of inflammation, on the formation of cerebral aneurysms.
Pharmacokinetics and human tissue penetration of flurithromycin

The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.
Integrin-Mediated First Signal for Inflammasome Activation in Intestinal Epithelial Cells

How intestinal epithelial cells (IECs) recognize pathogens and activate inflammasomes at intestinal surfaces is poorly understood. We hypothesized that IECs use integrin receptors to recognize pathogens and initiate inflammation within the intestinal tract. We find that IECs infected with Yersinia enterocolitica, an enteric pathogen, use β1 integrins as pathogen recognition receptors detecting the bacterial adhesin invasin (Inv). The Inv–integrin interaction provides the first signal for NLRP3 inflammasome activation with the type three secretion system translocon providing the second signal for inflammasome activation, resulting in release of IL-18. During infection, Yersinia employs two virulence factors, YopE and YopH, to counteract Inv-mediated integrin-dependent inflammasome activation. Furthermore, NLRP3 inflammasome activation in epithelial cells requires components of the focal adhesion complex signaling pathway, focal adhesion kinase, and rac1. The binding of Inv to β1 integrins rapidly induces IL-18 mRNA expression, suggesting integrins provide a first signal for NLRP3 inflammasome activation. These data suggest integrins function as pathogen recognition receptors on IECs to rapidly induce inflammasome-derived IL-18–mediated responses.
Foraging Behavior of Subantarctic Fur Seals Supports Efficiency of a Marine Reserve’s Design

Foraging behaviour of marine top predators is increasingly being used to identify areas of ecological importance. This is largely enabled by the ability of many such species to forage extensively in search of prey that is often concentrated in oceanographically productive areas. To identify important habitat in the Southern Indian Ocean within and around South Africa’s Prince Edward Islands’ Marine Protected Area (MPA), satellite transmitters were deployed on 12 lactating Subantarctic fur seals Arctocephalus tropicalis at Prince Edward Island (PEI) itself. Switching state space models were employed to correct ARGOS tracks and estimate behavioural states for locations along predicted tracks, namely travelling or area restricted search (ARS). A random forest model showed that distance from the study colony, longitude and distance from the Subantarctic Front were the most important predictors of suitable foraging habitat (inferred from ARS). Model-predicted suitable habitat occurred within the MPA in relatively close access to the colony during summer and autumn, but shifted northwards concurrently with frontal movements in winter and spring. The association of ARS with the MPA during summer-autumn was highly significant, highlighting the effectiveness of the recently declared reserve’s design for capturing suitable foraging habitat for this and probably other marine top predator species.
Pre-season dietary intake of professional soccer players

Background: Despite the well-documented importance of nutrition in optimizing performance and health, the dietary intake of soccer players has attracted little attention. Aim: We aimed to assess the pre-season dietary intake of professional soccer players and its adequacy in macro and micronutrients. Methods: The pre-season dietary intake of 19 male athletes was assessed using a semi-structured 3-day food record. To determine dietary adequacy and excess, energy and macronutrient intake were compared with the Brazilian dietary reference values for athletes, and micronutrients were compared with the Estimated Average Requirement – EAR (minimum recommendation) and Tolerable Upper Intake Level – UL (maximum recommendation). Results: Mean daily energy intake (40.74±12.81 kcal/kg) was adequate. However, there was a low carbohydrate intake (5.44±1.86 g/kg/day) and a high amount of protein and fat (1.91±0.75 and 1.27±0.50 g/kg/day, respectively). Sodium intake (3141.77±939.76 mg/day) was higher than UL (2300 mg/day), while the majority of players showed daily intake of vitamin A (74%), vitamin D (100%), folate (58%), calcium and magnesium (68%) below the EAR (625, 10 and 320 µg/day, 800 and 330 mg/day, respectively). Conclusion: The dietary intake of professional soccer players was adequate in energy, but inadequate in macro and micronutrients, which suggests the need to improve nutritional practices to sustain the physical demands of soccer during pre-season.
Retracted: CDP/cut is an osteoblastic coactivator of the vitamin D receptor (VDR)

