Miracle-dz/UniFAR-FTUs huggingface dataset:
Release of Free F2-isoprostanes from Esterified Phospholipids Is Catalyzed by Intracellular and Plasma Platelet-activating Factor Acetylhydrolases*

F2-isoprostanes are produced in vivo by nonenzymatic peroxidation of arachidonic acid esterified in phospholipids. Increased urinary and plasma F2-isoprostane levels are associated with a number of human diseases. These metabolites are regarded as excellent markers of oxidant stress in vivo. Isoprostanes are initially generated in situ, i.e. when the arachidonate precursor is esterified in phospholipids, and they are subsequently released in free form. Although the mechanism(s) responsible for the release of free isoprostanes after in situ generation in membrane phospholipids is, for the most part, unknown, this process is likely mediated by phospholipase A2 activity(ies). Here we reported that human plasma contains an enzymatic activity that catalyzes this reaction. The activity associates with high density and low density lipoprotein and comigrates with platelet-activating factor (PAF) acetylhydrolase on KBr density gradients. Plasma samples from subjects deficient in PAF acetylhydrolase do not release F2-isoprostanes from esterified precursors. The intracellular PAF acetylhydrolase II, which shares homology to the plasma enzyme, also catalyzes this reaction. We found that both the intracellular and plasma PAF acetylhydrolases have high affinity for esterified F2-isoprostanes. However, the rate of esterified F2-isoprostane hydrolysis is much slower compared with the rate of hydrolysis of other substrates utilized by these enzymes. Studies using PAF acetylhydrolase transgenic mice indicated that these animals have a higher capacity to release F2-isoprostanes compared with nontransgenic littermates. Our results suggested that PAF acetylhydrolases play key roles in the hydrolysis of F2-isoprostanes esterified on phospholipids in vivo.
Is measured hearing aid benefit affected by seeing baseline outcome questionnaire responses?

PURPOSE To determine whether hearing aid outcome measured by the Hearing Handicap Inventory (HHI) for the Elderly/Adults (Newman, Weinstein, Jacobson, & Hug, 1990; Ventry & Weinstein, 1982) is differentially affected by informed vs. blind administration of the postfitting questionnaire. METHOD Participants completed the HHI at their hearing aid evaluation and again at their hearing aid follow-up visit. At follow-up, half received a clean HHI form (blind administration), whereas the remainder responded on their original form (informed administration) and could thus base their follow-up responses on those they gave at the hearing aid evaluation. RESULTS The data show that for the population examined here, informed administration of the follow-up HHI did not yield a different outcome to blind administration of the follow-up HHI. This was not influenced by past hearing aid use, age of the participant, or the duration of time between baseline questionnaire completion and follow-up completion. CONCLUSION These data suggest that completion of follow-up questionnaires in either informed or blind format will have little impact on HHI responses, most likely because of the many other factors that combined to influence hearing aid outcome.
Ovariotomy for menstrual madness and premenstrual syndrome – 19th century history and lessons for current practice

Ovariotomy – the removal of normal ovaries, known as Battey's Operation – began in 1872 and became the fashionable treatment of menstrual madness, neurasthenia, nymphomania, masturbation and “all cases of insanity”. This practice was supported by distinguished gynecologists and psychiatrists, becoming one of the great medical scandals of the 19th century. In modern times, if menstrual madness is considered to be premenstrual dysphoric disorder (PMDD), and ovariotomy, the surgical equivalent of ovulation suppression of GnRH analogues, it can be argued that the surgery would have been effective for this limited indication, although the side effects of long-term estrogen deficiency would have made the treatment unacceptable. Currently, the successful hormonal treatment of PMDD is one of suppression of ovulation and removal of the cyclical hormonal changes in the luteal phase, probably progesterone, which is the essential cause of PMDD. Such therapy would be by GnRH analogues, transdermal estradiol and, in a few cases, the surgical option of hysterectomy and bilateral salpingo-oophorectomy with adequate hormone replacement. A study of medical history can help us prevent the mistakes of over-enthusiasm but positive lessons can be learned.
Glucagon-like peptide 1 and its potential in the treatment of non-insulin-dependent diabetes mellitus.

