Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-1 Enhances Pancreatic Islet Arachidonic Acid 12-Lipoxygenase Product Generation by Increasing Substrate Availability through a Nitric Oxide-dependent Mechanism (*)

Interleukin-1 (IL-1) impairs insulin secretion from pancreatic islets and may contribute to the pathogenesis of insulin-dependent diabetes mellitus. IL-1 increases islet expression of nitric oxide (NO) synthase, and the resultant overproduction of NO participates in inhibition of insulin secretion because NO synthase inhibitors, e.g.NG-monomethyl-arginine (NMMA), prevent this inhibition. While exploring effects of IL-1 on islet arachidonic acid metabolism, we found that IL-1 increases islet production of the 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid 12-(HETE). This effect requires NO production and is prevented by NMMA. Exploration of the mechanism of this effect indicates that it involves increased availabilty of the substrate arachidonic acid rather than enhanced expression of 12-lipoxygenase. Evidence supporting this conclusion includes the facts that IL-1 does not increase islet 12-lipoxygenase protein or mRNA levels and does not enhance islet conversion of exogenous arachidonate to 12-HETE. Mass spectrometric stereochemical analyses nonetheless indicate that 12-HETE produced by IL-1-treated islets consists only of the S-enantiomer and thus arises from enzyme action. IL-1 does enhance release of nonesterified arachidonate from islets, as measured by isotope dilution mass spectrometry, and this effect is suppressed by NMMA and mimicked by the NO-releasing compound 3-morpholinosydnonimine. Although IL-1 increases neither islet phospholipase A2 (PLA2) activities nor mRNA levels for cytosolic or secretory PLA2, a suicide substrate which inhibits an islet Ca2+-independent PLA2 prevents enhancement of islet arachidonate release by IL-1. IL-1 also impairs esterification of [3H8]arachidonate into islet phospholipids, and this effect is prevented by NMMA and mimicked by the mitochondrial ATP-synthase inhibitor oligomycin. Experiments with exogenous substrates indicate that NMMA does not inhibit and that the NO-releasing compound does not activate islet 12-lipoxygenase or PLA2 activities. These results indicate that a novel action of NO is to increase levels of nonesterified arachidonic acid in islets.
Monitored high-dose azathioprine treatment reduces acute rejection episodes after renal transplantation.

BACKGROUND Azathioprine (AZA) is widely used in organ transplantation. Common practice is to adjust dose according to body weight only, despite documented pharmacokinetic variability. The purpose of this study was to investigate whether high-dose AZA treatment monitored by 6-thioguanine nucleotides (6-TGN) levels reduces the incidence of rejection episodes in renal transplantation without a corresponding increase in myelotoxicity. METHODS Patients receiving cyclosporine, steroids, and AZA were randomized into either the low-dose AZA group (3 mg/kg on day 0, then 2 mg/kg/day the first week and 1 mg/kg/day thereafter) or the high-dose AZA group. In the latter, AZA was started at 5 mg/kg/day and then adjusted to keep 6-TGN concentrations (measured twice weekly) between 100 and 200 pmol/8 x 10(8) RBCs. RESULTS A total of 360 transplant recipients were included in the final analysis. The cumulative incidence of first rejection episodes was reduced by 21%, from 62.8% in the low-dose group to 49.4% in the high-dose group (difference: 13.3%; 95% confidence interval: 3.2-23.5). Similar results were found in subgroups according to HLA-DR match. The 6-TGN concentration was significantly higher in the high-dose AZA group during the first month, and the reduction in rejection episodes was achieved in the same period. A larger proportion of patients in the high-dose group had nadir white blood cell count below 2.0 x 10(9) leukocytes/L (13.3% vs. 4.4%; difference: 8.9%; confidence interval: 3.1-14.7). CONCLUSIONS High-dose AZA therapy in a triple-drug regimen, monitored by 6-TGN, will keep myelotoxicity within acceptable limits with the benefit of a reduction in acute rejection episodes.
Panic disorder and quality of life: variables predictive of functional impairment.