Retraction: The following article from the Journal of Bone and Mineral Research, “CDP/Cut Is an Osteoblastic Coactivator of the Vitamin D Receptor (VDR)” by Eiji Ochiai, Hirochika Kitagawa, Ichiro Takada, Sally Fujiyama, Shun Sawatsubashi, Mi‐sun Kim,Yoshihiro Mezaki, Yu Tsushima, Ken‐ichiro Takagi, Yoshiaki Azuma, Ken‐ichi Takeyama, Kazuyoshi Yamaoka, Shigeaki Kato, Takashi Kamimura, published online on December 11, 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Thomas Clemens, the American Society for Bone and Mineral Research and Wiley Periodicals, Inc. The authors have requested the retraction based on their acknowledgement that several of the figures did not reflect the observations presented.
Qualitative Study of Cervical Cancer Screening Among Lesbian and Bisexual Women and Transgender Men

Background: Lesbian, bisexual, and queer (LBQ) women, as well as transgender men, are less likely than their heterosexual and female-identifying counterparts to access cervical cancer screening services. Although numerous factors that influence receipt of cervical screening have been identified, several gaps in research and knowledge merit additional research. Objective: The aims of this study were to examine cervical cancer screening behaviors of LBQ women and transgender men using American Cancer Society guidelines as the standards for comparison and to determine factors that influence participation in cervical cancer screening. Methods: A convenience sample of 21- to 65-year-old LBQ women and transgender men was recruited from the Internet and community events. Qualitative data were collected through in-depth telephone interviews and open-ended questions on an online questionnaire. A deductive-inductive content analysis approach was used. Results: The sample was mostly non-Hispanic white women who identified as lesbian. Most were routine cervical cancer screeners. Eighteen factors/themes were identified in the data and were contextualized within a health services theoretical framework. Conclusions: This study showed that although some factors overlap with the general female population, there are other areas that are specific to LBQ women and transgender men. Creating welcoming and inclusive healthcare environments is particularly important to facilitating cervical screening among LBQ women. Implications for Practice: Nurse leaders can modify clinical environments, and clinical nurses can be educated to provide safe care for LBQ women and transgender men.
Epidemiology of respiratory syncytial virus infection in rural and urban Kenya.

BACKGROUND Information on the epidemiology of respiratory syncytial virus (RSV) infection in Africa is limited for crowded urban areas and for rural areas where the prevalence of malaria is high. METHODS At referral facilities in rural western Kenya and a Nairobi slum, we collected nasopharyngeal/oropharyngeal (NP/OP) swab specimens from patients with influenza-like illness (ILI) or severe acute respiratory illness (SARI) and from asymptomatic controls. Polymerase chain reaction assays were used for detection of viral pathogens. We calculated age-specific ratios of the odds of RSV detection among patients versus the odds among controls. Incidence was expressed as the number of episodes per 1000 person-years of observation. RESULTS Between March 2007 and February 2011, RSV was detected in 501 of 4012 NP/OP swab specimens (12.5%) from children and adults in the rural site and in 321 of 2744 NP/OP swab specimens (11.7%) from those in the urban site. Among children aged <5 years, RSV was detected more commonly among rural children with SARI (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3), urban children with SARI (OR, 8.5; 95% CI, 3.1-23.6), and urban children with ILI (OR, 3.4; 95% CI, 1.2-9.6), compared with controls. The incidence of RSV disease was highest among infants with SARI aged <1 year (86.9 and 62.8 episodes per 1000 person-years of observation in rural and urban sites, respectively). CONCLUSIONS An effective RSV vaccine would likely substantially reduce the burden of respiratory illness among children in rural and urban areas in Africa.
Neutrophil functions and cytokine production in patients with gastric cancer.

BACKGROUND/AIMS One of the most important factors in the prevention of postoperative infection is the patient's own capacity to protect against infection. Neutrophils play a major role in this protection through phagocytosis and superoxide generation. Inflammatory cytokines are suitable for estimating the degree of surgical stress. The present study was designed to elucidate whether neutrophil functions are impaired in gastric cancer patients, and are related with cytokine production after surgery. METHODOLOGY Phagocytosis and superoxide generation by neutrophils was studied in 84 patients with gastric cancer by flow cytometry. IL-6, IL-8 and tumor necrosis factor alpha were studied in 18 patients with gastric cancer by enzyme-linked immunosolubent assay. RESULTS In gastric cancer patients phagocytosis was not impaired, whereas superoxide generation was lower than benign diseases and it was inhibited relative to the clinical stage. Moreover, superoxide generation was correlated with the nutritional parameters and was more suppressed in 7 patients who suffered from postoperative infection than in 40 patients whose postoperative course were uneventful. The fluctuation of superoxide generation correlated well with the serum cytokine levels in the postoperative course and its correlation was clarified in vitro. Nine patients with gastric cancer received intravenous hyperalimentation, and their superoxide generation was increased. CONCLUSIONS Superoxide generation by neutrophils was suppressed in gastric cancer patients and it is suggested that nutritional support prevents postoperative infection via the augmentation of superoxide generation.
Non‐receptor‐mediated activation of IK(ATP) and inhibition of IK(ACh) by diadenosine polyphosphates in guinea‐pig atrial myocytes