Studies examining small groups of type 2-(NIDDM) diabetic patients have shown the potential of glucagon-like peptide 1 (GLP-1) to normalize fasting hyperglycaemia. Patient characteristics determining the size of the effect have not been reported. Therefore, the results of four studies were analysed. Exogenous GLP-1 was administered i.v. or s.c. in 37 type 2-diabetic patients, age 60 +/- 8 years; BMI 28.2 +/- 5.3 kg/m2; HbA1c 10.6 +/- 1.6%; diabetes duration 10 +/- 6 years, treatment with sulfonylureas, n = 33, metformin, n = 11, acarbose, n = 3. Results were analysed using repeated measures analysis of variance and multiple regression analysis. Exogenous GLP-1 lowered fasting plasma glucose within 4-5 h from 12.8 +/- 2.5 to 5.3 +/- 1.3 mmol/l (placebo: 12.8 +/- 2.3 to 10.0 +/- 2.2; p < 0.0001 for the interaction of treatment and time). Only fasting glycaemia (p = 0.0085) and the route (i.v. vs. s.c.; p = 0.05), but not gender, age, BMI, HbA1c, diabetes duration, treatment with sulfonylureas, metformin or acarbose, were significant predictors of the plasma glucose concentrations reached after the administration of GLP-1 (variation: 3.4-8.5 mmol/l). In conclusion, GLP-1 is able to normalize plasma glucose in all type 2-diabetic patients studied. This analysis underlines the great therapeutic potential of GLP-1.
Molecular mechanisms mediating protective effect of cAMP on lipopolysaccharide (LPS)‐induced human lung microvascular endothelial cells (HLMVEC) hyperpermeability

Up to date, the nature of the sepsis‐induced vascular leakage is understood only partially, which limits pharmacological approaches for its management. Here we studied the protective effect of cAMP using endotoxin‐induced hyperpermeability as a model for barrier dysfunction observed in gram‐negative sepsis. We demonstrated that the alleviation of lipopolysaccharide (LPS)‐induced barrier compromise could be achieved by the specific activation of either protein kinase A (PKA) or Epac with cAMP analogs Bnz‐cAMP or O‐Me‐cAMP, respectively. We next studied the involvement of PKA substrates VASP and filamin1 in barrier maintenance and LPS‐induced barrier compromise. Depletion of both VASP and filamin1 with the specific siRNAs significantly exacerbated both the quiescent cells barrier and LPS‐induced barrier dysfunction, suggesting barrier‐protective role of these proteins. VASP depletion was associated with the more severe loss of ZO‐1 peripheral staining in response to LPS, whereas filamin1‐depleted cells reacted to LPS with more robust stress fiber induction and more profound changes in ZO‐1 and VE‐cadherin peripheral organization. Both VASP and filamin1 phosphorylation was significantly increased as a result of PKA activation. We next analyzed the effect of VASP and filamin1 depletion on the PKA‐dependent alleviation of LPS‐induced barrier compromise. We observed that Bnz‐cAMP ability to counteract LPS‐induced hyperpermeability was attenuated only by VASP, but not filamin1 depletion. Our data indicate that while PKA‐dependent VASP phosphorylation contributes to the protective effect of cAMP elicited on LPS‐compromised monolayers, filamin1 phosphorylation is unlikely to play a significant role in this process. J. Cell. Physiol. 221: 750–759, 2009. © 2009 Wiley‐Liss, Inc.
Rescue of Dopamine Transporter Function in Hypoinsulinemic Rats by a D2 Receptor–ERK-Dependent Mechanism