OBJECTIVE The authors sought to characterize the functional impairment in patients with panic disorder, specifically the variance in impairment explained by demographic and clinical variables. METHOD Sixty-two patients with panic disorder and 61 comparison subjects from three primary care clinic sites were assessed with an adapted form of the Structured Clinical Interview for DSM-III-R. Impairment was assessed according to three measures from the 36-item Short-Form Health Survey (general health perception, mental health, and physical functioning) as well as a principal component factor of the survey. Subjects were also compared with respect to personality variables, presence and severity of chronic medical illness, and demographic characteristics. Stepwise multiple regressions with and without pairwise interactions were used to construct models of disability in the patients with panic disorder. RESULTS The patients with panic disorder were more impaired than comparison subjects on each measure of the Short-Form Health Survey. The panic disorder diagnosis combined with major depression, increasing neuroticism and age, less education, and an interaction between panic disorder and age accounted for 48%-77% of the variance in impairment scores. Gender and ethnicity contributed modestly to the variance in impairment in physical functioning, whereas no contribution was demonstrated for chronic medical illness or city of residence. CONCLUSIONS Factors in addition to panic phenomena contribute to the severe impairment seen in patients with panic disorder. Further research about factors that affect impairment may help improve clinical approaches to this illness.
Dynamics of maternal union dissolution and childhood mortality in sub-Saharan Africa

ABSTRACT The family setting has implications for child survival. In this study, the dynamics of maternal union dissolution and childhood mortality were investigated in sub-Saharan Africa (SSA). Birth history data of 235 454 children from the most recent Demographic and Health Survey conducted in 23 SSA countries were analysed using life table techniques and piecewise exponential hazards models. The results revealed that the childhood mortality rates were 35 vs 32 per 1000 live births (one month), 61 vs 54 per 1000 (11 months) and 95 vs 86 per 1000 (48 months) for children of women in marital dissolution compared with those with intact marriages. Despite controlling for background variables, the risk of under-five mortality was significantly higher among children of women in marital dissolution (relative risk = 1.35, confidence interval: 1.30–1.40). The effect of dissolution on childhood mortality has not changed since the 1990s. Marital stability is an important social structure for child survival.
Extensive Phylogenetic Analysis of a Soil Bacterial Community Illustrates Extreme Taxon Evenness and the Effects of Amplicon Length, Degree of Coverage, and DNA Fractionation on Classification and Ecological Parameters

ABSTRACT To thoroughly investigate the bacterial community diversity present in a single composite sample from an agricultural soil and to examine potential biases resulting from data acquisition and analytical approaches, we examined the effects of percent G+C DNA fractionation, sequence length, and degree of coverage of bacterial diversity on several commonly used ecological parameters (species estimation, diversity indices, and evenness). We also examined variation in phylogenetic placement based on multiple commonly used approaches (ARB alignments and multiple RDP tools). The results demonstrate that this soil bacterial community is highly diverse, with 1,714 operational taxonomic units demonstrated and 3,555 estimated (based on the Chao1 richness estimation) at 97% sequence similarity using the 16S rRNA gene. The results also demonstrate a fundamental lack of dominance (i.e., a high degree of evenness), with 82% of phylotypes being encountered three times or less. The data also indicate that generally accepted cutoff values for phylum-level taxonomic classification might not be as applicable or as general as previously assumed and that such values likely vary between prokaryotic phyla or groups.
Are Internet Message Boards Used to Facilitate Stock Price Manipulation? Evidence from an Emerging Market, Thailand

The impact of messages posted on the top three financial discussion boards in Thailand is investigated using an event study approach. Heightened message board posting activity for small firms is associated with a strong pre‐event share price run‐up over many days and a partial post‐event return reversal, consistent with manipulative activity whereby traders sometimes ‘talk up’ small‐firm prospects on message boards and then dump them. Close to 90 percent of the price falls associated with bad discussion board news get reversed within 75 days, consistent with short sellers utilising heightened self‐serving message board activity when targeting companies for short selling.
SPoIM: A close look at pollution attacks in P2P live streaming