1 The effects of diadenosine polyphosphates (APnA, where n= 4–6) were studied on beating frequency of perfused guinea‐pig hearts and on muscarinic K+ current (IK(ACh)) and ATP‐regulated K+ current (IK(ATP)) in atrial myocytes from guinea‐pig hearts using whole‐cell voltage clamp. 2 Bradycardia induced by APnA in perfused hearts was completely inhibited by 8‐cyclopentyl‐ 1,3‐dipropylxanthine (CPX, 20 μm), a selective antagonist at A1 adenosine receptors, and was augmented by dipyridamole (Dipy), an inhibitor of cellular adenosine (Ado) uptake. 3 Whereas exposure of atrial myocytes to Ado (100 μm) within about 1 s induced a significant whole‐cell IK(ACh), APnA up to 1 mm applied for some tens of seconds failed to activate IK(ACh). If present for periods > 2 min, APnA caused inhibition of agonist‐evoked IK(ACh) and activation of a weakly inward rectifying K+ current, which was identified as IK(ATP) by its sensitivity to glibenclamide and its current‐voltage curve. 4 The actions of extracellular APnA on IK(ACh) and IK(ATP) were mimicked by intracellular loading of compounds via the patch clamp pipette and by intracellular loading of AMP. 5 The results from isolated myocytes exclude APnA acting as A1 agonists. It is suggested that myocytes can take up APnA, which are degraded to AMP. In the presence of ATP, AMP is converted to ADP, a physiological activator of ATP‐regulated K+ channels, by adenylate kinase. A similar mechanism resulting in a reduction of the [GTP]/[GDP] ratio might be responsible for inhibition of IK(ACh). 6 In the perfused heart and other multicellular cardiac preparations the actions of APnA are mediated by Ado via A1 receptors. It is suggested that APnA in multicellular cardiac tissue are hydrolysed by an ectohydrolase to yield AMP which is converted to Ado by ectonucleotidases.
An assessment of the surgical outcome and urodynamic effects of the pubovaginal sling for stress incontinence and the associated urge syndrome.

PURPOSE We assessed the urodynamic changes after pubovaginal sling procedure for stress incontinence, particularly in regard to the associated symptoms of urgency, frequency, nocturia and urge incontinence, known as the urge syndrome. MATERIALS AND METHODS A total of 85 women with proved stress incontinence underwent a pubovaginal sling procedure using rectus fascia between 1992 and August 1996. Of the women 41 (48%) had undergone previous anti-incontinence surgery and 59 (69%) had the associated urge syndrome. There was at least some degree of hypermobility in 51 cases and type III stress incontinence was diagnosed in 34. Patients were assessed with a questionnaire and video urodynamics preoperatively and 3 months postoperatively. Preoperative and postoperative ambulatory studies were performed in 25 cases. RESULTS Of the 85 patients 83 (97%) were symptomatically cured of stress incontinence. The urge syndrome resolved in 32 patients (69%), almost all of whom had a closed bladder neck at rest. Overall bladder neck incompetence at rest decreased from 57 to 18% (p<0.001). Of 27 patients with the persistent urge syndrome postoperatively 9 (41%) had an open bladder neck at rest compared to 4 of 50 (8%) without urge incontinence (p<0.01). Despite symptomatic control of stress incontinence in 83 patients (97%), only 66 were satisfied with the surgical result, mainly because of the persistent urge syndrome in 27. Despite care to avoid obstruction overall, there were statistically significant obstructive changes in detrusor pressure at maximum flow rate, maximum flow rate and residual urine volumes. CONCLUSIONS The pubovaginal sling is effective in curing genuine stress incontinence and, when correctly placed at the right tension, the associated urge syndrome also can be managed, usually by achieving bladder neck closure at rest. However, despite careful maneuvers, obstruction occasionally persists.
Protection to Fasciola hepatica in the gut mucosa of immune rats is associated with infiltrates of eosinophils, IgG1 and IgG2a antibodies around the parasites