The dopamine (DA) transporter (DAT) is a major target for abused drugs and a key regulator of extracellular DA. A rapidly growing literature implicates insulin as an important regulator of DAT function. We showed previously that amphetamine (AMPH)-evoked DA release is markedly impaired in rats depleted of insulin with the diabetogenic agent streptozotocin (STZ). Similarly, functional magnetic resonance imaging experiments revealed that the blood oxygenation level-dependent signal following acute AMPH administration in STZ-treated rats is reduced. Here, we report that these deficits are restored by repeated, systemic administration of AMPH (1.78 mg/kg, every other day for 8 d). AMPH stimulates DA D2 receptors indirectly by increasing extracellular DA. Supporting a role for D2 receptors in mediating this “rescue,” the effect was completely blocked by pre-treatment of STZ-treated rats with the D2 receptor antagonist raclopride before systemic AMPH. D2 receptors regulate DAT cell surface expression through ERK1/2 signaling. In ex vivo striatal preparations, repeated AMPH injections increased immunoreactivity of phosphorylated ERK1/2 (p-ERK1/2) in STZ-treated but not control rats. These data suggest that repeated exposure to AMPH can rescue, by activating D2 receptors and p-ERK signaling, deficits in DAT function that result from hypoinsulinemia. Our data confirm the idea that disorders influencing insulin levels and/or signaling, such as diabetes and anorexia, can degrade DAT function and that insulin-independent pathways are present that may be exploited as potential therapeutic targets to restore normal DAT function.
Novel Cadmium Resistance Determinant in Listeria monocytogenes

ABSTRACT Listeria monocytogenes is a foodborne pathogen that can cause severe disease (listeriosis) in susceptible individuals. It is ubiquitous in the environment and often exhibits resistance to heavy metals. One of the determinants that enables Listeria to tolerate exposure to cadmium is the cadAC efflux system, with CadA being a P-type ATPase. Three different cadA genes (designated cadA1 to cadA3) were previously characterized in L. monocytogenes. A novel putative cadmium resistance gene (cadA4) was recently identified through whole-genome sequencing, but experimental confirmation for its involvement in cadmium resistance is lacking. In this study, we characterized cadA4 in L. monocytogenes strain F8027, a cadmium-resistant strain of serotype 4b. By screening a mariner-based transposon library of this strain, we identified a mutant with reduced tolerance to cadmium and that harbored a single transposon insertion in cadA4. The tolerance to cadmium was restored by genetic complementation with the cadmium resistance cassette (cadA4C), and enhanced cadmium tolerance was conferred to two unrelated cadmium-sensitive strains via heterologous complementation with cadA4C. Cadmium exposure induced cadA4 expression, even at noninhibitory levels. Virulence assessments in the Galleria mellonella model suggested that a functional cadA4 suppressed virulence, potentially promoting commensal colonization of the insect larvae. Biofilm assays suggested that cadA4 inactivation reduced biofilm formation. These data not only confirm cadA4 as a novel cadmium resistance determinant in L. monocytogenes but also provide evidence for roles in virulence and biofilm formation. IMPORTANCE Listeria monocytogenes is an intracellular foodborne pathogen causing the disease listeriosis, which is responsible for numerous hospitalizations and deaths every year. Among the adaptations that enable the survival of Listeria in the environment are the abilities to persist in biofilms, grow in the cold, and tolerate toxic compounds, such as heavy metals. Here, we characterized a novel determinant that was recently identified on a larger mobile genetic island through whole-genome sequencing. This gene (cadA4) was found to be responsible for cadmium detoxification and to be a divergent member of the Cad family of cadmium efflux pumps. Virulence assessments in a Galleria mellonella model suggested that cadA4 may suppress virulence. Additionally, cadA4 may be involved in the ability of Listeria to form biofilms. Beyond the role in cadmium detoxification, the involvement of cadA4 in other cellular functions potentially explains its retention and wide distribution in L. monocytogenes.
Critical junctures and the Department of Finance: from DPS to DPER?