Peer-to-Peer (P2P) live streaming traffic has been growing at a phenomenal rate over the past few years. When the original streaming content is mixed with bogus data, the corresponding P2P streaming network is being subjected to a “pollution attack. ” As the content is shared by peers, the bogus data can be spread widely in minutes. In this paper, we study the impact of a pollution attack in popular streaming models, under various network settings and configurations. The study was conducted in SPoIM, our emulation of real-world P2P streaming systems under pollution attacks, through which we observed that the feasibility of the attack is sensitive to the speed at which an attacker can modify content. Our experimental results showed that different streaming approaches are more vulnerable in one network configuration than the others, and that the impact and effectiveness of the attack is not dependent on the network size, but does highly depend on the network stability and the bandwidth availability of the polluters and the source. Based the experimental results, we suggested possible improvements in streaming models to defend themselves against the pollution attack. Finally, we examined possible defense mechanisms and demonstrated the effectiveness of a reputation-based defense mechanism against a typical pollution attack.
An Actuarial Balance Sheet of the Swiss Old‐Age Pension Scheme

Following the recent update of the international System of National Accounts (2008 SNA), internationally comparable estimates of accrued‐to‐date pension liabilities (ADL) of unfunded social security pension schemes will soon be available in the supplementary table to the National Accounts. Against this background, this article analyzes the medium‐term sustainability of the Swiss old‐age pension scheme (Alters‐ und Hinterlassenenversicherung – AHV). This is achieved by estimating a “Swedish” actuarial balance sheet, which compares pension liabilities with the explicit and implicit assets of the pension scheme. Our results show that the current financing of the AHV is unsustainable, with about 30 per cent of the liabilities not backed by corresponding assets. In order to close this financing gap either the contribution rate should rise from 8.4 per cent to 12 per cent or all pension liabilities should be cut by about 38 per cent. Apres la recente mise a jour des normes internationales etablies par le Systeme de comptabilite nationale (SCN 2008), le tableau supplementaire produit dans le cadre des comptes nationaux suisses presentera prochainement des estimations, comparables sur le plan international, du montant cumule des engagements des regimes de retraite de la securite sociale finances par repartition. Dans le prolongement de cette evolution comptable, cet article analyse la viabilite a moyen terme du regime suisse de pensions de vieillesse (Alters‐ und Hinterlassenenversicherung – AHV). Pour ce faire, l’auteur dresse un bilan actuariel estimatif, inspire du modele suedois, qui compare les engagements et les actifs implicites et explicites du regime de pensions. Les resultats de cette estimation montrent que le mode de financement actuel de l’AHV n’est pas viable, etant donne qu’environ 30 pour cent de ses engagements ne sont pas garantis par des actifs d’une valeur correspondante. Pour combler ce deficit de financement, il faudrait soit relever le taux de cotisation de 8,4 a 12 pour cent, soit reduire d’environ 38 pour cent l’ensemble des engagements du regime au titre des retraites.
Assessment of frozen storage duration effect on quality characteristics of various horse muscles

Objective The study aimed at assessing the effects of frozen storage duration on quality characteristics, lipid oxidation and sensory quality of various horse muscles. Methods Five representative muscles: longissimus dorsi (LD), gluteus medius (GM), semimembranosus (SM), biceps femoris (BF), and triceps brachii (TB) at 24 h post-mortem obtained from 28-mo-old Jeju female breed horses (n = 8) were used in the present investigation. The muscles were vacuum-packaged and frozen at −20°C for 120, 240, and 360 days. All the samples were analyzed for thawing and cooking losses, pH, Warner–Bratzler shear forces (WBSF), color traits, total volatile basic nitrogen (TVBN), thiobarbituric acid reactive substances (TBARS) and sensory traits. The muscle samples analyzed on day 0 of frozen storage (fresh, non-frozen) were used for comparison. Results Results revealed that thawing and cooking losses significantly (p<0.05) increased in all the muscles after 120 days and then remained unchanged up to 360 days of frozen storage. The TBARS and TVBN contents significantly increased as increasing frozen storage time up to 360 days (p<0.05). While, significant decreases in WBSF values were observed for all the muscles with increased frozen storage time (p<0.05). Frozen storage variously affected the color traits of the muscles for instance; the redness of LD, GM, and BF muscles showed a decreasing tendency during frozen storage while it was not changed in TB and SM muscles. Furthermore, the frozen storage did not produce detrimental effects on sensory quality as it did not cause flavor and juiciness defects whereas it partially improved the tenderness of all the muscles studied. Conclusion Based on the results obtained from our work, it is concluded that frozen storage could be applied to increase the long-term shelf life of horsemeat while still retaining its sensory quality.
Health‐related quality of life of older Asian patients with multimorbidity in primary care in a developed nation