We investigated the immune effector mechanisms that underlie protection against F. hepatica in the gut wall of immune rats, using (immuno)histochemistry. In the lamina propria of immune Wistar rats, four weeks after oral infection, frequencies of IgE‐positive cells, eosinophils and mucosal mast cells were significantly increased, compared with naïve rats. These factors represent the traditional effector mechanisms against helminths. No significant differences were detected between the two groups in frequencies of IgM‐, IgG2a‐, IgG1‐ and IgA‐ positive cells, CD4‐ and CD8‐positive cells, NK cells, macrophages, neutrophils or goblet cells. Upon challenge of immune rats with F. hepatica in an ex vivo gut segment, NEJs that migrated through the (sub)mucosa were coated with IgG1 and IgG2a antibodies and surrounded by eosinophils. No IgE or IgA antibodies were detected on the parasites. The onset of these immune effector responses, two h after challenge, was related to the expression of protection. These results suggest that NEJs are killed by an eosinophil‐mediated cytotoxic response involving IgG antibodies. These antibodies were not produced in the intestine, but infiltrated the gut upon challenge. The observed immune effector responses were not restricted to the site where the primary infection is located, namely the small intestine, but were also detected in the large intestine. The presence of the protective immune mechanisms in two other rat strains demonstrates the pivotal importance of these responses, irrespective the genetic background of the host.
A human retinal pigment epithelial cell line that retains epithelial characteristics after prolonged culture.

PURPOSE A spontaneously arising, apparently transformed, cell line has been cloned from a primary culture of human retinal pigment epithelial (RPE) cells and has been subcultured more than 200 times. The similarities of these cells to human RPE cells in vivo have been determined. METHODS The structure of the transformed cells has been determined by light and electron microscopy and by immunocytochemistry using antibodies that detect cytoskeletal and other proteins. The ability of the cell line to bind and phagocytose photoreceptor material has also been assessed by fluorescence and electron microscopy. The metabolism of all-trans-retinol has been investigated by incubation of the cells with 3H-all-trans-retinol and analysis of the metabolic products by high-performance liquid chromatography. RESULTS The transformed cells possess an epithelial cobblestone morphology with intercellular junctional complexes containing N-cadherin. The cytoskeleton of these cells comprises cytokeratins that are characteristic of epithelial cells, together with actin, spectrin, and vimentin. The keratins expressed are those typical of RPE cells. The cells also express cellular retinaldehyde binding protein and retinol dehydrogenase activity but do not express retinoid isomerase or lecithin retinol acyl transferase activities. These cells also exhibit phagocytic activity. CONCLUSIONS This cell line retains many of the metabolic and morphologic characteristics of RPE cells in vivo although there are some differences, particularly the loss of some enzymatic activities and cytoskeletal polarization. These cells should be useful in further studies of RPE cell metabolism and other functions.
Setting Conservation Priorities

A generic framework for setting conservation priorities based on the principles of classic decision theory is provided. This framework encapsulates the key elements of any problem, including the objective, the constraints, and knowledge of the system. Within the context of this framework the broad array of approaches for setting conservation priorities are reviewed. While some approaches prioritize assets or locations for conservation investment, it is concluded here that prioritization is incomplete without consideration of the conservation actions required to conserve the assets at particular locations. The challenges associated with prioritizing investments through time in the face of threats (and also spatially and temporally heterogeneous costs) can be aided by proper problem definition. Using the authors’ general framework for setting conservation priorities, multiple criteria can be rationally integrated and where, how, and when to invest conservation resources can be scheduled. Trade‐offs are unavoidable in priority setting when there are multiple considerations, and budgets are almost always finite. The authors discuss how trade‐offs, risks, uncertainty, feedbacks, and learning can be explicitly evaluated within their generic framework for setting conservation priorities. Finally, they suggest ways that current priority‐setting approaches may be improved.