ABSTRACT Critical junctures are an enduring concept in the study of institutional change, but the literature prompts a certain amount of definitional ambiguity around what a critical juncture is, and how best we should approach describing and explaining these rare instances of change. This paper presents and utilises a revised critical juncture framework, which helps to explore the role of context, openings, institutions, ideas, agents and discourse in these significant change events. The framework is then utilised in relation to the Irish Department of Finance (DoF), which is a pivotal institution at the heart of the Irish system of government. It is argued that the DoF’s position and influence in government have been impacted by three institutional change events, involving the establishment of the Department of the Public Service (DPS) in 1973; its disbandment in 1987; and the establishment of the Department of Public Expenditure and Reform (DPER) in 2011. The available evidence supports a linkage between DPS’ establishment and DPER’s establishment almost 40 years later.
Involvement of CRM1, a nuclear export receptor, in mRNA export in mammalian cells and fission yeast

CRM1, an evolutionarily conserved protein, was shown to be a receptor for leucine‐rich nuclear export signal (NES)‐dependent protein transport. In lower eukaryotes CRM1 is reported to be required for the export of mRNA, however, involvement of the NES‐dependent transport pathway in mRNA export in higher eukaryotes has not been established.
Dynamic visual saliency modeling based on spatiotemporal analysis

Producing an appropriate extent of visually salient regions in video sequences is a challenging task. In this work, we propose a novel approach for modeling dynamic visual attention based on spatiotemporal analysis. Our model first detects salient points in three-dimensional video volumes, and then uses them as seeds to search the extent of salient regions in a motion attention map. To determine the extent of attended regions, the maximum entropy in the spatial domain is used to analyze the dynamics obtained from spatiotemporal analysis. The experiment results show that the proposed dynamic visual attention model can effectively detect visual saliency through successive video volumes.
Current Landscape and Potential of Mobile Computing Research in the Least Developed Countries

Despite the huge potentialities, the actual growth of information and communications technology (ICT) in the least developed countries (LDCs) is still hindered by a number of factors beyond the infrastructural constraints. However, over the last decade, mobile computing has emerged as an important means to bridge the longstanding digital divide between LDCs and first world countries by accelerating the diffusion of various services (government, business, health, education and environment) through mobile devices. These services can be classified according to their domain of application, such as m‐agriculture, m‐finance, m‐banking, m‐commerce, m‐government, m‐health and m‐learning. The overreaching goal of this paper is to explore mobile applications and services in LDCs and to assess the extent of research that has permeated in this area within the LDCs. The research questions that this paper seeks to answer are: what has existing research in LDCs identified regarding mobile technology applications, services and usage; and what are the typical characteristics and trends of mobile computing technology innovation and services within LDCs? The paper presents a comprehensive literature review of 480 articles on mobile technology application and services in the LDCs from the basket of Information Systems literature. The review draws on the current landscape of mobile computing studies in the LDCs to analyse and evaluate research trends, focus, regional priorities and gaps. Through the meta‐analysis of secondary data, the paper highlights some interesting comparisons about mobile technologies among the LDCs as regards to research themes, focus areas and applications. Also, based on an assessment of current state of research, the paper identifies gaps and potential research directions.
Fresh-keeping and Pricing Strategy for Fresh Agricultural Product Based on Customer Choice

According to the deteriorating characteristics of the fresh agricultural product and the variety of consumer preference,a time-varying consumer choice model influenced by the greenness and price of the fresh agricultures product is developed.Based on the change of the ordering quantity and potential market capacity,the optimal pricing and optimal input for fresh-keeping of the retailer are analyzed.The results indicate that the profit gained from fresh-keeping,the optimal price and optimal input for fresh-keeping all decrease with the increase of the order quantity when the potential market capacity is small.And when the potential market capacity is large,the profit gained from fresh-keeping and the optimal price also decrease with the increase of the order quantity,however,the optimal input for fresh-keeping increase with the order quantity rise.
Intraoperative fracture of the femur in revision total hip arthroplasty with a diaphyseal fitting stem.