Older adults are susceptible to two or more chronic ailments or multimorbidity. The present study aimed to establish the relationship between multimorbidity and health‐related quality of life (HRQoL) amongst Asian elderly patients in primary care in a developed nation. It also assessed how functional disability and chronic musculoskeletal pain are associated with HRQoL.
Evaluation and comparison of xylazine hydrochloride and dexmedetomidine hydrochloride for the induction of emesis in cats: 47 cases (2007-2013).

OBJECTIVE To evaluate and compare i.m. administration of xylazine hydrochloride and dexmedetomidine hydrochloride for the induction of emesis in cats. DESIGN Retrospective case series. ANIMALS 47 cats with a history of suspected ingestion of a toxic substance or foreign material between June 2007 and June 2013. PROCEDURES Data collected for analysis from the medical records included signalment, drug dose and route of administration, whether a repeated dose of the emetic agent was administered, and outcome (emesis, yes or no). RESULTS Cats in the 2 treatment groups did not differ with regard to age, sex, or breed distribution. The range of doses of xylazine administered i.m. was 0.36 to 0.64 mg/kg (0.16 to 0.29 mg/lb). The range of doses of dexmedetomidine administered i.m. was 6 to 18 μg/kg (2.7 to 8.2 μg/lb). A repeated dose of xylazine or dexmedetomidine was given to 3 and 1 cats, respectively. Emesis was successfully induced in 24 of the 47 (51.1%) cats. Nine of the 21 (43%) cats that received xylazine vomited and 15 of the 26 (58%) cats that received dexmedetomidine vomited. Percentage of cats that vomited after either drug administration did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Following i.m. administration in cats, xylazine and dexmedetomidine were similarly effective for induction of emesis, indicating that dexmedetomidine is a comparable alternative to xylazine for this purpose. Prospective studies are needed to determine the optimal i.m. dose of dexmedetomidine for induction of emesis in cats.
Sexual risk behaviours, HIV and other sexually transmitted infections among female sex workers in Indonesia

Objectives To assess the HIV/AIDS epidemic situation among female sex workers (FSW) in Indonesia using data from the 2007 Integrated Biological-Behavioural Surveillance (IBBS). Methods Behavioural data were collected from time–location samples of 5947 FSW in 10 cities in late 2007. HIV, syphilis, gonorrhoea and chlamydia test results were obtained for 4396, 4324, 3291 and 3316 FSW, respectively. Trends in HIV prevalence were assessed via linkage with sentinel surveillance data. Factors associated with HIV, gonorrhoea and chlamydia infection were assessed using multivariable logistic regression. Results HIV prevalence averaged 10.5% among direct and 4.9% among indirect FSW, and had increased steadily among direct FSW from 2002 to 2007. Prevalence of chlamydia, gonorrhoea and active syphilis averaged 35.6%, 31.8% and 7.3%, respectively, among direct FSW, and 28.7%, 14.3% and 3.5% among indirect FSW. Being a direct FSW, younger age and having current infection with syphilis and gonorrhoea and/or chlamydia were associated with a higher likelihood of HIV infection. Number of clients in the past week and consumption of alcohol before having sex were associated with a higher likelihood of gonorrhoea and/or chlamydia infection, while having received a STI clinic check-up in the previous 3 months and/or periodic presumptive treatment for sexually transmitted infections (STIs) in the past 6 months were associated with reduced likelihood of infection. Conclusions The HIV/AIDS epidemic among FSW in Indonesia appears to be expanding, albeit unevenly across provinces and types of FSW. High STI prevalence is conducive to further expansion, but recent efforts to strengthen STI control appear promising.
Diverse Effects of Mutations in Exon II of the von Hippel-Lindau (VHL) Tumor Suppressor Gene on the Interaction of pVHL with the Cytosolic Chaperonin and pVHL-Dependent Ubiquitin Ligase Activity

