Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for distinct alterations in the FGF axis in prostate cancer progression to an aggressive clinical phenotype

Multiple fibroblast growth factor (FGF) axis alterations are known to occur in prostate cancer. Here we simultaneously profiled key components of this axis to determine their relevance in disease progression. An optimized immunohistochemistry protocol was used in expression analysis of FGF2, FGF8, FGFR1, FGFR4, and Sef (similar expression to FGF) in a single TMA of prostate cancer. FGF ligands and receptors were overexpressed in cancers compared to benign samples (p < 0.0001), while Sef expression was reduced (p < 0.0001). There was a positive association between higher grades and increased FGFR4 (p = 0.02), FGF2, and FGF8 (p = 0.002 and p < 0.0001). Sef expression was progressively lower with increasing grade (p = 0.005). Clinical stage was positively associated with FGF2, FGF8, and FGFR4 expression (p = 0.005, 0.03, and 0.012) but not with FGFR1 or Sef expression. Only reduced Sef was associated with bone metastasis (p = 0.02) and was also predictive of subsequent metastasis in initially localized tumours (p = 0.004). Down‐regulation of Sef and increased FGFR4 were also the only independent variables associated with disease‐specific survival (HR 1.73, p = 0.04 and HR 0.56, p = 0.01). In in vitro studies, silencing Sef enhanced the cell response to FGFs (p < 0.001) and substantially mitigated the effectiveness of an FGFR1 inhibitor. Conversely, increased Sef blocked the response to FGFs and had a comparable suppressive effect to the inhibitor. This study demonstrates that increased FGFR4 and reduced Sef may be critical FGF alterations associated with prostate cancer progression. Sef may also have a role in the tumour response to FGFR inhibition and warrants further investigation in this context. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Norepinephrine and dopamine transmission in 2 limbic regions differentially respond to acute noxious stimulation

Abstract Central dopamine and norepinephrine regulate behavioral and physiological responses during rewarding and aversive stimuli. Here, we investigated and compared norepinephrine and dopamine transmission in 2 limbic structures, the ventral bed nucleus of the stria terminalis and the nucleus accumbens shell of anesthetized rats, respectively, in response to acute tail pinch, a noxious stimulus. Norepinephrine release in the ventral bed nucleus of the stria terminalis responded monophasically, increasing at the time of the tail pinch and remaining elevated for a period after its cessation. In contrast, dopamine transmission in the nucleus accumbens shell displayed a heterogeneous and time-locked response to tail pinch. For most trials, there was a suppression of extracellular dopamine concentration throughout the duration of the stimuli. At the termination of the stimuli, however, extracellular dopamine either recovered back to or spiked above the initial baseline concentration. These signaling patterns were more clearly observed after administration of selective catecholamine autoreceptor and transporter inhibitors. The results suggest that the opposing responses of these catecholamines can provide integration of noxious inputs to influence behavioral outputs appropriate for survival such as escape or fighting.
Association between housework overload and common mental disorders in women.

INTRODUCTION Common mental disorders (CMD) are more frequent in women. Low reward and lack of visibility in performing housework are the determining factors for these psychological illnesses. OBJECTIVES To evaluate the association between housework overload and the occurrence of common mental disorders in women living in the urban zone of the municipality of Feira de Santana, Bahia. METHODS cross-sectional epidemiological study that included 2,057 women aged 15 years or over selected by random sampling in clusters. The housework overload indicator was created from the domestic activities of washing, ironing, cleaning and cooking, weighted according to the number of individuals living in the home. The common mental disorders were assessed using SRQ-20. RESULTS Women with a high housework overload had a higher prevalence of CMD than women with a low overload (45.6% versus 36.2%). Multiple logistic regression analysis confirmed the association between housework overload and CMD (PR: 1.23; 95% CI: 1.05 - 1.44), adjusted for income, level of schooling and leisure activities. CONCLUSION The findings support the hypothesis that high housework overload is associated with mental disorders.
Development of a scale to evaluate postoperative pain in dogs.