BACKGROUND In revision total hip arthroplasty, intraoperative split fractures and cortical perforation fractures are becoming a more common concern with the increasing use of diaphyseal fitting cementless stems. The purpose of this study was to evaluate the risk factors and frequency of intraoperative fractures with the use of these stems and their effect on radiographic and functional outcomes. METHODS We performed a retrospective case-control study of 211 consecutive patients who had undergone revision hip arthroplasty with a diaphyseal fitting cementless stem between December 1998 and March 2002. Sixty-four patients sustained an intraoperative fracture of the femur. One hundred and fifteen patients were followed for a minimum of two years; function was analyzed with self-administered outcome questionnaires, and radiographs were evaluated for evidence of bone ingrowth into the femoral stem. RESULTS Risk factors associated with an intraoperative fracture were a substantial degree of preoperative bone loss, a low femoral cortex-to-canal ratio, underreaming of the cortex, and the use of a large-diameter stem. The majority of the diaphyseal undisplaced linear fractures occurred at the distal end of an extended trochanteric osteotomy during stem insertion. Fracture due to cortical perforation occurred most often during cement removal. These intraoperative fractures had no significant effect on the functional outcome or radiographic evidence of bone ingrowth. CONCLUSIONS There was a surprisingly high rate of intraoperative femoral fractures associated with the use of a diaphyseal fitting stem in revision total hip arthroplasty. Identification of risk factors such as preoperative bone loss and a low cortex-to-canal ratio may permit planning to avoid such fractures. However, the final functional and radiographic outcomes appear to have been unaffected by the fracture when it had been managed appropriately. LEVEL OF EVIDENCE Prognostic study, Level II-1 (retrospective cohort study). See Instructions to Authors for a complete description of levels of evidence.
Assessment of enthesitis in ankylosing spondylitis

Objective: To assess, firstly, the validity of the enthesis index published by Mander (Mander enthesis index (MEI)) and, secondly, to investigate whether it is possible to define a new enthesis index that is less time consuming to perform with at least similar or better properties. Methods: Data from the OASIS cohort, an international, longitudinal, observational study on outcome in ankylosing spondylitis, were used. In this study, measures of disease activity, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the MEI, were assessed regularly in 217 patients. With the MEI, for each measurement period independently, a process of data reduction was performed to identify the entheses most commonly reported as painful by the patients. A more concise enthesis index was constructed with aid of the entheses found in this way. Correlations with measures of disease activity were used to test the validity of several entheses indices. Results: Reduction of the number of entheses from 66 to 13 and omitting grading of the intensity of pain resulted in an index which was named the “Maastricht Ankylosing Spondylitis Enthesitis Score” (MASES). The MASES (range 0–13) has much greater feasibility than the MEI (range 0–90). However, up to 21% of patients with a score >0 on the MEI were not identified by a score on the MASES >0. Only 2.1% of the patients with an original enthesis score >0 had an original score on the MEI >3 (range 0–90) and it can be questioned whether a low score on the MEI index represents clinically important enthesitis. The Spearman correlation coefficient between the MASES score and the MEI was 0.90 and between the MASES and the BASDAI was 0.53 compared with a correlation of 0.59 between the MEI and the BASDAI. Conclusions: MASES seems to be a good alternative to the MEI with much better feasibility.
Detection of Intrastrain Antigenic Variation of Bacteroides fragilis Surface Polysaccharides by Monoclonal Antibody Labelling

ABSTRACT Bacteroides fragilis is a constituent of the normal resident microbiota of the human intestine and is the gram-negative obligately anaerobic bacterium most frequently isolated from clinical infection. Surface polysaccharides are implicated as potential virulence determinants. We present evidence of within strain immunochemical variation of surface polysaccharides in populations that are noncapsulate by light microscopy as determined by monoclonal antibody labelling. Expression of individual epitopes can be enriched from a population of an individual strain by use of immunomagnetic beads. Also, individual colonies in which either >94% or <7% of the bacteria carry an individual epitope retain this level of expression when subcultured into broth. In broth cultures where >94% of the bacteria carry a given epitope, there is no enrichment for other epitopes recognized by different polysaccharide-specific monoclonal antibodies. This intrastrain variation has important implications for the development of potential vaccines or immunodiagnostic tests.