ABSTRACT We examined the biogenesis of the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL) in vitro and in vivo. pVHL formed a complex with the cytosolic chaperonin containing TCP-1 (CCT or TRiC) en route to assembly with elongin B/C and the subsequent formation of the VCB-Cul2 ubiquitin ligase. Blocking the interaction of pVHL with elongin B/C resulted in accumulation of pVHL within the CCT complex. pVHL present in purified VHL-CCT complexes, when added to rabbit reticulocyte lysate, proceeded to form VCB and VCB-Cul2. Thus, CCT likely functions, at least in part, by retaining VHL chains pending the availability of elongin B/C for final folding and/or assembly. Tumor-associated mutations within exon II of the VHL syndrome had diverse effects upon the stability and/or function of pVHL-containing complexes. First, a pVHL mutant lacking the entire region encoded by exon II did not bind to CCT and yet could still assemble into complexes with elongin B/C and elongin B/C-Cul2. Second, a number of tumor-derived missense mutations in exon II did not decrease CCT binding, and most had no detectable effect upon VCB-Cul2 assembly. Many exon II mutants, however, were found to be defective in the binding to and subsequent ubiquitination of hypoxia-inducible factor 1α (HIF-1α), a substrate of the VCB-Cul2 ubiquitin ligase. We conclude that the selection pressure to mutate VHL exon II during tumorigenesis does not relate to loss of CCT binding but may reflect quantitative or qualitative defects in HIF binding and/or in pVHL-dependent ubiquitin ligase activity.
Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status

The phospholipid transfer protein STARD10 cooperates with c‐erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome. The central findings were independently validated by immunohistochemistry in a retrospective cohort of 222 patients with breast cancer with a median follow‐up of 64 months. Kaplan–Meier and Cox proportional hazards analyses were used for univariate and multivariate analyses. Patients with low STARD10 or high HER2 tumor mRNA levels formed discrete groups each associated with a poor disease‐specific survival (p = 0.0001 and p = 0.0058, respectively). In the immunohistochemical study low/absent STARD10 expression i.e. ≤10% positive cells was observed in 24 of 222 (11%) tumors. In a univariate model, low/absent STARD10 expression was significantly associated with decreased patient survival (p = 0.0008). In multivariate analyses incorporating tumor size, tumor grade, lymph node status, ER, PR and HER2 status, low STARD10 expression was an independent predictor of death from breast cancer (HR: 2.56 (95% CI: 1.27–5.18), p = 0.0086). Furthermore, low/absent STARD10 expression, HER2 amplification and triple negative status were independent prognostic variables. Loss of STARD10 expression may provide an additional marker of poor outcome in breast cancer identifying a subgroup of patients with a particularly adverse prognosis, which is independent of HER2 amplification and the triple negative phenotype.
Colon Cancer: Prevalence, Screening, Gene Expression and Mutation, and Risk Factors and Assessment

Abstract Colon cancer detection at an early stage and identifying susceptible individuals can result in reduced mortality from this prevalent cancer. Genetic events leading to the development of this cancer involve a multistage progression of adenoma polyps to invasive metastatic carcinomas. Currently, there is no satisfactory screening method that is highly specific, sensitive, or reliable. Dietary patterns associated with the greatest increase in colon cancer risk are the ones that typify a diet rich in fat and calories, and low in vegetable, fruits, and fibers. Genetic susceptibility to environmental carcinogenesis must be factored into the risk assessment for this cancer. Many genes have been shown to be associated with increased expression and mutations in colorectal cancer patients. These genes have been reviewed; it is hoped that by carefully selecting a number of them, a molecular approach that is suitable for arriving at a tumorigenic expression index is developed, which will reliably detect this cancer at an early stage (i.e., before it metastasizes), especially in exfoliated samples (e.g., stool and blood), so that appropriate intervention strategies can be implemented. Illustrated herein is the utility of employing real-time reverse transcriptase polymerase chain reaction (RT-PCR) to quantitatively measure gene expression, and develop an index that is specific for this cancer, which if perfected may result in a reliable and sensitive screening technique for colorectal cancer detection.