OBJECTIVE To design and evaluate a scale for measurement of postoperative pain in dogs. DESIGN Randomized, blinded, prospective study, with positive- and negative-control groups. ANIMALS 36 dogs undergoing general anesthesia for ovariohysterectomy and 12 dogs undergoing general anesthesia without surgery. PROCEDURE A pain assessment scale was developed for dogs, which incorporated physiologic data (heart and respiratory rates) and behavioral responses (response to palpation, activity, mental status, posture, and vocalization). This pain scale was then applied to a study in which dogs were allocated to 2 groups, depending on the type of medication administered (acepromazine maleate only or acepromazine and butorphanol) before induction of general anesthesia. The 36 dogs that had ovariohysterectomy were allocated to 3 groups, members of which received butorphanol, carprofen, or no analgesic after surgery. Dogs were scored for signs of pain and videotaped at 0, 1, 2, 4, 6, 8, 12, and 18 hours after surgery by an assessor who was blinded to the groups. Results were analyzed for significant differences in pain scores for single categories and total pain scores among groups. Video segments were scrambled and then scored by a second external assessor to test the repeatability of the results, using the pain assessment scale. RESULTS Mean total pain scores were significantly different between the group of dogs that underwent general anesthesia only and each group of dogs that underwent general anesthesia and surgery. Pain scores for the analgesic-treatment groups reflected the known onset and duration of action of the analgesic used. Agreement between the internal and external assessors was excellent and indicated high precision between the 2 assessors for the population of dogs as a whole. CLINICAL IMPLICATIONS Behavioral and physiologic measurements can be used reliably to evaluate degree of pain in dogs during the postoperative period and their response to analgesics.
Flexibility and Security within European Labor Markets

In this comparative qualitative study, the authors examine how local bargaining shapes the trade-off between labor flexibility and employment security policies in four multinational subsidiaries in Belgium, Britain, and Germany. They also consider whether and how union power to shape flexibility and security policies is affected by national institutions, the way that multinationals organize their subsidiaries, and local contextual factors. Findings support this multilevel, interdependent framework. Trade-offs are shaped by differences in workers’ structural power in specific local subsidiaries. Differences in inter-subsidiary organizational configurations, markets, and technologies modify how unions can leverage collective resources to wield power in their relationship with management.
Fiscal Policy and Presidential Elections, 1880-1992

Fiscal policy is both a contributor to and an effect of presidential electoral fortunes in the United States. An analysis of presidential election results between 1880 and 1992 shows that, except in periods of major war, an increase in the ratio of federal outlays to GNP has a negative effect on presidential reelection independent of inflation or growth rate. Yet even though faced with voters who punish expansion and reward cutbacks, presidents do not react consistently. At most, there is evidence that presidents leave spending levels about the same in their first term and act more boldly to change spending levels up or down only after reelection.
Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs: clinical, histologic, and immunohistochemical evaluation.

OBJECTIVES To reclassify canine small intestinal and cecal leiomyoma (LM) and leiomyosarcoma (LMS) into smooth muscle and gastrointestinal stromal tumors (GIST) using histologic and immunohistochemical (IH) analysis and to report clinical findings and survival data. STUDY DESIGN Retrospective review of cases. ANIMALS Dogs (n=47) with small intestinal (40 LMS; 7 LM) and 25 dogs with cecal tumors (23 LMS; 2 LM). METHODS Clinical and survival data were reviewed. Tissue sections were reevaluated for light-microscopic malignancy criteria and examined for expression of SMA, desmin, vimentin, S-100, and CD117 (KIT) by immunohistochemistry. RESULTS Reclassification resulted in 2 LM, 9 LMS, 19 GIST, and 17 GIST-like tumors in the small intestine and 23 GIST and 2 GIST-like tumors in the cecum. GIST-like tumors were morphologic and IH identical to GIST but lacked KIT expression. No significant difference in survival was observed for tumor type, location, histologic, or IH characteristics; however, dogs with cecal tumors were significantly older in age, presented more commonly with intestinal perforation and peritonitis, and less commonly with weight loss. Cecal tumors had more histologic malignancy criteria than small intestinal tumors. After excision, 1 and 2 year recurrence-free periods were 80.1% and 67.2% for small intestinal and 83.3% and 61.9% for cecal tumors. CONCLUSION Prognosis for intestinal tumors with histologic smooth muscle appearance is good after excision and not related to tumor type, location, histologic, or IH characteristics. CLINICAL RELEVANCE Clinical importance could not be demonstrated for reclassification, but may be for future treatment, of intestinal smooth muscle or stromal tumors.
Children in the streets of Brazil: drug use, crime, violence, and HIV risks.

The presence of vast numbers of unsupervised and unprotected children is a phenomenon that is common throughout Latin America, and in few places are the street children more visible, and reviled, than in Brazil. Estimates of their numbers in Brazil have ranged from 7 to 17 million, but more informed assessments suggest that between 7 and 8 million children, ages 5 to 18, live and/or work on the streets of urban Brazil. Accounts of drug misuse among street youths in Brazil are commonplace. Numerous scientific studies and media stories have reported the widespread use of inhalants, marijuana and cocaine, and Valium among street children. Also common is the use of coca paste and Rohypnol. Risk of exposure to HIV is rapidly becoming an area of concern because of the large number of street youths engaging in unprotected sexual acts, both renumerated and nonrenumerated. Moreover, Brazil's street children are targets of fear. Because of their drug use, predatory crimes, and general unacceptability on urban thoroughfares, they are frequently the targets of local vigilante groups, drug gangs, and police "death squads. " Although there have been many proposals and programs for addressing the problems of Brazilian street youth, it would appear that only minimal headway has been achieved.
Human MRE11 is inactivated in mismatch repair‐deficient cancers

Mutations of the ATM and NBS1 genes are responsible for the inherited Ataxia‐Telangiectasia and Nijmegen Breakage Syndrome, both of which are associated with a predisposition to cancer. A related syndrome, the Ataxia‐Telangiectasia‐like disorder, is due to mutations of the MRE11 gene. However, the role of this gene in cancer development has not been established. Here we describe an often homozygous mutation of the poly(T)11 repeat within human MRE11 intron 4 that leads to aberrant splicing, impairment of wild‐type MRE11 expression and generation of a truncated protein. This mutation is present in mismatch repair‐deficient, but not proficient, colorectal cancer cell lines and primary tumours and is associated with reduced expression of the MRE11–NBS1–RAD50 complex, an impaired S‐phase checkpoint and abrogation of MRE11 and NBS1 ionizing radiation‐induced nuclear foci. Our findings identify MRE11 as a novel and major target for inactivation in mismatch repair‐defective cells and suggest its impairment may contribute to the development of colorectal cancer.
Bluetongue in Europe: past, present and future

The recent arrival in Northern and Western (NW) Europe of bluetongue virus (BTV), which causes the ruminant disease ‘bluetongue’, has raised the profile of this vector-borne ruminant disease and sparked discussions on the reasons for its sudden emergence so far north. This expansion has not happened in isolation and the disease has been expanding into Southern and Eastern Europe for the last decade. This shifting disease distribution is being facilitated by a number of different introduction mechanisms including the movement of infected livestock, the passive movement of infected Culicoides on the wind and, in NW Europe, an unknown route of introduction. The expansion of BTV in Europe has forced a re-evaluation of the importance of Palaearctic Culicoides species in transmission, as well as the importance of secondary transmission routes, such as transplacental transmission, in facilitating the persistence of the virus. The current European outbreak of BTV-8 is believed to have caused greater economic damage than any previous single-serotype outbreak. Although attempts are being made to improve the capacity of European countries to cope with future BTV incursions, the options available are limited by a lack of basic entomological data and limited virological surveillance.
Achilles Tendon characterization in GDF‐7 deficient mice

Growth/differentiation factors (GDFs) play a significant role in numerous skeletal tissues and processes. Previous work using the brachypod mouse has suggested that GDF‐5 affects Achilles tendon composition, ultrastructure, and material behavior, as well as tendon repair. The aim of the present study was to examine the role of a related GDF family member, GDF‐7 (BMP‐12), in intact tendon by studying the Achilles tendon of genetically engineered knockout mice. Achilles tendons from 16‐week‐old GDF‐7 −/− mice contained 14% less GAG/DNA than did wild type littermates (p = 0.0481), although collagen content was comparable to controls. Quantitative reverse transcriptase‐polymerase chain reaction (QRT‐PCR) results show that GDF‐5 was upregulated two–threefold in response to the absence of GDF‐7 protein. GDF‐6 was also upregulated in knockouts, but to a lesser extent (twofold, p = 0.0013). On an ultrastructural level, GDF‐7 deficient Achilles tendons exhibited a shift towards smaller diameter fibrils which resulted in a small but significant reduction in mean fibril diameter (−8%, p = 0.05). GDF‐7 deficiency did not noticeably affect the expression of fibrillar collagens (I, III, V) or tendon proteoglycans (decorin, fibromodulin, lumican, biglycan, versican, aggrecan). Differences in tendon composition and ultrastructure were not biologically significant enough to have a noticeable effect on the structural or material behavior of the tendons. These results demonstrate that GDF‐7 deficiency has a subtle effect on the composition and ultrastructure of murine Achilles tendon. The small magnitude of the observed differences may be due to overcompensation by related GDF family members. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels

Objective:The initiation of antiretroviral therapy (ART) during primary infection may offer clinical benefits for HIV-infected individuals by reducing HIV DNA reservoir size and chronic T-cell activation. Current evidence for the advantages of early ART, however, are mostly derived from cross-sectional studies, with the long-term benefits yet to be ascertained. Design/methods:We conducted an open-label, nonrandomized study, monitoring for 3 years: plasma viral load (pVL), T-cell phenotypes, and peripheral CD4+ T-cell associated total, integrated and 2-long terminal repeat HIV DNA species. The study included 16 treatment-naive individuals initiating ART with raltegravir and Truvada during either primary (PHI, n = 8) or chronic (CHI, n = 8) HIV infection. Results:ART initiated during PHI compared with CHI generated significant reductions of peripheral CD4+ T-cell HIV DNA reservoirs that were sustained for 3 years of therapy. Median log10 HIV DNA copies/106 CD4+ T cells at the final visit: total; CHI = 3.23 > PHI = 2.72, P < 0.01; integrated; CHI = 2.64 > PHI = 1.77, P < 0.01. Similar trends were observed for pVL, however, did not reach significance: log10 HIV RNA copies/ml plasma at the final visit: CHI = 1.3 ≥ PHI = 0.39, P = 0.08. Both cohorts displayed similar and elevated levels of CD38/HLA-DR coexpression on CD4+ and CD8+ T cells relative to uninfected healthy controls. Conclusion:The reduction in HIV DNA reservoirs generated by the early initiation of ART was sustained for 3 years of therapy. Although the PHI cohort trended to lower levels of pVL, and pVL was associated with CD8+ T-cell activation, no differences in T-cell activation were observed between the PHI and CHI groups.
Monetary Policy, Country Size and Labour Market Flexibility in the European Monetary Union

This paper explores the impact of country size on labour market flexibility in a monetary union with a common monetary policy as conducted in EMU. I apply a Barro-Gordon framework and test its result empirically for EMU. Results confirm that small countries demand higher labour market flexibility than large countries. Small countries use labour market flexibility to be protected against monetary policy in favour of large countries and use flexibility as a substitute for monetary policy. Thereby, national inflation volatilities and unemployment volatility are important determinants. Business cycle synchronization reduces the need of small countries for additional labour market flexibility.
Beryllium Alters Lipopolysaccharide-Mediated Intracellular Phosphorylation and Cytokine Release in Human Peripheral Blood Mononuclear Cells

Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1β is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1β secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.
Dual Role of Signaling Pathways Leading to Ca2+ and Cyclic AMP Elevation in Host Cell Invasion byTrypanosoma cruzi

ABSTRACT Cell invasion by the protozoan parasite Trypanosoma cruzi involves activation of host signaling pathways and the recruitment and fusion of lysosomes at the parasite entry site. A major signaling pathway regulating invasion of fibroblasts, epithelial cells, and myoblasts involves mobilization of Ca2+ from intracellular stores and requires the activity of a T. cruzi serine peptidase, oligopeptidase B (OPB). Deletion of the OPB gene results in a marked defect in trypomastigote virulence, consistent with a greatly reduced cell invasion capacity. Here we show that uptake by macrophages, on the other hand, is largely independent of OPB expression and sensitive to inhibition of by cytochalasin D. The residual invasion capacity of OPBnull trypomastigotes in fibroblasts still involves lysosome recruitment, although in a significantly delayed fashion. Transient elevations in intracellular Ca2+concentrations were observed in host cells exposed to both wild-type and OPBnull trypomastigotes, but the signals triggered by the mutant parasites were less vigorous and delayed. The capacity of triggering elevation in host cell cyclic AMP (cAMP), however, was unaltered in OPBnull trypomastigotes. Modulation in cAMP levels preferentially affected the residual cell invasion capacity of OPBnull parasites, suggesting that this signaling pathway can play a dominant role in promoting cell invasion in the absence of the major OPB-dependent pathway.
Analysis of Effects of Manhole Covers on Motorcycle Driver Maneuvers: A Nonparametric Classification Tree Approach

Objective: A manhole cover is a removable plate forming the lid over the opening of a manhole to allow traffic to pass over the manhole and to prevent people from falling in. Because most manhole covers are placed in roadway traffic lanes, if these manhole covers are not appropriately installed or maintained, they can represent unexpected hazards on the road, especially for motorcycle drivers. The objective of this study is to identify the effects of manhole cover characteristics as well as driver factors and traffic and roadway conditions on motorcycle driver maneuvers. Method: A video camera was used to record motorcycle drivers’ maneuvers when they encountered an inappropriately installed or maintained manhole cover. Information on 3059 drivers’ maneuver decisions was recorded. Classification and regression tree (CART) models were applied to explore factors that can significantly affect motorcycle driver maneuvers when passing a manhole cover. Results: Nearly 50 percent of the motorcycle drivers decelerated or changed their driving path to reduce the effects of the manhole cover. The manhole cover characteristics including the level difference between manhole cover and pavement, the pavement condition over the manhole cover, and the size of the manhole cover can significantly affect motorcycle driver maneuvers. Other factors, including traffic conditions, lane width, motorcycle speed, and loading conditions, also have significant effects on motorcycle driver maneuvers. Conclusions: To reduce the effects and potential risks from the manhole covers, highway authorities not only need to make sure that any newly installed manhole covers are as level as possible but also need to regularly maintain all the manhole covers to ensure that they are in good condition. In the long run, the size of manhole covers should be kept as small as possible so that the impact of manhole covers on motorcycle drivers can be effectively reduced. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.